SGLT2 Inhibitor Reduces Risk for Neurodegenerative Diseases in T2D

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MADRID — Patients with type 2 diabetes treated with sodium-glucose cotransporter 2 inhibitors (SGLT2is) show significant reductions in the risk of developing neurodegenerative disorders including Alzheimer’s disease, vascular dementia, and Parkinson’s disease, compared with those treated with other antidiabetic drugs, results from a large population-based cohort show.

“This was the largest nationwide population-based longitudinal cohort study to investigate the association between the use of SGLT2 inhibitors and the incidence of all-cause dementia and Parkinson’s disease,” said first author Hae Kyung Kim, MD, of the Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea, in presenting the findings at the annual meeting of the European Association for the Study of Diabetes.

Type 2 diabetes is known to increase the risk for neurodegenerative diseases such as dementia or Alzheimer’s disease, said Dr. Kim. Key factors attributed to the risk include shared pathophysiological mechanisms such as central nervous system insulin resistance and reduced cerebral glucose metabolism.

While research is lacking on the role of antidiabetic drugs in the treatment of neurodegenerative diseases, the researcher noted that “SGLT2 inhibitors, which have shown significant cardiorenal benefits and enhanced energy metabolism through ketogenesis, offer promise.”

To further investigate, Dr. Kim and her colleagues conducted the retrospective study, evaluating data on more than 1.3 million enrollees in Korea’s National Health Insurance Service Database who were aged 40 years or older, diagnosed with type 2 diabetes, and had initiated antidiabetic drugs between September 2014 and December 2019.

In the propensity score analysis, 358,862 patients were matched 1:1, in groups of 179,431 participants each, based on whether they were treated with SGLT2is or other oral antidiabetic drugs. Patients with a history of neurodegenerative disease, cancer, or use of glucagon-like peptide 1 receptor agonists were excluded.

The patients had a mean age of 57.8 years, 57.9% were men, and 6837 had incident dementia or Parkinson’s disease events reported.

With a mean follow-up of 2.88 years, after adjustment for key variables, those treated with SGLT2is had a 19% reduced risk of developing Alzheimer’s disease (adjusted hazard ratio [aHR], 0.81), a 31% reduced risk for vascular dementia (aHR, 0.69), and a 20% reduced risk for Parkinson’s disease (aHR, 0.80) compared with the non-SGLT2i group.

Furthermore, those receiving SGLT2i treatment had a 21% reduced risk for all-cause dementia (aHR, 0.79) and a 22% reduced risk for all-cause dementia and Parkinson’s disease compared with the oral antidiabetic drug group (aHR, 0.78) with a 6-month drug use lag period.

The association was observed regardless of SGLT2i exposure duration. Subgroup analyses indicated that the reductions in neurodegenerative disorders among those receiving SGLT2is were not associated with factors including age, sex, body mass index, blood pressure, glucose, lipid profiles, kidney function, health behaviors, comorbidities, diabetic complications, or other medication use.

Dr. Kim speculated that mechanisms underlying the reduced dementia risk could include SGLT2i effects of mitigating the common severe risk factors of type 2 diabetes and neurodegenerative diseases, including hypertension, heart failure, and chronic kidney disease, and improving hyperperfusion in the heart and cerebral vascular insufficiency.

Commenting on the study to this news organization, Erik H. Serné, MD, of the VU University Medical Centre, Amsterdam, the Netherlands, who comoderated the session, noted that “people with type 2 diabetes have a 50%-100% increased risk of developing dementia, particularly Alzheimer’s disease and vascular dementia.”

“The increasing prevalence of both conditions poses significant public health challenges, highlighting the need for effective prevention strategies and interventions.”

Currently, treatments for dementia are limited, with most primarily addressing symptoms and not the underlying cause of the neurodegenerative disease, he said.

He noted that, in addition to the effects mentioned by Dr. Kim, SGLT2is are also speculated to provide potential neuroprotective effects through improved glycemic control and insulin sensitivity, reduced inflammation and oxidative stress, enhanced mitochondrial function and energy metabolism, and reduced beta-amyloid and tau pathology.

“These mechanisms collectively may reduce the risk of cognitive decline, particularly in diabetic patients, and warrant further investigation in clinical trials to solidify the neuroprotective role of SGLT2 inhibitors,” said Dr. Serné.

In addition to their benefits in type 2 diabetes, SGLT2is “now offer hope in the prevention of dementia, a disease that has very limited therapeutic options thus far. The current data [presented by Dr. Kim] seem to corroborate this,” he added.

Dr. Kim and Dr. Serné had no disclosures to report.

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

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MADRID — Patients with type 2 diabetes treated with sodium-glucose cotransporter 2 inhibitors (SGLT2is) show significant reductions in the risk of developing neurodegenerative disorders including Alzheimer’s disease, vascular dementia, and Parkinson’s disease, compared with those treated with other antidiabetic drugs, results from a large population-based cohort show.

“This was the largest nationwide population-based longitudinal cohort study to investigate the association between the use of SGLT2 inhibitors and the incidence of all-cause dementia and Parkinson’s disease,” said first author Hae Kyung Kim, MD, of the Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea, in presenting the findings at the annual meeting of the European Association for the Study of Diabetes.

Type 2 diabetes is known to increase the risk for neurodegenerative diseases such as dementia or Alzheimer’s disease, said Dr. Kim. Key factors attributed to the risk include shared pathophysiological mechanisms such as central nervous system insulin resistance and reduced cerebral glucose metabolism.

While research is lacking on the role of antidiabetic drugs in the treatment of neurodegenerative diseases, the researcher noted that “SGLT2 inhibitors, which have shown significant cardiorenal benefits and enhanced energy metabolism through ketogenesis, offer promise.”

To further investigate, Dr. Kim and her colleagues conducted the retrospective study, evaluating data on more than 1.3 million enrollees in Korea’s National Health Insurance Service Database who were aged 40 years or older, diagnosed with type 2 diabetes, and had initiated antidiabetic drugs between September 2014 and December 2019.

In the propensity score analysis, 358,862 patients were matched 1:1, in groups of 179,431 participants each, based on whether they were treated with SGLT2is or other oral antidiabetic drugs. Patients with a history of neurodegenerative disease, cancer, or use of glucagon-like peptide 1 receptor agonists were excluded.

The patients had a mean age of 57.8 years, 57.9% were men, and 6837 had incident dementia or Parkinson’s disease events reported.

With a mean follow-up of 2.88 years, after adjustment for key variables, those treated with SGLT2is had a 19% reduced risk of developing Alzheimer’s disease (adjusted hazard ratio [aHR], 0.81), a 31% reduced risk for vascular dementia (aHR, 0.69), and a 20% reduced risk for Parkinson’s disease (aHR, 0.80) compared with the non-SGLT2i group.

Furthermore, those receiving SGLT2i treatment had a 21% reduced risk for all-cause dementia (aHR, 0.79) and a 22% reduced risk for all-cause dementia and Parkinson’s disease compared with the oral antidiabetic drug group (aHR, 0.78) with a 6-month drug use lag period.

The association was observed regardless of SGLT2i exposure duration. Subgroup analyses indicated that the reductions in neurodegenerative disorders among those receiving SGLT2is were not associated with factors including age, sex, body mass index, blood pressure, glucose, lipid profiles, kidney function, health behaviors, comorbidities, diabetic complications, or other medication use.

Dr. Kim speculated that mechanisms underlying the reduced dementia risk could include SGLT2i effects of mitigating the common severe risk factors of type 2 diabetes and neurodegenerative diseases, including hypertension, heart failure, and chronic kidney disease, and improving hyperperfusion in the heart and cerebral vascular insufficiency.

Commenting on the study to this news organization, Erik H. Serné, MD, of the VU University Medical Centre, Amsterdam, the Netherlands, who comoderated the session, noted that “people with type 2 diabetes have a 50%-100% increased risk of developing dementia, particularly Alzheimer’s disease and vascular dementia.”

“The increasing prevalence of both conditions poses significant public health challenges, highlighting the need for effective prevention strategies and interventions.”

Currently, treatments for dementia are limited, with most primarily addressing symptoms and not the underlying cause of the neurodegenerative disease, he said.

He noted that, in addition to the effects mentioned by Dr. Kim, SGLT2is are also speculated to provide potential neuroprotective effects through improved glycemic control and insulin sensitivity, reduced inflammation and oxidative stress, enhanced mitochondrial function and energy metabolism, and reduced beta-amyloid and tau pathology.

“These mechanisms collectively may reduce the risk of cognitive decline, particularly in diabetic patients, and warrant further investigation in clinical trials to solidify the neuroprotective role of SGLT2 inhibitors,” said Dr. Serné.

In addition to their benefits in type 2 diabetes, SGLT2is “now offer hope in the prevention of dementia, a disease that has very limited therapeutic options thus far. The current data [presented by Dr. Kim] seem to corroborate this,” he added.

Dr. Kim and Dr. Serné had no disclosures to report.

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

MADRID — Patients with type 2 diabetes treated with sodium-glucose cotransporter 2 inhibitors (SGLT2is) show significant reductions in the risk of developing neurodegenerative disorders including Alzheimer’s disease, vascular dementia, and Parkinson’s disease, compared with those treated with other antidiabetic drugs, results from a large population-based cohort show.

“This was the largest nationwide population-based longitudinal cohort study to investigate the association between the use of SGLT2 inhibitors and the incidence of all-cause dementia and Parkinson’s disease,” said first author Hae Kyung Kim, MD, of the Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea, in presenting the findings at the annual meeting of the European Association for the Study of Diabetes.

Type 2 diabetes is known to increase the risk for neurodegenerative diseases such as dementia or Alzheimer’s disease, said Dr. Kim. Key factors attributed to the risk include shared pathophysiological mechanisms such as central nervous system insulin resistance and reduced cerebral glucose metabolism.

While research is lacking on the role of antidiabetic drugs in the treatment of neurodegenerative diseases, the researcher noted that “SGLT2 inhibitors, which have shown significant cardiorenal benefits and enhanced energy metabolism through ketogenesis, offer promise.”

To further investigate, Dr. Kim and her colleagues conducted the retrospective study, evaluating data on more than 1.3 million enrollees in Korea’s National Health Insurance Service Database who were aged 40 years or older, diagnosed with type 2 diabetes, and had initiated antidiabetic drugs between September 2014 and December 2019.

In the propensity score analysis, 358,862 patients were matched 1:1, in groups of 179,431 participants each, based on whether they were treated with SGLT2is or other oral antidiabetic drugs. Patients with a history of neurodegenerative disease, cancer, or use of glucagon-like peptide 1 receptor agonists were excluded.

The patients had a mean age of 57.8 years, 57.9% were men, and 6837 had incident dementia or Parkinson’s disease events reported.

With a mean follow-up of 2.88 years, after adjustment for key variables, those treated with SGLT2is had a 19% reduced risk of developing Alzheimer’s disease (adjusted hazard ratio [aHR], 0.81), a 31% reduced risk for vascular dementia (aHR, 0.69), and a 20% reduced risk for Parkinson’s disease (aHR, 0.80) compared with the non-SGLT2i group.

Furthermore, those receiving SGLT2i treatment had a 21% reduced risk for all-cause dementia (aHR, 0.79) and a 22% reduced risk for all-cause dementia and Parkinson’s disease compared with the oral antidiabetic drug group (aHR, 0.78) with a 6-month drug use lag period.

The association was observed regardless of SGLT2i exposure duration. Subgroup analyses indicated that the reductions in neurodegenerative disorders among those receiving SGLT2is were not associated with factors including age, sex, body mass index, blood pressure, glucose, lipid profiles, kidney function, health behaviors, comorbidities, diabetic complications, or other medication use.

Dr. Kim speculated that mechanisms underlying the reduced dementia risk could include SGLT2i effects of mitigating the common severe risk factors of type 2 diabetes and neurodegenerative diseases, including hypertension, heart failure, and chronic kidney disease, and improving hyperperfusion in the heart and cerebral vascular insufficiency.

Commenting on the study to this news organization, Erik H. Serné, MD, of the VU University Medical Centre, Amsterdam, the Netherlands, who comoderated the session, noted that “people with type 2 diabetes have a 50%-100% increased risk of developing dementia, particularly Alzheimer’s disease and vascular dementia.”

“The increasing prevalence of both conditions poses significant public health challenges, highlighting the need for effective prevention strategies and interventions.”

Currently, treatments for dementia are limited, with most primarily addressing symptoms and not the underlying cause of the neurodegenerative disease, he said.

He noted that, in addition to the effects mentioned by Dr. Kim, SGLT2is are also speculated to provide potential neuroprotective effects through improved glycemic control and insulin sensitivity, reduced inflammation and oxidative stress, enhanced mitochondrial function and energy metabolism, and reduced beta-amyloid and tau pathology.

“These mechanisms collectively may reduce the risk of cognitive decline, particularly in diabetic patients, and warrant further investigation in clinical trials to solidify the neuroprotective role of SGLT2 inhibitors,” said Dr. Serné.

In addition to their benefits in type 2 diabetes, SGLT2is “now offer hope in the prevention of dementia, a disease that has very limited therapeutic options thus far. The current data [presented by Dr. Kim] seem to corroborate this,” he added.

Dr. Kim and Dr. Serné had no disclosures to report.

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

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Neuroendocrine Tumor of Ampulla of Vater: A Rare Case Report and Review of Literature

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Background

Ampulla of Vater is an extremely rare site for neuroendocrine tumors (NET), accounting for less than 0.3% of gastrointestinal (GI) and 2% of ampullary malignancies. This case report highlights the circuitous diagnosis of this rare tumor in a patient with a history of primary biliary cholangitis presenting with epigastric pain and severe pruritis.

Case Presentation

A 58-year-old female with history of sarcoidosis and primary biliary cholangitis status post sphincterotomy eight months prior, presented with worsening epigastric pain, fatigue, and weight loss over 6 months. Physical exam showed right upper quadrant tenderness. Labs revealed elevated alanine and aspartate aminotransferases at 415 and 195 units/L, with bilirubin of 0.3 mg/dl. Computerized tomography (CT) revealed a 2.3x3.2x4.0 cm peripancreatic hypodensity associated with phlegmon, pancreatic ductal dilation and pneumobilia. Magnetic resonance imaging (MRI) demonstrated a pancreatic head mass. Positron emission tomogram (PET) was negative for distant metastases. After discussion of management options, patient opted for Whipple procedure. The surgical pathology was consistent with invasive ampullary ductal carcinoma of the small intestine, pancreaticobiliary type. However, staining for synaptophysin and chromogranin were positive, with Ki-67 < 55%. Tumor board review confirmed neuroendocrine tumor of the ampulla of Vater. NCCN guidelines recommended active surveillance due to locoregional disease without positive margins or lymph nodes, advising routine follow-up and imaging.

Discussion

Neuroendocrine tumors (NET) at the Ampulla of Vater are exceedingly rare. Often manifesting as obstructive jaundice, they pose diagnostic hurdles, especially in patients with anatomical variations like scarring from primary biliary cholangitis. In a case series of 20 ampullary tumors, only one was neuroendocrine, highlighting their rarity. Accurate diagnosis, achieved through surgical biopsy and immunohistochemical testing, is crucial for appropriate management. Following NCCN guidelines for gastrointestinal NETs, our patient avoided unnecessary systemic treatment meant for adenocarcinoma, preserving her quality of life. Reporting such cases is essential for advancing understanding and refining patient care.

Conclusions

This case had evolving diagnoses, altering both the prognosis and treatment standards. Comorbid primary biliary cholangitis and high-grade tumor complexity posed diagnostic challenges, which was finally confirmed by surgical biopsy. Reporting such cases is vital in aiding tumor management and patient outcomes.

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Background

Ampulla of Vater is an extremely rare site for neuroendocrine tumors (NET), accounting for less than 0.3% of gastrointestinal (GI) and 2% of ampullary malignancies. This case report highlights the circuitous diagnosis of this rare tumor in a patient with a history of primary biliary cholangitis presenting with epigastric pain and severe pruritis.

Case Presentation

A 58-year-old female with history of sarcoidosis and primary biliary cholangitis status post sphincterotomy eight months prior, presented with worsening epigastric pain, fatigue, and weight loss over 6 months. Physical exam showed right upper quadrant tenderness. Labs revealed elevated alanine and aspartate aminotransferases at 415 and 195 units/L, with bilirubin of 0.3 mg/dl. Computerized tomography (CT) revealed a 2.3x3.2x4.0 cm peripancreatic hypodensity associated with phlegmon, pancreatic ductal dilation and pneumobilia. Magnetic resonance imaging (MRI) demonstrated a pancreatic head mass. Positron emission tomogram (PET) was negative for distant metastases. After discussion of management options, patient opted for Whipple procedure. The surgical pathology was consistent with invasive ampullary ductal carcinoma of the small intestine, pancreaticobiliary type. However, staining for synaptophysin and chromogranin were positive, with Ki-67 < 55%. Tumor board review confirmed neuroendocrine tumor of the ampulla of Vater. NCCN guidelines recommended active surveillance due to locoregional disease without positive margins or lymph nodes, advising routine follow-up and imaging.

Discussion

Neuroendocrine tumors (NET) at the Ampulla of Vater are exceedingly rare. Often manifesting as obstructive jaundice, they pose diagnostic hurdles, especially in patients with anatomical variations like scarring from primary biliary cholangitis. In a case series of 20 ampullary tumors, only one was neuroendocrine, highlighting their rarity. Accurate diagnosis, achieved through surgical biopsy and immunohistochemical testing, is crucial for appropriate management. Following NCCN guidelines for gastrointestinal NETs, our patient avoided unnecessary systemic treatment meant for adenocarcinoma, preserving her quality of life. Reporting such cases is essential for advancing understanding and refining patient care.

Conclusions

This case had evolving diagnoses, altering both the prognosis and treatment standards. Comorbid primary biliary cholangitis and high-grade tumor complexity posed diagnostic challenges, which was finally confirmed by surgical biopsy. Reporting such cases is vital in aiding tumor management and patient outcomes.

Background

Ampulla of Vater is an extremely rare site for neuroendocrine tumors (NET), accounting for less than 0.3% of gastrointestinal (GI) and 2% of ampullary malignancies. This case report highlights the circuitous diagnosis of this rare tumor in a patient with a history of primary biliary cholangitis presenting with epigastric pain and severe pruritis.

Case Presentation

A 58-year-old female with history of sarcoidosis and primary biliary cholangitis status post sphincterotomy eight months prior, presented with worsening epigastric pain, fatigue, and weight loss over 6 months. Physical exam showed right upper quadrant tenderness. Labs revealed elevated alanine and aspartate aminotransferases at 415 and 195 units/L, with bilirubin of 0.3 mg/dl. Computerized tomography (CT) revealed a 2.3x3.2x4.0 cm peripancreatic hypodensity associated with phlegmon, pancreatic ductal dilation and pneumobilia. Magnetic resonance imaging (MRI) demonstrated a pancreatic head mass. Positron emission tomogram (PET) was negative for distant metastases. After discussion of management options, patient opted for Whipple procedure. The surgical pathology was consistent with invasive ampullary ductal carcinoma of the small intestine, pancreaticobiliary type. However, staining for synaptophysin and chromogranin were positive, with Ki-67 < 55%. Tumor board review confirmed neuroendocrine tumor of the ampulla of Vater. NCCN guidelines recommended active surveillance due to locoregional disease without positive margins or lymph nodes, advising routine follow-up and imaging.

Discussion

Neuroendocrine tumors (NET) at the Ampulla of Vater are exceedingly rare. Often manifesting as obstructive jaundice, they pose diagnostic hurdles, especially in patients with anatomical variations like scarring from primary biliary cholangitis. In a case series of 20 ampullary tumors, only one was neuroendocrine, highlighting their rarity. Accurate diagnosis, achieved through surgical biopsy and immunohistochemical testing, is crucial for appropriate management. Following NCCN guidelines for gastrointestinal NETs, our patient avoided unnecessary systemic treatment meant for adenocarcinoma, preserving her quality of life. Reporting such cases is essential for advancing understanding and refining patient care.

Conclusions

This case had evolving diagnoses, altering both the prognosis and treatment standards. Comorbid primary biliary cholangitis and high-grade tumor complexity posed diagnostic challenges, which was finally confirmed by surgical biopsy. Reporting such cases is vital in aiding tumor management and patient outcomes.

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Diabetes Increases Injury Risk: A Troubling Trend

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In 2024, a record number of people are celebrating their 65th birthdays. Increasing age is associated with a higher risk for falls, fractures, and other injuries that may require hospitalization. 

In older adults with type 1 and type 2 diabetes, the risk for falls is double that seen in older people without these conditions. Increased clinician awareness of the many factors that result in this higher risk in people with diabetes, and timely implementation of strategies to prevent falls, are essential.

The annual incidence of falls in people with diabetes older than 65 years is about 39%, compared with 19% among those without diabetes. People with diabetes on insulin face an even greater increased risk for falls compared with those who are not using insulin (94% vs 27% increased risk).

Many well-known aspects of diabetes contribute to this greater risk. These include decreased sensorimotor function, musculoskeletal and neuromuscular deficits, foot and body pain, poor vision, hypoglycemic episodes, pharmacologic complications, and problems with hearing and balance. 

Optimal management of diabetes and its complications is essential, and the American Diabetes Association has developed clear guidelines for clinicians to follow to reduce the risk for diabetes related complications and manage these conditions.

The prevalence of diabetic peripheral neuropathy increases with age and duration of diabetes. People with diabetic peripheral neuropathy and diminished sensation on their feet are at increased risk for loss of postural control. Loss of proprioceptive feedback (the ability to sense movement, action and location) during standing and walking leads increases the risk for falls.

In addition, less physical activity, impaired muscle strength, and suboptimal postural control all influence gait patterns and increase the risk for falling. Adults with diabetes have a two to three times higher risk for sarcopenia (decreased muscle strength and muscle mass). They also have low plantar flexion strength, causing increased displacement of their center of gravity, which in turn reduces their maximum forward stride and may result in falls and injury.

Many people with diabetes experience neuropathic foot and body pain, requiring psychotropic and other medications that may exacerbate the risk, such as amitriptyline and duloxetine. Furthermore, older adults with diabetes are more likely to take more prescription medications and may be more sensitive to effects of multiple medications than are individuals without diabetes.

A hazard of managing diabetes, particularly with insulin, is the increased risk for unexpected low blood glucose levels. These episodes can also occur in patients taking certain kinds of oral diabetes medications, but they are more common in those on insulin. Low blood glucose can cause dizziness, confusion, and postural instability, increasing the risk for falling.

Diabetic eye complications include retinopathy, macular edema, cataracts, and glaucoma. In a study of close to 10,000 middle-aged and older adults with diabetes, those with moderate eye complications had almost double the risk of falls as those without eye complications.

Another concern with diabetes is its effect on nerves and blood vessels in the inner ear, leading to a negative effect on balance and hearing loss, both of which are also associated with a higher risk for falling and injury.

Clinicians can reduce the risk for falls in patients by taking measures to improve diabetes control and reduce the risk for microvascular disease affecting the nerves, eyes, and ears. 

In addition, exercises that optimize muscle mass, bone strength, gait, and balance, and use of specialized footwear in people with neuropathy, may reduce fall risk. Chair yoga and tai chi have also been shown to be helpful. Clinicians can also advise patients on commonsense strategies to implement in their homes, such as ensuring proper lighting, reducing, clutter and minimizing the use of floor rugs.

The risk for falls and the associated risk for fracture and possible hospitalization are of significant concern in older adults — particularly those with diabetes, and even more so in those with diabetes who are on insulin. It is our responsibility as clinicians to implement strategies to optimize diabetes control in our patients and monitor them for microvascular and other complications that may increase this risk, and manage them appropriately if and when these complications occur.

Madhusmita Misra, Professor, Chair, Physician-in-Chief, Department of Pediatrics, University of Virginia and UVA Health Children’s, Charlottesville, has disclosed being a key opinion leader for Lumos Pharma. Sidhartha Pani, Assistant Professor, Department of Internal Medicine, UVA School of Medicine; Medical Director, Department of General Medicine, Same Day Care Clinic, Charlottesville, disclosed no relevant financial relationships.

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

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In 2024, a record number of people are celebrating their 65th birthdays. Increasing age is associated with a higher risk for falls, fractures, and other injuries that may require hospitalization. 

In older adults with type 1 and type 2 diabetes, the risk for falls is double that seen in older people without these conditions. Increased clinician awareness of the many factors that result in this higher risk in people with diabetes, and timely implementation of strategies to prevent falls, are essential.

The annual incidence of falls in people with diabetes older than 65 years is about 39%, compared with 19% among those without diabetes. People with diabetes on insulin face an even greater increased risk for falls compared with those who are not using insulin (94% vs 27% increased risk).

Many well-known aspects of diabetes contribute to this greater risk. These include decreased sensorimotor function, musculoskeletal and neuromuscular deficits, foot and body pain, poor vision, hypoglycemic episodes, pharmacologic complications, and problems with hearing and balance. 

Optimal management of diabetes and its complications is essential, and the American Diabetes Association has developed clear guidelines for clinicians to follow to reduce the risk for diabetes related complications and manage these conditions.

The prevalence of diabetic peripheral neuropathy increases with age and duration of diabetes. People with diabetic peripheral neuropathy and diminished sensation on their feet are at increased risk for loss of postural control. Loss of proprioceptive feedback (the ability to sense movement, action and location) during standing and walking leads increases the risk for falls.

In addition, less physical activity, impaired muscle strength, and suboptimal postural control all influence gait patterns and increase the risk for falling. Adults with diabetes have a two to three times higher risk for sarcopenia (decreased muscle strength and muscle mass). They also have low plantar flexion strength, causing increased displacement of their center of gravity, which in turn reduces their maximum forward stride and may result in falls and injury.

Many people with diabetes experience neuropathic foot and body pain, requiring psychotropic and other medications that may exacerbate the risk, such as amitriptyline and duloxetine. Furthermore, older adults with diabetes are more likely to take more prescription medications and may be more sensitive to effects of multiple medications than are individuals without diabetes.

A hazard of managing diabetes, particularly with insulin, is the increased risk for unexpected low blood glucose levels. These episodes can also occur in patients taking certain kinds of oral diabetes medications, but they are more common in those on insulin. Low blood glucose can cause dizziness, confusion, and postural instability, increasing the risk for falling.

Diabetic eye complications include retinopathy, macular edema, cataracts, and glaucoma. In a study of close to 10,000 middle-aged and older adults with diabetes, those with moderate eye complications had almost double the risk of falls as those without eye complications.

Another concern with diabetes is its effect on nerves and blood vessels in the inner ear, leading to a negative effect on balance and hearing loss, both of which are also associated with a higher risk for falling and injury.

Clinicians can reduce the risk for falls in patients by taking measures to improve diabetes control and reduce the risk for microvascular disease affecting the nerves, eyes, and ears. 

In addition, exercises that optimize muscle mass, bone strength, gait, and balance, and use of specialized footwear in people with neuropathy, may reduce fall risk. Chair yoga and tai chi have also been shown to be helpful. Clinicians can also advise patients on commonsense strategies to implement in their homes, such as ensuring proper lighting, reducing, clutter and minimizing the use of floor rugs.

The risk for falls and the associated risk for fracture and possible hospitalization are of significant concern in older adults — particularly those with diabetes, and even more so in those with diabetes who are on insulin. It is our responsibility as clinicians to implement strategies to optimize diabetes control in our patients and monitor them for microvascular and other complications that may increase this risk, and manage them appropriately if and when these complications occur.

Madhusmita Misra, Professor, Chair, Physician-in-Chief, Department of Pediatrics, University of Virginia and UVA Health Children’s, Charlottesville, has disclosed being a key opinion leader for Lumos Pharma. Sidhartha Pani, Assistant Professor, Department of Internal Medicine, UVA School of Medicine; Medical Director, Department of General Medicine, Same Day Care Clinic, Charlottesville, disclosed no relevant financial relationships.

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

 

In 2024, a record number of people are celebrating their 65th birthdays. Increasing age is associated with a higher risk for falls, fractures, and other injuries that may require hospitalization. 

In older adults with type 1 and type 2 diabetes, the risk for falls is double that seen in older people without these conditions. Increased clinician awareness of the many factors that result in this higher risk in people with diabetes, and timely implementation of strategies to prevent falls, are essential.

The annual incidence of falls in people with diabetes older than 65 years is about 39%, compared with 19% among those without diabetes. People with diabetes on insulin face an even greater increased risk for falls compared with those who are not using insulin (94% vs 27% increased risk).

Many well-known aspects of diabetes contribute to this greater risk. These include decreased sensorimotor function, musculoskeletal and neuromuscular deficits, foot and body pain, poor vision, hypoglycemic episodes, pharmacologic complications, and problems with hearing and balance. 

Optimal management of diabetes and its complications is essential, and the American Diabetes Association has developed clear guidelines for clinicians to follow to reduce the risk for diabetes related complications and manage these conditions.

The prevalence of diabetic peripheral neuropathy increases with age and duration of diabetes. People with diabetic peripheral neuropathy and diminished sensation on their feet are at increased risk for loss of postural control. Loss of proprioceptive feedback (the ability to sense movement, action and location) during standing and walking leads increases the risk for falls.

In addition, less physical activity, impaired muscle strength, and suboptimal postural control all influence gait patterns and increase the risk for falling. Adults with diabetes have a two to three times higher risk for sarcopenia (decreased muscle strength and muscle mass). They also have low plantar flexion strength, causing increased displacement of their center of gravity, which in turn reduces their maximum forward stride and may result in falls and injury.

Many people with diabetes experience neuropathic foot and body pain, requiring psychotropic and other medications that may exacerbate the risk, such as amitriptyline and duloxetine. Furthermore, older adults with diabetes are more likely to take more prescription medications and may be more sensitive to effects of multiple medications than are individuals without diabetes.

A hazard of managing diabetes, particularly with insulin, is the increased risk for unexpected low blood glucose levels. These episodes can also occur in patients taking certain kinds of oral diabetes medications, but they are more common in those on insulin. Low blood glucose can cause dizziness, confusion, and postural instability, increasing the risk for falling.

Diabetic eye complications include retinopathy, macular edema, cataracts, and glaucoma. In a study of close to 10,000 middle-aged and older adults with diabetes, those with moderate eye complications had almost double the risk of falls as those without eye complications.

Another concern with diabetes is its effect on nerves and blood vessels in the inner ear, leading to a negative effect on balance and hearing loss, both of which are also associated with a higher risk for falling and injury.

Clinicians can reduce the risk for falls in patients by taking measures to improve diabetes control and reduce the risk for microvascular disease affecting the nerves, eyes, and ears. 

In addition, exercises that optimize muscle mass, bone strength, gait, and balance, and use of specialized footwear in people with neuropathy, may reduce fall risk. Chair yoga and tai chi have also been shown to be helpful. Clinicians can also advise patients on commonsense strategies to implement in their homes, such as ensuring proper lighting, reducing, clutter and minimizing the use of floor rugs.

The risk for falls and the associated risk for fracture and possible hospitalization are of significant concern in older adults — particularly those with diabetes, and even more so in those with diabetes who are on insulin. It is our responsibility as clinicians to implement strategies to optimize diabetes control in our patients and monitor them for microvascular and other complications that may increase this risk, and manage them appropriately if and when these complications occur.

Madhusmita Misra, Professor, Chair, Physician-in-Chief, Department of Pediatrics, University of Virginia and UVA Health Children’s, Charlottesville, has disclosed being a key opinion leader for Lumos Pharma. Sidhartha Pani, Assistant Professor, Department of Internal Medicine, UVA School of Medicine; Medical Director, Department of General Medicine, Same Day Care Clinic, Charlottesville, disclosed no relevant financial relationships.

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

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What Do We Know About Postoperative Cognitive Dysfunction?

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Postoperative cognitive dysfunction (POCD) is a form of cognitive decline that involves a functional deterioration of activities of the nervous system, such as selective attention, vigilance, perception, learning, memory, executive function, verbal and language abilities, emotion, visuospatial and visuomotor skills. It occurs in the absence of cranial trauma or other brain injuries, and prevalence rates range from 36.6% in young adults to 42.4% in older adults, as a consequence of significant invasive procedures such as cardiac, noncardiac, and carotid surgeries that are lengthy and intensive.

Alzheimer’s disease (AD), the most common form of dementia, accounts for about two thirds of all cases of dementia globally. It is estimated that 41 million patients with dementia remain undiagnosed worldwide, and 25% of patients are diagnosed only when they are fully symptomatic. AD is a neurodegenerative disorder defined by neuropathologic changes, including beta-amyloid (Abeta) plaques composed of aggregated Abeta and neurofibrillary tangles containing aggregated tau proteins.

Patients with AD are unaware of their condition. Dementia, especially in its early stages, is often a hidden disease. Even when suspected, patients and families may believe that the symptoms are part of normal aging and may not report them to the doctor. In these patients, surgery may unmask subclinical dementia.

The complex correlation between POCD and AD has sparked debate following numerous anecdotal reports of how older adults undergoing surgical procedures may experience long-term cognitive decline with clinical characteristics such as those of patients with dementia. Despite advances in knowledge, it is still difficult to establish a priori how much surgery and anesthesia can increase the risk or accelerate the progression of a prodromal and asymptomatic AD condition (stages I-II) to clinically evident stage III AD. The current trend of an aging population poses a challenge for anesthesiology surgery because as the age of patients undergoing surgery increases, so does the likelihood of developing POCD.

Recent research in these fields has improved knowledge of the characteristics, epidemiology, risk factors, pathogenesis, and potential prevention strategies associated with POCD. It has improved the perspectives of future prevention and treatment.
 

Definition and Diagnostic Criteria

POCD, according to the cognitive impairment classification in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, is characterized by mild neurologic disturbance resulting from routine surgical procedures, excluding conditions such as deafness, dementia, or amnesia. The definition of POCD involves prolonged cognitive decline that can last for weeks, months, or even years. POCD may be confused with postoperative delirium, an acute and fluctuating disorder of consciousness that typically occurs within 3 days of surgery.

The diagnosis of POCD is based primarily on neurocognitive function scales. Widely used assessments include the Montreal Cognitive Assessment, the Wechsler Memory Scale, and the Mini-Mental State Examination.
 

Epidemiology

POCD is prevalent among patients undergoing cardiac or orthopedic surgery. In patients undergoing aortic-coronary bypass and cardiopulmonary bypass, 50%-70% develop POCD 1 week after surgery. In addition, 10%-30% experience long-term effects on cognitive function at 6 months after the procedure. In patients undergoing hip arthroplasty, 20%-50% exhibit POCD within 1 week of surgery, with 10%-14% still presenting it after 3 months.

 

Risk Factors

Age

POCD is typically observed in patients older than 65 years. However, after surgery, around 30% of younger patients and about 40% of older patients develop POCD at the time of hospital discharge. Specifically, 12.7% of older patients continue to have POCD 3 months after surgery, compared with 5% of younger patients.

Type of Surgery 

Hip and knee arthroplasty procedures entail a higher risk for POCD than general surgery. The same is true of cardiac surgery, especially aortic-coronary bypass and cardiopulmonary bypass.

Types of Anesthesia 

Initial assessments of postoperative cognitive function in cardiac surgery did not provide significant correlations between observed changes and the type of anesthesia because of the high number of confounding factors involved. A more recent meta-analysis of 28 randomized clinical trials concluded that the incidence of POCD is lower in surgeries using intravenous anesthesia with propofol than in those using inhalation anesthesia with isoflurane or sevoflurane.

Pain

Postoperative pain is a common issue, mainly resulting from substantial surgical trauma or potential wound infection. Patient-controlled postoperative analgesia independently increases the risk for POCD, compared with oral postoperative analgesia. Meta-analyses indicate that persistent pain can lead to a decline in patients’ cognitive abilities, attention, memory, and information processing.

Evolving Scenarios

Current research on POCD has deepened our understanding of its pathogenesis, implicating factors such as central nervous system inflammation, neuronal apoptosis, synaptic plasticity damage, abnormal tau protein modification, chronic pain, and mitochondrial metabolic disorders. Several neuroprotective drugs are currently under study, but none have shown consistent benefits for the prevention and treatment of POCD. The available evidence on the subject does not unambiguously guide the practicing physician. But neither does it exclude the importance of a careful assessment of POCD risk factors and the cognitive status of an older patient before surgery to provide useful information to the patient, family, and doctors when deciding on appropriate and shared procedures.

This story was translated from Univadis Italy, which is part of the Medscape 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.

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Postoperative cognitive dysfunction (POCD) is a form of cognitive decline that involves a functional deterioration of activities of the nervous system, such as selective attention, vigilance, perception, learning, memory, executive function, verbal and language abilities, emotion, visuospatial and visuomotor skills. It occurs in the absence of cranial trauma or other brain injuries, and prevalence rates range from 36.6% in young adults to 42.4% in older adults, as a consequence of significant invasive procedures such as cardiac, noncardiac, and carotid surgeries that are lengthy and intensive.

Alzheimer’s disease (AD), the most common form of dementia, accounts for about two thirds of all cases of dementia globally. It is estimated that 41 million patients with dementia remain undiagnosed worldwide, and 25% of patients are diagnosed only when they are fully symptomatic. AD is a neurodegenerative disorder defined by neuropathologic changes, including beta-amyloid (Abeta) plaques composed of aggregated Abeta and neurofibrillary tangles containing aggregated tau proteins.

Patients with AD are unaware of their condition. Dementia, especially in its early stages, is often a hidden disease. Even when suspected, patients and families may believe that the symptoms are part of normal aging and may not report them to the doctor. In these patients, surgery may unmask subclinical dementia.

The complex correlation between POCD and AD has sparked debate following numerous anecdotal reports of how older adults undergoing surgical procedures may experience long-term cognitive decline with clinical characteristics such as those of patients with dementia. Despite advances in knowledge, it is still difficult to establish a priori how much surgery and anesthesia can increase the risk or accelerate the progression of a prodromal and asymptomatic AD condition (stages I-II) to clinically evident stage III AD. The current trend of an aging population poses a challenge for anesthesiology surgery because as the age of patients undergoing surgery increases, so does the likelihood of developing POCD.

Recent research in these fields has improved knowledge of the characteristics, epidemiology, risk factors, pathogenesis, and potential prevention strategies associated with POCD. It has improved the perspectives of future prevention and treatment.
 

Definition and Diagnostic Criteria

POCD, according to the cognitive impairment classification in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, is characterized by mild neurologic disturbance resulting from routine surgical procedures, excluding conditions such as deafness, dementia, or amnesia. The definition of POCD involves prolonged cognitive decline that can last for weeks, months, or even years. POCD may be confused with postoperative delirium, an acute and fluctuating disorder of consciousness that typically occurs within 3 days of surgery.

The diagnosis of POCD is based primarily on neurocognitive function scales. Widely used assessments include the Montreal Cognitive Assessment, the Wechsler Memory Scale, and the Mini-Mental State Examination.
 

Epidemiology

POCD is prevalent among patients undergoing cardiac or orthopedic surgery. In patients undergoing aortic-coronary bypass and cardiopulmonary bypass, 50%-70% develop POCD 1 week after surgery. In addition, 10%-30% experience long-term effects on cognitive function at 6 months after the procedure. In patients undergoing hip arthroplasty, 20%-50% exhibit POCD within 1 week of surgery, with 10%-14% still presenting it after 3 months.

 

Risk Factors

Age

POCD is typically observed in patients older than 65 years. However, after surgery, around 30% of younger patients and about 40% of older patients develop POCD at the time of hospital discharge. Specifically, 12.7% of older patients continue to have POCD 3 months after surgery, compared with 5% of younger patients.

Type of Surgery 

Hip and knee arthroplasty procedures entail a higher risk for POCD than general surgery. The same is true of cardiac surgery, especially aortic-coronary bypass and cardiopulmonary bypass.

Types of Anesthesia 

Initial assessments of postoperative cognitive function in cardiac surgery did not provide significant correlations between observed changes and the type of anesthesia because of the high number of confounding factors involved. A more recent meta-analysis of 28 randomized clinical trials concluded that the incidence of POCD is lower in surgeries using intravenous anesthesia with propofol than in those using inhalation anesthesia with isoflurane or sevoflurane.

Pain

Postoperative pain is a common issue, mainly resulting from substantial surgical trauma or potential wound infection. Patient-controlled postoperative analgesia independently increases the risk for POCD, compared with oral postoperative analgesia. Meta-analyses indicate that persistent pain can lead to a decline in patients’ cognitive abilities, attention, memory, and information processing.

Evolving Scenarios

Current research on POCD has deepened our understanding of its pathogenesis, implicating factors such as central nervous system inflammation, neuronal apoptosis, synaptic plasticity damage, abnormal tau protein modification, chronic pain, and mitochondrial metabolic disorders. Several neuroprotective drugs are currently under study, but none have shown consistent benefits for the prevention and treatment of POCD. The available evidence on the subject does not unambiguously guide the practicing physician. But neither does it exclude the importance of a careful assessment of POCD risk factors and the cognitive status of an older patient before surgery to provide useful information to the patient, family, and doctors when deciding on appropriate and shared procedures.

This story was translated from Univadis Italy, which is part of the Medscape 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.

 

Postoperative cognitive dysfunction (POCD) is a form of cognitive decline that involves a functional deterioration of activities of the nervous system, such as selective attention, vigilance, perception, learning, memory, executive function, verbal and language abilities, emotion, visuospatial and visuomotor skills. It occurs in the absence of cranial trauma or other brain injuries, and prevalence rates range from 36.6% in young adults to 42.4% in older adults, as a consequence of significant invasive procedures such as cardiac, noncardiac, and carotid surgeries that are lengthy and intensive.

Alzheimer’s disease (AD), the most common form of dementia, accounts for about two thirds of all cases of dementia globally. It is estimated that 41 million patients with dementia remain undiagnosed worldwide, and 25% of patients are diagnosed only when they are fully symptomatic. AD is a neurodegenerative disorder defined by neuropathologic changes, including beta-amyloid (Abeta) plaques composed of aggregated Abeta and neurofibrillary tangles containing aggregated tau proteins.

Patients with AD are unaware of their condition. Dementia, especially in its early stages, is often a hidden disease. Even when suspected, patients and families may believe that the symptoms are part of normal aging and may not report them to the doctor. In these patients, surgery may unmask subclinical dementia.

The complex correlation between POCD and AD has sparked debate following numerous anecdotal reports of how older adults undergoing surgical procedures may experience long-term cognitive decline with clinical characteristics such as those of patients with dementia. Despite advances in knowledge, it is still difficult to establish a priori how much surgery and anesthesia can increase the risk or accelerate the progression of a prodromal and asymptomatic AD condition (stages I-II) to clinically evident stage III AD. The current trend of an aging population poses a challenge for anesthesiology surgery because as the age of patients undergoing surgery increases, so does the likelihood of developing POCD.

Recent research in these fields has improved knowledge of the characteristics, epidemiology, risk factors, pathogenesis, and potential prevention strategies associated with POCD. It has improved the perspectives of future prevention and treatment.
 

Definition and Diagnostic Criteria

POCD, according to the cognitive impairment classification in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, is characterized by mild neurologic disturbance resulting from routine surgical procedures, excluding conditions such as deafness, dementia, or amnesia. The definition of POCD involves prolonged cognitive decline that can last for weeks, months, or even years. POCD may be confused with postoperative delirium, an acute and fluctuating disorder of consciousness that typically occurs within 3 days of surgery.

The diagnosis of POCD is based primarily on neurocognitive function scales. Widely used assessments include the Montreal Cognitive Assessment, the Wechsler Memory Scale, and the Mini-Mental State Examination.
 

Epidemiology

POCD is prevalent among patients undergoing cardiac or orthopedic surgery. In patients undergoing aortic-coronary bypass and cardiopulmonary bypass, 50%-70% develop POCD 1 week after surgery. In addition, 10%-30% experience long-term effects on cognitive function at 6 months after the procedure. In patients undergoing hip arthroplasty, 20%-50% exhibit POCD within 1 week of surgery, with 10%-14% still presenting it after 3 months.

 

Risk Factors

Age

POCD is typically observed in patients older than 65 years. However, after surgery, around 30% of younger patients and about 40% of older patients develop POCD at the time of hospital discharge. Specifically, 12.7% of older patients continue to have POCD 3 months after surgery, compared with 5% of younger patients.

Type of Surgery 

Hip and knee arthroplasty procedures entail a higher risk for POCD than general surgery. The same is true of cardiac surgery, especially aortic-coronary bypass and cardiopulmonary bypass.

Types of Anesthesia 

Initial assessments of postoperative cognitive function in cardiac surgery did not provide significant correlations between observed changes and the type of anesthesia because of the high number of confounding factors involved. A more recent meta-analysis of 28 randomized clinical trials concluded that the incidence of POCD is lower in surgeries using intravenous anesthesia with propofol than in those using inhalation anesthesia with isoflurane or sevoflurane.

Pain

Postoperative pain is a common issue, mainly resulting from substantial surgical trauma or potential wound infection. Patient-controlled postoperative analgesia independently increases the risk for POCD, compared with oral postoperative analgesia. Meta-analyses indicate that persistent pain can lead to a decline in patients’ cognitive abilities, attention, memory, and information processing.

Evolving Scenarios

Current research on POCD has deepened our understanding of its pathogenesis, implicating factors such as central nervous system inflammation, neuronal apoptosis, synaptic plasticity damage, abnormal tau protein modification, chronic pain, and mitochondrial metabolic disorders. Several neuroprotective drugs are currently under study, but none have shown consistent benefits for the prevention and treatment of POCD. The available evidence on the subject does not unambiguously guide the practicing physician. But neither does it exclude the importance of a careful assessment of POCD risk factors and the cognitive status of an older patient before surgery to provide useful information to the patient, family, and doctors when deciding on appropriate and shared procedures.

This story was translated from Univadis Italy, which is part of the Medscape 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.

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Wide Regional Variation in Dementia Risk Across the United States

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TOPLINE:

The likelihood of receiving a dementia diagnosis in older adults varies significantly by region across the United States, a new study suggests. Rates ranged from 1.7% to 5.4%, with variations more pronounced in those aged 66-74 years and Black or Hispanic individuals.

METHODOLOGY:

  • Researchers analyzed newly diagnosed cases of Alzheimer’s disease and related dementias (ADRD) using the 2018-2019 Medicare claims data for 4.8 million older adults across 306 hospital referral regions (HRRs).
  • Participants were categorized by age and race or ethnicity to examine variations in diagnosis rates.
  • Regional characteristics such as education level and prevalence of obesity, smoking, and diabetes were included to adjust for population risk factors.
  • ADRD-specific diagnostic intensity was calculated as the ratio of the observed-to-expected new cases of ADRD in each HRR.

TAKEAWAY:

  • Unadjusted analysis for that overall, 3% of older adults received a new ADRD diagnosis in 2019, with rates ranging from 1.7 to 5.4 per 100 individuals across HRRs and varied by age category.
  • Regions in the South had the highest unadjusted ADRD case concentration, and the areas in the West/Northwest had the lowest.
  • The ADRD-specific diagnosis intensity was 0.69-1.47 and varied the most in Black and Hispanic individuals and those aged 66-74 years.
  • Regional differences in ADRD diagnosis rates are not fully explained by population risk factors, indicating potential health system-level differences.

IN PRACTICE:

“From place to place, the likelihood of getting your dementia diagnosed varies, and that may happen because of everything from practice norms for healthcare providers to individual patients’ knowledge and care-seeking behavior. These findings go beyond demographic and population-level differences in risk and indicate that there are health system-level differences that could be targeted and remediated,” lead author Julie P.W. Bynum, MD, MPH, said in a press release.

SOURCE:

The study was led by Dr. Bynum, professor of internal medicine, University of Michigan Medical School, Ann Arbor, Michigan, and published online in Alzheimer’s & Dementia.

LIMITATIONS:

The results may not be generalizable to other groups. The observational design of the study cannot completely negate residual confounding. The measures of population risks are coarser than those used in well-characterized epidemiologic studies, leading to potential imprecision. Finally, the study was not designed to determine whether regional differences in the likelihood of ADRD diagnosis resulted in differences in the population health outcomes.

DISCLOSURES:

The study was supported by a grant from the National Institute on Aging. The authors reported no conflicts of interest.

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.

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TOPLINE:

The likelihood of receiving a dementia diagnosis in older adults varies significantly by region across the United States, a new study suggests. Rates ranged from 1.7% to 5.4%, with variations more pronounced in those aged 66-74 years and Black or Hispanic individuals.

METHODOLOGY:

  • Researchers analyzed newly diagnosed cases of Alzheimer’s disease and related dementias (ADRD) using the 2018-2019 Medicare claims data for 4.8 million older adults across 306 hospital referral regions (HRRs).
  • Participants were categorized by age and race or ethnicity to examine variations in diagnosis rates.
  • Regional characteristics such as education level and prevalence of obesity, smoking, and diabetes were included to adjust for population risk factors.
  • ADRD-specific diagnostic intensity was calculated as the ratio of the observed-to-expected new cases of ADRD in each HRR.

TAKEAWAY:

  • Unadjusted analysis for that overall, 3% of older adults received a new ADRD diagnosis in 2019, with rates ranging from 1.7 to 5.4 per 100 individuals across HRRs and varied by age category.
  • Regions in the South had the highest unadjusted ADRD case concentration, and the areas in the West/Northwest had the lowest.
  • The ADRD-specific diagnosis intensity was 0.69-1.47 and varied the most in Black and Hispanic individuals and those aged 66-74 years.
  • Regional differences in ADRD diagnosis rates are not fully explained by population risk factors, indicating potential health system-level differences.

IN PRACTICE:

“From place to place, the likelihood of getting your dementia diagnosed varies, and that may happen because of everything from practice norms for healthcare providers to individual patients’ knowledge and care-seeking behavior. These findings go beyond demographic and population-level differences in risk and indicate that there are health system-level differences that could be targeted and remediated,” lead author Julie P.W. Bynum, MD, MPH, said in a press release.

SOURCE:

The study was led by Dr. Bynum, professor of internal medicine, University of Michigan Medical School, Ann Arbor, Michigan, and published online in Alzheimer’s & Dementia.

LIMITATIONS:

The results may not be generalizable to other groups. The observational design of the study cannot completely negate residual confounding. The measures of population risks are coarser than those used in well-characterized epidemiologic studies, leading to potential imprecision. Finally, the study was not designed to determine whether regional differences in the likelihood of ADRD diagnosis resulted in differences in the population health outcomes.

DISCLOSURES:

The study was supported by a grant from the National Institute on Aging. The authors reported no conflicts of interest.

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:

The likelihood of receiving a dementia diagnosis in older adults varies significantly by region across the United States, a new study suggests. Rates ranged from 1.7% to 5.4%, with variations more pronounced in those aged 66-74 years and Black or Hispanic individuals.

METHODOLOGY:

  • Researchers analyzed newly diagnosed cases of Alzheimer’s disease and related dementias (ADRD) using the 2018-2019 Medicare claims data for 4.8 million older adults across 306 hospital referral regions (HRRs).
  • Participants were categorized by age and race or ethnicity to examine variations in diagnosis rates.
  • Regional characteristics such as education level and prevalence of obesity, smoking, and diabetes were included to adjust for population risk factors.
  • ADRD-specific diagnostic intensity was calculated as the ratio of the observed-to-expected new cases of ADRD in each HRR.

TAKEAWAY:

  • Unadjusted analysis for that overall, 3% of older adults received a new ADRD diagnosis in 2019, with rates ranging from 1.7 to 5.4 per 100 individuals across HRRs and varied by age category.
  • Regions in the South had the highest unadjusted ADRD case concentration, and the areas in the West/Northwest had the lowest.
  • The ADRD-specific diagnosis intensity was 0.69-1.47 and varied the most in Black and Hispanic individuals and those aged 66-74 years.
  • Regional differences in ADRD diagnosis rates are not fully explained by population risk factors, indicating potential health system-level differences.

IN PRACTICE:

“From place to place, the likelihood of getting your dementia diagnosed varies, and that may happen because of everything from practice norms for healthcare providers to individual patients’ knowledge and care-seeking behavior. These findings go beyond demographic and population-level differences in risk and indicate that there are health system-level differences that could be targeted and remediated,” lead author Julie P.W. Bynum, MD, MPH, said in a press release.

SOURCE:

The study was led by Dr. Bynum, professor of internal medicine, University of Michigan Medical School, Ann Arbor, Michigan, and published online in Alzheimer’s & Dementia.

LIMITATIONS:

The results may not be generalizable to other groups. The observational design of the study cannot completely negate residual confounding. The measures of population risks are coarser than those used in well-characterized epidemiologic studies, leading to potential imprecision. Finally, the study was not designed to determine whether regional differences in the likelihood of ADRD diagnosis resulted in differences in the population health outcomes.

DISCLOSURES:

The study was supported by a grant from the National Institute on Aging. The authors reported no conflicts of interest.

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.

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Parkinson’s Risk in Women and History of Migraine: New Data

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TOPLINE:

A history of migraine is not associated with an elevated risk for Parkinson’s disease (PD) in women, regardless of headache frequency or migraine subtype, a new study suggests.

METHODOLOGY:

  • Researchers analyzed data on 39,312 women health professionals aged ≥ 45 years and having no history of PD who enrolled in the Women’s Health Study between 1992 and 1995 and were followed until 2021.
  • At baseline, 7321 women (18.6%) had migraine.
  • The mean follow-up duration was 22 years.
  • The primary outcome was a self-reported, physician-confirmed diagnosis of PD.

TAKEAWAY:

  • During the study period, 685 women self-reported a diagnosis of PD.
  • Of these, 18.7% of reported cases were in women with any migraine and 81.3% in women without migraine.
  • No significant association was found between PD risk and a history of migraine, migraine subtypes (with or without aura), or migraine frequency.
  • Migraine was not associated with a higher risk for PD than that of nonmigraine headaches.

IN PRACTICE:

“These results are reassuring for women who have migraine, which itself causes many burdens, that they don’t have to worry about an increased risk of Parkinson’s disease in the future,” study author Tobias Kurth, Charité - Universitätsmedizin Berlin, Germany, said in a press release.

SOURCE:

The study was led by Ricarda S. Schulz, MSc, Charité - Universitätsmedizin Berlin. It was published online in Neurology.

LIMITATIONS:

The study’s findings may not be generalizable to other populations, such as men and non-White individuals. The self-reported data on migraine and PD may be subject to inaccuracies. PD is often not diagnosed until symptoms have reached an advanced stage, potentially leading to cases being underreported. Changes in the status and frequency of migraine over the study period were not accounted for, which may have affected the results.

DISCLOSURES:

The authors did not disclose any specific funding for this work. The Women’s Health Study was supported by the National Cancer Institute and National Heart, Lung, and Blood Institute. Two authors reported having financial ties outside this work. Full disclosures are available 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.

Publications
Topics
Sections

 

TOPLINE:

A history of migraine is not associated with an elevated risk for Parkinson’s disease (PD) in women, regardless of headache frequency or migraine subtype, a new study suggests.

METHODOLOGY:

  • Researchers analyzed data on 39,312 women health professionals aged ≥ 45 years and having no history of PD who enrolled in the Women’s Health Study between 1992 and 1995 and were followed until 2021.
  • At baseline, 7321 women (18.6%) had migraine.
  • The mean follow-up duration was 22 years.
  • The primary outcome was a self-reported, physician-confirmed diagnosis of PD.

TAKEAWAY:

  • During the study period, 685 women self-reported a diagnosis of PD.
  • Of these, 18.7% of reported cases were in women with any migraine and 81.3% in women without migraine.
  • No significant association was found between PD risk and a history of migraine, migraine subtypes (with or without aura), or migraine frequency.
  • Migraine was not associated with a higher risk for PD than that of nonmigraine headaches.

IN PRACTICE:

“These results are reassuring for women who have migraine, which itself causes many burdens, that they don’t have to worry about an increased risk of Parkinson’s disease in the future,” study author Tobias Kurth, Charité - Universitätsmedizin Berlin, Germany, said in a press release.

SOURCE:

The study was led by Ricarda S. Schulz, MSc, Charité - Universitätsmedizin Berlin. It was published online in Neurology.

LIMITATIONS:

The study’s findings may not be generalizable to other populations, such as men and non-White individuals. The self-reported data on migraine and PD may be subject to inaccuracies. PD is often not diagnosed until symptoms have reached an advanced stage, potentially leading to cases being underreported. Changes in the status and frequency of migraine over the study period were not accounted for, which may have affected the results.

DISCLOSURES:

The authors did not disclose any specific funding for this work. The Women’s Health Study was supported by the National Cancer Institute and National Heart, Lung, and Blood Institute. Two authors reported having financial ties outside this work. Full disclosures are available 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:

A history of migraine is not associated with an elevated risk for Parkinson’s disease (PD) in women, regardless of headache frequency or migraine subtype, a new study suggests.

METHODOLOGY:

  • Researchers analyzed data on 39,312 women health professionals aged ≥ 45 years and having no history of PD who enrolled in the Women’s Health Study between 1992 and 1995 and were followed until 2021.
  • At baseline, 7321 women (18.6%) had migraine.
  • The mean follow-up duration was 22 years.
  • The primary outcome was a self-reported, physician-confirmed diagnosis of PD.

TAKEAWAY:

  • During the study period, 685 women self-reported a diagnosis of PD.
  • Of these, 18.7% of reported cases were in women with any migraine and 81.3% in women without migraine.
  • No significant association was found between PD risk and a history of migraine, migraine subtypes (with or without aura), or migraine frequency.
  • Migraine was not associated with a higher risk for PD than that of nonmigraine headaches.

IN PRACTICE:

“These results are reassuring for women who have migraine, which itself causes many burdens, that they don’t have to worry about an increased risk of Parkinson’s disease in the future,” study author Tobias Kurth, Charité - Universitätsmedizin Berlin, Germany, said in a press release.

SOURCE:

The study was led by Ricarda S. Schulz, MSc, Charité - Universitätsmedizin Berlin. It was published online in Neurology.

LIMITATIONS:

The study’s findings may not be generalizable to other populations, such as men and non-White individuals. The self-reported data on migraine and PD may be subject to inaccuracies. PD is often not diagnosed until symptoms have reached an advanced stage, potentially leading to cases being underreported. Changes in the status and frequency of migraine over the study period were not accounted for, which may have affected the results.

DISCLOSURES:

The authors did not disclose any specific funding for this work. The Women’s Health Study was supported by the National Cancer Institute and National Heart, Lung, and Blood Institute. Two authors reported having financial ties outside this work. Full disclosures are available 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.

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Can Antihistamines Trigger Seizures in Young Kids?

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TOPLINE:

First-generation antihistamines are linked to a 22% higher risk for seizures in children, new research shows. The risk appears to be most pronounced in children aged 6-24 months.

METHODOLOGY:

  • Researchers in Korea used a self-controlled case-crossover design to assess the risk for seizures associated with prescriptions of first-generation antihistamines.
  • They analyzed data from 11,729 children who had a seizure event (an emergency department visit with a diagnosis of epilepsy, status epilepticus, or convulsion) and had previously received a prescription for a first-generation antihistamine, including chlorpheniramine maleate, mequitazine, oxatomide, piprinhydrinate, or hydroxyzine hydrochloride.
  • Prescriptions during the 15 days before a seizure were considered to have been received during a hazard period, whereas earlier prescriptions were considered to have been received during a control period.
  • The researchers excluded patients with febrile seizures.

TAKEAWAY:

  • In an adjusted analysis, a prescription for an antihistamine during the hazard period was associated with a 22% higher risk for seizures in children (adjusted odds ratio, 1.22; 95% CI, 1.13-1.31).
  • The seizure risk was significant in children aged 6-24 months, with an adjusted odds ratio of 1.49 (95% CI, 1.31-1.70).
  • For older children, the risk was not statistically significant.

IN PRACTICE:

“The study underscores a substantial increase in seizure risk associated with antihistamine prescription among children aged 6-24 months,” the authors of the study wrote. “We are not aware of any other studies that have pointed out the increased risk of seizures with first-generation antihistamines in this particular age group. ... The benefits and risks of antihistamine use should always be carefully considered, especially when prescribing H1 antihistamines to vulnerable infants.”

The findings raise a host of questions for clinicians, including how a “relatively small risk” should translate into practice, and whether the risk may be attenuated with newer antihistamines, wrote Frank Max Charles Besag, MB, ChB, with East London NHS Foundation Trust in England, in an editorial accompanying the study. “It would be reasonable to inform families that at least one study has suggested a relatively small increase in the risk of seizures with first-generation antihistamines, adding that there are still too few data to draw any firm conclusions and also providing families with the information on what to do if the child were to have a seizure.” 
 

SOURCE:

Seonkyeong Rhie, MD, and Man Yong Han, MD, both with the Department of Pediatrics at CHA University School of Medicine, in Seongnam, South Korea, were the corresponding authors on the study. The research was published online in JAMA Network Open.

LIMITATIONS:

The researchers did not have details about seizure symptoms, did not include children seen in outpatient clinics, and were unable to verify the actual intake of the prescribed antihistamines. Although second-generation antihistamines may be less likely to cross the blood-brain barrier, one newer medication, desloratadine, has been associated with seizures.

DISCLOSURES:

The study was supported by grants from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, the Ministry of Health and Welfare, Republic of Korea.

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.

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TOPLINE:

First-generation antihistamines are linked to a 22% higher risk for seizures in children, new research shows. The risk appears to be most pronounced in children aged 6-24 months.

METHODOLOGY:

  • Researchers in Korea used a self-controlled case-crossover design to assess the risk for seizures associated with prescriptions of first-generation antihistamines.
  • They analyzed data from 11,729 children who had a seizure event (an emergency department visit with a diagnosis of epilepsy, status epilepticus, or convulsion) and had previously received a prescription for a first-generation antihistamine, including chlorpheniramine maleate, mequitazine, oxatomide, piprinhydrinate, or hydroxyzine hydrochloride.
  • Prescriptions during the 15 days before a seizure were considered to have been received during a hazard period, whereas earlier prescriptions were considered to have been received during a control period.
  • The researchers excluded patients with febrile seizures.

TAKEAWAY:

  • In an adjusted analysis, a prescription for an antihistamine during the hazard period was associated with a 22% higher risk for seizures in children (adjusted odds ratio, 1.22; 95% CI, 1.13-1.31).
  • The seizure risk was significant in children aged 6-24 months, with an adjusted odds ratio of 1.49 (95% CI, 1.31-1.70).
  • For older children, the risk was not statistically significant.

IN PRACTICE:

“The study underscores a substantial increase in seizure risk associated with antihistamine prescription among children aged 6-24 months,” the authors of the study wrote. “We are not aware of any other studies that have pointed out the increased risk of seizures with first-generation antihistamines in this particular age group. ... The benefits and risks of antihistamine use should always be carefully considered, especially when prescribing H1 antihistamines to vulnerable infants.”

The findings raise a host of questions for clinicians, including how a “relatively small risk” should translate into practice, and whether the risk may be attenuated with newer antihistamines, wrote Frank Max Charles Besag, MB, ChB, with East London NHS Foundation Trust in England, in an editorial accompanying the study. “It would be reasonable to inform families that at least one study has suggested a relatively small increase in the risk of seizures with first-generation antihistamines, adding that there are still too few data to draw any firm conclusions and also providing families with the information on what to do if the child were to have a seizure.” 
 

SOURCE:

Seonkyeong Rhie, MD, and Man Yong Han, MD, both with the Department of Pediatrics at CHA University School of Medicine, in Seongnam, South Korea, were the corresponding authors on the study. The research was published online in JAMA Network Open.

LIMITATIONS:

The researchers did not have details about seizure symptoms, did not include children seen in outpatient clinics, and were unable to verify the actual intake of the prescribed antihistamines. Although second-generation antihistamines may be less likely to cross the blood-brain barrier, one newer medication, desloratadine, has been associated with seizures.

DISCLOSURES:

The study was supported by grants from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, the Ministry of Health and Welfare, Republic of Korea.

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:

First-generation antihistamines are linked to a 22% higher risk for seizures in children, new research shows. The risk appears to be most pronounced in children aged 6-24 months.

METHODOLOGY:

  • Researchers in Korea used a self-controlled case-crossover design to assess the risk for seizures associated with prescriptions of first-generation antihistamines.
  • They analyzed data from 11,729 children who had a seizure event (an emergency department visit with a diagnosis of epilepsy, status epilepticus, or convulsion) and had previously received a prescription for a first-generation antihistamine, including chlorpheniramine maleate, mequitazine, oxatomide, piprinhydrinate, or hydroxyzine hydrochloride.
  • Prescriptions during the 15 days before a seizure were considered to have been received during a hazard period, whereas earlier prescriptions were considered to have been received during a control period.
  • The researchers excluded patients with febrile seizures.

TAKEAWAY:

  • In an adjusted analysis, a prescription for an antihistamine during the hazard period was associated with a 22% higher risk for seizures in children (adjusted odds ratio, 1.22; 95% CI, 1.13-1.31).
  • The seizure risk was significant in children aged 6-24 months, with an adjusted odds ratio of 1.49 (95% CI, 1.31-1.70).
  • For older children, the risk was not statistically significant.

IN PRACTICE:

“The study underscores a substantial increase in seizure risk associated with antihistamine prescription among children aged 6-24 months,” the authors of the study wrote. “We are not aware of any other studies that have pointed out the increased risk of seizures with first-generation antihistamines in this particular age group. ... The benefits and risks of antihistamine use should always be carefully considered, especially when prescribing H1 antihistamines to vulnerable infants.”

The findings raise a host of questions for clinicians, including how a “relatively small risk” should translate into practice, and whether the risk may be attenuated with newer antihistamines, wrote Frank Max Charles Besag, MB, ChB, with East London NHS Foundation Trust in England, in an editorial accompanying the study. “It would be reasonable to inform families that at least one study has suggested a relatively small increase in the risk of seizures with first-generation antihistamines, adding that there are still too few data to draw any firm conclusions and also providing families with the information on what to do if the child were to have a seizure.” 
 

SOURCE:

Seonkyeong Rhie, MD, and Man Yong Han, MD, both with the Department of Pediatrics at CHA University School of Medicine, in Seongnam, South Korea, were the corresponding authors on the study. The research was published online in JAMA Network Open.

LIMITATIONS:

The researchers did not have details about seizure symptoms, did not include children seen in outpatient clinics, and were unable to verify the actual intake of the prescribed antihistamines. Although second-generation antihistamines may be less likely to cross the blood-brain barrier, one newer medication, desloratadine, has been associated with seizures.

DISCLOSURES:

The study was supported by grants from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, the Ministry of Health and Welfare, Republic of Korea.

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.

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The Link Between Vision Impairment and Dementia in Older Adults

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TOPLINE:

Addressing vision impairments could help with dementia prevention, as vision impairment is linked to 19% of dementia cases in older adults.
 

METHODOLOGY:

  • Researchers conducted a cross-sectional analysis using data from the National Health and Aging Trends Study (NHATS).
  • The analysis included 2767 US adults aged 71 years or older (54.7% female and 45.3% male).
  • Vision impairments were defined using 2019 World Health Organization criteria. Near and distance vision impairments were defined as greater than 0.30 logMAR, and contrast sensitivity impairment was identified by scores below 1.55 logCS.
  • Dementia was classified using a standardized algorithm developed in NHATS, which incorporated a series of tests measuring cognition, memory and orientation, reports of Alzheimer’s disease, or a dementia diagnosis from the patient or a proxy, and an informant questionnaire (Ascertain Dementia-8 Dementia Screening Interview).
  • The study analyzed data from 2021, with the primary outcome being the population attributable fraction (PAF) of dementia from vision impairment.

TAKEAWAY:

  • The PAF of dementia associated with at least one vision impairment was 19% (95% CI, 8.2-29.7).
  • Impairment in contrast sensitivity had the highest PAF among all other vision issues, at 15% (95% CI, 6.6-23.6). This figure was higher than that for impairment of near acuity, at 9.7% (95% CI, 2.6-17.0), or distance acuity, at 4.9% (95% CI, 0.1-9.9).
  • The highest PAFs for dementia due to vision impairment was among participants aged 71-79 years (24.3%; 95% CI, 6.6-41.8), women (26.8%; 95% CI, 12.2-39.9), and non-Hispanic White participants (22.3%; 95% CI, 9.6-34.5).

IN PRACTICE:

“While not proving a cause-and-effect relationship, these findings support inclusion of multiple objective measures of vision impairments, including contrast sensitivity and visual acuity, to capture the total potential impact of addressing vision impairment on dementia,” study authors wrote.

SOURCE:

This study was led by Jason R. Smith, ScM, of the Department of Epidemiology at the Johns Hopkins Bloomberg School of Public Health in Baltimore. It was published online in JAMA Ophthalmology.

LIMITATIONS:

The limited sample sizes for American Indian, Alaska Native, Asian, and Hispanic groups prevented researchers from calculating PAFs for these populations. The cross-sectional design prevented the researchers from examining the timing of vision impairment in relation to a diagnosis of dementia. The study did not explore links between other measures of vision and dementia. Those with early cognitive impairment may not have updated glasses, affecting visual performance. The findings from the study may not apply to institutionalized older adults.

DISCLOSURES:

Jennifer A. Deal, PhD, MHS, reported receiving personal fees from Frontiers in Epidemiology, Velux Stiftung, and Medical Education Speakers Network outside the submitted work. Nicholas S. Reed, AuD, PhD, reported receiving stock options from Neosensory outside the submitted work. No other disclosures were reported.

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 appeared on Medscape.com.

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TOPLINE:

Addressing vision impairments could help with dementia prevention, as vision impairment is linked to 19% of dementia cases in older adults.
 

METHODOLOGY:

  • Researchers conducted a cross-sectional analysis using data from the National Health and Aging Trends Study (NHATS).
  • The analysis included 2767 US adults aged 71 years or older (54.7% female and 45.3% male).
  • Vision impairments were defined using 2019 World Health Organization criteria. Near and distance vision impairments were defined as greater than 0.30 logMAR, and contrast sensitivity impairment was identified by scores below 1.55 logCS.
  • Dementia was classified using a standardized algorithm developed in NHATS, which incorporated a series of tests measuring cognition, memory and orientation, reports of Alzheimer’s disease, or a dementia diagnosis from the patient or a proxy, and an informant questionnaire (Ascertain Dementia-8 Dementia Screening Interview).
  • The study analyzed data from 2021, with the primary outcome being the population attributable fraction (PAF) of dementia from vision impairment.

TAKEAWAY:

  • The PAF of dementia associated with at least one vision impairment was 19% (95% CI, 8.2-29.7).
  • Impairment in contrast sensitivity had the highest PAF among all other vision issues, at 15% (95% CI, 6.6-23.6). This figure was higher than that for impairment of near acuity, at 9.7% (95% CI, 2.6-17.0), or distance acuity, at 4.9% (95% CI, 0.1-9.9).
  • The highest PAFs for dementia due to vision impairment was among participants aged 71-79 years (24.3%; 95% CI, 6.6-41.8), women (26.8%; 95% CI, 12.2-39.9), and non-Hispanic White participants (22.3%; 95% CI, 9.6-34.5).

IN PRACTICE:

“While not proving a cause-and-effect relationship, these findings support inclusion of multiple objective measures of vision impairments, including contrast sensitivity and visual acuity, to capture the total potential impact of addressing vision impairment on dementia,” study authors wrote.

SOURCE:

This study was led by Jason R. Smith, ScM, of the Department of Epidemiology at the Johns Hopkins Bloomberg School of Public Health in Baltimore. It was published online in JAMA Ophthalmology.

LIMITATIONS:

The limited sample sizes for American Indian, Alaska Native, Asian, and Hispanic groups prevented researchers from calculating PAFs for these populations. The cross-sectional design prevented the researchers from examining the timing of vision impairment in relation to a diagnosis of dementia. The study did not explore links between other measures of vision and dementia. Those with early cognitive impairment may not have updated glasses, affecting visual performance. The findings from the study may not apply to institutionalized older adults.

DISCLOSURES:

Jennifer A. Deal, PhD, MHS, reported receiving personal fees from Frontiers in Epidemiology, Velux Stiftung, and Medical Education Speakers Network outside the submitted work. Nicholas S. Reed, AuD, PhD, reported receiving stock options from Neosensory outside the submitted work. No other disclosures were reported.

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 appeared on Medscape.com.

 

TOPLINE:

Addressing vision impairments could help with dementia prevention, as vision impairment is linked to 19% of dementia cases in older adults.
 

METHODOLOGY:

  • Researchers conducted a cross-sectional analysis using data from the National Health and Aging Trends Study (NHATS).
  • The analysis included 2767 US adults aged 71 years or older (54.7% female and 45.3% male).
  • Vision impairments were defined using 2019 World Health Organization criteria. Near and distance vision impairments were defined as greater than 0.30 logMAR, and contrast sensitivity impairment was identified by scores below 1.55 logCS.
  • Dementia was classified using a standardized algorithm developed in NHATS, which incorporated a series of tests measuring cognition, memory and orientation, reports of Alzheimer’s disease, or a dementia diagnosis from the patient or a proxy, and an informant questionnaire (Ascertain Dementia-8 Dementia Screening Interview).
  • The study analyzed data from 2021, with the primary outcome being the population attributable fraction (PAF) of dementia from vision impairment.

TAKEAWAY:

  • The PAF of dementia associated with at least one vision impairment was 19% (95% CI, 8.2-29.7).
  • Impairment in contrast sensitivity had the highest PAF among all other vision issues, at 15% (95% CI, 6.6-23.6). This figure was higher than that for impairment of near acuity, at 9.7% (95% CI, 2.6-17.0), or distance acuity, at 4.9% (95% CI, 0.1-9.9).
  • The highest PAFs for dementia due to vision impairment was among participants aged 71-79 years (24.3%; 95% CI, 6.6-41.8), women (26.8%; 95% CI, 12.2-39.9), and non-Hispanic White participants (22.3%; 95% CI, 9.6-34.5).

IN PRACTICE:

“While not proving a cause-and-effect relationship, these findings support inclusion of multiple objective measures of vision impairments, including contrast sensitivity and visual acuity, to capture the total potential impact of addressing vision impairment on dementia,” study authors wrote.

SOURCE:

This study was led by Jason R. Smith, ScM, of the Department of Epidemiology at the Johns Hopkins Bloomberg School of Public Health in Baltimore. It was published online in JAMA Ophthalmology.

LIMITATIONS:

The limited sample sizes for American Indian, Alaska Native, Asian, and Hispanic groups prevented researchers from calculating PAFs for these populations. The cross-sectional design prevented the researchers from examining the timing of vision impairment in relation to a diagnosis of dementia. The study did not explore links between other measures of vision and dementia. Those with early cognitive impairment may not have updated glasses, affecting visual performance. The findings from the study may not apply to institutionalized older adults.

DISCLOSURES:

Jennifer A. Deal, PhD, MHS, reported receiving personal fees from Frontiers in Epidemiology, Velux Stiftung, and Medical Education Speakers Network outside the submitted work. Nicholas S. Reed, AuD, PhD, reported receiving stock options from Neosensory outside the submitted work. No other disclosures were reported.

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 appeared on Medscape.com.

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Not Kidding: Yellow Dye 5 May Lead to Invisibility

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The same dye that gives Twinkies their yellowish hue could be the key to invisibility. 

Applying the dye to lab mice made their skin temporarily transparent, allowing Stanford University researchers to observe the rodents’ digestive system, muscle fibers, and blood vessels, according to a study published in Science.

“It’s a stunning result,” said senior author Guosong Hong, PhD, who is assistant professor of materials science and engineering at Stanford University in California. “If the same technique could be applied to humans, it could offer a variety of benefits in biology, diagnostics, and even cosmetics.” 

The work drew upon optical concepts first described in the early 20th century to form a surprising theory: Applying a light-absorbing substance could render skin transparent by reducing the chaotic scattering of light as it strikes proteins, fats, and water in tissue. 

A search for a suitable light absorber led to FD&C Yellow 5, also called tartrazine, a synthetic color additive certified by the Food and Drug Administration (FDA) for use in foods, cosmetics, and medications. 

Rubbed on live mice (after areas of fur were removed using a drugstore depilatory cream), tartrazine rendered skin on their bellies, hind legs, and heads transparent within 5 minutes. With the naked eye, the researchers watched a mouse’s intestines, bladder, and liver at work. Using a microscope, they observed muscle fibers and saw blood vessels in a living mouse’s brain — all without making incisions. Transparency faded quickly when the dye was washed off.

Someday, the concept could be used in doctors’ offices and hospitals, Dr. Hong said. 

“Instead of relying on invasive biopsies, doctors might be able to diagnose deep-seated tumors by simply examining a person’s tissue without the need for invasive surgical removal,” he said. “This technique could potentially make blood draws less painful by helping phlebotomists easily locate veins under the skin. It could also enhance procedures like laser tattoo removal by allowing more precise targeting of the pigment beneath the skin.”
 

From Cake Frosting to Groundbreaking Research

Yellow 5 food dye can be found in everything from cereal, soda, spices, and cake frosting to lipstick, mouthwash, shampoo, dietary supplements, and house paint. Although it’s in some topical medications, more research is needed before it could be used in human diagnostics, said Christopher J. Rowlands, PhD, a senior lecturer in the Department of Bioengineering at Imperial College London, England, where he studies biophotonic instrumentation — ways to image structures inside the body more quickly and clearly. 

But the finding could prove useful in research. In a commentary published in Science, Dr. Rowlands and his colleague Jon Gorecki, PhD, an experimental optical physicist also at Imperial College London, noted that the dye could be an alternative to other optical clearing agents currently used in lab studies, such as glycerol, fructose, or acetic acid. Advantages are the effect is reversible and works at lower concentrations with fewer side effects. This could broaden the types of studies possible in lab animals, so researchers don’t have to rely on naturally transparent creatures like nematodes and zebrafish. 

The dye could also be paired with imaging techniques such as MRI or electron microscopy. 

“Imaging techniques all have pros and cons,” Dr. Rowlands said. “MRI can see all the way through the body albeit with limited resolution and contrast. Electron microscopy has excellent resolution but limited compatibility with live tissue and penetration depth. Optical microscopy has subcellular resolution, the ability to label things, excellent biocompatibility but less than 1 millimeter of penetration depth. This clearing method will give a substantial boost to optical imaging for medicine and biology.”

The discovery could improve the depth imaging equipment can achieve by tenfold, according to the commentary. 

Brain research especially stands to benefit. “Neurobiology in particular will have great use for combinations of multiphoton, optogenetics, and tissue clearing to record and control neural activity over (potentially) the whole mouse brain,” he said.
 

Refraction, Absorption, and The Invisible Man

The dye discovery has distant echoes in H.G. Wells’ 1897 novel The Invisible Man, Dr. Rowlands noted. In the book, a serum makes the main character invisible by changing the light scattering — or refractive index (RI) — of his cells to match the air around him.

The Stanford engineers looked to the past for inspiration, but not to fiction. They turned to a concept first described in the 1920s called the Kramers-Kronig relations, a mathematical principle that can be applied to relationships between the way light is refracted and absorbed in different materials. They also read up on Lorentz oscillation, which describes how electrons and atoms inside molecules react to light. 

They reasoned that light-absorbing compounds could equalize the differences between the light-scattering properties of proteins, lipids, and water that make skin opaque. 

With that, the search was on. The study’s first author, postdoctoral researcher Zihao Ou, PhD, began testing strong dyes to find a candidate. Tartrazine was a front-runner. 

“We found that dye molecules are more efficient in raising the refractive index of water than conventional RI-matching agents, thus resulting in transparency at a much lower concentration,” Dr. Hong said. “The underlying physics, explained by the Lorentz oscillator model and Kramers-Kronig relations, reveals that conventional RI matching agents like fructose are not as efficient because they are not ‘colored’ enough.”
 

What’s Next

Though the dye is already in products that people consume and apply to their skin, medical use is years away. In some people, tartrazine can cause skin or respiratory reactions. 

The National Science Foundation (NSF), which helped fund the research, posted a home or classroom activity related to the work on its website. It involves painting a tartrazine solution on a thin slice of raw chicken breast, making it transparent. The experiment should only be done while wearing a mask, eye protection, lab coat, and lab-quality nitrile gloves for protection, according to the NSF.

Meanwhile, Dr. Hong said his lab is looking for new compounds that will improve visibility through transparent skin, removing a red tone seen in the current experiments. And they’re looking for ways to induce cells to make their own “see-through” compounds. 

“We are exploring methods for cells to express intensely absorbing molecules endogenously, enabling genetically encoded tissue transparency in live animals,” he said.

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

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The same dye that gives Twinkies their yellowish hue could be the key to invisibility. 

Applying the dye to lab mice made their skin temporarily transparent, allowing Stanford University researchers to observe the rodents’ digestive system, muscle fibers, and blood vessels, according to a study published in Science.

“It’s a stunning result,” said senior author Guosong Hong, PhD, who is assistant professor of materials science and engineering at Stanford University in California. “If the same technique could be applied to humans, it could offer a variety of benefits in biology, diagnostics, and even cosmetics.” 

The work drew upon optical concepts first described in the early 20th century to form a surprising theory: Applying a light-absorbing substance could render skin transparent by reducing the chaotic scattering of light as it strikes proteins, fats, and water in tissue. 

A search for a suitable light absorber led to FD&C Yellow 5, also called tartrazine, a synthetic color additive certified by the Food and Drug Administration (FDA) for use in foods, cosmetics, and medications. 

Rubbed on live mice (after areas of fur were removed using a drugstore depilatory cream), tartrazine rendered skin on their bellies, hind legs, and heads transparent within 5 minutes. With the naked eye, the researchers watched a mouse’s intestines, bladder, and liver at work. Using a microscope, they observed muscle fibers and saw blood vessels in a living mouse’s brain — all without making incisions. Transparency faded quickly when the dye was washed off.

Someday, the concept could be used in doctors’ offices and hospitals, Dr. Hong said. 

“Instead of relying on invasive biopsies, doctors might be able to diagnose deep-seated tumors by simply examining a person’s tissue without the need for invasive surgical removal,” he said. “This technique could potentially make blood draws less painful by helping phlebotomists easily locate veins under the skin. It could also enhance procedures like laser tattoo removal by allowing more precise targeting of the pigment beneath the skin.”
 

From Cake Frosting to Groundbreaking Research

Yellow 5 food dye can be found in everything from cereal, soda, spices, and cake frosting to lipstick, mouthwash, shampoo, dietary supplements, and house paint. Although it’s in some topical medications, more research is needed before it could be used in human diagnostics, said Christopher J. Rowlands, PhD, a senior lecturer in the Department of Bioengineering at Imperial College London, England, where he studies biophotonic instrumentation — ways to image structures inside the body more quickly and clearly. 

But the finding could prove useful in research. In a commentary published in Science, Dr. Rowlands and his colleague Jon Gorecki, PhD, an experimental optical physicist also at Imperial College London, noted that the dye could be an alternative to other optical clearing agents currently used in lab studies, such as glycerol, fructose, or acetic acid. Advantages are the effect is reversible and works at lower concentrations with fewer side effects. This could broaden the types of studies possible in lab animals, so researchers don’t have to rely on naturally transparent creatures like nematodes and zebrafish. 

The dye could also be paired with imaging techniques such as MRI or electron microscopy. 

“Imaging techniques all have pros and cons,” Dr. Rowlands said. “MRI can see all the way through the body albeit with limited resolution and contrast. Electron microscopy has excellent resolution but limited compatibility with live tissue and penetration depth. Optical microscopy has subcellular resolution, the ability to label things, excellent biocompatibility but less than 1 millimeter of penetration depth. This clearing method will give a substantial boost to optical imaging for medicine and biology.”

The discovery could improve the depth imaging equipment can achieve by tenfold, according to the commentary. 

Brain research especially stands to benefit. “Neurobiology in particular will have great use for combinations of multiphoton, optogenetics, and tissue clearing to record and control neural activity over (potentially) the whole mouse brain,” he said.
 

Refraction, Absorption, and The Invisible Man

The dye discovery has distant echoes in H.G. Wells’ 1897 novel The Invisible Man, Dr. Rowlands noted. In the book, a serum makes the main character invisible by changing the light scattering — or refractive index (RI) — of his cells to match the air around him.

The Stanford engineers looked to the past for inspiration, but not to fiction. They turned to a concept first described in the 1920s called the Kramers-Kronig relations, a mathematical principle that can be applied to relationships between the way light is refracted and absorbed in different materials. They also read up on Lorentz oscillation, which describes how electrons and atoms inside molecules react to light. 

They reasoned that light-absorbing compounds could equalize the differences between the light-scattering properties of proteins, lipids, and water that make skin opaque. 

With that, the search was on. The study’s first author, postdoctoral researcher Zihao Ou, PhD, began testing strong dyes to find a candidate. Tartrazine was a front-runner. 

“We found that dye molecules are more efficient in raising the refractive index of water than conventional RI-matching agents, thus resulting in transparency at a much lower concentration,” Dr. Hong said. “The underlying physics, explained by the Lorentz oscillator model and Kramers-Kronig relations, reveals that conventional RI matching agents like fructose are not as efficient because they are not ‘colored’ enough.”
 

What’s Next

Though the dye is already in products that people consume and apply to their skin, medical use is years away. In some people, tartrazine can cause skin or respiratory reactions. 

The National Science Foundation (NSF), which helped fund the research, posted a home or classroom activity related to the work on its website. It involves painting a tartrazine solution on a thin slice of raw chicken breast, making it transparent. The experiment should only be done while wearing a mask, eye protection, lab coat, and lab-quality nitrile gloves for protection, according to the NSF.

Meanwhile, Dr. Hong said his lab is looking for new compounds that will improve visibility through transparent skin, removing a red tone seen in the current experiments. And they’re looking for ways to induce cells to make their own “see-through” compounds. 

“We are exploring methods for cells to express intensely absorbing molecules endogenously, enabling genetically encoded tissue transparency in live animals,” he said.

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

 

The same dye that gives Twinkies their yellowish hue could be the key to invisibility. 

Applying the dye to lab mice made their skin temporarily transparent, allowing Stanford University researchers to observe the rodents’ digestive system, muscle fibers, and blood vessels, according to a study published in Science.

“It’s a stunning result,” said senior author Guosong Hong, PhD, who is assistant professor of materials science and engineering at Stanford University in California. “If the same technique could be applied to humans, it could offer a variety of benefits in biology, diagnostics, and even cosmetics.” 

The work drew upon optical concepts first described in the early 20th century to form a surprising theory: Applying a light-absorbing substance could render skin transparent by reducing the chaotic scattering of light as it strikes proteins, fats, and water in tissue. 

A search for a suitable light absorber led to FD&C Yellow 5, also called tartrazine, a synthetic color additive certified by the Food and Drug Administration (FDA) for use in foods, cosmetics, and medications. 

Rubbed on live mice (after areas of fur were removed using a drugstore depilatory cream), tartrazine rendered skin on their bellies, hind legs, and heads transparent within 5 minutes. With the naked eye, the researchers watched a mouse’s intestines, bladder, and liver at work. Using a microscope, they observed muscle fibers and saw blood vessels in a living mouse’s brain — all without making incisions. Transparency faded quickly when the dye was washed off.

Someday, the concept could be used in doctors’ offices and hospitals, Dr. Hong said. 

“Instead of relying on invasive biopsies, doctors might be able to diagnose deep-seated tumors by simply examining a person’s tissue without the need for invasive surgical removal,” he said. “This technique could potentially make blood draws less painful by helping phlebotomists easily locate veins under the skin. It could also enhance procedures like laser tattoo removal by allowing more precise targeting of the pigment beneath the skin.”
 

From Cake Frosting to Groundbreaking Research

Yellow 5 food dye can be found in everything from cereal, soda, spices, and cake frosting to lipstick, mouthwash, shampoo, dietary supplements, and house paint. Although it’s in some topical medications, more research is needed before it could be used in human diagnostics, said Christopher J. Rowlands, PhD, a senior lecturer in the Department of Bioengineering at Imperial College London, England, where he studies biophotonic instrumentation — ways to image structures inside the body more quickly and clearly. 

But the finding could prove useful in research. In a commentary published in Science, Dr. Rowlands and his colleague Jon Gorecki, PhD, an experimental optical physicist also at Imperial College London, noted that the dye could be an alternative to other optical clearing agents currently used in lab studies, such as glycerol, fructose, or acetic acid. Advantages are the effect is reversible and works at lower concentrations with fewer side effects. This could broaden the types of studies possible in lab animals, so researchers don’t have to rely on naturally transparent creatures like nematodes and zebrafish. 

The dye could also be paired with imaging techniques such as MRI or electron microscopy. 

“Imaging techniques all have pros and cons,” Dr. Rowlands said. “MRI can see all the way through the body albeit with limited resolution and contrast. Electron microscopy has excellent resolution but limited compatibility with live tissue and penetration depth. Optical microscopy has subcellular resolution, the ability to label things, excellent biocompatibility but less than 1 millimeter of penetration depth. This clearing method will give a substantial boost to optical imaging for medicine and biology.”

The discovery could improve the depth imaging equipment can achieve by tenfold, according to the commentary. 

Brain research especially stands to benefit. “Neurobiology in particular will have great use for combinations of multiphoton, optogenetics, and tissue clearing to record and control neural activity over (potentially) the whole mouse brain,” he said.
 

Refraction, Absorption, and The Invisible Man

The dye discovery has distant echoes in H.G. Wells’ 1897 novel The Invisible Man, Dr. Rowlands noted. In the book, a serum makes the main character invisible by changing the light scattering — or refractive index (RI) — of his cells to match the air around him.

The Stanford engineers looked to the past for inspiration, but not to fiction. They turned to a concept first described in the 1920s called the Kramers-Kronig relations, a mathematical principle that can be applied to relationships between the way light is refracted and absorbed in different materials. They also read up on Lorentz oscillation, which describes how electrons and atoms inside molecules react to light. 

They reasoned that light-absorbing compounds could equalize the differences between the light-scattering properties of proteins, lipids, and water that make skin opaque. 

With that, the search was on. The study’s first author, postdoctoral researcher Zihao Ou, PhD, began testing strong dyes to find a candidate. Tartrazine was a front-runner. 

“We found that dye molecules are more efficient in raising the refractive index of water than conventional RI-matching agents, thus resulting in transparency at a much lower concentration,” Dr. Hong said. “The underlying physics, explained by the Lorentz oscillator model and Kramers-Kronig relations, reveals that conventional RI matching agents like fructose are not as efficient because they are not ‘colored’ enough.”
 

What’s Next

Though the dye is already in products that people consume and apply to their skin, medical use is years away. In some people, tartrazine can cause skin or respiratory reactions. 

The National Science Foundation (NSF), which helped fund the research, posted a home or classroom activity related to the work on its website. It involves painting a tartrazine solution on a thin slice of raw chicken breast, making it transparent. The experiment should only be done while wearing a mask, eye protection, lab coat, and lab-quality nitrile gloves for protection, according to the NSF.

Meanwhile, Dr. Hong said his lab is looking for new compounds that will improve visibility through transparent skin, removing a red tone seen in the current experiments. And they’re looking for ways to induce cells to make their own “see-through” compounds. 

“We are exploring methods for cells to express intensely absorbing molecules endogenously, enabling genetically encoded tissue transparency in live animals,” he said.

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

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Brain Network Significantly Larger in People With Depression, Even in Childhood

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Researchers have discovered that a brain network involved in reward processing and attention to stimuli is markedly bigger in people with depression, remains stable over time, is unaffected by mood changes, and can be detected in children before onset of depression symptoms.

Using a novel brain-mapping technique, researchers found that the frontostriatal salience network was expanded nearly twofold in the brains of most individuals studied with depression compared with controls.

“This expansion in cortex was trait-like, meaning it was stable over time and did not change as symptoms changed over time,” said lead author Charles Lynch, PhD, assistant professor of neuroscience, Department of Psychiatry, Weill Cornell Medicine in New York.

It could also be detected in children who later developed depression, suggesting it may serve as a biomarker of depression risk. Investigators said the findings could aid in prevention and early detection of depression, as well as the development of more personalized treatment.

The study was published online in Nature.
 

Prewired for Depression?

Precision functional mapping is a relatively new approach to brain mapping in individuals that uses large amounts of fMRI data from hours of scans per person. The technique has been used to show differences in brain networks between and in healthy individuals but had not been used to study brain networks in people with depression.

“We leveraged our large longitudinal datasets — with many hours of functional MRI scanning per subject — to construct individual-specific maps of functional brain networks in each patient using precision functional mapping, instead of relying on group average,” Dr. Lynch said.

In the primary analysis of 141 adults with major depression and 37 healthy controls, the frontostriatal salience network — which is involved in reward processing and attention to internal and external stimuli — was markedly larger in these individuals with depression.

“This is one of the first times these kinds of personalized maps have been created in individuals with depression, and this is how we first observed of the salience network being larger in individuals with depression,” Dr. Lynch said.

In four of the six individuals, the salience network was expanded more than twofold, outside the range observed in all 37 healthy controls. On average, the salience network occupied 73% more of the cortical surface relative to the average in healthy controls.

The findings were replicated using independent samples of repeatedly sampled individuals with depression and in large-scale group average data.

The expansion of the salience network did not change over time and was unaffected by changes in mood state.

“These observations led us to propose that instead of driving changes in depressive symptoms over time, salience network expansion may be a stable marker of risk for developing depression,” the study team wrote.

An analysis of brain scans from 57 children who went on to develop depressive symptoms during adolescence and an equal number of children who did not develop depressive symptoms supports this theory.

On average, the salience network occupied roughly 36% more of cortex in the children with no current or previous symptoms of depression at the time of their fMRI scans but who subsequently developed clinically significant symptoms of depression, relative to children with no depressive symptoms at any study time point, the researchers found.
 

 

 

Immediate Clinical Impact?

Reached for comment, Shaheen Lakhan, MD, PhD, neurologist and researcher based in Miami, said this research “exemplifies the promising intersection of neurology and digital health, where advanced neuroimaging and data-driven approaches can transform mental health care into a more precise and individualized practice,” Dr. Lakhan said. “By identifying this brain network expansion, we’re unlocking new possibilities for precision medicine in mental health.”

Dr. Lakhan, who wasn’t involved in this research, said identifying the expansion of the frontostriatal salience network in individuals with depression opens new avenues for developing novel therapeutics.

“By targeting this network through neuromodulation techniques like deep brain stimulation, transcranial magnetic stimulation, and prescription digital therapeutics, treatments can be more precisely tailored to individual neurobiological profiles,” Dr. Lakhan said. “Additionally, this network expansion could serve as a biomarker for early detection, allowing for preventive strategies or personalized treatment plans, particularly for those at risk of developing depression.”

In addition, a greater understanding of the mechanisms driving salience network expansion offers potential for discovering new pharmacological targets, Dr. Lakhan noted.

“Drugs that modulate synaptic plasticity or network connectivity might be developed to reverse or mitigate these neural changes. The findings also support the use of longitudinal monitoring to predict and preempt symptom emergence, improving outcomes through timely intervention. This research paves the way for more personalized, precise, and proactive approaches in treating depression,” Dr. Lakhan concluded.

Also weighing in, Teddy Akiki, MD, with the Department of Psychiatry and Behavioral Sciences at Stanford Medicine in California, noted that the effect size of the frontostriatal salience network difference in depression is “remarkably larger than typically seen in neuroimaging studies of depression, which often describe subtle differences. The consistency across multiple datasets and across time at the individual level adds significant weight to these findings, suggesting that it is a trait marker rather than a state-dependent marker.”

“The observation that this expansion is present even before the onset of depressive symptoms in adolescence suggests its potential as a biomarker for depression risk,” Dr. Akiki said. “This approach could lead to earlier identification of at-risk individuals and potentially inform the development of targeted preventive interventions.”

He cautioned that it remains to be seen whether interventions targeting the salience network can effectively prevent or treat depression.

This research was supported in part by the National Institute of Mental Health, the National Institute on Drug Addiction, the Hope for Depression Research Foundation, and the Foundation for OCD Research. Dr. Lynch and a coauthor are listed as inventors for Cornell University patent applications on neuroimaging biomarkers for depression which are pending or in preparation. Dr. Liston has served as a scientific advisor or consultant to Compass Pathways PLC, Delix Therapeutics, and Brainify.AI. Dr. Lakhan and Dr. Akiki had no relevant disclosures.

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

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Researchers have discovered that a brain network involved in reward processing and attention to stimuli is markedly bigger in people with depression, remains stable over time, is unaffected by mood changes, and can be detected in children before onset of depression symptoms.

Using a novel brain-mapping technique, researchers found that the frontostriatal salience network was expanded nearly twofold in the brains of most individuals studied with depression compared with controls.

“This expansion in cortex was trait-like, meaning it was stable over time and did not change as symptoms changed over time,” said lead author Charles Lynch, PhD, assistant professor of neuroscience, Department of Psychiatry, Weill Cornell Medicine in New York.

It could also be detected in children who later developed depression, suggesting it may serve as a biomarker of depression risk. Investigators said the findings could aid in prevention and early detection of depression, as well as the development of more personalized treatment.

The study was published online in Nature.
 

Prewired for Depression?

Precision functional mapping is a relatively new approach to brain mapping in individuals that uses large amounts of fMRI data from hours of scans per person. The technique has been used to show differences in brain networks between and in healthy individuals but had not been used to study brain networks in people with depression.

“We leveraged our large longitudinal datasets — with many hours of functional MRI scanning per subject — to construct individual-specific maps of functional brain networks in each patient using precision functional mapping, instead of relying on group average,” Dr. Lynch said.

In the primary analysis of 141 adults with major depression and 37 healthy controls, the frontostriatal salience network — which is involved in reward processing and attention to internal and external stimuli — was markedly larger in these individuals with depression.

“This is one of the first times these kinds of personalized maps have been created in individuals with depression, and this is how we first observed of the salience network being larger in individuals with depression,” Dr. Lynch said.

In four of the six individuals, the salience network was expanded more than twofold, outside the range observed in all 37 healthy controls. On average, the salience network occupied 73% more of the cortical surface relative to the average in healthy controls.

The findings were replicated using independent samples of repeatedly sampled individuals with depression and in large-scale group average data.

The expansion of the salience network did not change over time and was unaffected by changes in mood state.

“These observations led us to propose that instead of driving changes in depressive symptoms over time, salience network expansion may be a stable marker of risk for developing depression,” the study team wrote.

An analysis of brain scans from 57 children who went on to develop depressive symptoms during adolescence and an equal number of children who did not develop depressive symptoms supports this theory.

On average, the salience network occupied roughly 36% more of cortex in the children with no current or previous symptoms of depression at the time of their fMRI scans but who subsequently developed clinically significant symptoms of depression, relative to children with no depressive symptoms at any study time point, the researchers found.
 

 

 

Immediate Clinical Impact?

Reached for comment, Shaheen Lakhan, MD, PhD, neurologist and researcher based in Miami, said this research “exemplifies the promising intersection of neurology and digital health, where advanced neuroimaging and data-driven approaches can transform mental health care into a more precise and individualized practice,” Dr. Lakhan said. “By identifying this brain network expansion, we’re unlocking new possibilities for precision medicine in mental health.”

Dr. Lakhan, who wasn’t involved in this research, said identifying the expansion of the frontostriatal salience network in individuals with depression opens new avenues for developing novel therapeutics.

“By targeting this network through neuromodulation techniques like deep brain stimulation, transcranial magnetic stimulation, and prescription digital therapeutics, treatments can be more precisely tailored to individual neurobiological profiles,” Dr. Lakhan said. “Additionally, this network expansion could serve as a biomarker for early detection, allowing for preventive strategies or personalized treatment plans, particularly for those at risk of developing depression.”

In addition, a greater understanding of the mechanisms driving salience network expansion offers potential for discovering new pharmacological targets, Dr. Lakhan noted.

“Drugs that modulate synaptic plasticity or network connectivity might be developed to reverse or mitigate these neural changes. The findings also support the use of longitudinal monitoring to predict and preempt symptom emergence, improving outcomes through timely intervention. This research paves the way for more personalized, precise, and proactive approaches in treating depression,” Dr. Lakhan concluded.

Also weighing in, Teddy Akiki, MD, with the Department of Psychiatry and Behavioral Sciences at Stanford Medicine in California, noted that the effect size of the frontostriatal salience network difference in depression is “remarkably larger than typically seen in neuroimaging studies of depression, which often describe subtle differences. The consistency across multiple datasets and across time at the individual level adds significant weight to these findings, suggesting that it is a trait marker rather than a state-dependent marker.”

“The observation that this expansion is present even before the onset of depressive symptoms in adolescence suggests its potential as a biomarker for depression risk,” Dr. Akiki said. “This approach could lead to earlier identification of at-risk individuals and potentially inform the development of targeted preventive interventions.”

He cautioned that it remains to be seen whether interventions targeting the salience network can effectively prevent or treat depression.

This research was supported in part by the National Institute of Mental Health, the National Institute on Drug Addiction, the Hope for Depression Research Foundation, and the Foundation for OCD Research. Dr. Lynch and a coauthor are listed as inventors for Cornell University patent applications on neuroimaging biomarkers for depression which are pending or in preparation. Dr. Liston has served as a scientific advisor or consultant to Compass Pathways PLC, Delix Therapeutics, and Brainify.AI. Dr. Lakhan and Dr. Akiki had no relevant disclosures.

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

Researchers have discovered that a brain network involved in reward processing and attention to stimuli is markedly bigger in people with depression, remains stable over time, is unaffected by mood changes, and can be detected in children before onset of depression symptoms.

Using a novel brain-mapping technique, researchers found that the frontostriatal salience network was expanded nearly twofold in the brains of most individuals studied with depression compared with controls.

“This expansion in cortex was trait-like, meaning it was stable over time and did not change as symptoms changed over time,” said lead author Charles Lynch, PhD, assistant professor of neuroscience, Department of Psychiatry, Weill Cornell Medicine in New York.

It could also be detected in children who later developed depression, suggesting it may serve as a biomarker of depression risk. Investigators said the findings could aid in prevention and early detection of depression, as well as the development of more personalized treatment.

The study was published online in Nature.
 

Prewired for Depression?

Precision functional mapping is a relatively new approach to brain mapping in individuals that uses large amounts of fMRI data from hours of scans per person. The technique has been used to show differences in brain networks between and in healthy individuals but had not been used to study brain networks in people with depression.

“We leveraged our large longitudinal datasets — with many hours of functional MRI scanning per subject — to construct individual-specific maps of functional brain networks in each patient using precision functional mapping, instead of relying on group average,” Dr. Lynch said.

In the primary analysis of 141 adults with major depression and 37 healthy controls, the frontostriatal salience network — which is involved in reward processing and attention to internal and external stimuli — was markedly larger in these individuals with depression.

“This is one of the first times these kinds of personalized maps have been created in individuals with depression, and this is how we first observed of the salience network being larger in individuals with depression,” Dr. Lynch said.

In four of the six individuals, the salience network was expanded more than twofold, outside the range observed in all 37 healthy controls. On average, the salience network occupied 73% more of the cortical surface relative to the average in healthy controls.

The findings were replicated using independent samples of repeatedly sampled individuals with depression and in large-scale group average data.

The expansion of the salience network did not change over time and was unaffected by changes in mood state.

“These observations led us to propose that instead of driving changes in depressive symptoms over time, salience network expansion may be a stable marker of risk for developing depression,” the study team wrote.

An analysis of brain scans from 57 children who went on to develop depressive symptoms during adolescence and an equal number of children who did not develop depressive symptoms supports this theory.

On average, the salience network occupied roughly 36% more of cortex in the children with no current or previous symptoms of depression at the time of their fMRI scans but who subsequently developed clinically significant symptoms of depression, relative to children with no depressive symptoms at any study time point, the researchers found.
 

 

 

Immediate Clinical Impact?

Reached for comment, Shaheen Lakhan, MD, PhD, neurologist and researcher based in Miami, said this research “exemplifies the promising intersection of neurology and digital health, where advanced neuroimaging and data-driven approaches can transform mental health care into a more precise and individualized practice,” Dr. Lakhan said. “By identifying this brain network expansion, we’re unlocking new possibilities for precision medicine in mental health.”

Dr. Lakhan, who wasn’t involved in this research, said identifying the expansion of the frontostriatal salience network in individuals with depression opens new avenues for developing novel therapeutics.

“By targeting this network through neuromodulation techniques like deep brain stimulation, transcranial magnetic stimulation, and prescription digital therapeutics, treatments can be more precisely tailored to individual neurobiological profiles,” Dr. Lakhan said. “Additionally, this network expansion could serve as a biomarker for early detection, allowing for preventive strategies or personalized treatment plans, particularly for those at risk of developing depression.”

In addition, a greater understanding of the mechanisms driving salience network expansion offers potential for discovering new pharmacological targets, Dr. Lakhan noted.

“Drugs that modulate synaptic plasticity or network connectivity might be developed to reverse or mitigate these neural changes. The findings also support the use of longitudinal monitoring to predict and preempt symptom emergence, improving outcomes through timely intervention. This research paves the way for more personalized, precise, and proactive approaches in treating depression,” Dr. Lakhan concluded.

Also weighing in, Teddy Akiki, MD, with the Department of Psychiatry and Behavioral Sciences at Stanford Medicine in California, noted that the effect size of the frontostriatal salience network difference in depression is “remarkably larger than typically seen in neuroimaging studies of depression, which often describe subtle differences. The consistency across multiple datasets and across time at the individual level adds significant weight to these findings, suggesting that it is a trait marker rather than a state-dependent marker.”

“The observation that this expansion is present even before the onset of depressive symptoms in adolescence suggests its potential as a biomarker for depression risk,” Dr. Akiki said. “This approach could lead to earlier identification of at-risk individuals and potentially inform the development of targeted preventive interventions.”

He cautioned that it remains to be seen whether interventions targeting the salience network can effectively prevent or treat depression.

This research was supported in part by the National Institute of Mental Health, the National Institute on Drug Addiction, the Hope for Depression Research Foundation, and the Foundation for OCD Research. Dr. Lynch and a coauthor are listed as inventors for Cornell University patent applications on neuroimaging biomarkers for depression which are pending or in preparation. Dr. Liston has served as a scientific advisor or consultant to Compass Pathways PLC, Delix Therapeutics, and Brainify.AI. Dr. Lakhan and Dr. Akiki had no relevant disclosures.

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

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