Geriatrics

In the case of a hip fracture, operating on a patient with dementia can be a difficult decision to make. Indeed, surgery exposes patients with dementia to a higher mortality rate, more delirium and postoperative complications, and a greater loss of mobility than patients of the same age without cognitive impairments. For patients with dementia in institutional settings, survival is better for those who undergo surgery than for those who do not. But what about the prognosis of surgery vs no surgery for patients with dementia who live at home?

To answer this question, researchers in the United States conducted a cohort study using Medicare data. This retrospective study included patients aged 66 years and older with dementia who were living at home and not placed in institutions and who had a hip fracture between January 2017 and June 2018. Patients with incomplete observations, particularly regarding the location and type of residence (home/institution), were excluded from the analysis. Fractures were categorized as (i) fractures of the head and neck, (ii) pertrochanteric, (iii) subtrochanteric, and (iv) multiple/complex. The type and severity (mild, moderate, or severe) of dementia were identified using the diagnostic code list in the International Statistical Classification of Diseases, Tenth Revision.
 

Examining Mortality

The primary outcome was mortality at 30, 90, and 180 days. Secondary outcomes included hospital delirium; the need for subsequent hospitalization (within 6 months) or home health services (within 10 days); and intensive care interventions such as dialysis, intubation, resuscitation maneuvers, mechanical ventilation, or the insertion of a feeding tube.

Postoperative medical facility admissions were distinguished according to whether there was a plan to return home. To compare the surgery and nonsurgery groups, an inverse propensity score analysis was conducted within subgroups determined by fracture type, comorbidities (using the Elixhauser score), the person or entity responsible for admission (ie, physician, clinic, hospital, etc.), dual eligibility (Medicare and Medicaid), place of residence (ie, urban or rural), race, and sex. Dementia severity was estimated using a frailty index on the basis of evaluation tests that were systematically collected in the Medicare database.
 

Results Favored Surgery

Among 56,209 patients with dementia who were admitted for a hip fracture (73.0% women; mean age, 86.4 ± 7.0 years), 33,142 (59.0%) underwent surgery and 23,067 (41.0%) did not. Among surgically treated patients, 73.3% had fractures of the head or neck of the femur, and 40.2% had moderate to severe dementia. The nonsurgically treated fractures were 78.5% pertrochanteric. Comorbidities were evenly distributed between the two groups.

At 180 days, mortality was 31.8% in the surgery group compared with 45.7% in the nonsurgery group, resulting in a significant reduction in the unadjusted relative risk (RR) for death in favor of surgery (RR, 0.67; 95% CI, 0.60-0.76; P < .001). Among patients with mild dementia and a fracture of the head or neck of the femur, mortality at 180 days was 26.5% among surgical patients and 34.9% among nonsurgical patients (RR, 0.67; 95% CI, 0.60-0.76; P < .001). After the investigators adjusted for risk according to propensity score, the benefit of surgery remained significant at 30, 90, and 180 days, regardless of dementia severity. There was no significant difference in mortality for other types of hip fractures between the surgery and nonsurgery groups, however.

The adjusted RR for in-hospital delirium was 1.23 (P = .008), which was significant for the surgery group, but only for those with moderate to severe dementia. There were also fewer permanent placements (P < .001) among the surgically treated patients, and fewer patients with mild dementia required nurse care at home. There was no difference in resuscitation maneuvers between surgery and nonsurgery patients, whether the dementia was mild or not. For patients with a fracture of the head or neck of the femur, there was no difference in the likelihood of rehabilitation admission within 180 days, whether they were operated on or not.
 

Ethical Considerations

This study can inform discussions among healthcare professionals, patients, and patients’ families about which goals to set and which strategy to choose. The main interest of this study lies in its comparison of outcomes between patients with dementia who were operated on and those who were not, rather than comparing patients with and without dementia. Among patients with dementia living at home with a fracture of the head or neck of the femur, those who underwent surgery had a lower risk for death than those who did not, regardless of the severity of dementia.

It is noteworthy that less than two thirds of patients with dementia underwent surgery, which contradicts recommendations for almost routine surgery for patients with dementia. This observation raises questions about respecting patient wishes and advance directives when known, possible detrimental delays in referrals, and legal-medical issues.

Furthermore, the treatment choices of American surgeons are clearly influenced by the type of hip fracture. Fractures of the head and neck of the femur are typically treated with prosthetic arthroplasty, which simplifies postoperative care, compared with osteosynthesis. The latter procedure is more often used for extra-articular hip fractures but entails higher risks. While survival is an apparently more easily achievable goal through surgery, ethical considerations about other treatment objectives such as pain control, functional recovery, and treatment adequacy cannot be overlooked. It is worth noting that the French National Authority for Health issued recommendations in 2018 regarding the care pathway for patients hospitalized for a hip fracture within an orthogeriatric organization.

This story was translated from JIM, which is part of the Medscape Medical News professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

In the case of a hip fracture, operating on a patient with dementia can be a difficult decision to make. Indeed, surgery exposes patients with dementia to a higher mortality rate, more delirium and postoperative complications, and a greater loss of mobility than patients of the same age without cognitive impairments. For patients with dementia in institutional settings, survival is better for those who undergo surgery than for those who do not. But what about the prognosis of surgery vs no surgery for patients with dementia who live at home?

To answer this question, researchers in the United States conducted a cohort study using Medicare data. This retrospective study included patients aged 66 years and older with dementia who were living at home and not placed in institutions and who had a hip fracture between January 2017 and June 2018. Patients with incomplete observations, particularly regarding the location and type of residence (home/institution), were excluded from the analysis. Fractures were categorized as (i) fractures of the head and neck, (ii) pertrochanteric, (iii) subtrochanteric, and (iv) multiple/complex. The type and severity (mild, moderate, or severe) of dementia were identified using the diagnostic code list in the International Statistical Classification of Diseases, Tenth Revision.
 

Examining Mortality

The primary outcome was mortality at 30, 90, and 180 days. Secondary outcomes included hospital delirium; the need for subsequent hospitalization (within 6 months) or home health services (within 10 days); and intensive care interventions such as dialysis, intubation, resuscitation maneuvers, mechanical ventilation, or the insertion of a feeding tube.

Postoperative medical facility admissions were distinguished according to whether there was a plan to return home. To compare the surgery and nonsurgery groups, an inverse propensity score analysis was conducted within subgroups determined by fracture type, comorbidities (using the Elixhauser score), the person or entity responsible for admission (ie, physician, clinic, hospital, etc.), dual eligibility (Medicare and Medicaid), place of residence (ie, urban or rural), race, and sex. Dementia severity was estimated using a frailty index on the basis of evaluation tests that were systematically collected in the Medicare database.
 

Results Favored Surgery

Among 56,209 patients with dementia who were admitted for a hip fracture (73.0% women; mean age, 86.4 ± 7.0 years), 33,142 (59.0%) underwent surgery and 23,067 (41.0%) did not. Among surgically treated patients, 73.3% had fractures of the head or neck of the femur, and 40.2% had moderate to severe dementia. The nonsurgically treated fractures were 78.5% pertrochanteric. Comorbidities were evenly distributed between the two groups.

At 180 days, mortality was 31.8% in the surgery group compared with 45.7% in the nonsurgery group, resulting in a significant reduction in the unadjusted relative risk (RR) for death in favor of surgery (RR, 0.67; 95% CI, 0.60-0.76; P < .001). Among patients with mild dementia and a fracture of the head or neck of the femur, mortality at 180 days was 26.5% among surgical patients and 34.9% among nonsurgical patients (RR, 0.67; 95% CI, 0.60-0.76; P < .001). After the investigators adjusted for risk according to propensity score, the benefit of surgery remained significant at 30, 90, and 180 days, regardless of dementia severity. There was no significant difference in mortality for other types of hip fractures between the surgery and nonsurgery groups, however.

The adjusted RR for in-hospital delirium was 1.23 (P = .008), which was significant for the surgery group, but only for those with moderate to severe dementia. There were also fewer permanent placements (P < .001) among the surgically treated patients, and fewer patients with mild dementia required nurse care at home. There was no difference in resuscitation maneuvers between surgery and nonsurgery patients, whether the dementia was mild or not. For patients with a fracture of the head or neck of the femur, there was no difference in the likelihood of rehabilitation admission within 180 days, whether they were operated on or not.
 

Ethical Considerations

This study can inform discussions among healthcare professionals, patients, and patients’ families about which goals to set and which strategy to choose. The main interest of this study lies in its comparison of outcomes between patients with dementia who were operated on and those who were not, rather than comparing patients with and without dementia. Among patients with dementia living at home with a fracture of the head or neck of the femur, those who underwent surgery had a lower risk for death than those who did not, regardless of the severity of dementia.

It is noteworthy that less than two thirds of patients with dementia underwent surgery, which contradicts recommendations for almost routine surgery for patients with dementia. This observation raises questions about respecting patient wishes and advance directives when known, possible detrimental delays in referrals, and legal-medical issues.

Furthermore, the treatment choices of American surgeons are clearly influenced by the type of hip fracture. Fractures of the head and neck of the femur are typically treated with prosthetic arthroplasty, which simplifies postoperative care, compared with osteosynthesis. The latter procedure is more often used for extra-articular hip fractures but entails higher risks. While survival is an apparently more easily achievable goal through surgery, ethical considerations about other treatment objectives such as pain control, functional recovery, and treatment adequacy cannot be overlooked. It is worth noting that the French National Authority for Health issued recommendations in 2018 regarding the care pathway for patients hospitalized for a hip fracture within an orthogeriatric organization.

This story was translated from JIM, which is part of the Medscape Medical News professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

In the case of a hip fracture, operating on a patient with dementia can be a difficult decision to make. Indeed, surgery exposes patients with dementia to a higher mortality rate, more delirium and postoperative complications, and a greater loss of mobility than patients of the same age without cognitive impairments. For patients with dementia in institutional settings, survival is better for those who undergo surgery than for those who do not. But what about the prognosis of surgery vs no surgery for patients with dementia who live at home?

To answer this question, researchers in the United States conducted a cohort study using Medicare data. This retrospective study included patients aged 66 years and older with dementia who were living at home and not placed in institutions and who had a hip fracture between January 2017 and June 2018. Patients with incomplete observations, particularly regarding the location and type of residence (home/institution), were excluded from the analysis. Fractures were categorized as (i) fractures of the head and neck, (ii) pertrochanteric, (iii) subtrochanteric, and (iv) multiple/complex. The type and severity (mild, moderate, or severe) of dementia were identified using the diagnostic code list in the International Statistical Classification of Diseases, Tenth Revision.
 

Examining Mortality

The primary outcome was mortality at 30, 90, and 180 days. Secondary outcomes included hospital delirium; the need for subsequent hospitalization (within 6 months) or home health services (within 10 days); and intensive care interventions such as dialysis, intubation, resuscitation maneuvers, mechanical ventilation, or the insertion of a feeding tube.

Postoperative medical facility admissions were distinguished according to whether there was a plan to return home. To compare the surgery and nonsurgery groups, an inverse propensity score analysis was conducted within subgroups determined by fracture type, comorbidities (using the Elixhauser score), the person or entity responsible for admission (ie, physician, clinic, hospital, etc.), dual eligibility (Medicare and Medicaid), place of residence (ie, urban or rural), race, and sex. Dementia severity was estimated using a frailty index on the basis of evaluation tests that were systematically collected in the Medicare database.
 

Results Favored Surgery

Among 56,209 patients with dementia who were admitted for a hip fracture (73.0% women; mean age, 86.4 ± 7.0 years), 33,142 (59.0%) underwent surgery and 23,067 (41.0%) did not. Among surgically treated patients, 73.3% had fractures of the head or neck of the femur, and 40.2% had moderate to severe dementia. The nonsurgically treated fractures were 78.5% pertrochanteric. Comorbidities were evenly distributed between the two groups.

At 180 days, mortality was 31.8% in the surgery group compared with 45.7% in the nonsurgery group, resulting in a significant reduction in the unadjusted relative risk (RR) for death in favor of surgery (RR, 0.67; 95% CI, 0.60-0.76; P < .001). Among patients with mild dementia and a fracture of the head or neck of the femur, mortality at 180 days was 26.5% among surgical patients and 34.9% among nonsurgical patients (RR, 0.67; 95% CI, 0.60-0.76; P < .001). After the investigators adjusted for risk according to propensity score, the benefit of surgery remained significant at 30, 90, and 180 days, regardless of dementia severity. There was no significant difference in mortality for other types of hip fractures between the surgery and nonsurgery groups, however.

The adjusted RR for in-hospital delirium was 1.23 (P = .008), which was significant for the surgery group, but only for those with moderate to severe dementia. There were also fewer permanent placements (P < .001) among the surgically treated patients, and fewer patients with mild dementia required nurse care at home. There was no difference in resuscitation maneuvers between surgery and nonsurgery patients, whether the dementia was mild or not. For patients with a fracture of the head or neck of the femur, there was no difference in the likelihood of rehabilitation admission within 180 days, whether they were operated on or not.
 

Ethical Considerations

This study can inform discussions among healthcare professionals, patients, and patients’ families about which goals to set and which strategy to choose. The main interest of this study lies in its comparison of outcomes between patients with dementia who were operated on and those who were not, rather than comparing patients with and without dementia. Among patients with dementia living at home with a fracture of the head or neck of the femur, those who underwent surgery had a lower risk for death than those who did not, regardless of the severity of dementia.

It is noteworthy that less than two thirds of patients with dementia underwent surgery, which contradicts recommendations for almost routine surgery for patients with dementia. This observation raises questions about respecting patient wishes and advance directives when known, possible detrimental delays in referrals, and legal-medical issues.

Furthermore, the treatment choices of American surgeons are clearly influenced by the type of hip fracture. Fractures of the head and neck of the femur are typically treated with prosthetic arthroplasty, which simplifies postoperative care, compared with osteosynthesis. The latter procedure is more often used for extra-articular hip fractures but entails higher risks. While survival is an apparently more easily achievable goal through surgery, ethical considerations about other treatment objectives such as pain control, functional recovery, and treatment adequacy cannot be overlooked. It is worth noting that the French National Authority for Health issued recommendations in 2018 regarding the care pathway for patients hospitalized for a hip fracture within an orthogeriatric organization.

This story was translated from JIM, which is part of the Medscape Medical News professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Primary care physicians know the complexities of treating older patients, from increased complications from medications and procedures to comorbidities stemming from having multiple medical conditions. The Beers Criteria were established by the American Geriatrics Society as a guide for physicians about medications that may possess more risks than benefits in older patients, specifically those aged 65 years and older.

There are approximately 100 medications on the list. Criteria used to establish the list include medications to avoid over the age of 65 in an outpatient setting, medications to avoid in certain medical conditions, medications to avoid that may interact with other medications, medications to avoid with renal impairment, and medications to avoid where harmful side effects outweigh the possible benefits. The American Geriatrics Society updates the list as new published evidence becomes available.

The latest updates to the Beers Criteria include several medications commonly used in primary care. Regarding anticoagulation, warfarin should be avoided as initial therapy and apixaban should be used in patients with reduced renal function. These guidelines looked particularly at antithrombotic medications because of new evidence arising in nonvalvular atrial fibrillation and venous thromboembolism. In addition to the previous recommendations, the use of aspirin is no longer recommended in older adults.

The latest guidelines also make recommendations regarding certain diabetic medications as well as combinations to avoid. The Beers Criteria now place all sulfonylureas in the class to avoid, and not just the long-acting formulations as was recommended in the previous guidelines. If a sulfonylurea is necessary, use of a short-acting one is advised. Several other classes of medications were addressed and doctors practicing primary care medicine should be aware of these guidelines, especially as the population continues to age.

Overall, these guidelines are a great resource for treating patients aged 65 and older. It is important to keep in mind that they look at a whole population of patients and it is not patient specific. As primary care doctors, we know many of our patients don’t fit into the textbook box. While these guidelines consider the dangers of a certain medication, sometimes the benefits do outweigh the risks at the patient-specific level.

As doctors, we are trained to weigh the risks and benefits when prescribing any medication to our patients. These guidelines shouldn’t be approached as a do or don’t list but should be considered in the overall plan when prescribing for our patients. Sometimes, these medications can be used with careful observation by the prescribing physician. When they are utilized, we need to make the patient aware of specific side effects and what to watch out for. We need to make these decisions together with our patients and their caregivers.

For example, we all know how agonizing taking care of an older dementia patient can be, and sometimes there is nothing left to try except one of the medications on the list.

An additional practical point not considered in the guidelines is real-world use. Often, certain medications are not covered by a patient’s insurance company. The cost can be prohibitive to use the recommended agent. We are left in the middle to go off script with a medication that the patient may be able to access easily or keep pushing for the most appropriate medication for the patient. Unfortunately, in our current healthcare climate, prior authorizations can sometimes take weeks to obtain (or to be denied). For most of the conditions we treat in our older patients, it is not safe to leave them without any medication while we fight this prior authorizations war.

Our older patients often have multiple specialists as well. Each of these specialists may be prescribing different medications. It is imperative that we know all the medications a patient is taking so that we may look for potentially dangerous drug interactions. Many patients don’t remember the names of all their medications, nor do they realize that many classes of medications are “little white pills.” Asking them to bring their pill bottles to every visit can be a great help in searching out interactions.

That being said, the Beers Criteria do an excellent job reviewing the latest evidence and developing guidelines. As primary care physicians, we have never been busier and having someone do the research and set it forth so clearly is a great tool. We should be aware of the Beers Criteria and the medications and interactions listed there.

Dr. Girgis practices family medicine in South River, New Jersey, and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, New Jersey. She has no conflicts of interest.

Primary care physicians know the complexities of treating older patients, from increased complications from medications and procedures to comorbidities stemming from having multiple medical conditions. The Beers Criteria were established by the American Geriatrics Society as a guide for physicians about medications that may possess more risks than benefits in older patients, specifically those aged 65 years and older.

There are approximately 100 medications on the list. Criteria used to establish the list include medications to avoid over the age of 65 in an outpatient setting, medications to avoid in certain medical conditions, medications to avoid that may interact with other medications, medications to avoid with renal impairment, and medications to avoid where harmful side effects outweigh the possible benefits. The American Geriatrics Society updates the list as new published evidence becomes available.

The latest updates to the Beers Criteria include several medications commonly used in primary care. Regarding anticoagulation, warfarin should be avoided as initial therapy and apixaban should be used in patients with reduced renal function. These guidelines looked particularly at antithrombotic medications because of new evidence arising in nonvalvular atrial fibrillation and venous thromboembolism. In addition to the previous recommendations, the use of aspirin is no longer recommended in older adults.

The latest guidelines also make recommendations regarding certain diabetic medications as well as combinations to avoid. The Beers Criteria now place all sulfonylureas in the class to avoid, and not just the long-acting formulations as was recommended in the previous guidelines. If a sulfonylurea is necessary, use of a short-acting one is advised. Several other classes of medications were addressed and doctors practicing primary care medicine should be aware of these guidelines, especially as the population continues to age.

Overall, these guidelines are a great resource for treating patients aged 65 and older. It is important to keep in mind that they look at a whole population of patients and it is not patient specific. As primary care doctors, we know many of our patients don’t fit into the textbook box. While these guidelines consider the dangers of a certain medication, sometimes the benefits do outweigh the risks at the patient-specific level.

As doctors, we are trained to weigh the risks and benefits when prescribing any medication to our patients. These guidelines shouldn’t be approached as a do or don’t list but should be considered in the overall plan when prescribing for our patients. Sometimes, these medications can be used with careful observation by the prescribing physician. When they are utilized, we need to make the patient aware of specific side effects and what to watch out for. We need to make these decisions together with our patients and their caregivers.

For example, we all know how agonizing taking care of an older dementia patient can be, and sometimes there is nothing left to try except one of the medications on the list.

An additional practical point not considered in the guidelines is real-world use. Often, certain medications are not covered by a patient’s insurance company. The cost can be prohibitive to use the recommended agent. We are left in the middle to go off script with a medication that the patient may be able to access easily or keep pushing for the most appropriate medication for the patient. Unfortunately, in our current healthcare climate, prior authorizations can sometimes take weeks to obtain (or to be denied). For most of the conditions we treat in our older patients, it is not safe to leave them without any medication while we fight this prior authorizations war.

Our older patients often have multiple specialists as well. Each of these specialists may be prescribing different medications. It is imperative that we know all the medications a patient is taking so that we may look for potentially dangerous drug interactions. Many patients don’t remember the names of all their medications, nor do they realize that many classes of medications are “little white pills.” Asking them to bring their pill bottles to every visit can be a great help in searching out interactions.

That being said, the Beers Criteria do an excellent job reviewing the latest evidence and developing guidelines. As primary care physicians, we have never been busier and having someone do the research and set it forth so clearly is a great tool. We should be aware of the Beers Criteria and the medications and interactions listed there.

Dr. Girgis practices family medicine in South River, New Jersey, and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, New Jersey. She has no conflicts of interest.

Primary care physicians know the complexities of treating older patients, from increased complications from medications and procedures to comorbidities stemming from having multiple medical conditions. The Beers Criteria were established by the American Geriatrics Society as a guide for physicians about medications that may possess more risks than benefits in older patients, specifically those aged 65 years and older.

There are approximately 100 medications on the list. Criteria used to establish the list include medications to avoid over the age of 65 in an outpatient setting, medications to avoid in certain medical conditions, medications to avoid that may interact with other medications, medications to avoid with renal impairment, and medications to avoid where harmful side effects outweigh the possible benefits. The American Geriatrics Society updates the list as new published evidence becomes available.

The latest updates to the Beers Criteria include several medications commonly used in primary care. Regarding anticoagulation, warfarin should be avoided as initial therapy and apixaban should be used in patients with reduced renal function. These guidelines looked particularly at antithrombotic medications because of new evidence arising in nonvalvular atrial fibrillation and venous thromboembolism. In addition to the previous recommendations, the use of aspirin is no longer recommended in older adults.

The latest guidelines also make recommendations regarding certain diabetic medications as well as combinations to avoid. The Beers Criteria now place all sulfonylureas in the class to avoid, and not just the long-acting formulations as was recommended in the previous guidelines. If a sulfonylurea is necessary, use of a short-acting one is advised. Several other classes of medications were addressed and doctors practicing primary care medicine should be aware of these guidelines, especially as the population continues to age.

Overall, these guidelines are a great resource for treating patients aged 65 and older. It is important to keep in mind that they look at a whole population of patients and it is not patient specific. As primary care doctors, we know many of our patients don’t fit into the textbook box. While these guidelines consider the dangers of a certain medication, sometimes the benefits do outweigh the risks at the patient-specific level.

As doctors, we are trained to weigh the risks and benefits when prescribing any medication to our patients. These guidelines shouldn’t be approached as a do or don’t list but should be considered in the overall plan when prescribing for our patients. Sometimes, these medications can be used with careful observation by the prescribing physician. When they are utilized, we need to make the patient aware of specific side effects and what to watch out for. We need to make these decisions together with our patients and their caregivers.

For example, we all know how agonizing taking care of an older dementia patient can be, and sometimes there is nothing left to try except one of the medications on the list.

An additional practical point not considered in the guidelines is real-world use. Often, certain medications are not covered by a patient’s insurance company. The cost can be prohibitive to use the recommended agent. We are left in the middle to go off script with a medication that the patient may be able to access easily or keep pushing for the most appropriate medication for the patient. Unfortunately, in our current healthcare climate, prior authorizations can sometimes take weeks to obtain (or to be denied). For most of the conditions we treat in our older patients, it is not safe to leave them without any medication while we fight this prior authorizations war.

Our older patients often have multiple specialists as well. Each of these specialists may be prescribing different medications. It is imperative that we know all the medications a patient is taking so that we may look for potentially dangerous drug interactions. Many patients don’t remember the names of all their medications, nor do they realize that many classes of medications are “little white pills.” Asking them to bring their pill bottles to every visit can be a great help in searching out interactions.

That being said, the Beers Criteria do an excellent job reviewing the latest evidence and developing guidelines. As primary care physicians, we have never been busier and having someone do the research and set it forth so clearly is a great tool. We should be aware of the Beers Criteria and the medications and interactions listed there.

Dr. Girgis practices family medicine in South River, New Jersey, and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, New Jersey. She has no conflicts of interest.

People over age 60 who drink alcohol regularly are at an increased risk of early death, particularly from cancer or issues related to the heart and blood vessels.

That’s according to the findings of a new, large study that was published in JAMA Network Openand build upon numerous other recent studies concluding that any amount of alcohol consumption is linked to significant health risks. That’s a change from decades of public health messaging suggesting that moderate alcohol intake (one or two drinks per day) wasn’t dangerous. Recently, experts have uncovered flaws in how researchers came to those earlier conclusions.

In this latest study, researchers in Spain analyzed health data for more than 135,000 people, all of whom were at least 60 years old, lived in the United Kingdom, and provided their health information to the UK Biobank database. The average age of people at the start of the analysis period was 64.

The researchers compared 12 years of health outcomes for occasional drinkers with those who averaged drinking at least some alcohol on a daily basis. The greatest health risks were seen between occasional drinkers and those whom the researchers labeled “high risk.” Occasional drinkers had less than about two drinks per week. The high-risk group included men who averaged nearly three drinks per day or more, and women who averaged about a drink and a half per day or more. The analysis showed that, compared with occasional drinking, high-risk drinking was linked to a 33% increased risk of early death, a 39% increased risk of dying from cancer, and a 21% increased risk of dying from problems with the heart and blood vessels.

More moderate drinking habits were also linked to an increased risk of early death and dying from cancer, and even just averaging about one drink or less daily was associated with an 11% higher risk of dying from cancer. Low and moderate drinkers were most at risk if they also had health problems or experienced socioeconomic factors like living in less affluent neighborhoods.

The findings also suggested the potential that mostly drinking wine, or drinking mostly with meals, may be lower risk, but the researchers called for further study on those topics since “it may mostly reflect the effect of healthier lifestyles, slower alcohol absorption, or nonalcoholic components of beverages.”

A recent Gallup poll showed that overall, Americans’ attitudes toward the health impacts of alcohol are changing, with 65% of young adults (ages 18-34) saying that drinking can have negative health effects. But just 39% of adults age 55 or older agreed that drinking is bad for a person’s health. The gap in perspectives between younger and older adults about drinking is the largest on record, Gallup reported.

The study investigators reported no conflicts of interest.

A version of this article first appeared on WebMD.com.

People over age 60 who drink alcohol regularly are at an increased risk of early death, particularly from cancer or issues related to the heart and blood vessels.

That’s according to the findings of a new, large study that was published in JAMA Network Openand build upon numerous other recent studies concluding that any amount of alcohol consumption is linked to significant health risks. That’s a change from decades of public health messaging suggesting that moderate alcohol intake (one or two drinks per day) wasn’t dangerous. Recently, experts have uncovered flaws in how researchers came to those earlier conclusions.

In this latest study, researchers in Spain analyzed health data for more than 135,000 people, all of whom were at least 60 years old, lived in the United Kingdom, and provided their health information to the UK Biobank database. The average age of people at the start of the analysis period was 64.

The researchers compared 12 years of health outcomes for occasional drinkers with those who averaged drinking at least some alcohol on a daily basis. The greatest health risks were seen between occasional drinkers and those whom the researchers labeled “high risk.” Occasional drinkers had less than about two drinks per week. The high-risk group included men who averaged nearly three drinks per day or more, and women who averaged about a drink and a half per day or more. The analysis showed that, compared with occasional drinking, high-risk drinking was linked to a 33% increased risk of early death, a 39% increased risk of dying from cancer, and a 21% increased risk of dying from problems with the heart and blood vessels.

More moderate drinking habits were also linked to an increased risk of early death and dying from cancer, and even just averaging about one drink or less daily was associated with an 11% higher risk of dying from cancer. Low and moderate drinkers were most at risk if they also had health problems or experienced socioeconomic factors like living in less affluent neighborhoods.

The findings also suggested the potential that mostly drinking wine, or drinking mostly with meals, may be lower risk, but the researchers called for further study on those topics since “it may mostly reflect the effect of healthier lifestyles, slower alcohol absorption, or nonalcoholic components of beverages.”

A recent Gallup poll showed that overall, Americans’ attitudes toward the health impacts of alcohol are changing, with 65% of young adults (ages 18-34) saying that drinking can have negative health effects. But just 39% of adults age 55 or older agreed that drinking is bad for a person’s health. The gap in perspectives between younger and older adults about drinking is the largest on record, Gallup reported.

The study investigators reported no conflicts of interest.

A version of this article first appeared on WebMD.com.

People over age 60 who drink alcohol regularly are at an increased risk of early death, particularly from cancer or issues related to the heart and blood vessels.

That’s according to the findings of a new, large study that was published in JAMA Network Openand build upon numerous other recent studies concluding that any amount of alcohol consumption is linked to significant health risks. That’s a change from decades of public health messaging suggesting that moderate alcohol intake (one or two drinks per day) wasn’t dangerous. Recently, experts have uncovered flaws in how researchers came to those earlier conclusions.

In this latest study, researchers in Spain analyzed health data for more than 135,000 people, all of whom were at least 60 years old, lived in the United Kingdom, and provided their health information to the UK Biobank database. The average age of people at the start of the analysis period was 64.

The researchers compared 12 years of health outcomes for occasional drinkers with those who averaged drinking at least some alcohol on a daily basis. The greatest health risks were seen between occasional drinkers and those whom the researchers labeled “high risk.” Occasional drinkers had less than about two drinks per week. The high-risk group included men who averaged nearly three drinks per day or more, and women who averaged about a drink and a half per day or more. The analysis showed that, compared with occasional drinking, high-risk drinking was linked to a 33% increased risk of early death, a 39% increased risk of dying from cancer, and a 21% increased risk of dying from problems with the heart and blood vessels.

More moderate drinking habits were also linked to an increased risk of early death and dying from cancer, and even just averaging about one drink or less daily was associated with an 11% higher risk of dying from cancer. Low and moderate drinkers were most at risk if they also had health problems or experienced socioeconomic factors like living in less affluent neighborhoods.

The findings also suggested the potential that mostly drinking wine, or drinking mostly with meals, may be lower risk, but the researchers called for further study on those topics since “it may mostly reflect the effect of healthier lifestyles, slower alcohol absorption, or nonalcoholic components of beverages.”

A recent Gallup poll showed that overall, Americans’ attitudes toward the health impacts of alcohol are changing, with 65% of young adults (ages 18-34) saying that drinking can have negative health effects. But just 39% of adults age 55 or older agreed that drinking is bad for a person’s health. The gap in perspectives between younger and older adults about drinking is the largest on record, Gallup reported.

The study investigators reported no conflicts of interest.

A version of this article first appeared on WebMD.com.

Poorer physical function, not poorer bone mineral density (BMD), could be the principal reason for the increased fracture risk in older women with type 2 diabetes (T2D), according to a Swedish prospective observational study in JAMA Network Open.

The study was conducted in more than 3000 Swedish women by Mattias Lorentzon, MD, a professor of geriatric medicine at Gothenburg University, and chief physician at the Osteoporosis Clinic at Sahlgrenska University Hospital in Mölndal, and colleagues.

Study Details

A fractures study was performed in the Gothenburg area from March 2013 to May 2016 with follow-up of incident fracture data completed in March 2023. Data were collected from questionnaires and through examination of anthropometrics, physical function, and bone measurements using dual-energy x-ray absorptiometry and high-resolution peripheral computed tomography. A subsample underwent bone microindentation to assess BMSi.

Among the cohort’s 3008 women, ages 75-80 (mean, 77.8), 294 patients with T2D were compared with 2714 same-age unaffected women.

During a median follow-up of 7.3 years, 1071 incident fractures, 853 major osteoporotic fractures, and 232 hip fractures occurred. In models adjusted for age, BMI, clinical risk factors, and femoral neck BMD, T2D was associated with an increased risk of any fracture: hazard ratio (HR), 1.26; (95% CI, 1.04-1.54), and major osteoporotic fracture (HR, 1.25; 95% CI, 1.00-1.56).

Most fractures were due to falls, with the most common affected sites being the forearm, upper arm, spine, and hip, Dr. Lorentzon said.

Among the findings:

• In bone microarchitecture, women with T2D had higher BMD at all sites: total hip, 4.4% higher; femoral neck, 4.9% higher; and lumbar spine, 5.2% higher.
• At the tibia, the T2D group had 7.4% greater cortical area and 1.3% greater density, as well as 8.7% higher trabecular bone volume fraction.

“Our findings regarding BMD are consistent with previous publications showing higher BMD in individuals with T2D compared with those without diabetes,” Dr. Lorentzon said. A 2012 meta-analysis, for example, showed higher BMD levels in T2D patients. “Some smaller studies, however, have found worse bone microstructure and lower bone material strength in contrast to the results from our study,” Dr. Lorentzon said.

• There was no difference in BMSi, with a mean of 78 in both groups.
• The T2D group had lower performance on all physical function tests: a 9.7% lower grip strength, 9.9% slower gait speed, and 13.9% slower timed up-and-go time than women without diabetes.

“We found all parameters regarding physical function, such as muscle strength, balance, and performance, were much worse in women with diabetes than in those without,” Dr. Lorentzon said. “Dizziness could also be a contributor to the increased risk of falls, but this factor was not investigated in our study.”

Commenting on the study but not involved in it, Anthony J. Pick, MD, an endocrinologist at Northwestern Medicine Lake Forest Hospital in Lake Forest, Illinois, said sarcopenia is a common and often under-recognized problem in older adults and is especially prevalent in T2D, obesity, and heart failure. “I believe that ‘exercise is medicine’ is a key concept for metabolic and osteoporosis patients — and wellness and longevity in general — and I certainly hope studies like this drive awareness of the importance of engaging in strengthening exercises.”

Poorer physical function, not poorer bone mineral density (BMD), could be the principal reason for the increased fracture risk in older women with type 2 diabetes (T2D), according to a Swedish prospective observational study in JAMA Network Open.

The study was conducted in more than 3000 Swedish women by Mattias Lorentzon, MD, a professor of geriatric medicine at Gothenburg University, and chief physician at the Osteoporosis Clinic at Sahlgrenska University Hospital in Mölndal, and colleagues.

Study Details

A fractures study was performed in the Gothenburg area from March 2013 to May 2016 with follow-up of incident fracture data completed in March 2023. Data were collected from questionnaires and through examination of anthropometrics, physical function, and bone measurements using dual-energy x-ray absorptiometry and high-resolution peripheral computed tomography. A subsample underwent bone microindentation to assess BMSi.

Among the cohort’s 3008 women, ages 75-80 (mean, 77.8), 294 patients with T2D were compared with 2714 same-age unaffected women.

During a median follow-up of 7.3 years, 1071 incident fractures, 853 major osteoporotic fractures, and 232 hip fractures occurred. In models adjusted for age, BMI, clinical risk factors, and femoral neck BMD, T2D was associated with an increased risk of any fracture: hazard ratio (HR), 1.26; (95% CI, 1.04-1.54), and major osteoporotic fracture (HR, 1.25; 95% CI, 1.00-1.56).

Most fractures were due to falls, with the most common affected sites being the forearm, upper arm, spine, and hip, Dr. Lorentzon said.

Among the findings:

• In bone microarchitecture, women with T2D had higher BMD at all sites: total hip, 4.4% higher; femoral neck, 4.9% higher; and lumbar spine, 5.2% higher.
• At the tibia, the T2D group had 7.4% greater cortical area and 1.3% greater density, as well as 8.7% higher trabecular bone volume fraction.

“Our findings regarding BMD are consistent with previous publications showing higher BMD in individuals with T2D compared with those without diabetes,” Dr. Lorentzon said. A 2012 meta-analysis, for example, showed higher BMD levels in T2D patients. “Some smaller studies, however, have found worse bone microstructure and lower bone material strength in contrast to the results from our study,” Dr. Lorentzon said.

• There was no difference in BMSi, with a mean of 78 in both groups.
• The T2D group had lower performance on all physical function tests: a 9.7% lower grip strength, 9.9% slower gait speed, and 13.9% slower timed up-and-go time than women without diabetes.

“We found all parameters regarding physical function, such as muscle strength, balance, and performance, were much worse in women with diabetes than in those without,” Dr. Lorentzon said. “Dizziness could also be a contributor to the increased risk of falls, but this factor was not investigated in our study.”

Commenting on the study but not involved in it, Anthony J. Pick, MD, an endocrinologist at Northwestern Medicine Lake Forest Hospital in Lake Forest, Illinois, said sarcopenia is a common and often under-recognized problem in older adults and is especially prevalent in T2D, obesity, and heart failure. “I believe that ‘exercise is medicine’ is a key concept for metabolic and osteoporosis patients — and wellness and longevity in general — and I certainly hope studies like this drive awareness of the importance of engaging in strengthening exercises.”

Poorer physical function, not poorer bone mineral density (BMD), could be the principal reason for the increased fracture risk in older women with type 2 diabetes (T2D), according to a Swedish prospective observational study in JAMA Network Open.

The study was conducted in more than 3000 Swedish women by Mattias Lorentzon, MD, a professor of geriatric medicine at Gothenburg University, and chief physician at the Osteoporosis Clinic at Sahlgrenska University Hospital in Mölndal, and colleagues.

Study Details

A fractures study was performed in the Gothenburg area from March 2013 to May 2016 with follow-up of incident fracture data completed in March 2023. Data were collected from questionnaires and through examination of anthropometrics, physical function, and bone measurements using dual-energy x-ray absorptiometry and high-resolution peripheral computed tomography. A subsample underwent bone microindentation to assess BMSi.

Among the cohort’s 3008 women, ages 75-80 (mean, 77.8), 294 patients with T2D were compared with 2714 same-age unaffected women.

During a median follow-up of 7.3 years, 1071 incident fractures, 853 major osteoporotic fractures, and 232 hip fractures occurred. In models adjusted for age, BMI, clinical risk factors, and femoral neck BMD, T2D was associated with an increased risk of any fracture: hazard ratio (HR), 1.26; (95% CI, 1.04-1.54), and major osteoporotic fracture (HR, 1.25; 95% CI, 1.00-1.56).

Most fractures were due to falls, with the most common affected sites being the forearm, upper arm, spine, and hip, Dr. Lorentzon said.

Among the findings:

• In bone microarchitecture, women with T2D had higher BMD at all sites: total hip, 4.4% higher; femoral neck, 4.9% higher; and lumbar spine, 5.2% higher.
• At the tibia, the T2D group had 7.4% greater cortical area and 1.3% greater density, as well as 8.7% higher trabecular bone volume fraction.

“Our findings regarding BMD are consistent with previous publications showing higher BMD in individuals with T2D compared with those without diabetes,” Dr. Lorentzon said. A 2012 meta-analysis, for example, showed higher BMD levels in T2D patients. “Some smaller studies, however, have found worse bone microstructure and lower bone material strength in contrast to the results from our study,” Dr. Lorentzon said.

• There was no difference in BMSi, with a mean of 78 in both groups.
• The T2D group had lower performance on all physical function tests: a 9.7% lower grip strength, 9.9% slower gait speed, and 13.9% slower timed up-and-go time than women without diabetes.

“We found all parameters regarding physical function, such as muscle strength, balance, and performance, were much worse in women with diabetes than in those without,” Dr. Lorentzon said. “Dizziness could also be a contributor to the increased risk of falls, but this factor was not investigated in our study.”

Commenting on the study but not involved in it, Anthony J. Pick, MD, an endocrinologist at Northwestern Medicine Lake Forest Hospital in Lake Forest, Illinois, said sarcopenia is a common and often under-recognized problem in older adults and is especially prevalent in T2D, obesity, and heart failure. “I believe that ‘exercise is medicine’ is a key concept for metabolic and osteoporosis patients — and wellness and longevity in general — and I certainly hope studies like this drive awareness of the importance of engaging in strengthening exercises.”

What if a drug could help you live a longer, healthier life?

Scientists at the University of Connecticut are working on it. In a new study in Cell Metabolism, researchers described how to target specific cells to extend the lifespan and improve the health of mice late in life.

The study builds on a growing body of research, mostly in animals, testing interventions to slow aging and prolong health span, the length of time that one is not just alive but also healthy.

“Aging is the most important risk factor for every disease that we deal with in adult human beings,” said cardiologist Douglas Vaughan, MD, director of the Potocsnak Longevity Institute at Northwestern University’s Feinberg School of Medicine, Chicago. (Dr. Vaughan was not involved in the new study.) “So the big hypothesis is: If we could slow down aging just a little bit, we can push back the onset of disease.”

As we age, our cells wear out. It’s called cellular senescence — a state of irreversible cell cycle arrest — and it’s increasingly recognized as a key contributor to aging.

Senescent cells — or “zombie cells” — secrete harmful substances that disrupt tissue functioning. They’ve been linked to chronic inflammation, tissue damage, and the development of age-related diseases.

Senescence can be characterized by the accumulation of cells with high levels of specific markers like p21, or p21^high cells. Almost any cell can become a p21^high cell, and they accumulate with age, said Ming Xu, PhD, a professor at the UConn Center on Aging, UConn Health, Farmington, Connecticut, who led the study.

By targeting and eliminating p21^high senescent cells, Dr. Xu hopes to develop novel therapies that might help people live longer and enjoy more years in good health.

Such a treatment could be ready for human trials in 2-5 years, Dr. Xu said.
 

What the Researchers Did

Xu and colleagues used genetic engineering to eliminate p21^high cells in mice, introducing into their genome something they describe as an inducible “suicide gene.” Giving the mice a certain drug (a low dose of tamoxifen) activated the suicide gene in all p21^high cells, causing them to die. Administering this treatment once a month, from age 20 months (older age) until the end of life, significantly extended the rodents’ lifespan, reduced inflammation, and decreased gene activity linked to aging.

Treated mice lived, on average, for 33 months — 3 months longer than the untreated mice. The oldest treated mouse lived to 43 months — roughly 130 in human years.

But the treated mice didn’t just live longer; they were also healthier. In humans, walking speed and grip strength can be clues of overall health and vitality. The old, treated mice were able to walk faster and grip objects with greater strength than untreated mice of the same age.

Dr. Xu’s lab is now testing drugs that target p21^high cells in hopes of finding one that would work in humans. Leveraging immunotherapy technology to target these cells could be another option, Dr. Xu said.

The team also plans to test whether eliminating p21^high cells could prevent or alleviate diabetes or Alzheimer’s disease.
 

Challenges and Criticisms

The research provides “important evidence that targeting senescence and the molecular components of that pathway might provide some benefit in the long term,” Dr. Vaughan said.

But killing senescent cells could come with downsides.

“Senescence protects us from hyperproliferative responses,” potentially blocking cells from becoming malignant, Dr. Vaughan said. “There’s this effect on aging that is desirable, but at the same time, you may enhance your risk of cancer or malignancy or excessive proliferation in some cells.”

And of course, we don’t necessarily need drugs to prolong healthy life, Dr. Vaughan pointed out.

For many people, a long healthy life is already within reach. Humans live longer on average than they used to, and simple lifestyle choices — nourishing your body well, staying active, and maintaining a healthy weight — can increase one’s chances of good health.

The most consistently demonstrated intervention for extending lifespan “in almost every animal species is caloric restriction,” Dr. Vaughan said. (Dr. Xu’s team is also investigating whether fasting and exercise can lead to a decrease in p21^high cells.)

As for brain health, Dr. Vaughan and colleagues at Northwestern are studying “super agers,” people who are cognitively intact into their 90s.

“The one single thing that they found that contributes to that process, and contributes to that success, is really a social network and human bonds and interaction,” Dr. Vaughan said.

A version of this article appeared on Medscape.com.

What if a drug could help you live a longer, healthier life?

Scientists at the University of Connecticut are working on it. In a new study in Cell Metabolism, researchers described how to target specific cells to extend the lifespan and improve the health of mice late in life.

The study builds on a growing body of research, mostly in animals, testing interventions to slow aging and prolong health span, the length of time that one is not just alive but also healthy.

“Aging is the most important risk factor for every disease that we deal with in adult human beings,” said cardiologist Douglas Vaughan, MD, director of the Potocsnak Longevity Institute at Northwestern University’s Feinberg School of Medicine, Chicago. (Dr. Vaughan was not involved in the new study.) “So the big hypothesis is: If we could slow down aging just a little bit, we can push back the onset of disease.”

As we age, our cells wear out. It’s called cellular senescence — a state of irreversible cell cycle arrest — and it’s increasingly recognized as a key contributor to aging.

Senescent cells — or “zombie cells” — secrete harmful substances that disrupt tissue functioning. They’ve been linked to chronic inflammation, tissue damage, and the development of age-related diseases.

Senescence can be characterized by the accumulation of cells with high levels of specific markers like p21, or p21^high cells. Almost any cell can become a p21^high cell, and they accumulate with age, said Ming Xu, PhD, a professor at the UConn Center on Aging, UConn Health, Farmington, Connecticut, who led the study.

By targeting and eliminating p21^high senescent cells, Dr. Xu hopes to develop novel therapies that might help people live longer and enjoy more years in good health.

Such a treatment could be ready for human trials in 2-5 years, Dr. Xu said.
 

What the Researchers Did

Xu and colleagues used genetic engineering to eliminate p21^high cells in mice, introducing into their genome something they describe as an inducible “suicide gene.” Giving the mice a certain drug (a low dose of tamoxifen) activated the suicide gene in all p21^high cells, causing them to die. Administering this treatment once a month, from age 20 months (older age) until the end of life, significantly extended the rodents’ lifespan, reduced inflammation, and decreased gene activity linked to aging.

Treated mice lived, on average, for 33 months — 3 months longer than the untreated mice. The oldest treated mouse lived to 43 months — roughly 130 in human years.

But the treated mice didn’t just live longer; they were also healthier. In humans, walking speed and grip strength can be clues of overall health and vitality. The old, treated mice were able to walk faster and grip objects with greater strength than untreated mice of the same age.

Dr. Xu’s lab is now testing drugs that target p21^high cells in hopes of finding one that would work in humans. Leveraging immunotherapy technology to target these cells could be another option, Dr. Xu said.

The team also plans to test whether eliminating p21^high cells could prevent or alleviate diabetes or Alzheimer’s disease.
 

Challenges and Criticisms

The research provides “important evidence that targeting senescence and the molecular components of that pathway might provide some benefit in the long term,” Dr. Vaughan said.

But killing senescent cells could come with downsides.

“Senescence protects us from hyperproliferative responses,” potentially blocking cells from becoming malignant, Dr. Vaughan said. “There’s this effect on aging that is desirable, but at the same time, you may enhance your risk of cancer or malignancy or excessive proliferation in some cells.”

And of course, we don’t necessarily need drugs to prolong healthy life, Dr. Vaughan pointed out.

For many people, a long healthy life is already within reach. Humans live longer on average than they used to, and simple lifestyle choices — nourishing your body well, staying active, and maintaining a healthy weight — can increase one’s chances of good health.

The most consistently demonstrated intervention for extending lifespan “in almost every animal species is caloric restriction,” Dr. Vaughan said. (Dr. Xu’s team is also investigating whether fasting and exercise can lead to a decrease in p21^high cells.)

As for brain health, Dr. Vaughan and colleagues at Northwestern are studying “super agers,” people who are cognitively intact into their 90s.

“The one single thing that they found that contributes to that process, and contributes to that success, is really a social network and human bonds and interaction,” Dr. Vaughan said.

A version of this article appeared on Medscape.com.

What if a drug could help you live a longer, healthier life?

Scientists at the University of Connecticut are working on it. In a new study in Cell Metabolism, researchers described how to target specific cells to extend the lifespan and improve the health of mice late in life.

The study builds on a growing body of research, mostly in animals, testing interventions to slow aging and prolong health span, the length of time that one is not just alive but also healthy.

“Aging is the most important risk factor for every disease that we deal with in adult human beings,” said cardiologist Douglas Vaughan, MD, director of the Potocsnak Longevity Institute at Northwestern University’s Feinberg School of Medicine, Chicago. (Dr. Vaughan was not involved in the new study.) “So the big hypothesis is: If we could slow down aging just a little bit, we can push back the onset of disease.”

As we age, our cells wear out. It’s called cellular senescence — a state of irreversible cell cycle arrest — and it’s increasingly recognized as a key contributor to aging.

Senescent cells — or “zombie cells” — secrete harmful substances that disrupt tissue functioning. They’ve been linked to chronic inflammation, tissue damage, and the development of age-related diseases.

Senescence can be characterized by the accumulation of cells with high levels of specific markers like p21, or p21^high cells. Almost any cell can become a p21^high cell, and they accumulate with age, said Ming Xu, PhD, a professor at the UConn Center on Aging, UConn Health, Farmington, Connecticut, who led the study.

By targeting and eliminating p21^high senescent cells, Dr. Xu hopes to develop novel therapies that might help people live longer and enjoy more years in good health.

Such a treatment could be ready for human trials in 2-5 years, Dr. Xu said.
 

What the Researchers Did

Xu and colleagues used genetic engineering to eliminate p21^high cells in mice, introducing into their genome something they describe as an inducible “suicide gene.” Giving the mice a certain drug (a low dose of tamoxifen) activated the suicide gene in all p21^high cells, causing them to die. Administering this treatment once a month, from age 20 months (older age) until the end of life, significantly extended the rodents’ lifespan, reduced inflammation, and decreased gene activity linked to aging.

Treated mice lived, on average, for 33 months — 3 months longer than the untreated mice. The oldest treated mouse lived to 43 months — roughly 130 in human years.

But the treated mice didn’t just live longer; they were also healthier. In humans, walking speed and grip strength can be clues of overall health and vitality. The old, treated mice were able to walk faster and grip objects with greater strength than untreated mice of the same age.

Dr. Xu’s lab is now testing drugs that target p21^high cells in hopes of finding one that would work in humans. Leveraging immunotherapy technology to target these cells could be another option, Dr. Xu said.

The team also plans to test whether eliminating p21^high cells could prevent or alleviate diabetes or Alzheimer’s disease.
 

Challenges and Criticisms

The research provides “important evidence that targeting senescence and the molecular components of that pathway might provide some benefit in the long term,” Dr. Vaughan said.

But killing senescent cells could come with downsides.

“Senescence protects us from hyperproliferative responses,” potentially blocking cells from becoming malignant, Dr. Vaughan said. “There’s this effect on aging that is desirable, but at the same time, you may enhance your risk of cancer or malignancy or excessive proliferation in some cells.”

And of course, we don’t necessarily need drugs to prolong healthy life, Dr. Vaughan pointed out.

For many people, a long healthy life is already within reach. Humans live longer on average than they used to, and simple lifestyle choices — nourishing your body well, staying active, and maintaining a healthy weight — can increase one’s chances of good health.

The most consistently demonstrated intervention for extending lifespan “in almost every animal species is caloric restriction,” Dr. Vaughan said. (Dr. Xu’s team is also investigating whether fasting and exercise can lead to a decrease in p21^high cells.)

As for brain health, Dr. Vaughan and colleagues at Northwestern are studying “super agers,” people who are cognitively intact into their 90s.

“The one single thing that they found that contributes to that process, and contributes to that success, is really a social network and human bonds and interaction,” Dr. Vaughan said.

A version of this article appeared on Medscape.com.

TOPLINE:

Primary care visits within 90 days after cancer surgery are linked to a lower mortality rate in older adults. Patients with a primary care visit had a 90-day mortality rate of 0.3% compared with 3.3% for those without. 

METHODOLOGY:

• A total of 2566 patients aged 65 years or older who underwent inpatient cancer surgery between January 1, 2017, and December 31, 2019, were included in a retrospective cohort study.
• Patients were categorized on the basis of having a primary care practitioner (PCP) and whether they had a primary care visit within 90 postoperative days.
• The primary outcome was 90-day postoperative mortality, analyzed using inverse propensity weighted Kaplan-Meier curves.

TAKEAWAY: 

• Patients with a primary care visit within 90 postoperative days had a significantly lower 90-day mortality rate (0.3%) than those without a visit (3.3%; P = .001).
• Older adults without a PCP had a higher 90-day postoperative mortality rate (3.6%) than those with a PCP (2.0%; P = .01).
• Patients who had a primary care visit were more likely to be older, have a higher comorbidity score, and have higher rates of emergency department visits and readmissions.

IN PRACTICE:

“Identifying older patients with cancer who do not have a PCP in the preoperative setting is, therefore, a potential intervention point; such patients could be referred to establish primary care or prioritized for assessment in a preoperative optimization clinic,” wrote the study authors. 

SOURCE:

The study was led by Hadiza S. Kazaure, MD, of Duke University Medical Center in Durham, North Carolina. It was published online in JAMA Surgery.

LIMITATIONS:

The study was retrospective and performed at a single institution, which may limit the generalizability of the results. Coding errors were possible, and details on potential confounders such as frailty and severity of comorbidities are lacking. Mortality was low overall, limiting further adjusted and cancer-specific analyses. Data linkage between the electronic health record and Medicare and Medicaid databases was not possible, limiting analysis of data from patients with external PCPs.

DISCLOSURES:

Dr. Kazaure disclosed receiving grants from the National Cancer Institute. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Primary care visits within 90 days after cancer surgery are linked to a lower mortality rate in older adults. Patients with a primary care visit had a 90-day mortality rate of 0.3% compared with 3.3% for those without. 

METHODOLOGY:

• A total of 2566 patients aged 65 years or older who underwent inpatient cancer surgery between January 1, 2017, and December 31, 2019, were included in a retrospective cohort study.
• Patients were categorized on the basis of having a primary care practitioner (PCP) and whether they had a primary care visit within 90 postoperative days.
• The primary outcome was 90-day postoperative mortality, analyzed using inverse propensity weighted Kaplan-Meier curves.

TAKEAWAY: 

• Patients with a primary care visit within 90 postoperative days had a significantly lower 90-day mortality rate (0.3%) than those without a visit (3.3%; P = .001).
• Older adults without a PCP had a higher 90-day postoperative mortality rate (3.6%) than those with a PCP (2.0%; P = .01).
• Patients who had a primary care visit were more likely to be older, have a higher comorbidity score, and have higher rates of emergency department visits and readmissions.

IN PRACTICE:

“Identifying older patients with cancer who do not have a PCP in the preoperative setting is, therefore, a potential intervention point; such patients could be referred to establish primary care or prioritized for assessment in a preoperative optimization clinic,” wrote the study authors. 

SOURCE:

The study was led by Hadiza S. Kazaure, MD, of Duke University Medical Center in Durham, North Carolina. It was published online in JAMA Surgery.

LIMITATIONS:

The study was retrospective and performed at a single institution, which may limit the generalizability of the results. Coding errors were possible, and details on potential confounders such as frailty and severity of comorbidities are lacking. Mortality was low overall, limiting further adjusted and cancer-specific analyses. Data linkage between the electronic health record and Medicare and Medicaid databases was not possible, limiting analysis of data from patients with external PCPs.

DISCLOSURES:

Dr. Kazaure disclosed receiving grants from the National Cancer Institute. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Primary care visits within 90 days after cancer surgery are linked to a lower mortality rate in older adults. Patients with a primary care visit had a 90-day mortality rate of 0.3% compared with 3.3% for those without. 

METHODOLOGY:

• A total of 2566 patients aged 65 years or older who underwent inpatient cancer surgery between January 1, 2017, and December 31, 2019, were included in a retrospective cohort study.
• Patients were categorized on the basis of having a primary care practitioner (PCP) and whether they had a primary care visit within 90 postoperative days.
• The primary outcome was 90-day postoperative mortality, analyzed using inverse propensity weighted Kaplan-Meier curves.

TAKEAWAY: 

• Patients with a primary care visit within 90 postoperative days had a significantly lower 90-day mortality rate (0.3%) than those without a visit (3.3%; P = .001).
• Older adults without a PCP had a higher 90-day postoperative mortality rate (3.6%) than those with a PCP (2.0%; P = .01).
• Patients who had a primary care visit were more likely to be older, have a higher comorbidity score, and have higher rates of emergency department visits and readmissions.

IN PRACTICE:

“Identifying older patients with cancer who do not have a PCP in the preoperative setting is, therefore, a potential intervention point; such patients could be referred to establish primary care or prioritized for assessment in a preoperative optimization clinic,” wrote the study authors. 

SOURCE:

The study was led by Hadiza S. Kazaure, MD, of Duke University Medical Center in Durham, North Carolina. It was published online in JAMA Surgery.

LIMITATIONS:

The study was retrospective and performed at a single institution, which may limit the generalizability of the results. Coding errors were possible, and details on potential confounders such as frailty and severity of comorbidities are lacking. Mortality was low overall, limiting further adjusted and cancer-specific analyses. Data linkage between the electronic health record and Medicare and Medicaid databases was not possible, limiting analysis of data from patients with external PCPs.

DISCLOSURES:

Dr. Kazaure disclosed receiving grants from the National Cancer Institute. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Elevated depression symptoms are linked to an increased risk for severe chemotherapy toxicity in older adults with cancer. This risk is mitigated by geriatric assessment (GA)-driven interventions.

METHODOLOGY:

• Researchers conducted a secondary analysis of a randomized controlled trial to evaluate whether greater reductions in grade 3 chemotherapy-related toxicities occurred with geriatric assessment-driven interventions vs standard care.
• A total of 605 patients aged 65 years and older with any stage of solid malignancy were included, with 402 randomized to the intervention arm and 203 to the standard-of-care arm.
• Mental health was assessed using the Mental Health Inventory 13, and chemotherapy toxicity was graded by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.
• Patients in the intervention arm received recommendations from a multidisciplinary team based on their baseline GA, while those in the standard-of-care arm received only the baseline assessment results.
• The study was conducted at City of Hope National Medical Center in Duarte, California, and patients were followed throughout treatment or for up to 6 months from starting chemotherapy.

TAKEAWAY:

• According to the authors, patients with depression had increased chemotherapy toxicity in the standard-of-care arm (70.7% vs 54.3%; P = .02) but not in the GA-driven intervention arm (54.3% vs 48.5%; P = .27).
• The association between depression and chemotherapy toxicity was also seen after adjustment for the Cancer and Aging Research Group toxicity score (odds ratio, [OR], 1.98; 95% CI, 1.07-3.65) and for demographic, disease, and treatment factors (OR, 2.00; 95% CI, 1.03-3.85).
• No significant association was found between anxiety and chemotherapy toxicity in either the standard-of-care arm (univariate OR, 1.07; 95% CI, 0.61-1.88) or the GA-driven intervention arm (univariate OR, 1.15; 95% CI, 0.78-1.71).
• The authors stated that depression was associated with increased odds of hematologic-only toxicities (OR, 2.50; 95% CI, 1.13-5.56) in the standard-of-care arm.
• An analysis of a small subgroup found associations between elevated anxiety symptoms and increased risk for hematologic and nonhematologic chemotherapy toxicities.

IN PRACTICE:

“The current study showed that elevated depression symptoms are associated with increased risk of severe chemotherapy toxicities in older adults with cancer. This risk was mitigated in those in the GA intervention arm, which suggests that addressing elevated depression symptoms may lower the risk of toxicities,” the authors wrote. “Overall, elevated anxiety symptoms were not associated with risk for severe chemotherapy toxicity.”

SOURCE:

Reena V. Jayani, MD, MSCI, of Vanderbilt University Medical Center in Nashville, Tennessee, was the first and corresponding author for this paper. This study was published online August 4, 2024, in Cancer. 

LIMITATIONS:

The thresholds for depression and anxiety used in the Mental Health Inventory 13 were based on an English-speaking population, which may not be fully applicable to Chinese- and Spanish-speaking patients included in the study. Depression and anxiety were not evaluated by a mental health professional or with a structured interview to assess formal diagnostic criteria. Psychiatric medication used at the time of baseline GA was not included in the analysis. The study is a secondary analysis of a randomized controlled trial, and it is not known which components of the interventions affected mental health.

DISCLOSURES:

This research project was supported by the UniHealth Foundation, the City of Hope Center for Cancer and Aging, and the National Institutes of Health. One coauthor disclosed receiving institutional research funding from AstraZeneca and Brooklyn ImmunoTherapeutics and consulting for multiple pharmaceutical companies, including AbbVie, Adagene, and Bayer HealthCare Pharmaceuticals. William Dale, MD, PhD, of City of Hope National Medical Center, served as senior author and a principal investigator. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Elevated depression symptoms are linked to an increased risk for severe chemotherapy toxicity in older adults with cancer. This risk is mitigated by geriatric assessment (GA)-driven interventions.

METHODOLOGY:

• Researchers conducted a secondary analysis of a randomized controlled trial to evaluate whether greater reductions in grade 3 chemotherapy-related toxicities occurred with geriatric assessment-driven interventions vs standard care.
• A total of 605 patients aged 65 years and older with any stage of solid malignancy were included, with 402 randomized to the intervention arm and 203 to the standard-of-care arm.
• Mental health was assessed using the Mental Health Inventory 13, and chemotherapy toxicity was graded by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.
• Patients in the intervention arm received recommendations from a multidisciplinary team based on their baseline GA, while those in the standard-of-care arm received only the baseline assessment results.
• The study was conducted at City of Hope National Medical Center in Duarte, California, and patients were followed throughout treatment or for up to 6 months from starting chemotherapy.

TAKEAWAY:

• According to the authors, patients with depression had increased chemotherapy toxicity in the standard-of-care arm (70.7% vs 54.3%; P = .02) but not in the GA-driven intervention arm (54.3% vs 48.5%; P = .27).
• The association between depression and chemotherapy toxicity was also seen after adjustment for the Cancer and Aging Research Group toxicity score (odds ratio, [OR], 1.98; 95% CI, 1.07-3.65) and for demographic, disease, and treatment factors (OR, 2.00; 95% CI, 1.03-3.85).
• No significant association was found between anxiety and chemotherapy toxicity in either the standard-of-care arm (univariate OR, 1.07; 95% CI, 0.61-1.88) or the GA-driven intervention arm (univariate OR, 1.15; 95% CI, 0.78-1.71).
• The authors stated that depression was associated with increased odds of hematologic-only toxicities (OR, 2.50; 95% CI, 1.13-5.56) in the standard-of-care arm.
• An analysis of a small subgroup found associations between elevated anxiety symptoms and increased risk for hematologic and nonhematologic chemotherapy toxicities.

IN PRACTICE:

“The current study showed that elevated depression symptoms are associated with increased risk of severe chemotherapy toxicities in older adults with cancer. This risk was mitigated in those in the GA intervention arm, which suggests that addressing elevated depression symptoms may lower the risk of toxicities,” the authors wrote. “Overall, elevated anxiety symptoms were not associated with risk for severe chemotherapy toxicity.”

SOURCE:

Reena V. Jayani, MD, MSCI, of Vanderbilt University Medical Center in Nashville, Tennessee, was the first and corresponding author for this paper. This study was published online August 4, 2024, in Cancer. 

LIMITATIONS:

The thresholds for depression and anxiety used in the Mental Health Inventory 13 were based on an English-speaking population, which may not be fully applicable to Chinese- and Spanish-speaking patients included in the study. Depression and anxiety were not evaluated by a mental health professional or with a structured interview to assess formal diagnostic criteria. Psychiatric medication used at the time of baseline GA was not included in the analysis. The study is a secondary analysis of a randomized controlled trial, and it is not known which components of the interventions affected mental health.

DISCLOSURES:

This research project was supported by the UniHealth Foundation, the City of Hope Center for Cancer and Aging, and the National Institutes of Health. One coauthor disclosed receiving institutional research funding from AstraZeneca and Brooklyn ImmunoTherapeutics and consulting for multiple pharmaceutical companies, including AbbVie, Adagene, and Bayer HealthCare Pharmaceuticals. William Dale, MD, PhD, of City of Hope National Medical Center, served as senior author and a principal investigator. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Elevated depression symptoms are linked to an increased risk for severe chemotherapy toxicity in older adults with cancer. This risk is mitigated by geriatric assessment (GA)-driven interventions.

METHODOLOGY:

• Researchers conducted a secondary analysis of a randomized controlled trial to evaluate whether greater reductions in grade 3 chemotherapy-related toxicities occurred with geriatric assessment-driven interventions vs standard care.
• A total of 605 patients aged 65 years and older with any stage of solid malignancy were included, with 402 randomized to the intervention arm and 203 to the standard-of-care arm.
• Mental health was assessed using the Mental Health Inventory 13, and chemotherapy toxicity was graded by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.
• Patients in the intervention arm received recommendations from a multidisciplinary team based on their baseline GA, while those in the standard-of-care arm received only the baseline assessment results.
• The study was conducted at City of Hope National Medical Center in Duarte, California, and patients were followed throughout treatment or for up to 6 months from starting chemotherapy.

TAKEAWAY:

• According to the authors, patients with depression had increased chemotherapy toxicity in the standard-of-care arm (70.7% vs 54.3%; P = .02) but not in the GA-driven intervention arm (54.3% vs 48.5%; P = .27).
• The association between depression and chemotherapy toxicity was also seen after adjustment for the Cancer and Aging Research Group toxicity score (odds ratio, [OR], 1.98; 95% CI, 1.07-3.65) and for demographic, disease, and treatment factors (OR, 2.00; 95% CI, 1.03-3.85).
• No significant association was found between anxiety and chemotherapy toxicity in either the standard-of-care arm (univariate OR, 1.07; 95% CI, 0.61-1.88) or the GA-driven intervention arm (univariate OR, 1.15; 95% CI, 0.78-1.71).
• The authors stated that depression was associated with increased odds of hematologic-only toxicities (OR, 2.50; 95% CI, 1.13-5.56) in the standard-of-care arm.
• An analysis of a small subgroup found associations between elevated anxiety symptoms and increased risk for hematologic and nonhematologic chemotherapy toxicities.

IN PRACTICE:

“The current study showed that elevated depression symptoms are associated with increased risk of severe chemotherapy toxicities in older adults with cancer. This risk was mitigated in those in the GA intervention arm, which suggests that addressing elevated depression symptoms may lower the risk of toxicities,” the authors wrote. “Overall, elevated anxiety symptoms were not associated with risk for severe chemotherapy toxicity.”

SOURCE:

Reena V. Jayani, MD, MSCI, of Vanderbilt University Medical Center in Nashville, Tennessee, was the first and corresponding author for this paper. This study was published online August 4, 2024, in Cancer. 

LIMITATIONS:

The thresholds for depression and anxiety used in the Mental Health Inventory 13 were based on an English-speaking population, which may not be fully applicable to Chinese- and Spanish-speaking patients included in the study. Depression and anxiety were not evaluated by a mental health professional or with a structured interview to assess formal diagnostic criteria. Psychiatric medication used at the time of baseline GA was not included in the analysis. The study is a secondary analysis of a randomized controlled trial, and it is not known which components of the interventions affected mental health.

DISCLOSURES:

This research project was supported by the UniHealth Foundation, the City of Hope Center for Cancer and Aging, and the National Institutes of Health. One coauthor disclosed receiving institutional research funding from AstraZeneca and Brooklyn ImmunoTherapeutics and consulting for multiple pharmaceutical companies, including AbbVie, Adagene, and Bayer HealthCare Pharmaceuticals. William Dale, MD, PhD, of City of Hope National Medical Center, served as senior author and a principal investigator. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

WASHINGTON — Immunoglobulin E (IgE) and eosinophils appeared to be reliable biomarkers of type 2 inflammation in chronic pruritus of unknown origin (CPUO) and predictors of a positive response to immunomodulatory therapies, Shawn G. Kwatra, MD, said at the ElderDerm conference on dermatology in older patients hosted by the GW School of Medicine & Health Sciences.

“We found a few years ago that eosinophils seem to differentiate this group, and now we’re finding that IgE and CBC [complete blood count] differential can help you get a little better sense of who has an immune-driven itch vs something more neuropathic,” said Dr. Kwatra, professor and chair of dermatology at the University of Maryland, Baltimore, who founded and directed the Johns Hopkins Itch Center before coming to the University of Maryland in 2023. Not all patients with immune-driven itch will have these biomarkers, “but it’s a helpful tool,” he said.

Dr. Kwatra

CPUO is the term that is increasingly being used, he said, to describe intense, chronic pruritus without primary skin lesions or rashes and without any known systemic cause. It becomes more common as people get older and is sometimes debilitating. The initial evaluation should be kept “simple and straightforward,” he advised, with heightened concern for underlying malignancy in those who present with an itch of less than 12 months’ duration.
 

Biologics, JAK Inhibitors: Case Reports, Ongoing Research 

Research conducted by Dr. Kwatra and Jaya Manjunath, a fourth-year medical student at The George Washington University, Washington, documented higher levels of Th2-associated cytokines and inflammatory markers in patients with CPUO who had elevated IgE or eosinophil levels, or both than in patients with itch who had low IgE and eosinophil levels. The patients with higher levels also had a greater response to off-label treatment with immunomodulatory therapy.

“Multiple Th2-related inflammatory markers, like IL [interleukin]-5 and eotaxin-3, were reduced after dupilumab” in patients who responded to the therapy, said Ms. Manjunath, who co-presented the meeting session on chronic itch with Dr. Kwatra. Other changes in the plasma cytokine profile included a reduction in the serum level of thymus and activation-regulated chemokine, which is a biomarker for atopic dermatitis. The research is under review for publication.

Meanwhile, a phase 3 trial (LIBERTY-CPUO-CHIC) of dupilumab for CPUO is currently underway, Dr. Kwatra noted. Investigators are randomizing patients with severe pruritus (Worst Itch Numeric Rating Scale [WI-NRS] ≥ 7) to dupilumab or placebo for 12 or 24 weeks.

In one of several cases shared by Dr. Kwatra and Ms. Manjunath, a 71-year-old Black woman with a 6-month history of generalized itch (WI-NRS = 10) and a history of type 2 diabetes, hypertension, and chronic kidney disease was found to have elevated eosinophil levels and a negative malignancy workup. Previous therapies included antihistamines and topical steroids. She was started on a 600-mg loading dose of subcutaneous dupilumab followed by 300 mg every 14 days. At the 2-month follow-up, her WI-NRS score was 0.

Because “dupilumab is off label right now for this form of itch, oftentimes our first line is methotrexate,” Dr. Kwatra said. Patients “can have a good response with this therapeutic.”

He also described the case of a 72-year-old Black woman with total body itch for 2 years (WI-NRS = 10) and a history of seasonal allergies, thyroid disease, and hypertension. Previous therapies included prednisone, antihistamines, topical steroids, and gabapentin. The patient was found to have high IgE (447 kU/L) and eosinophil levels (4.9%), was started on methotrexate, and had an itch score of 0 at the 8-month follow-up.

JAK inhibitors may also have a role in the management of CPUO. A phase 2 nonrandomized controlled trial of abrocitinib for adults with prurigo nodularis (PN) or CPUO, recently published in JAMA Dermatology, showed itch scores decreased by 53.7% in the CPUO group (and 78.3% in the PN group) after 12 weeks of treatment with oral abrocitinib 200 mg daily. Patients had significant improvements in quality of life and no serious adverse events, said Dr. Kwatra, the lead author of the paper.

One of these patients was a 73-year-old White man who had experienced total body itch for 1.5 years (predominantly affecting his upper extremities; WI-NRS = 10) and a history of ascending aortic aneurysm, hypertension, and hyperlipidemia. Previous failed therapies included dupilumab (> 6 months), topical steroids, tacrolimus, and antihistamines. Labs showed elevated IgE (456 kU/L) and eosinophil levels (11.7%). After 12 weeks of treatment with abrocitinib, the WI-NRS decreased to 2.
 

PD-1 Inhibitors As a Trigger

Chronic pruritus caused by the anticancer PD-1 inhibitors is becoming more common as the utilization of these immune checkpoint inhibitors increases, Dr. Kwatra noted. “You don’t see much in the skin, but [these patients have] very high IgE and eosinophils,” he said. “We’ve been seeing more reports recently of utilizing agents that target type 2 inflammation off label for PD-1 inhibitor–related skin manifestations.”

One such patient with PD-1 inhibitor–induced pruritus was a 65-year-old White man with metastatic melanoma who reported a 6-month history of itching that began 3 weeks after the start of treatment with the PD-1 inhibitor pembrolizumab. His WI-NRS score was 10 despite treatment with topical steroids and antihistamines. He had a history of psoriasis. Labs showed elevated IgE (1350 kU/L) and eosinophil levels (4.5%). At a 4-month follow-up after treatment with off-label dupilumab (a 600-mg subcutaneous loading dose followed by 300 mg every 14 days), his WI-NRS score was 0.

In a paper recently published in JAAD International, Dr. Kwatra, Ms. Manjunath, and coinvestigators reported on a series of 15 patients who developed chronic pruritus following an immune stimulus exposure, including immunotherapy and vaccination (2024 Apr 7:16:97-102. doi: 10.1016/j.jdin.2024.03.022). Most immunotherapy-treated patients experienced pruritus during treatment or after 21-60 days of receiving treatment, and the patients with vaccine-stimulated pruritus (after Tdap and messenger RNA COVID-19 vaccination) developed pruritus within a week of vaccination.

In addition to the elevated levels of IgE and eosinophils, plasma cytokine analysis showed elevated levels of IL-5, thymic stromal lymphopoietin, and other Th2-related cytokines and inflammatory markers in patients with immune-stimulated pruritus compared with healthy controls, Ms. Manjunath said at the meeting.

When a Malignancy Workup Becomes Important

The initial part of any diagnostic workup for CPUO should include CBC with differential, liver function tests, renal function tests, and thyroid function testing, said Kwatra, referring to a diagnostic algorithm he developed, which was published as part of a CME review in the Journal of the American Academy of Dermatology in 2022.

Then, as indicated by risk factors in the history and physical, one could order other tests such as HIV serology, hepatitis B/C serologies, bullous pemphigoid testing, chest x-rays, evaluation for gammopathies, stool examination for ova and parasites, or heavy metal testing. “Do you do everything at once? We like to keep it straightforward,” Dr. Kwatra said. “Depending on the patient’s risk factors, you could order more or less.”

A malignancy workup should be strongly considered in patients whose itch duration is less than 12 months — and especially if the duration is less than 3 months — with an emphasis on cancers more frequently associated with itch: Hematologic and hepatobiliary cancers. This is “when concern should be heightened ... when there should be a lower threshold for workup,” he said.

The 12-month recommendation stems from a Danish cohort study published in 2014 that demonstrated a twofold increased incidence of cancer among patients with pruritus in the first 3 months after the diagnosis of pruritus. The 1-year absolute cancer risk was 1.63%.

Other risk factors for underlying malignancy or malignancy development in patients with CPUO include age older than 60 years, male sex, liver disease, and current or prior smoking, according to another study, noted Dr. Kwatra.

Dr. Kwatra disclosed that he is an advisory board member/consultant for Pfizer, Regeneron, Sanofi, and other companies and an investigator for Galderma, Incyte, Pfizer, and Sanofi. Manjunath served as the codirector of the ElderDerm conference.
 

A version of this article first appeared on Medscape.com.

WASHINGTON — Immunoglobulin E (IgE) and eosinophils appeared to be reliable biomarkers of type 2 inflammation in chronic pruritus of unknown origin (CPUO) and predictors of a positive response to immunomodulatory therapies, Shawn G. Kwatra, MD, said at the ElderDerm conference on dermatology in older patients hosted by the GW School of Medicine & Health Sciences.

“We found a few years ago that eosinophils seem to differentiate this group, and now we’re finding that IgE and CBC [complete blood count] differential can help you get a little better sense of who has an immune-driven itch vs something more neuropathic,” said Dr. Kwatra, professor and chair of dermatology at the University of Maryland, Baltimore, who founded and directed the Johns Hopkins Itch Center before coming to the University of Maryland in 2023. Not all patients with immune-driven itch will have these biomarkers, “but it’s a helpful tool,” he said.

Dr. Kwatra

CPUO is the term that is increasingly being used, he said, to describe intense, chronic pruritus without primary skin lesions or rashes and without any known systemic cause. It becomes more common as people get older and is sometimes debilitating. The initial evaluation should be kept “simple and straightforward,” he advised, with heightened concern for underlying malignancy in those who present with an itch of less than 12 months’ duration.
 

Biologics, JAK Inhibitors: Case Reports, Ongoing Research 

Research conducted by Dr. Kwatra and Jaya Manjunath, a fourth-year medical student at The George Washington University, Washington, documented higher levels of Th2-associated cytokines and inflammatory markers in patients with CPUO who had elevated IgE or eosinophil levels, or both than in patients with itch who had low IgE and eosinophil levels. The patients with higher levels also had a greater response to off-label treatment with immunomodulatory therapy.

“Multiple Th2-related inflammatory markers, like IL [interleukin]-5 and eotaxin-3, were reduced after dupilumab” in patients who responded to the therapy, said Ms. Manjunath, who co-presented the meeting session on chronic itch with Dr. Kwatra. Other changes in the plasma cytokine profile included a reduction in the serum level of thymus and activation-regulated chemokine, which is a biomarker for atopic dermatitis. The research is under review for publication.

Meanwhile, a phase 3 trial (LIBERTY-CPUO-CHIC) of dupilumab for CPUO is currently underway, Dr. Kwatra noted. Investigators are randomizing patients with severe pruritus (Worst Itch Numeric Rating Scale [WI-NRS] ≥ 7) to dupilumab or placebo for 12 or 24 weeks.

In one of several cases shared by Dr. Kwatra and Ms. Manjunath, a 71-year-old Black woman with a 6-month history of generalized itch (WI-NRS = 10) and a history of type 2 diabetes, hypertension, and chronic kidney disease was found to have elevated eosinophil levels and a negative malignancy workup. Previous therapies included antihistamines and topical steroids. She was started on a 600-mg loading dose of subcutaneous dupilumab followed by 300 mg every 14 days. At the 2-month follow-up, her WI-NRS score was 0.

Because “dupilumab is off label right now for this form of itch, oftentimes our first line is methotrexate,” Dr. Kwatra said. Patients “can have a good response with this therapeutic.”

He also described the case of a 72-year-old Black woman with total body itch for 2 years (WI-NRS = 10) and a history of seasonal allergies, thyroid disease, and hypertension. Previous therapies included prednisone, antihistamines, topical steroids, and gabapentin. The patient was found to have high IgE (447 kU/L) and eosinophil levels (4.9%), was started on methotrexate, and had an itch score of 0 at the 8-month follow-up.

JAK inhibitors may also have a role in the management of CPUO. A phase 2 nonrandomized controlled trial of abrocitinib for adults with prurigo nodularis (PN) or CPUO, recently published in JAMA Dermatology, showed itch scores decreased by 53.7% in the CPUO group (and 78.3% in the PN group) after 12 weeks of treatment with oral abrocitinib 200 mg daily. Patients had significant improvements in quality of life and no serious adverse events, said Dr. Kwatra, the lead author of the paper.

One of these patients was a 73-year-old White man who had experienced total body itch for 1.5 years (predominantly affecting his upper extremities; WI-NRS = 10) and a history of ascending aortic aneurysm, hypertension, and hyperlipidemia. Previous failed therapies included dupilumab (> 6 months), topical steroids, tacrolimus, and antihistamines. Labs showed elevated IgE (456 kU/L) and eosinophil levels (11.7%). After 12 weeks of treatment with abrocitinib, the WI-NRS decreased to 2.
 

PD-1 Inhibitors As a Trigger

Chronic pruritus caused by the anticancer PD-1 inhibitors is becoming more common as the utilization of these immune checkpoint inhibitors increases, Dr. Kwatra noted. “You don’t see much in the skin, but [these patients have] very high IgE and eosinophils,” he said. “We’ve been seeing more reports recently of utilizing agents that target type 2 inflammation off label for PD-1 inhibitor–related skin manifestations.”

One such patient with PD-1 inhibitor–induced pruritus was a 65-year-old White man with metastatic melanoma who reported a 6-month history of itching that began 3 weeks after the start of treatment with the PD-1 inhibitor pembrolizumab. His WI-NRS score was 10 despite treatment with topical steroids and antihistamines. He had a history of psoriasis. Labs showed elevated IgE (1350 kU/L) and eosinophil levels (4.5%). At a 4-month follow-up after treatment with off-label dupilumab (a 600-mg subcutaneous loading dose followed by 300 mg every 14 days), his WI-NRS score was 0.

In a paper recently published in JAAD International, Dr. Kwatra, Ms. Manjunath, and coinvestigators reported on a series of 15 patients who developed chronic pruritus following an immune stimulus exposure, including immunotherapy and vaccination (2024 Apr 7:16:97-102. doi: 10.1016/j.jdin.2024.03.022). Most immunotherapy-treated patients experienced pruritus during treatment or after 21-60 days of receiving treatment, and the patients with vaccine-stimulated pruritus (after Tdap and messenger RNA COVID-19 vaccination) developed pruritus within a week of vaccination.

In addition to the elevated levels of IgE and eosinophils, plasma cytokine analysis showed elevated levels of IL-5, thymic stromal lymphopoietin, and other Th2-related cytokines and inflammatory markers in patients with immune-stimulated pruritus compared with healthy controls, Ms. Manjunath said at the meeting.

When a Malignancy Workup Becomes Important

The initial part of any diagnostic workup for CPUO should include CBC with differential, liver function tests, renal function tests, and thyroid function testing, said Kwatra, referring to a diagnostic algorithm he developed, which was published as part of a CME review in the Journal of the American Academy of Dermatology in 2022.

Then, as indicated by risk factors in the history and physical, one could order other tests such as HIV serology, hepatitis B/C serologies, bullous pemphigoid testing, chest x-rays, evaluation for gammopathies, stool examination for ova and parasites, or heavy metal testing. “Do you do everything at once? We like to keep it straightforward,” Dr. Kwatra said. “Depending on the patient’s risk factors, you could order more or less.”

A malignancy workup should be strongly considered in patients whose itch duration is less than 12 months — and especially if the duration is less than 3 months — with an emphasis on cancers more frequently associated with itch: Hematologic and hepatobiliary cancers. This is “when concern should be heightened ... when there should be a lower threshold for workup,” he said.

The 12-month recommendation stems from a Danish cohort study published in 2014 that demonstrated a twofold increased incidence of cancer among patients with pruritus in the first 3 months after the diagnosis of pruritus. The 1-year absolute cancer risk was 1.63%.

Other risk factors for underlying malignancy or malignancy development in patients with CPUO include age older than 60 years, male sex, liver disease, and current or prior smoking, according to another study, noted Dr. Kwatra.

Dr. Kwatra disclosed that he is an advisory board member/consultant for Pfizer, Regeneron, Sanofi, and other companies and an investigator for Galderma, Incyte, Pfizer, and Sanofi. Manjunath served as the codirector of the ElderDerm conference.
 

A version of this article first appeared on Medscape.com.

WASHINGTON — Immunoglobulin E (IgE) and eosinophils appeared to be reliable biomarkers of type 2 inflammation in chronic pruritus of unknown origin (CPUO) and predictors of a positive response to immunomodulatory therapies, Shawn G. Kwatra, MD, said at the ElderDerm conference on dermatology in older patients hosted by the GW School of Medicine & Health Sciences.

“We found a few years ago that eosinophils seem to differentiate this group, and now we’re finding that IgE and CBC [complete blood count] differential can help you get a little better sense of who has an immune-driven itch vs something more neuropathic,” said Dr. Kwatra, professor and chair of dermatology at the University of Maryland, Baltimore, who founded and directed the Johns Hopkins Itch Center before coming to the University of Maryland in 2023. Not all patients with immune-driven itch will have these biomarkers, “but it’s a helpful tool,” he said.

Dr. Kwatra

CPUO is the term that is increasingly being used, he said, to describe intense, chronic pruritus without primary skin lesions or rashes and without any known systemic cause. It becomes more common as people get older and is sometimes debilitating. The initial evaluation should be kept “simple and straightforward,” he advised, with heightened concern for underlying malignancy in those who present with an itch of less than 12 months’ duration.
 

Biologics, JAK Inhibitors: Case Reports, Ongoing Research 

Research conducted by Dr. Kwatra and Jaya Manjunath, a fourth-year medical student at The George Washington University, Washington, documented higher levels of Th2-associated cytokines and inflammatory markers in patients with CPUO who had elevated IgE or eosinophil levels, or both than in patients with itch who had low IgE and eosinophil levels. The patients with higher levels also had a greater response to off-label treatment with immunomodulatory therapy.

“Multiple Th2-related inflammatory markers, like IL [interleukin]-5 and eotaxin-3, were reduced after dupilumab” in patients who responded to the therapy, said Ms. Manjunath, who co-presented the meeting session on chronic itch with Dr. Kwatra. Other changes in the plasma cytokine profile included a reduction in the serum level of thymus and activation-regulated chemokine, which is a biomarker for atopic dermatitis. The research is under review for publication.

Meanwhile, a phase 3 trial (LIBERTY-CPUO-CHIC) of dupilumab for CPUO is currently underway, Dr. Kwatra noted. Investigators are randomizing patients with severe pruritus (Worst Itch Numeric Rating Scale [WI-NRS] ≥ 7) to dupilumab or placebo for 12 or 24 weeks.

In one of several cases shared by Dr. Kwatra and Ms. Manjunath, a 71-year-old Black woman with a 6-month history of generalized itch (WI-NRS = 10) and a history of type 2 diabetes, hypertension, and chronic kidney disease was found to have elevated eosinophil levels and a negative malignancy workup. Previous therapies included antihistamines and topical steroids. She was started on a 600-mg loading dose of subcutaneous dupilumab followed by 300 mg every 14 days. At the 2-month follow-up, her WI-NRS score was 0.

Because “dupilumab is off label right now for this form of itch, oftentimes our first line is methotrexate,” Dr. Kwatra said. Patients “can have a good response with this therapeutic.”

He also described the case of a 72-year-old Black woman with total body itch for 2 years (WI-NRS = 10) and a history of seasonal allergies, thyroid disease, and hypertension. Previous therapies included prednisone, antihistamines, topical steroids, and gabapentin. The patient was found to have high IgE (447 kU/L) and eosinophil levels (4.9%), was started on methotrexate, and had an itch score of 0 at the 8-month follow-up.

JAK inhibitors may also have a role in the management of CPUO. A phase 2 nonrandomized controlled trial of abrocitinib for adults with prurigo nodularis (PN) or CPUO, recently published in JAMA Dermatology, showed itch scores decreased by 53.7% in the CPUO group (and 78.3% in the PN group) after 12 weeks of treatment with oral abrocitinib 200 mg daily. Patients had significant improvements in quality of life and no serious adverse events, said Dr. Kwatra, the lead author of the paper.

One of these patients was a 73-year-old White man who had experienced total body itch for 1.5 years (predominantly affecting his upper extremities; WI-NRS = 10) and a history of ascending aortic aneurysm, hypertension, and hyperlipidemia. Previous failed therapies included dupilumab (> 6 months), topical steroids, tacrolimus, and antihistamines. Labs showed elevated IgE (456 kU/L) and eosinophil levels (11.7%). After 12 weeks of treatment with abrocitinib, the WI-NRS decreased to 2.
 

PD-1 Inhibitors As a Trigger

Chronic pruritus caused by the anticancer PD-1 inhibitors is becoming more common as the utilization of these immune checkpoint inhibitors increases, Dr. Kwatra noted. “You don’t see much in the skin, but [these patients have] very high IgE and eosinophils,” he said. “We’ve been seeing more reports recently of utilizing agents that target type 2 inflammation off label for PD-1 inhibitor–related skin manifestations.”

One such patient with PD-1 inhibitor–induced pruritus was a 65-year-old White man with metastatic melanoma who reported a 6-month history of itching that began 3 weeks after the start of treatment with the PD-1 inhibitor pembrolizumab. His WI-NRS score was 10 despite treatment with topical steroids and antihistamines. He had a history of psoriasis. Labs showed elevated IgE (1350 kU/L) and eosinophil levels (4.5%). At a 4-month follow-up after treatment with off-label dupilumab (a 600-mg subcutaneous loading dose followed by 300 mg every 14 days), his WI-NRS score was 0.

In a paper recently published in JAAD International, Dr. Kwatra, Ms. Manjunath, and coinvestigators reported on a series of 15 patients who developed chronic pruritus following an immune stimulus exposure, including immunotherapy and vaccination (2024 Apr 7:16:97-102. doi: 10.1016/j.jdin.2024.03.022). Most immunotherapy-treated patients experienced pruritus during treatment or after 21-60 days of receiving treatment, and the patients with vaccine-stimulated pruritus (after Tdap and messenger RNA COVID-19 vaccination) developed pruritus within a week of vaccination.

In addition to the elevated levels of IgE and eosinophils, plasma cytokine analysis showed elevated levels of IL-5, thymic stromal lymphopoietin, and other Th2-related cytokines and inflammatory markers in patients with immune-stimulated pruritus compared with healthy controls, Ms. Manjunath said at the meeting.

When a Malignancy Workup Becomes Important

The initial part of any diagnostic workup for CPUO should include CBC with differential, liver function tests, renal function tests, and thyroid function testing, said Kwatra, referring to a diagnostic algorithm he developed, which was published as part of a CME review in the Journal of the American Academy of Dermatology in 2022.

Then, as indicated by risk factors in the history and physical, one could order other tests such as HIV serology, hepatitis B/C serologies, bullous pemphigoid testing, chest x-rays, evaluation for gammopathies, stool examination for ova and parasites, or heavy metal testing. “Do you do everything at once? We like to keep it straightforward,” Dr. Kwatra said. “Depending on the patient’s risk factors, you could order more or less.”

A malignancy workup should be strongly considered in patients whose itch duration is less than 12 months — and especially if the duration is less than 3 months — with an emphasis on cancers more frequently associated with itch: Hematologic and hepatobiliary cancers. This is “when concern should be heightened ... when there should be a lower threshold for workup,” he said.

The 12-month recommendation stems from a Danish cohort study published in 2014 that demonstrated a twofold increased incidence of cancer among patients with pruritus in the first 3 months after the diagnosis of pruritus. The 1-year absolute cancer risk was 1.63%.

Other risk factors for underlying malignancy or malignancy development in patients with CPUO include age older than 60 years, male sex, liver disease, and current or prior smoking, according to another study, noted Dr. Kwatra.

Dr. Kwatra disclosed that he is an advisory board member/consultant for Pfizer, Regeneron, Sanofi, and other companies and an investigator for Galderma, Incyte, Pfizer, and Sanofi. Manjunath served as the codirector of the ElderDerm conference.
 

A version of this article first appeared on Medscape.com.

Patients experiencing memory problems often come to neurologist David Jones, MD, for second opinions. They repeat questions and sometimes misplace items. Their primary care clinician has suggested they may have Alzheimer’s disease or something else.

In many cases, Dr. Jones, a neurologist with Mayo Clinic in Rochester, Minnesota, performs a series of investigations and finds the patient instead has a different type of neurodegenerative syndrome, one that progresses slowly, seems limited chiefly to loss of memory, and which tests show affects only the limbic system.

The news of diagnosis can be reassuring to patients.

“Memory problems are not always Alzheimer’s disease,” Dr. Jones said. “It’s important to broaden the differential diagnosis and seek diagnostic clarity and precision for patients who experience problems with brain functioning later in life.”

Dr. Jones and colleagues recently published clinical criteria for what they call limbic-predominant amnestic neurodegenerative syndrome (LANS).

Various underlying etiologies are known to cause degeneration of the limbic system, the most frequent being a buildup of deposits of the TAR DNA-binding protein 43 (TDP-43) protein referred to as limbic-predominant, age-related TDP-43 encephalopathy neuropathological change (LATE-NC). LATE-NC first involves the amygdala, followed by the hippocampus, and then the middle frontal gyrus, and is found in about 40% of autopsied brains in people over age of 85 years.

By contrast, amnestic syndromes originating from neocortical degeneration are largely caused by neuropathological changes from Alzheimer’s disease and often present with non-memory features.
 

Criteria for LANS

Broken down into core, standard, and advanced features

Core clinical features:

The patient must present with a slow, amnestic, predominant neurodegenerative syndrome — an insidious onset with gradual progression over 2 or more years — without another condition that better accounts for the clinical deficits.

Standard supportive features:

1. Older age at evaluation.

• Most patients are at least the age of 75 years. Older age increases the likelihood that the amnestic syndrome is caused by degeneration of the limbic system.

2. Mild clinical syndrome.

• A diagnosis of mild cognitive impairment or mild amnestic dementia (ie, a score of ≤ 4 on the Clinical Dementia Rating Sum of Boxes [CDR-SB]) at the first visit.

3. Hippocampal atrophy out of proportion to syndrome severity.

• Hippocampal volume was smaller than expected on MRI, compared with the CDR-SB score.

4. Mildly impaired semantic memory.

Advanced supportive features:

1.Limbic hypometabolism and absence of neocortical degenerative pattern on fludeoxyglucose-18-PET imaging.

2. Low likelihood of significant neocortical tau pathology.


Dr. Jones and colleagues also classified a degree of certainty for LANS to use when making a diagnosis. Those with the highest likelihood meet all core, standard, and advanced features.

Patients with a high likelihood of having LANS meet core features, at least three standard features and one advanced feature; or meet core features, at least two standard features as well as two advanced features. Those with a moderate likelihood meet core features and at least three standard features or meet core features and at least two standard features and one advanced feature. Those with a low likelihood of LANS meet core features and two or fewer standard features.

To develop these criteria, the group screened 218 autopsied patients participating in databases for the Mayo Clinic Study of Aging and the multicenter Alzheimer’s Disease Neuroimaging Initiative. They conducted neuropathological assessments, reviewed MRI and PET scans of the brains, and studied fluid biomarkers from samples of cerebrospinal fluid.

In LANS, the neocortex exhibits normal function, Dr. Jones said. High-level language functions, visual spatial functions, and executive function are preserved, and the disease stays mild for many years. LANS is highly associated with LATE, for which no biomarkers are yet available.

The National Institute on Aging in May 2023 held a workshop on LATE, and a consensus group was formed to publish criteria to help with the diagnosis. Many LANS criteria likely will be in that publication as well, Dr. Jones said.

Several steps lay ahead to improve the definition of LANS, the authors wrote, including conducting prospective studies and developing clinical tools that are sensitive and specific to its cognitive features. The development of in vivo diagnostic markers of TDP-43 pathology is needed to embed LANS into a disease state driven by LATE-NC, according to Dr. Jones’ group. Because LANS is newly defined, clinical trials are needed to determine the best treatments.
 

Heterogeneous Dementia

“We are increasingly recognizing that the syndrome of dementia in older adults is heterogeneous,” said Sudha Seshadri, MD, DM, a behavioral neurologist and founding director of the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases at the University of Texas Health Science Center at San Antonio.

LANS “is something that needs to be diagnosed early but also needs to be worked up in a nuanced manner, with assessment of the pattern of cognitive deficits, the pattern of brain shrinkage on MRI, and also how the disease progresses over, say, a year,” said Dr. Seshadri. “We need to have both some primary care physicians and geriatricians who are comfortable doing this kind of nuanced advising and others who may refer patients to behavioral neurologists, geriatricians, or psychiatrists who have that kind of expertise.”

About 10% of people presenting to dementia clinics potentially could fit the LANS definition, Dr. Seshadri said. Dr. Seshadri was not a coauthor of the classification article but sees patients in the clinic who fit this description.

“It may be that as we start more freely giving the diagnosis of a possible LANS, the proportion of people will go up,” Dr. Seshadri said.

Primary care physicians can use a variety of assessments to help diagnose dementias, she said. These include the Montreal Cognitive Assessment (MoCA), which takes about 10 minutes to administer, or an MRI to determine the level of hippocampal atrophy. Blood tests for p-tau 217 and other plasma tests can stratify risk and guide referrals to a neurologist. Clinicians also should look for reversible causes of memory complaints, such as deficiencies in vitamin B12, folate, or the thyroid hormone.

“There aren’t enough behavioral neurologists around to work up every single person who has memory problems,” Dr. Seshadri said. “We really need to partner on educating and learning from our primary care partners as to what challenges they face, advocating for them to be able to address that, and then sharing what we know, because what we know is an evolving thing.”

Other tools primary care clinicians can use in the initial evaluation of dementia include the General Practitioner Assessment of Cognition and the Mini-Cog, as part of annual Medicare wellness visits or in response to patient or caregiver concerns about memory, said Allison Kaplan, MD, a family physician at Desert Grove Family Medical in Gilbert, Arizona, who coauthored a point-of-care guide for the American Academy of Family Physicians. Each of these tests takes just 3-4 minutes to administer.

If a patient has a positive result on the Mini-Cog or similar test, they should return for further dementia evaluation using the MoCA, Mini-Mental State Examination, or Saint Louis University Mental Status examination, she said. Physicians also can order brain imaging and lab work, as Dr. Seshadri noted. Dementias often accompany some type of cardiovascular disease, which should be managed.

Even if a patient or family member doesn’t express concern about memory, physicians can look for certain signs during medical visits.

“Patients will keep asking the same question, or you notice they’re having difficulty taking care of themselves, especially independent activities of daily living, which could clue you in to a dementia diagnosis,” she said.

Dr. Jones ,Dr. Seshadri, and Dr. Kaplan disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Patients experiencing memory problems often come to neurologist David Jones, MD, for second opinions. They repeat questions and sometimes misplace items. Their primary care clinician has suggested they may have Alzheimer’s disease or something else.

In many cases, Dr. Jones, a neurologist with Mayo Clinic in Rochester, Minnesota, performs a series of investigations and finds the patient instead has a different type of neurodegenerative syndrome, one that progresses slowly, seems limited chiefly to loss of memory, and which tests show affects only the limbic system.

The news of diagnosis can be reassuring to patients.

“Memory problems are not always Alzheimer’s disease,” Dr. Jones said. “It’s important to broaden the differential diagnosis and seek diagnostic clarity and precision for patients who experience problems with brain functioning later in life.”

Dr. Jones and colleagues recently published clinical criteria for what they call limbic-predominant amnestic neurodegenerative syndrome (LANS).

Various underlying etiologies are known to cause degeneration of the limbic system, the most frequent being a buildup of deposits of the TAR DNA-binding protein 43 (TDP-43) protein referred to as limbic-predominant, age-related TDP-43 encephalopathy neuropathological change (LATE-NC). LATE-NC first involves the amygdala, followed by the hippocampus, and then the middle frontal gyrus, and is found in about 40% of autopsied brains in people over age of 85 years.

By contrast, amnestic syndromes originating from neocortical degeneration are largely caused by neuropathological changes from Alzheimer’s disease and often present with non-memory features.
 

Criteria for LANS

Broken down into core, standard, and advanced features

Core clinical features:

The patient must present with a slow, amnestic, predominant neurodegenerative syndrome — an insidious onset with gradual progression over 2 or more years — without another condition that better accounts for the clinical deficits.

Standard supportive features:

1. Older age at evaluation.

• Most patients are at least the age of 75 years. Older age increases the likelihood that the amnestic syndrome is caused by degeneration of the limbic system.

2. Mild clinical syndrome.

• A diagnosis of mild cognitive impairment or mild amnestic dementia (ie, a score of ≤ 4 on the Clinical Dementia Rating Sum of Boxes [CDR-SB]) at the first visit.

3. Hippocampal atrophy out of proportion to syndrome severity.

• Hippocampal volume was smaller than expected on MRI, compared with the CDR-SB score.

4. Mildly impaired semantic memory.

Advanced supportive features:

1.Limbic hypometabolism and absence of neocortical degenerative pattern on fludeoxyglucose-18-PET imaging.

2. Low likelihood of significant neocortical tau pathology.


Dr. Jones and colleagues also classified a degree of certainty for LANS to use when making a diagnosis. Those with the highest likelihood meet all core, standard, and advanced features.

Patients with a high likelihood of having LANS meet core features, at least three standard features and one advanced feature; or meet core features, at least two standard features as well as two advanced features. Those with a moderate likelihood meet core features and at least three standard features or meet core features and at least two standard features and one advanced feature. Those with a low likelihood of LANS meet core features and two or fewer standard features.

To develop these criteria, the group screened 218 autopsied patients participating in databases for the Mayo Clinic Study of Aging and the multicenter Alzheimer’s Disease Neuroimaging Initiative. They conducted neuropathological assessments, reviewed MRI and PET scans of the brains, and studied fluid biomarkers from samples of cerebrospinal fluid.

In LANS, the neocortex exhibits normal function, Dr. Jones said. High-level language functions, visual spatial functions, and executive function are preserved, and the disease stays mild for many years. LANS is highly associated with LATE, for which no biomarkers are yet available.

The National Institute on Aging in May 2023 held a workshop on LATE, and a consensus group was formed to publish criteria to help with the diagnosis. Many LANS criteria likely will be in that publication as well, Dr. Jones said.

Several steps lay ahead to improve the definition of LANS, the authors wrote, including conducting prospective studies and developing clinical tools that are sensitive and specific to its cognitive features. The development of in vivo diagnostic markers of TDP-43 pathology is needed to embed LANS into a disease state driven by LATE-NC, according to Dr. Jones’ group. Because LANS is newly defined, clinical trials are needed to determine the best treatments.
 

Heterogeneous Dementia

“We are increasingly recognizing that the syndrome of dementia in older adults is heterogeneous,” said Sudha Seshadri, MD, DM, a behavioral neurologist and founding director of the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases at the University of Texas Health Science Center at San Antonio.

LANS “is something that needs to be diagnosed early but also needs to be worked up in a nuanced manner, with assessment of the pattern of cognitive deficits, the pattern of brain shrinkage on MRI, and also how the disease progresses over, say, a year,” said Dr. Seshadri. “We need to have both some primary care physicians and geriatricians who are comfortable doing this kind of nuanced advising and others who may refer patients to behavioral neurologists, geriatricians, or psychiatrists who have that kind of expertise.”

About 10% of people presenting to dementia clinics potentially could fit the LANS definition, Dr. Seshadri said. Dr. Seshadri was not a coauthor of the classification article but sees patients in the clinic who fit this description.

“It may be that as we start more freely giving the diagnosis of a possible LANS, the proportion of people will go up,” Dr. Seshadri said.

Primary care physicians can use a variety of assessments to help diagnose dementias, she said. These include the Montreal Cognitive Assessment (MoCA), which takes about 10 minutes to administer, or an MRI to determine the level of hippocampal atrophy. Blood tests for p-tau 217 and other plasma tests can stratify risk and guide referrals to a neurologist. Clinicians also should look for reversible causes of memory complaints, such as deficiencies in vitamin B12, folate, or the thyroid hormone.

“There aren’t enough behavioral neurologists around to work up every single person who has memory problems,” Dr. Seshadri said. “We really need to partner on educating and learning from our primary care partners as to what challenges they face, advocating for them to be able to address that, and then sharing what we know, because what we know is an evolving thing.”

Other tools primary care clinicians can use in the initial evaluation of dementia include the General Practitioner Assessment of Cognition and the Mini-Cog, as part of annual Medicare wellness visits or in response to patient or caregiver concerns about memory, said Allison Kaplan, MD, a family physician at Desert Grove Family Medical in Gilbert, Arizona, who coauthored a point-of-care guide for the American Academy of Family Physicians. Each of these tests takes just 3-4 minutes to administer.

If a patient has a positive result on the Mini-Cog or similar test, they should return for further dementia evaluation using the MoCA, Mini-Mental State Examination, or Saint Louis University Mental Status examination, she said. Physicians also can order brain imaging and lab work, as Dr. Seshadri noted. Dementias often accompany some type of cardiovascular disease, which should be managed.

Even if a patient or family member doesn’t express concern about memory, physicians can look for certain signs during medical visits.

“Patients will keep asking the same question, or you notice they’re having difficulty taking care of themselves, especially independent activities of daily living, which could clue you in to a dementia diagnosis,” she said.

Dr. Jones ,Dr. Seshadri, and Dr. Kaplan disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Patients experiencing memory problems often come to neurologist David Jones, MD, for second opinions. They repeat questions and sometimes misplace items. Their primary care clinician has suggested they may have Alzheimer’s disease or something else.

In many cases, Dr. Jones, a neurologist with Mayo Clinic in Rochester, Minnesota, performs a series of investigations and finds the patient instead has a different type of neurodegenerative syndrome, one that progresses slowly, seems limited chiefly to loss of memory, and which tests show affects only the limbic system.

The news of diagnosis can be reassuring to patients.

“Memory problems are not always Alzheimer’s disease,” Dr. Jones said. “It’s important to broaden the differential diagnosis and seek diagnostic clarity and precision for patients who experience problems with brain functioning later in life.”

Dr. Jones and colleagues recently published clinical criteria for what they call limbic-predominant amnestic neurodegenerative syndrome (LANS).

Various underlying etiologies are known to cause degeneration of the limbic system, the most frequent being a buildup of deposits of the TAR DNA-binding protein 43 (TDP-43) protein referred to as limbic-predominant, age-related TDP-43 encephalopathy neuropathological change (LATE-NC). LATE-NC first involves the amygdala, followed by the hippocampus, and then the middle frontal gyrus, and is found in about 40% of autopsied brains in people over age of 85 years.

By contrast, amnestic syndromes originating from neocortical degeneration are largely caused by neuropathological changes from Alzheimer’s disease and often present with non-memory features.
 

Criteria for LANS

Broken down into core, standard, and advanced features

Core clinical features:

The patient must present with a slow, amnestic, predominant neurodegenerative syndrome — an insidious onset with gradual progression over 2 or more years — without another condition that better accounts for the clinical deficits.

Standard supportive features:

1. Older age at evaluation.

• Most patients are at least the age of 75 years. Older age increases the likelihood that the amnestic syndrome is caused by degeneration of the limbic system.

2. Mild clinical syndrome.

• A diagnosis of mild cognitive impairment or mild amnestic dementia (ie, a score of ≤ 4 on the Clinical Dementia Rating Sum of Boxes [CDR-SB]) at the first visit.

3. Hippocampal atrophy out of proportion to syndrome severity.

• Hippocampal volume was smaller than expected on MRI, compared with the CDR-SB score.

4. Mildly impaired semantic memory.

Advanced supportive features:

1.Limbic hypometabolism and absence of neocortical degenerative pattern on fludeoxyglucose-18-PET imaging.

2. Low likelihood of significant neocortical tau pathology.


Dr. Jones and colleagues also classified a degree of certainty for LANS to use when making a diagnosis. Those with the highest likelihood meet all core, standard, and advanced features.

Patients with a high likelihood of having LANS meet core features, at least three standard features and one advanced feature; or meet core features, at least two standard features as well as two advanced features. Those with a moderate likelihood meet core features and at least three standard features or meet core features and at least two standard features and one advanced feature. Those with a low likelihood of LANS meet core features and two or fewer standard features.

To develop these criteria, the group screened 218 autopsied patients participating in databases for the Mayo Clinic Study of Aging and the multicenter Alzheimer’s Disease Neuroimaging Initiative. They conducted neuropathological assessments, reviewed MRI and PET scans of the brains, and studied fluid biomarkers from samples of cerebrospinal fluid.

In LANS, the neocortex exhibits normal function, Dr. Jones said. High-level language functions, visual spatial functions, and executive function are preserved, and the disease stays mild for many years. LANS is highly associated with LATE, for which no biomarkers are yet available.

The National Institute on Aging in May 2023 held a workshop on LATE, and a consensus group was formed to publish criteria to help with the diagnosis. Many LANS criteria likely will be in that publication as well, Dr. Jones said.

Several steps lay ahead to improve the definition of LANS, the authors wrote, including conducting prospective studies and developing clinical tools that are sensitive and specific to its cognitive features. The development of in vivo diagnostic markers of TDP-43 pathology is needed to embed LANS into a disease state driven by LATE-NC, according to Dr. Jones’ group. Because LANS is newly defined, clinical trials are needed to determine the best treatments.
 

Heterogeneous Dementia

“We are increasingly recognizing that the syndrome of dementia in older adults is heterogeneous,” said Sudha Seshadri, MD, DM, a behavioral neurologist and founding director of the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases at the University of Texas Health Science Center at San Antonio.

LANS “is something that needs to be diagnosed early but also needs to be worked up in a nuanced manner, with assessment of the pattern of cognitive deficits, the pattern of brain shrinkage on MRI, and also how the disease progresses over, say, a year,” said Dr. Seshadri. “We need to have both some primary care physicians and geriatricians who are comfortable doing this kind of nuanced advising and others who may refer patients to behavioral neurologists, geriatricians, or psychiatrists who have that kind of expertise.”

About 10% of people presenting to dementia clinics potentially could fit the LANS definition, Dr. Seshadri said. Dr. Seshadri was not a coauthor of the classification article but sees patients in the clinic who fit this description.

“It may be that as we start more freely giving the diagnosis of a possible LANS, the proportion of people will go up,” Dr. Seshadri said.

Primary care physicians can use a variety of assessments to help diagnose dementias, she said. These include the Montreal Cognitive Assessment (MoCA), which takes about 10 minutes to administer, or an MRI to determine the level of hippocampal atrophy. Blood tests for p-tau 217 and other plasma tests can stratify risk and guide referrals to a neurologist. Clinicians also should look for reversible causes of memory complaints, such as deficiencies in vitamin B12, folate, or the thyroid hormone.

“There aren’t enough behavioral neurologists around to work up every single person who has memory problems,” Dr. Seshadri said. “We really need to partner on educating and learning from our primary care partners as to what challenges they face, advocating for them to be able to address that, and then sharing what we know, because what we know is an evolving thing.”

Other tools primary care clinicians can use in the initial evaluation of dementia include the General Practitioner Assessment of Cognition and the Mini-Cog, as part of annual Medicare wellness visits or in response to patient or caregiver concerns about memory, said Allison Kaplan, MD, a family physician at Desert Grove Family Medical in Gilbert, Arizona, who coauthored a point-of-care guide for the American Academy of Family Physicians. Each of these tests takes just 3-4 minutes to administer.

If a patient has a positive result on the Mini-Cog or similar test, they should return for further dementia evaluation using the MoCA, Mini-Mental State Examination, or Saint Louis University Mental Status examination, she said. Physicians also can order brain imaging and lab work, as Dr. Seshadri noted. Dementias often accompany some type of cardiovascular disease, which should be managed.

Even if a patient or family member doesn’t express concern about memory, physicians can look for certain signs during medical visits.

“Patients will keep asking the same question, or you notice they’re having difficulty taking care of themselves, especially independent activities of daily living, which could clue you in to a dementia diagnosis,” she said.

Dr. Jones ,Dr. Seshadri, and Dr. Kaplan disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

A multicomponent nonpharmaceutical intervention improves sleep in people with dementia living at home, early results of a new phase 3 randomized controlled trial (RCT) show.

The benefits of the intervention — called DREAMS-START — were sustained at 8 months and extended to caregivers, the study found.

“We’re pleased with our results. We think that we were able to deliver it successfully and to a high rate of fidelity,” said study investigator Penny Rapaport, PhD, Division of Psychiatry, University College London, England.

The findings were presented at the Alzheimer’s Association International Conference (AAIC) 2024.
 

Sustained, Long-Term Effect

Sleep disturbances are very common in dementia. About 26% of people with all types of dementia will experience sleep disturbances, and that rate is higher in certain dementia subtypes, such as dementia with Lewy bodies, said Dr. Rapaport.

Such disturbances are distressing for people living with dementia as well as for those supporting them, she added. They’re “often the thing that will lead to people transitioning and moving into a care home.”

Dr. Rapaport noted there has not been full RCT evidence that any nonpharmacologic interventions or light-based treatments are effective in improving sleep disturbances.

Medications such as antipsychotics and benzodiazepines aren’t recommended as first-line treatment in people with dementia “because often these can be harmful,” she said.

The study recruited 377 dyads of people living with dementia (mean age, 79.4 years) and their caregivers from 12 national health service sites across England. “We were able to recruit an ethnically diverse sample from a broad socioeconomic background,” said Dr. Rapaport.

Researchers allocated the dyads to the intervention or to a treatment as usual group.

About 92% of participants were included in the intention-to-treat analysis at 8 months, which was the primary time point.

The intervention consists of six 1-hour interactive sessions that are “personalized and tailored to individual goals and needs,” said Dr. Rapaport. It was delivered by supervised, trained graduates, not clinicians.

The sessions focused on components of sleep hygiene (healthy habits, behaviors, and environments); activity and exercise; a tailored sleep routine; strategies to manage distress; natural and artificial light; and relaxation. A whole session was devoted to supporting sleep of caregivers.

The trial included masked outcome assessments, “so the people collecting the data were blinded to the intervention group,” said Dr. Rapaport.

The primary outcome was the Sleep Disorders Inventory (SDI) score. The SDI is a questionnaire about frequency and severity of sleep-disturbed behaviors completed by caregivers; a higher score indicates a worse outcome. The study adjusted for baseline SDI score and study site.

The adjusted mean difference between groups on the SDI was −4.7 points (95% confidence interval [CI], −7.65 to −1.74; P = .002) at 8 months.

The minimal clinically important difference on the SDI is a 4-point change, noted Dr. Rapaport.

The adjusted mean difference on the SDI at 4 months (a secondary outcome) was −4.4 points (95% CI, −7.3 to −1.5; P = .003).

Referring to illustrative graphs, Dr. Rapaport said that SDI scores decreased at both 4 and 8 months. “You can see statistically, there’s a significant difference between groups at both time points,” she said.

“We saw a sustained effect, so not just immediately after the intervention, but afterwards at 8 months.”

As for other secondary outcomes, the study found a significant reduction in neuropsychiatric symptoms among people with dementia at 8 months in the intervention arm relative to the control arm.

In addition, sleep and anxiety significantly improved among caregivers after 8 months. This shows “a picture of things getting better for the person with dementia, and the person who’s caring for them,” said Dr. Rapaport.

She noted the good adherence rate, with almost 83% of people in the intervention arm completing four or more sessions.

Fidelity to the intervention (ie, the extent to which it is implemented as intended) was also high, “so we feel it was delivered well,” said Dr. Rapaport.

Researchers also carried out a health economics analysis and looked at strategies for implementation of the program, but Dr. Rapaport did not discuss those results.
 

Encouraging Findings

Commenting for this news organization, Alex Bahar-Fuchs, PhD, Faculty of Health, School of Psychology, Deakin University, Victoria, Australia, who co-chaired the session featuring the research, said the findings of this “well-powered” RCT are “encouraging,” both for the primary outcome of sleep quality and for some of the secondary outcomes for the care-partner.

“The study adds to the growing evidence behind several nonpharmacological treatment approaches for cognitive and neuropsychiatric symptoms of people with dementia,” he said. 

The results “offer some hope for the treatment of a common disturbance in people with dementia which is associated with poorer outcomes and increased caregiver burden,” he added. 

An important area for further work would be to incorporate more objective measures of sleep quality, said Dr. Bahar-Fuchs.

Because the primary outcome was measured using a self-report questionnaire (the SDI) completed by care-partners, and because the intervention arm could not be blinded, “it remains possible that some detection bias may have affected the study findings,” said Dr. Bahar-Fuchs.

He said he would like to see the research extended to include an active control condition “to be able to better ascertain treatment mechanisms.”

The study was supported by the National Institute of Health and Care Research. Dr. Rapaport and Dr. Bahar-Fuchs reported no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

A multicomponent nonpharmaceutical intervention improves sleep in people with dementia living at home, early results of a new phase 3 randomized controlled trial (RCT) show.

The benefits of the intervention — called DREAMS-START — were sustained at 8 months and extended to caregivers, the study found.

“We’re pleased with our results. We think that we were able to deliver it successfully and to a high rate of fidelity,” said study investigator Penny Rapaport, PhD, Division of Psychiatry, University College London, England.

The findings were presented at the Alzheimer’s Association International Conference (AAIC) 2024.
 

Sustained, Long-Term Effect

Sleep disturbances are very common in dementia. About 26% of people with all types of dementia will experience sleep disturbances, and that rate is higher in certain dementia subtypes, such as dementia with Lewy bodies, said Dr. Rapaport.

Such disturbances are distressing for people living with dementia as well as for those supporting them, she added. They’re “often the thing that will lead to people transitioning and moving into a care home.”

Dr. Rapaport noted there has not been full RCT evidence that any nonpharmacologic interventions or light-based treatments are effective in improving sleep disturbances.

Medications such as antipsychotics and benzodiazepines aren’t recommended as first-line treatment in people with dementia “because often these can be harmful,” she said.

The study recruited 377 dyads of people living with dementia (mean age, 79.4 years) and their caregivers from 12 national health service sites across England. “We were able to recruit an ethnically diverse sample from a broad socioeconomic background,” said Dr. Rapaport.

Researchers allocated the dyads to the intervention or to a treatment as usual group.

About 92% of participants were included in the intention-to-treat analysis at 8 months, which was the primary time point.

The intervention consists of six 1-hour interactive sessions that are “personalized and tailored to individual goals and needs,” said Dr. Rapaport. It was delivered by supervised, trained graduates, not clinicians.

The sessions focused on components of sleep hygiene (healthy habits, behaviors, and environments); activity and exercise; a tailored sleep routine; strategies to manage distress; natural and artificial light; and relaxation. A whole session was devoted to supporting sleep of caregivers.

The trial included masked outcome assessments, “so the people collecting the data were blinded to the intervention group,” said Dr. Rapaport.

The primary outcome was the Sleep Disorders Inventory (SDI) score. The SDI is a questionnaire about frequency and severity of sleep-disturbed behaviors completed by caregivers; a higher score indicates a worse outcome. The study adjusted for baseline SDI score and study site.

The adjusted mean difference between groups on the SDI was −4.7 points (95% confidence interval [CI], −7.65 to −1.74; P = .002) at 8 months.

The minimal clinically important difference on the SDI is a 4-point change, noted Dr. Rapaport.

The adjusted mean difference on the SDI at 4 months (a secondary outcome) was −4.4 points (95% CI, −7.3 to −1.5; P = .003).

Referring to illustrative graphs, Dr. Rapaport said that SDI scores decreased at both 4 and 8 months. “You can see statistically, there’s a significant difference between groups at both time points,” she said.

“We saw a sustained effect, so not just immediately after the intervention, but afterwards at 8 months.”

As for other secondary outcomes, the study found a significant reduction in neuropsychiatric symptoms among people with dementia at 8 months in the intervention arm relative to the control arm.

In addition, sleep and anxiety significantly improved among caregivers after 8 months. This shows “a picture of things getting better for the person with dementia, and the person who’s caring for them,” said Dr. Rapaport.

She noted the good adherence rate, with almost 83% of people in the intervention arm completing four or more sessions.

Fidelity to the intervention (ie, the extent to which it is implemented as intended) was also high, “so we feel it was delivered well,” said Dr. Rapaport.

Researchers also carried out a health economics analysis and looked at strategies for implementation of the program, but Dr. Rapaport did not discuss those results.
 

Encouraging Findings

Commenting for this news organization, Alex Bahar-Fuchs, PhD, Faculty of Health, School of Psychology, Deakin University, Victoria, Australia, who co-chaired the session featuring the research, said the findings of this “well-powered” RCT are “encouraging,” both for the primary outcome of sleep quality and for some of the secondary outcomes for the care-partner.

“The study adds to the growing evidence behind several nonpharmacological treatment approaches for cognitive and neuropsychiatric symptoms of people with dementia,” he said. 

The results “offer some hope for the treatment of a common disturbance in people with dementia which is associated with poorer outcomes and increased caregiver burden,” he added. 

An important area for further work would be to incorporate more objective measures of sleep quality, said Dr. Bahar-Fuchs.

Because the primary outcome was measured using a self-report questionnaire (the SDI) completed by care-partners, and because the intervention arm could not be blinded, “it remains possible that some detection bias may have affected the study findings,” said Dr. Bahar-Fuchs.

He said he would like to see the research extended to include an active control condition “to be able to better ascertain treatment mechanisms.”

The study was supported by the National Institute of Health and Care Research. Dr. Rapaport and Dr. Bahar-Fuchs reported no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

A multicomponent nonpharmaceutical intervention improves sleep in people with dementia living at home, early results of a new phase 3 randomized controlled trial (RCT) show.

The benefits of the intervention — called DREAMS-START — were sustained at 8 months and extended to caregivers, the study found.

“We’re pleased with our results. We think that we were able to deliver it successfully and to a high rate of fidelity,” said study investigator Penny Rapaport, PhD, Division of Psychiatry, University College London, England.

The findings were presented at the Alzheimer’s Association International Conference (AAIC) 2024.
 

Sustained, Long-Term Effect

Sleep disturbances are very common in dementia. About 26% of people with all types of dementia will experience sleep disturbances, and that rate is higher in certain dementia subtypes, such as dementia with Lewy bodies, said Dr. Rapaport.

Such disturbances are distressing for people living with dementia as well as for those supporting them, she added. They’re “often the thing that will lead to people transitioning and moving into a care home.”

Dr. Rapaport noted there has not been full RCT evidence that any nonpharmacologic interventions or light-based treatments are effective in improving sleep disturbances.

Medications such as antipsychotics and benzodiazepines aren’t recommended as first-line treatment in people with dementia “because often these can be harmful,” she said.

The study recruited 377 dyads of people living with dementia (mean age, 79.4 years) and their caregivers from 12 national health service sites across England. “We were able to recruit an ethnically diverse sample from a broad socioeconomic background,” said Dr. Rapaport.

Researchers allocated the dyads to the intervention or to a treatment as usual group.

About 92% of participants were included in the intention-to-treat analysis at 8 months, which was the primary time point.

The intervention consists of six 1-hour interactive sessions that are “personalized and tailored to individual goals and needs,” said Dr. Rapaport. It was delivered by supervised, trained graduates, not clinicians.

The sessions focused on components of sleep hygiene (healthy habits, behaviors, and environments); activity and exercise; a tailored sleep routine; strategies to manage distress; natural and artificial light; and relaxation. A whole session was devoted to supporting sleep of caregivers.

The trial included masked outcome assessments, “so the people collecting the data were blinded to the intervention group,” said Dr. Rapaport.

The primary outcome was the Sleep Disorders Inventory (SDI) score. The SDI is a questionnaire about frequency and severity of sleep-disturbed behaviors completed by caregivers; a higher score indicates a worse outcome. The study adjusted for baseline SDI score and study site.

The adjusted mean difference between groups on the SDI was −4.7 points (95% confidence interval [CI], −7.65 to −1.74; P = .002) at 8 months.

The minimal clinically important difference on the SDI is a 4-point change, noted Dr. Rapaport.

The adjusted mean difference on the SDI at 4 months (a secondary outcome) was −4.4 points (95% CI, −7.3 to −1.5; P = .003).

Referring to illustrative graphs, Dr. Rapaport said that SDI scores decreased at both 4 and 8 months. “You can see statistically, there’s a significant difference between groups at both time points,” she said.

“We saw a sustained effect, so not just immediately after the intervention, but afterwards at 8 months.”

As for other secondary outcomes, the study found a significant reduction in neuropsychiatric symptoms among people with dementia at 8 months in the intervention arm relative to the control arm.

In addition, sleep and anxiety significantly improved among caregivers after 8 months. This shows “a picture of things getting better for the person with dementia, and the person who’s caring for them,” said Dr. Rapaport.

She noted the good adherence rate, with almost 83% of people in the intervention arm completing four or more sessions.

Fidelity to the intervention (ie, the extent to which it is implemented as intended) was also high, “so we feel it was delivered well,” said Dr. Rapaport.

Researchers also carried out a health economics analysis and looked at strategies for implementation of the program, but Dr. Rapaport did not discuss those results.
 

Encouraging Findings

Commenting for this news organization, Alex Bahar-Fuchs, PhD, Faculty of Health, School of Psychology, Deakin University, Victoria, Australia, who co-chaired the session featuring the research, said the findings of this “well-powered” RCT are “encouraging,” both for the primary outcome of sleep quality and for some of the secondary outcomes for the care-partner.

“The study adds to the growing evidence behind several nonpharmacological treatment approaches for cognitive and neuropsychiatric symptoms of people with dementia,” he said. 

The results “offer some hope for the treatment of a common disturbance in people with dementia which is associated with poorer outcomes and increased caregiver burden,” he added. 

An important area for further work would be to incorporate more objective measures of sleep quality, said Dr. Bahar-Fuchs.

Because the primary outcome was measured using a self-report questionnaire (the SDI) completed by care-partners, and because the intervention arm could not be blinded, “it remains possible that some detection bias may have affected the study findings,” said Dr. Bahar-Fuchs.

He said he would like to see the research extended to include an active control condition “to be able to better ascertain treatment mechanisms.”

The study was supported by the National Institute of Health and Care Research. Dr. Rapaport and Dr. Bahar-Fuchs reported no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.