Neurology

DALLAS – Low or undetectable levels of teriflunomide (Aubagio) occur in women who are sexually active with men taking the drug for relapsing multiple sclerosis, results from a small study demonstrated.

Doug Brunk/MDedge News

“One of the issues with this particular drug is that it carries a strong pregnancy warning because in animal studies the drug has been teratogenic,” Joseph B. Guarnaccia, MD, said in an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “The other issue is that it remains detectable in the body for some time. The issue of females taking this drug and conception are well known. There are strong warnings that, if a woman wants to become pregnant, the drug should be removed quickly from the system. But if their male partner is on the drug, does that pose a risk to their female partner? That question has never been addressed in a human study.”

The Food and Drug Administration prescribing information recommends that men wishing to father a child should discontinue use of teriflunomide and undergo the accelerated elimination procedure. It also recommends that female partners wishing to become pregnant should discontinue the drug and undergo an accelerated elimination procedure to verify that the plasma teriflunomide concentration is less than 0.020 mcg/mL.

In an effort to test the risk of female exposure to potentially teratogenic levels of teriflunomide through sexual intercourse, Dr. Guarnaccia, a neurologist with the Multiple Sclerosis Treatment Center at Griffin Hospital in Derby, Conn., and his colleagues recruited 10 couples and compared serum levels of teriflunomide in men with relapsing multiple sclerosis with those of their female partners. Enrollment criteria for men included a diagnosis of relapsing multiple sclerosis, age between 18 and 55 years, treatment with teriflunomide for at least 2 months prior to study entry, and frequency of sexual intercourse with their female partners at least twice a month. Pregnancy was excluded in females, and couples could not use barrier or withdrawal methods of contraception. The couples completed a brief questionnaire and underwent a one-time blood draw for teriflunomide levels either at the investigator’s office or at a LabCorp facility.

The mean age of study participants was 47 years and the mean frequency of intercourse was seven episodes per month. The mean teriflunomide concentration in men was 42.30 mcg/mL (ranged from 10.07 to 142.84 mcg/mL). Six women had teriflunomide below detection levels (0.020 mcg/mL). However, four women had detectable levels that averaged 0.045 mcg/mL (ranging from 0.022 to 0.077 mcg/mL).

“This small study demonstrates that low or undetectable levels of teriflunomide occur in females who are sexually active with males taking teriflunomide for relapsing multiple sclerosis,” the researchers wrote in their poster. They found that women who had low detectable levels of teriflunomide, compared with women with undetectable levels, did not engage in more frequent sexual intercourse nor were their levels associated with higher levels of teriflunomide in their male partners.

“Indeed, one might have expected a positive correlation between serum levels of teriflunomide in females and the frequency or concentration of inoculation in semen from their partners,” the researchers wrote. “While semen levels of teriflunomide were not measured in this study, it might be assumed that serum and semen concentrations of small molecules like teriflunomide are similar.”

The study was supported by a investigator-sponsored research grant from Sanofi-Genzyme. Dr. Guarnaccia reported that he has received speaking honoraria and educational grants from Sanofi-Genzyme, Biogen, Teva, Acorda Therapeutics, Bayer, EMD Serono, and Genentech.

[email protected]

SOURCE: Guarnaccia JB et al. ACTRIMS Forum 2019, Poster 115.

DALLAS – Low or undetectable levels of teriflunomide (Aubagio) occur in women who are sexually active with men taking the drug for relapsing multiple sclerosis, results from a small study demonstrated.

Doug Brunk/MDedge News

“One of the issues with this particular drug is that it carries a strong pregnancy warning because in animal studies the drug has been teratogenic,” Joseph B. Guarnaccia, MD, said in an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “The other issue is that it remains detectable in the body for some time. The issue of females taking this drug and conception are well known. There are strong warnings that, if a woman wants to become pregnant, the drug should be removed quickly from the system. But if their male partner is on the drug, does that pose a risk to their female partner? That question has never been addressed in a human study.”

The Food and Drug Administration prescribing information recommends that men wishing to father a child should discontinue use of teriflunomide and undergo the accelerated elimination procedure. It also recommends that female partners wishing to become pregnant should discontinue the drug and undergo an accelerated elimination procedure to verify that the plasma teriflunomide concentration is less than 0.020 mcg/mL.

In an effort to test the risk of female exposure to potentially teratogenic levels of teriflunomide through sexual intercourse, Dr. Guarnaccia, a neurologist with the Multiple Sclerosis Treatment Center at Griffin Hospital in Derby, Conn., and his colleagues recruited 10 couples and compared serum levels of teriflunomide in men with relapsing multiple sclerosis with those of their female partners. Enrollment criteria for men included a diagnosis of relapsing multiple sclerosis, age between 18 and 55 years, treatment with teriflunomide for at least 2 months prior to study entry, and frequency of sexual intercourse with their female partners at least twice a month. Pregnancy was excluded in females, and couples could not use barrier or withdrawal methods of contraception. The couples completed a brief questionnaire and underwent a one-time blood draw for teriflunomide levels either at the investigator’s office or at a LabCorp facility.

The mean age of study participants was 47 years and the mean frequency of intercourse was seven episodes per month. The mean teriflunomide concentration in men was 42.30 mcg/mL (ranged from 10.07 to 142.84 mcg/mL). Six women had teriflunomide below detection levels (0.020 mcg/mL). However, four women had detectable levels that averaged 0.045 mcg/mL (ranging from 0.022 to 0.077 mcg/mL).

“This small study demonstrates that low or undetectable levels of teriflunomide occur in females who are sexually active with males taking teriflunomide for relapsing multiple sclerosis,” the researchers wrote in their poster. They found that women who had low detectable levels of teriflunomide, compared with women with undetectable levels, did not engage in more frequent sexual intercourse nor were their levels associated with higher levels of teriflunomide in their male partners.

“Indeed, one might have expected a positive correlation between serum levels of teriflunomide in females and the frequency or concentration of inoculation in semen from their partners,” the researchers wrote. “While semen levels of teriflunomide were not measured in this study, it might be assumed that serum and semen concentrations of small molecules like teriflunomide are similar.”

The study was supported by a investigator-sponsored research grant from Sanofi-Genzyme. Dr. Guarnaccia reported that he has received speaking honoraria and educational grants from Sanofi-Genzyme, Biogen, Teva, Acorda Therapeutics, Bayer, EMD Serono, and Genentech.

[email protected]

SOURCE: Guarnaccia JB et al. ACTRIMS Forum 2019, Poster 115.

DALLAS – Low or undetectable levels of teriflunomide (Aubagio) occur in women who are sexually active with men taking the drug for relapsing multiple sclerosis, results from a small study demonstrated.

Doug Brunk/MDedge News

“One of the issues with this particular drug is that it carries a strong pregnancy warning because in animal studies the drug has been teratogenic,” Joseph B. Guarnaccia, MD, said in an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “The other issue is that it remains detectable in the body for some time. The issue of females taking this drug and conception are well known. There are strong warnings that, if a woman wants to become pregnant, the drug should be removed quickly from the system. But if their male partner is on the drug, does that pose a risk to their female partner? That question has never been addressed in a human study.”

The Food and Drug Administration prescribing information recommends that men wishing to father a child should discontinue use of teriflunomide and undergo the accelerated elimination procedure. It also recommends that female partners wishing to become pregnant should discontinue the drug and undergo an accelerated elimination procedure to verify that the plasma teriflunomide concentration is less than 0.020 mcg/mL.

In an effort to test the risk of female exposure to potentially teratogenic levels of teriflunomide through sexual intercourse, Dr. Guarnaccia, a neurologist with the Multiple Sclerosis Treatment Center at Griffin Hospital in Derby, Conn., and his colleagues recruited 10 couples and compared serum levels of teriflunomide in men with relapsing multiple sclerosis with those of their female partners. Enrollment criteria for men included a diagnosis of relapsing multiple sclerosis, age between 18 and 55 years, treatment with teriflunomide for at least 2 months prior to study entry, and frequency of sexual intercourse with their female partners at least twice a month. Pregnancy was excluded in females, and couples could not use barrier or withdrawal methods of contraception. The couples completed a brief questionnaire and underwent a one-time blood draw for teriflunomide levels either at the investigator’s office or at a LabCorp facility.

The mean age of study participants was 47 years and the mean frequency of intercourse was seven episodes per month. The mean teriflunomide concentration in men was 42.30 mcg/mL (ranged from 10.07 to 142.84 mcg/mL). Six women had teriflunomide below detection levels (0.020 mcg/mL). However, four women had detectable levels that averaged 0.045 mcg/mL (ranging from 0.022 to 0.077 mcg/mL).

“This small study demonstrates that low or undetectable levels of teriflunomide occur in females who are sexually active with males taking teriflunomide for relapsing multiple sclerosis,” the researchers wrote in their poster. They found that women who had low detectable levels of teriflunomide, compared with women with undetectable levels, did not engage in more frequent sexual intercourse nor were their levels associated with higher levels of teriflunomide in their male partners.

“Indeed, one might have expected a positive correlation between serum levels of teriflunomide in females and the frequency or concentration of inoculation in semen from their partners,” the researchers wrote. “While semen levels of teriflunomide were not measured in this study, it might be assumed that serum and semen concentrations of small molecules like teriflunomide are similar.”

The study was supported by a investigator-sponsored research grant from Sanofi-Genzyme. Dr. Guarnaccia reported that he has received speaking honoraria and educational grants from Sanofi-Genzyme, Biogen, Teva, Acorda Therapeutics, Bayer, EMD Serono, and Genentech.

[email protected]

SOURCE: Guarnaccia JB et al. ACTRIMS Forum 2019, Poster 115.

Clinical trials represent future hope for patients seeking better care, and there is no disease more in need of better care than Alzheimer’s disease. While death rates among most cancers, as well as heart disease, HIV-related illness, and other categories, have declined in the past decade, there has been no progress for Alzheimer’s disease. Better health and wellness overall may be having a beneficial effect that has produced a reduction in age-adjusted dementia rates, but with the aging of the population there are a greater absolute number of dementia cases than ever before, and that number is expected to continue rising. Finding a disease-modifying therapy seems to be the best hope for changing this dim outlook. Clinical trials intend to do just that but are hampered by patient enrollment rates that remain low. Far fewer eligible patients enroll than are needed, causing studies to take longer to complete, driving up their costs and essentially slowing progress. There is a need to increase patient enrollment, and there has been a variety of efforts intended to address this, not the least of which has been an explosion of media coverage of Alzheimer’s disease.

The Global Alzheimer’s Platform (GAP) Foundation, a nonprofit, self-described patient-centric entity dedicated to reducing the time and cost of Alzheimer’s disease clinical trials, recently announced an initiative to increase participation in Alzheimer’s clinical trials by supporting and collaborating with “memory fitness programs” through select Medicare Advantage plans. At worst, this seems a harmless way to increase attention and hopefully interest in clinical trial participation. At best, this may be a cost-effective way to increase enrollment and even improve dementia care. Dementia is notoriously underdiagnosed, especially by overworked, busy primary care providers who simply lack the time to perform the time-consuming testing that is typically required to diagnose and follow such patients.

There are some caveats to consider. First, memory fitness programs are of dubious benefit. They generally fit the description of being harmless, but there is little compelling evidence that they preserve or improve memory.

Second, enrollment in a clinical trial, for a patient, is not always a winning proposition. To date, there has been little success and in the absence of benefit, any downside – even if simply an inconvenience – is a net negative. Recently at the 2018 Clinical Trials on Alzheimer’s Disease meeting, Merck reported that patients with mild cognitive impairment receiving active treatment in the BACE1 inhibitor verubecestat trial actually declined at a more rapid rate than did those on placebo. While the absolute difference was small, and one could argue whether it was clinically significant or simply a random occurrence, it was a reminder that intervention with an experimental agent is not necessarily benign.

Third, Medicare Advantage plans, while popular in some circles, are not considered advantageous to providers so that the proliferation of inadequate reimbursement will potentially fuel the accelerating number of providers who opt out of insurance plans altogether. This is not necessarily an issue for the GAP Foundation specifically but is nonetheless an issue for anything that promotes MA plans).

Finally, it remains important to help patients and families maintain a positive outlook, especially when we have nothing better to offer. Alzheimer’s disease is not a death sentence for every patient affected. While many have difficult and heartbreaking courses, some have slowly progressive courses with relatively little impairment for an extended period of time. There are also the dementia-phobic, cognitively unimpaired individuals (or who simply have normal age-associated cognitive changes) in whom the continued drumbeat of dementia awareness and memory testing raises their paranoia ever higher. We treat deficits (or try to), but we have to live based on our preserved skills. The challenge clinicians must face with patients and families is how to maximize function while compensating for deficits and making sure that patients and families maintain their hope.

Dr. Caselli is professor of neurology at the Mayo Clinic Arizona in Scottsdale and associate director and clinical core director of the Arizona Alzheimer’s Disease Center.

Clinical trials represent future hope for patients seeking better care, and there is no disease more in need of better care than Alzheimer’s disease. While death rates among most cancers, as well as heart disease, HIV-related illness, and other categories, have declined in the past decade, there has been no progress for Alzheimer’s disease. Better health and wellness overall may be having a beneficial effect that has produced a reduction in age-adjusted dementia rates, but with the aging of the population there are a greater absolute number of dementia cases than ever before, and that number is expected to continue rising. Finding a disease-modifying therapy seems to be the best hope for changing this dim outlook. Clinical trials intend to do just that but are hampered by patient enrollment rates that remain low. Far fewer eligible patients enroll than are needed, causing studies to take longer to complete, driving up their costs and essentially slowing progress. There is a need to increase patient enrollment, and there has been a variety of efforts intended to address this, not the least of which has been an explosion of media coverage of Alzheimer’s disease.

The Global Alzheimer’s Platform (GAP) Foundation, a nonprofit, self-described patient-centric entity dedicated to reducing the time and cost of Alzheimer’s disease clinical trials, recently announced an initiative to increase participation in Alzheimer’s clinical trials by supporting and collaborating with “memory fitness programs” through select Medicare Advantage plans. At worst, this seems a harmless way to increase attention and hopefully interest in clinical trial participation. At best, this may be a cost-effective way to increase enrollment and even improve dementia care. Dementia is notoriously underdiagnosed, especially by overworked, busy primary care providers who simply lack the time to perform the time-consuming testing that is typically required to diagnose and follow such patients.

There are some caveats to consider. First, memory fitness programs are of dubious benefit. They generally fit the description of being harmless, but there is little compelling evidence that they preserve or improve memory.

Second, enrollment in a clinical trial, for a patient, is not always a winning proposition. To date, there has been little success and in the absence of benefit, any downside – even if simply an inconvenience – is a net negative. Recently at the 2018 Clinical Trials on Alzheimer’s Disease meeting, Merck reported that patients with mild cognitive impairment receiving active treatment in the BACE1 inhibitor verubecestat trial actually declined at a more rapid rate than did those on placebo. While the absolute difference was small, and one could argue whether it was clinically significant or simply a random occurrence, it was a reminder that intervention with an experimental agent is not necessarily benign.

Third, Medicare Advantage plans, while popular in some circles, are not considered advantageous to providers so that the proliferation of inadequate reimbursement will potentially fuel the accelerating number of providers who opt out of insurance plans altogether. This is not necessarily an issue for the GAP Foundation specifically but is nonetheless an issue for anything that promotes MA plans).

Finally, it remains important to help patients and families maintain a positive outlook, especially when we have nothing better to offer. Alzheimer’s disease is not a death sentence for every patient affected. While many have difficult and heartbreaking courses, some have slowly progressive courses with relatively little impairment for an extended period of time. There are also the dementia-phobic, cognitively unimpaired individuals (or who simply have normal age-associated cognitive changes) in whom the continued drumbeat of dementia awareness and memory testing raises their paranoia ever higher. We treat deficits (or try to), but we have to live based on our preserved skills. The challenge clinicians must face with patients and families is how to maximize function while compensating for deficits and making sure that patients and families maintain their hope.

Dr. Caselli is professor of neurology at the Mayo Clinic Arizona in Scottsdale and associate director and clinical core director of the Arizona Alzheimer’s Disease Center.

Clinical trials represent future hope for patients seeking better care, and there is no disease more in need of better care than Alzheimer’s disease. While death rates among most cancers, as well as heart disease, HIV-related illness, and other categories, have declined in the past decade, there has been no progress for Alzheimer’s disease. Better health and wellness overall may be having a beneficial effect that has produced a reduction in age-adjusted dementia rates, but with the aging of the population there are a greater absolute number of dementia cases than ever before, and that number is expected to continue rising. Finding a disease-modifying therapy seems to be the best hope for changing this dim outlook. Clinical trials intend to do just that but are hampered by patient enrollment rates that remain low. Far fewer eligible patients enroll than are needed, causing studies to take longer to complete, driving up their costs and essentially slowing progress. There is a need to increase patient enrollment, and there has been a variety of efforts intended to address this, not the least of which has been an explosion of media coverage of Alzheimer’s disease.

The Global Alzheimer’s Platform (GAP) Foundation, a nonprofit, self-described patient-centric entity dedicated to reducing the time and cost of Alzheimer’s disease clinical trials, recently announced an initiative to increase participation in Alzheimer’s clinical trials by supporting and collaborating with “memory fitness programs” through select Medicare Advantage plans. At worst, this seems a harmless way to increase attention and hopefully interest in clinical trial participation. At best, this may be a cost-effective way to increase enrollment and even improve dementia care. Dementia is notoriously underdiagnosed, especially by overworked, busy primary care providers who simply lack the time to perform the time-consuming testing that is typically required to diagnose and follow such patients.

There are some caveats to consider. First, memory fitness programs are of dubious benefit. They generally fit the description of being harmless, but there is little compelling evidence that they preserve or improve memory.

Second, enrollment in a clinical trial, for a patient, is not always a winning proposition. To date, there has been little success and in the absence of benefit, any downside – even if simply an inconvenience – is a net negative. Recently at the 2018 Clinical Trials on Alzheimer’s Disease meeting, Merck reported that patients with mild cognitive impairment receiving active treatment in the BACE1 inhibitor verubecestat trial actually declined at a more rapid rate than did those on placebo. While the absolute difference was small, and one could argue whether it was clinically significant or simply a random occurrence, it was a reminder that intervention with an experimental agent is not necessarily benign.

Third, Medicare Advantage plans, while popular in some circles, are not considered advantageous to providers so that the proliferation of inadequate reimbursement will potentially fuel the accelerating number of providers who opt out of insurance plans altogether. This is not necessarily an issue for the GAP Foundation specifically but is nonetheless an issue for anything that promotes MA plans).

Finally, it remains important to help patients and families maintain a positive outlook, especially when we have nothing better to offer. Alzheimer’s disease is not a death sentence for every patient affected. While many have difficult and heartbreaking courses, some have slowly progressive courses with relatively little impairment for an extended period of time. There are also the dementia-phobic, cognitively unimpaired individuals (or who simply have normal age-associated cognitive changes) in whom the continued drumbeat of dementia awareness and memory testing raises their paranoia ever higher. We treat deficits (or try to), but we have to live based on our preserved skills. The challenge clinicians must face with patients and families is how to maximize function while compensating for deficits and making sure that patients and families maintain their hope.

Dr. Caselli is professor of neurology at the Mayo Clinic Arizona in Scottsdale and associate director and clinical core director of the Arizona Alzheimer’s Disease Center.

A recently developed blood-based signature can help predict the status of an early Alzheimer’s disease risk indicator with high accuracy, investigators are reporting.

Courtesy NIH

By analyzing as few as four proteins, the machine learning-derived test can predict the status of cerebrospinal fluid (CSF) amyloid beta_1-42 (Abeta1-42), according to Noel G. Faux, PHD, of IBM Australia and the University of Melbourne, and co-investigators.

While shifts in Abeta1-42 may signal the presence of disease long before significant cognitive decline is clinically apparent, collection of CSF is highly invasive and expensive, Faux and investigators said in their report.

By contrast, blood biomarkers could prove to be a useful alternative not only to invasive lumbar punctures, they said, but also to the positron emission tomography (PET) evaluation of Abeta1-42, which is expensive and limited in some regions.

“In conjunction with biomarkers for neocortical amyloid burden, the CSF Abeta1-42biomarkers presented in this work may help yield a cheap, non-invasive tool for both improving clinical trials targeting amyloid and population screening,” Dr. Faux and co-authors said in Scientific Reports.

Dr. Faux and colleagues used a Random Forest approach to build models for CSF Abeta1-42 using blood biomarkers and other variables.

They found that a model incorporating age, APOEe4 carrier status, and a number of plasma protein levels predicted Abeta1-42 normal/abnormalstatus with an AUC, sensitivity and specificity of 0.84, 0.78 and 0.73 respectively.

In a model they said was more suitable for clinical application, they narrowed down the variables to 4 plasma analytes and APOEe4 carrier status, which had an AUC, sensitivity, and specificity of 0.81, 0.81 and 0.64 respectively.

They validated the models on a cohort of individuals in the Alzheimer’s Disease Neuroimaging Initiative (ADNI), a large, longitudinal, multicenter study.

Patients with mild cognitive impairment with predicted abnormal CSF Abeta1-42 levels indeed did transition to a diagnosis of Alzheimer’s disease more quickly than those with predicted normal levels, according to investigators.

That helps provide “strong evidence” that the blood-based model is generalizable, robust, and could help stratify patients based on risk of progressing to Alzheimer’s disease, they said in their report.

Dr. Faux and colleagues declared no conflicts of interest related to the research.
 

SOURCE: Goudey B, et al. Sci Rep. 2019 Mar 10. doi: 10.1101/190207v3.

A recently developed blood-based signature can help predict the status of an early Alzheimer’s disease risk indicator with high accuracy, investigators are reporting.

Courtesy NIH

By analyzing as few as four proteins, the machine learning-derived test can predict the status of cerebrospinal fluid (CSF) amyloid beta_1-42 (Abeta1-42), according to Noel G. Faux, PHD, of IBM Australia and the University of Melbourne, and co-investigators.

While shifts in Abeta1-42 may signal the presence of disease long before significant cognitive decline is clinically apparent, collection of CSF is highly invasive and expensive, Faux and investigators said in their report.

By contrast, blood biomarkers could prove to be a useful alternative not only to invasive lumbar punctures, they said, but also to the positron emission tomography (PET) evaluation of Abeta1-42, which is expensive and limited in some regions.

“In conjunction with biomarkers for neocortical amyloid burden, the CSF Abeta1-42biomarkers presented in this work may help yield a cheap, non-invasive tool for both improving clinical trials targeting amyloid and population screening,” Dr. Faux and co-authors said in Scientific Reports.

Dr. Faux and colleagues used a Random Forest approach to build models for CSF Abeta1-42 using blood biomarkers and other variables.

They found that a model incorporating age, APOEe4 carrier status, and a number of plasma protein levels predicted Abeta1-42 normal/abnormalstatus with an AUC, sensitivity and specificity of 0.84, 0.78 and 0.73 respectively.

In a model they said was more suitable for clinical application, they narrowed down the variables to 4 plasma analytes and APOEe4 carrier status, which had an AUC, sensitivity, and specificity of 0.81, 0.81 and 0.64 respectively.

They validated the models on a cohort of individuals in the Alzheimer’s Disease Neuroimaging Initiative (ADNI), a large, longitudinal, multicenter study.

Patients with mild cognitive impairment with predicted abnormal CSF Abeta1-42 levels indeed did transition to a diagnosis of Alzheimer’s disease more quickly than those with predicted normal levels, according to investigators.

That helps provide “strong evidence” that the blood-based model is generalizable, robust, and could help stratify patients based on risk of progressing to Alzheimer’s disease, they said in their report.

Dr. Faux and colleagues declared no conflicts of interest related to the research.
 

SOURCE: Goudey B, et al. Sci Rep. 2019 Mar 10. doi: 10.1101/190207v3.

A recently developed blood-based signature can help predict the status of an early Alzheimer’s disease risk indicator with high accuracy, investigators are reporting.

Courtesy NIH

By analyzing as few as four proteins, the machine learning-derived test can predict the status of cerebrospinal fluid (CSF) amyloid beta_1-42 (Abeta1-42), according to Noel G. Faux, PHD, of IBM Australia and the University of Melbourne, and co-investigators.

While shifts in Abeta1-42 may signal the presence of disease long before significant cognitive decline is clinically apparent, collection of CSF is highly invasive and expensive, Faux and investigators said in their report.

By contrast, blood biomarkers could prove to be a useful alternative not only to invasive lumbar punctures, they said, but also to the positron emission tomography (PET) evaluation of Abeta1-42, which is expensive and limited in some regions.

“In conjunction with biomarkers for neocortical amyloid burden, the CSF Abeta1-42biomarkers presented in this work may help yield a cheap, non-invasive tool for both improving clinical trials targeting amyloid and population screening,” Dr. Faux and co-authors said in Scientific Reports.

Dr. Faux and colleagues used a Random Forest approach to build models for CSF Abeta1-42 using blood biomarkers and other variables.

They found that a model incorporating age, APOEe4 carrier status, and a number of plasma protein levels predicted Abeta1-42 normal/abnormalstatus with an AUC, sensitivity and specificity of 0.84, 0.78 and 0.73 respectively.

In a model they said was more suitable for clinical application, they narrowed down the variables to 4 plasma analytes and APOEe4 carrier status, which had an AUC, sensitivity, and specificity of 0.81, 0.81 and 0.64 respectively.

They validated the models on a cohort of individuals in the Alzheimer’s Disease Neuroimaging Initiative (ADNI), a large, longitudinal, multicenter study.

Patients with mild cognitive impairment with predicted abnormal CSF Abeta1-42 levels indeed did transition to a diagnosis of Alzheimer’s disease more quickly than those with predicted normal levels, according to investigators.

That helps provide “strong evidence” that the blood-based model is generalizable, robust, and could help stratify patients based on risk of progressing to Alzheimer’s disease, they said in their report.

Dr. Faux and colleagues declared no conflicts of interest related to the research.
 

SOURCE: Goudey B, et al. Sci Rep. 2019 Mar 10. doi: 10.1101/190207v3.

DALLAS – Of 95 patients referred to two multiple sclerosis (MS) centers for a possible diagnosis of MS, 74% did not have MS, according to a study presented at ACTRIMS Forum 2019. A majority had clinical syndromes or imaging findings that are atypical for MS, which “underscores the importance of familiarity with typical MS clinical and imaging findings in avoiding misdiagnosis,” said Marwa Kaisey, MD, and her research colleagues. Dr. Kaisey is a neurologist at Cedars-Sinai Medical Center in Los Angeles.

designer491/Thinkstock

Physicians often refer patients to academic MS centers to determine whether patients have MS or one of its many mimics. To study the characteristics and final diagnoses of patients referred to MS centers for evaluation of possible MS, the investigators reviewed electronic medical records and MRI from all new patient evaluations at the Cedars-Sinai Medical Center and University of California, Los Angeles MS clinics between July 2016 and June 2017. The researchers excluded patients referred with a previously established diagnosis of MS.

There were 366 new patients evaluated, including 236 patients with previously established MS diagnoses and 35 patients whose evaluations were not related to MS. Of the 95 patients referred for a question of MS diagnosis, 60% had clinical syndromes that were atypical for MS, 22% had normal neurologic exams, and a third had pain or sensory changes that were not localizable to the CNS.

Sixty-seven percent had MRI that was atypical for MS, and nearly half of the patients without MS had nonspecific MRI changes. “Often, these MRI changes alone prompted referral for an MS evaluation,” Dr. Kaisey and colleagues reported. “This suggests that novel, specific imaging tools may increase diagnostic confidence in the clinical setting.”

In all, the referred patients received 28 diagnoses other than MS, most commonly migraine (10 patients), anxiety or conversion disorder (9), postinfectious or idiopathic transverse myelitis (8), compression myelopathy or spondylopathy (8), and peripheral neuropathy or radiculopathy (7).

The researchers did not have any relevant disclosures.

[email protected]

SOURCE: Kaisey M et al. ACTRIMS Forum 2019, Abstract 90.

DALLAS – Of 95 patients referred to two multiple sclerosis (MS) centers for a possible diagnosis of MS, 74% did not have MS, according to a study presented at ACTRIMS Forum 2019. A majority had clinical syndromes or imaging findings that are atypical for MS, which “underscores the importance of familiarity with typical MS clinical and imaging findings in avoiding misdiagnosis,” said Marwa Kaisey, MD, and her research colleagues. Dr. Kaisey is a neurologist at Cedars-Sinai Medical Center in Los Angeles.

designer491/Thinkstock

Physicians often refer patients to academic MS centers to determine whether patients have MS or one of its many mimics. To study the characteristics and final diagnoses of patients referred to MS centers for evaluation of possible MS, the investigators reviewed electronic medical records and MRI from all new patient evaluations at the Cedars-Sinai Medical Center and University of California, Los Angeles MS clinics between July 2016 and June 2017. The researchers excluded patients referred with a previously established diagnosis of MS.

There were 366 new patients evaluated, including 236 patients with previously established MS diagnoses and 35 patients whose evaluations were not related to MS. Of the 95 patients referred for a question of MS diagnosis, 60% had clinical syndromes that were atypical for MS, 22% had normal neurologic exams, and a third had pain or sensory changes that were not localizable to the CNS.

Sixty-seven percent had MRI that was atypical for MS, and nearly half of the patients without MS had nonspecific MRI changes. “Often, these MRI changes alone prompted referral for an MS evaluation,” Dr. Kaisey and colleagues reported. “This suggests that novel, specific imaging tools may increase diagnostic confidence in the clinical setting.”

In all, the referred patients received 28 diagnoses other than MS, most commonly migraine (10 patients), anxiety or conversion disorder (9), postinfectious or idiopathic transverse myelitis (8), compression myelopathy or spondylopathy (8), and peripheral neuropathy or radiculopathy (7).

The researchers did not have any relevant disclosures.

[email protected]

SOURCE: Kaisey M et al. ACTRIMS Forum 2019, Abstract 90.

DALLAS – Of 95 patients referred to two multiple sclerosis (MS) centers for a possible diagnosis of MS, 74% did not have MS, according to a study presented at ACTRIMS Forum 2019. A majority had clinical syndromes or imaging findings that are atypical for MS, which “underscores the importance of familiarity with typical MS clinical and imaging findings in avoiding misdiagnosis,” said Marwa Kaisey, MD, and her research colleagues. Dr. Kaisey is a neurologist at Cedars-Sinai Medical Center in Los Angeles.

designer491/Thinkstock

Physicians often refer patients to academic MS centers to determine whether patients have MS or one of its many mimics. To study the characteristics and final diagnoses of patients referred to MS centers for evaluation of possible MS, the investigators reviewed electronic medical records and MRI from all new patient evaluations at the Cedars-Sinai Medical Center and University of California, Los Angeles MS clinics between July 2016 and June 2017. The researchers excluded patients referred with a previously established diagnosis of MS.

There were 366 new patients evaluated, including 236 patients with previously established MS diagnoses and 35 patients whose evaluations were not related to MS. Of the 95 patients referred for a question of MS diagnosis, 60% had clinical syndromes that were atypical for MS, 22% had normal neurologic exams, and a third had pain or sensory changes that were not localizable to the CNS.

Sixty-seven percent had MRI that was atypical for MS, and nearly half of the patients without MS had nonspecific MRI changes. “Often, these MRI changes alone prompted referral for an MS evaluation,” Dr. Kaisey and colleagues reported. “This suggests that novel, specific imaging tools may increase diagnostic confidence in the clinical setting.”

In all, the referred patients received 28 diagnoses other than MS, most commonly migraine (10 patients), anxiety or conversion disorder (9), postinfectious or idiopathic transverse myelitis (8), compression myelopathy or spondylopathy (8), and peripheral neuropathy or radiculopathy (7).

The researchers did not have any relevant disclosures.

[email protected]

SOURCE: Kaisey M et al. ACTRIMS Forum 2019, Abstract 90.

Children whose mothers experienced any type of infection during pregnancy were nearly 80 times more likely to be diagnosed with autism than those whose mothers did not have infections, based on data from more than one million children in Sweden.

Katarzyna Bialasiewicz/Thinkstock

Although previous studies have shown associations between specific infections in utero and specific conditions, such as schizophrenia, “Whether maternal infection and inflammation can alter fetal neurodevelopment to a degree that imparts risk for a broad spectrum of psychopathologic conditions across the child’s lifetime is unknown,” wrote Benjamin J. S. al-Haddad, MD, formerly of Seattle Children’s Hospital, Washington, currently with Doctors without Borders,Katiola, Côte d’Ivoire, and his colleagues.

In a study published In JAMA Psychiatry, the researchers followed 1,791,520 children (48.6% girls) born between Jan. 1, 1973, and Dec. 31, 2014, for up to 41 years using population-based registry data.

Overall, researchers found a 79% increased risk of an autism diagnosis (hazard ratio 1.79) and a 24% increased risk of a depression diagnosis (HR 1.24) for individuals exposed to any maternal infection in utero compared with those not exposed.

Similar increases in risk appeared when the data were broken down by type of infection. Hazard ratios for an autism diagnosis were 1.81 for exposure to a severe maternal infection and 1.89 for a maternal urinary tract infection; hazard ratios for depression were 1.24 and 1.30, respectively, for severe maternal infection and maternal urinary tract infection.

No increased risk in bipolar disorder, or other psychoses including schizophrenia were observed.

The findings were limited by several factors including the inclusion only of infections diagnosed in a hospital setting, and thus may not be generalizable to infections diagnosed in an outpatient setting, the researchers noted. However, the results “amplify the urgency to better understand the role of maternal infection during pregnancy on fetal brain development and suggest that prevention of infection (such as by influenza vaccination) or anti-inflammatory therapies may be important strategies for the primary prevention of some portion of autism and depression,” they said.

The researchers had no conflicts to disclose. The study was funded by grants from several organizations including the National Institutes of Health.

SOURCE: al-Haddad BJS et al. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2019.0029.

Children whose mothers experienced any type of infection during pregnancy were nearly 80 times more likely to be diagnosed with autism than those whose mothers did not have infections, based on data from more than one million children in Sweden.

Katarzyna Bialasiewicz/Thinkstock

Although previous studies have shown associations between specific infections in utero and specific conditions, such as schizophrenia, “Whether maternal infection and inflammation can alter fetal neurodevelopment to a degree that imparts risk for a broad spectrum of psychopathologic conditions across the child’s lifetime is unknown,” wrote Benjamin J. S. al-Haddad, MD, formerly of Seattle Children’s Hospital, Washington, currently with Doctors without Borders,Katiola, Côte d’Ivoire, and his colleagues.

In a study published In JAMA Psychiatry, the researchers followed 1,791,520 children (48.6% girls) born between Jan. 1, 1973, and Dec. 31, 2014, for up to 41 years using population-based registry data.

Overall, researchers found a 79% increased risk of an autism diagnosis (hazard ratio 1.79) and a 24% increased risk of a depression diagnosis (HR 1.24) for individuals exposed to any maternal infection in utero compared with those not exposed.

Similar increases in risk appeared when the data were broken down by type of infection. Hazard ratios for an autism diagnosis were 1.81 for exposure to a severe maternal infection and 1.89 for a maternal urinary tract infection; hazard ratios for depression were 1.24 and 1.30, respectively, for severe maternal infection and maternal urinary tract infection.

No increased risk in bipolar disorder, or other psychoses including schizophrenia were observed.

The findings were limited by several factors including the inclusion only of infections diagnosed in a hospital setting, and thus may not be generalizable to infections diagnosed in an outpatient setting, the researchers noted. However, the results “amplify the urgency to better understand the role of maternal infection during pregnancy on fetal brain development and suggest that prevention of infection (such as by influenza vaccination) or anti-inflammatory therapies may be important strategies for the primary prevention of some portion of autism and depression,” they said.

The researchers had no conflicts to disclose. The study was funded by grants from several organizations including the National Institutes of Health.

SOURCE: al-Haddad BJS et al. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2019.0029.

Children whose mothers experienced any type of infection during pregnancy were nearly 80 times more likely to be diagnosed with autism than those whose mothers did not have infections, based on data from more than one million children in Sweden.

Katarzyna Bialasiewicz/Thinkstock

Although previous studies have shown associations between specific infections in utero and specific conditions, such as schizophrenia, “Whether maternal infection and inflammation can alter fetal neurodevelopment to a degree that imparts risk for a broad spectrum of psychopathologic conditions across the child’s lifetime is unknown,” wrote Benjamin J. S. al-Haddad, MD, formerly of Seattle Children’s Hospital, Washington, currently with Doctors without Borders,Katiola, Côte d’Ivoire, and his colleagues.

In a study published In JAMA Psychiatry, the researchers followed 1,791,520 children (48.6% girls) born between Jan. 1, 1973, and Dec. 31, 2014, for up to 41 years using population-based registry data.

Overall, researchers found a 79% increased risk of an autism diagnosis (hazard ratio 1.79) and a 24% increased risk of a depression diagnosis (HR 1.24) for individuals exposed to any maternal infection in utero compared with those not exposed.

Similar increases in risk appeared when the data were broken down by type of infection. Hazard ratios for an autism diagnosis were 1.81 for exposure to a severe maternal infection and 1.89 for a maternal urinary tract infection; hazard ratios for depression were 1.24 and 1.30, respectively, for severe maternal infection and maternal urinary tract infection.

No increased risk in bipolar disorder, or other psychoses including schizophrenia were observed.

The findings were limited by several factors including the inclusion only of infections diagnosed in a hospital setting, and thus may not be generalizable to infections diagnosed in an outpatient setting, the researchers noted. However, the results “amplify the urgency to better understand the role of maternal infection during pregnancy on fetal brain development and suggest that prevention of infection (such as by influenza vaccination) or anti-inflammatory therapies may be important strategies for the primary prevention of some portion of autism and depression,” they said.

The researchers had no conflicts to disclose. The study was funded by grants from several organizations including the National Institutes of Health.

SOURCE: al-Haddad BJS et al. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2019.0029.

The total tau level in blood plasma appears to predict both onset and progression of dementia and could be used to help refine research cohorts.

Kheng Guan Toh/Thinkstock

Blood samples from two large dementia research cohorts confirmed the finding: Each standard deviation in plasma tau above the median is associated with a 29% greater risk of incident all-cause dementia and a 35%increase in the risk of incident Alzheimer’s disease, Matthew P. Pase, PhD and colleagues wrote in JAMA Neurology. It also correlated positively with some neuropathological aspects of dementia: smaller hippocampus and a higher burden of neurofibrillary tangles in the medial temporal lobe, said Dr. Pase of The Florey Institute for Neuroscience and Mental Health. Victoria, Australia.

Plasma tau isn’t the highly sought Holy Grail of a simple Alzheimer’s blood test. But the finding could benefit the research world. As a study entry criteria, it could substantially decrease the number of subjects needed to validate an outcome of either all-cause dementia or Alzheimer’s disease. Abnormal tau is also a required finding for an Alzheimer’s diagnosis in revised NIA-AA Research Framework. And, the authors noted, although plasma tau wasn’t quite as accurate a predictor as CSF tau, a needle in the arm would be much more acceptable to many more patients than a lumbar puncture.

“Whereas we do not expect plasma t-tau cutoffs to enhance diagnostic certainty for any single patient, our results suggest that plasma t-tau could be associated with improved risk stratification at a population level, targeting persons for inclusion in prevention trials, thus improving the power and precision of clinical trials and potentially accelerating therapeutic pipelines and drug discovery,” the team wrote.

The study drew on stored plasma samples from subjects enrolled in the Framingham Heart Study (1,453) and the Memento study, a multicenter cohort of persons with mild cognitive impairment or subjective cognitive complaints recruited from memory clinics across France (367).

The Framingham cohort was followed for up to 10 years between baseline examination to incident event (median 6 years).

Over that time, 134 (9.2%) cases of dementia developed; most of these (105) were due possible, probable, or definite Alzheimer’s.

Plasma tau levels rose linearly as the cohort aged. Higher plasma t-tau levels were associated with proven AD risk factors, including female sex, lower education, and higher vascular risk factors. They did not differ by apolipoprotein epsilon 4 status (APOEe4).

After adjusting for age and sex, each stand deviation unit increase in the log of tau was associated with a 29% greater risk of incident all-cause dementia, and a 35% increase in the risk of incident Alzheimer’s dementia. Subjects with tau levels above the median had a 62% increased risk of all-cause dementia and a 76% greater risk of AD. Adding APOEe4 status and vascular risk factors to the analysis didn’t alter the associations.

“Plasma t-tau level improved risk discrimination for all dementia and AD dementia beyond age and sex,” the investigators wrote. “[It] was associated with improved risk discrimination … in both APOEe4 carriers and noncarriers.”

In a hypothetical 5-year clinical trial, enrolling subjects with total plasma tau greater than the median could reduce the estimated necessary sample size by 38% for an outcome of all-cause dementia and by 50% for one of Alzheimer’s. Selecting those with both elevated plasma tau and APOEe4 carriage could reduce the required sample by 69% for all-cause dementia outcomes and by 80% for Alzheimer’s outcomes.

In the neuropathologic study, each standard deviation unit increase was associated with more neurofibrillary tangles in the medial temporal lobe, more microinfarcts, and smaller hippocampal volume. There was no association with amyloid plaque in any brain region.

Subjects in the Memento study had a meant of 4 years of follow-up. Over that time, there were 76 cases of incident dementia, 55 of which were probable Alzheimer’s.

Each standard deviation unit increase was associated with a nonsignificant 14% greater risk of all-cause dementia and a significant 54% increase in the risk of incident Alzheimer’s.

CSF was drawn on the same day as plasma in 140 of these subjects. The addition of CSF boosted the predictive value; each standard deviation increase more than doubled the risk of both Alzheimer’s (HR 2.33). Each standard deviation unit increase in CSF t-tau increased the risk by 2.14.

“Plasma t-tau was weakly correlated with CSF t-tau in our study. This finding is consistent

with previous studies showing that the associations of plasma t-tau with CSF t-tau have been weak or nonexistent,” the authors wrote. But, “Despite a weak correlation between plasma and CSF t-tau, plasma t-tau was at least as strongly associated with the development of incident AD dementia.”

“Use of plasma t-tau in this manner could be likened to the measurement of the APOEe4 allele, which is not a biomarker of AD pathology providing diagnostic certainty for AD dementia but is still routinely used to power clinical trials by selecting at-risk individuals,” they concluded.

Dr. Pase had no financial disclosures.

[email protected]

SOURCE: Pase, M et al JAMA Neurol 2019 doi:10.1001/jamaneurol.2018.4666

The total tau level in blood plasma appears to predict both onset and progression of dementia and could be used to help refine research cohorts.

Kheng Guan Toh/Thinkstock

Blood samples from two large dementia research cohorts confirmed the finding: Each standard deviation in plasma tau above the median is associated with a 29% greater risk of incident all-cause dementia and a 35%increase in the risk of incident Alzheimer’s disease, Matthew P. Pase, PhD and colleagues wrote in JAMA Neurology. It also correlated positively with some neuropathological aspects of dementia: smaller hippocampus and a higher burden of neurofibrillary tangles in the medial temporal lobe, said Dr. Pase of The Florey Institute for Neuroscience and Mental Health. Victoria, Australia.

Plasma tau isn’t the highly sought Holy Grail of a simple Alzheimer’s blood test. But the finding could benefit the research world. As a study entry criteria, it could substantially decrease the number of subjects needed to validate an outcome of either all-cause dementia or Alzheimer’s disease. Abnormal tau is also a required finding for an Alzheimer’s diagnosis in revised NIA-AA Research Framework. And, the authors noted, although plasma tau wasn’t quite as accurate a predictor as CSF tau, a needle in the arm would be much more acceptable to many more patients than a lumbar puncture.

“Whereas we do not expect plasma t-tau cutoffs to enhance diagnostic certainty for any single patient, our results suggest that plasma t-tau could be associated with improved risk stratification at a population level, targeting persons for inclusion in prevention trials, thus improving the power and precision of clinical trials and potentially accelerating therapeutic pipelines and drug discovery,” the team wrote.

The study drew on stored plasma samples from subjects enrolled in the Framingham Heart Study (1,453) and the Memento study, a multicenter cohort of persons with mild cognitive impairment or subjective cognitive complaints recruited from memory clinics across France (367).

The Framingham cohort was followed for up to 10 years between baseline examination to incident event (median 6 years).

Over that time, 134 (9.2%) cases of dementia developed; most of these (105) were due possible, probable, or definite Alzheimer’s.

Plasma tau levels rose linearly as the cohort aged. Higher plasma t-tau levels were associated with proven AD risk factors, including female sex, lower education, and higher vascular risk factors. They did not differ by apolipoprotein epsilon 4 status (APOEe4).

After adjusting for age and sex, each stand deviation unit increase in the log of tau was associated with a 29% greater risk of incident all-cause dementia, and a 35% increase in the risk of incident Alzheimer’s dementia. Subjects with tau levels above the median had a 62% increased risk of all-cause dementia and a 76% greater risk of AD. Adding APOEe4 status and vascular risk factors to the analysis didn’t alter the associations.

“Plasma t-tau level improved risk discrimination for all dementia and AD dementia beyond age and sex,” the investigators wrote. “[It] was associated with improved risk discrimination … in both APOEe4 carriers and noncarriers.”

In a hypothetical 5-year clinical trial, enrolling subjects with total plasma tau greater than the median could reduce the estimated necessary sample size by 38% for an outcome of all-cause dementia and by 50% for one of Alzheimer’s. Selecting those with both elevated plasma tau and APOEe4 carriage could reduce the required sample by 69% for all-cause dementia outcomes and by 80% for Alzheimer’s outcomes.

In the neuropathologic study, each standard deviation unit increase was associated with more neurofibrillary tangles in the medial temporal lobe, more microinfarcts, and smaller hippocampal volume. There was no association with amyloid plaque in any brain region.

Subjects in the Memento study had a meant of 4 years of follow-up. Over that time, there were 76 cases of incident dementia, 55 of which were probable Alzheimer’s.

Each standard deviation unit increase was associated with a nonsignificant 14% greater risk of all-cause dementia and a significant 54% increase in the risk of incident Alzheimer’s.

CSF was drawn on the same day as plasma in 140 of these subjects. The addition of CSF boosted the predictive value; each standard deviation increase more than doubled the risk of both Alzheimer’s (HR 2.33). Each standard deviation unit increase in CSF t-tau increased the risk by 2.14.

“Plasma t-tau was weakly correlated with CSF t-tau in our study. This finding is consistent

with previous studies showing that the associations of plasma t-tau with CSF t-tau have been weak or nonexistent,” the authors wrote. But, “Despite a weak correlation between plasma and CSF t-tau, plasma t-tau was at least as strongly associated with the development of incident AD dementia.”

“Use of plasma t-tau in this manner could be likened to the measurement of the APOEe4 allele, which is not a biomarker of AD pathology providing diagnostic certainty for AD dementia but is still routinely used to power clinical trials by selecting at-risk individuals,” they concluded.

Dr. Pase had no financial disclosures.

[email protected]

SOURCE: Pase, M et al JAMA Neurol 2019 doi:10.1001/jamaneurol.2018.4666

The total tau level in blood plasma appears to predict both onset and progression of dementia and could be used to help refine research cohorts.

Kheng Guan Toh/Thinkstock

Blood samples from two large dementia research cohorts confirmed the finding: Each standard deviation in plasma tau above the median is associated with a 29% greater risk of incident all-cause dementia and a 35%increase in the risk of incident Alzheimer’s disease, Matthew P. Pase, PhD and colleagues wrote in JAMA Neurology. It also correlated positively with some neuropathological aspects of dementia: smaller hippocampus and a higher burden of neurofibrillary tangles in the medial temporal lobe, said Dr. Pase of The Florey Institute for Neuroscience and Mental Health. Victoria, Australia.

Plasma tau isn’t the highly sought Holy Grail of a simple Alzheimer’s blood test. But the finding could benefit the research world. As a study entry criteria, it could substantially decrease the number of subjects needed to validate an outcome of either all-cause dementia or Alzheimer’s disease. Abnormal tau is also a required finding for an Alzheimer’s diagnosis in revised NIA-AA Research Framework. And, the authors noted, although plasma tau wasn’t quite as accurate a predictor as CSF tau, a needle in the arm would be much more acceptable to many more patients than a lumbar puncture.

“Whereas we do not expect plasma t-tau cutoffs to enhance diagnostic certainty for any single patient, our results suggest that plasma t-tau could be associated with improved risk stratification at a population level, targeting persons for inclusion in prevention trials, thus improving the power and precision of clinical trials and potentially accelerating therapeutic pipelines and drug discovery,” the team wrote.

The study drew on stored plasma samples from subjects enrolled in the Framingham Heart Study (1,453) and the Memento study, a multicenter cohort of persons with mild cognitive impairment or subjective cognitive complaints recruited from memory clinics across France (367).

The Framingham cohort was followed for up to 10 years between baseline examination to incident event (median 6 years).

Over that time, 134 (9.2%) cases of dementia developed; most of these (105) were due possible, probable, or definite Alzheimer’s.

Plasma tau levels rose linearly as the cohort aged. Higher plasma t-tau levels were associated with proven AD risk factors, including female sex, lower education, and higher vascular risk factors. They did not differ by apolipoprotein epsilon 4 status (APOEe4).

After adjusting for age and sex, each stand deviation unit increase in the log of tau was associated with a 29% greater risk of incident all-cause dementia, and a 35% increase in the risk of incident Alzheimer’s dementia. Subjects with tau levels above the median had a 62% increased risk of all-cause dementia and a 76% greater risk of AD. Adding APOEe4 status and vascular risk factors to the analysis didn’t alter the associations.

“Plasma t-tau level improved risk discrimination for all dementia and AD dementia beyond age and sex,” the investigators wrote. “[It] was associated with improved risk discrimination … in both APOEe4 carriers and noncarriers.”

In a hypothetical 5-year clinical trial, enrolling subjects with total plasma tau greater than the median could reduce the estimated necessary sample size by 38% for an outcome of all-cause dementia and by 50% for one of Alzheimer’s. Selecting those with both elevated plasma tau and APOEe4 carriage could reduce the required sample by 69% for all-cause dementia outcomes and by 80% for Alzheimer’s outcomes.

In the neuropathologic study, each standard deviation unit increase was associated with more neurofibrillary tangles in the medial temporal lobe, more microinfarcts, and smaller hippocampal volume. There was no association with amyloid plaque in any brain region.

Subjects in the Memento study had a meant of 4 years of follow-up. Over that time, there were 76 cases of incident dementia, 55 of which were probable Alzheimer’s.

Each standard deviation unit increase was associated with a nonsignificant 14% greater risk of all-cause dementia and a significant 54% increase in the risk of incident Alzheimer’s.

CSF was drawn on the same day as plasma in 140 of these subjects. The addition of CSF boosted the predictive value; each standard deviation increase more than doubled the risk of both Alzheimer’s (HR 2.33). Each standard deviation unit increase in CSF t-tau increased the risk by 2.14.

“Plasma t-tau was weakly correlated with CSF t-tau in our study. This finding is consistent

with previous studies showing that the associations of plasma t-tau with CSF t-tau have been weak or nonexistent,” the authors wrote. But, “Despite a weak correlation between plasma and CSF t-tau, plasma t-tau was at least as strongly associated with the development of incident AD dementia.”

“Use of plasma t-tau in this manner could be likened to the measurement of the APOEe4 allele, which is not a biomarker of AD pathology providing diagnostic certainty for AD dementia but is still routinely used to power clinical trials by selecting at-risk individuals,” they concluded.

Dr. Pase had no financial disclosures.

[email protected]

SOURCE: Pase, M et al JAMA Neurol 2019 doi:10.1001/jamaneurol.2018.4666

HONOLULU – Administering glyceryl trinitrate (GTN) early after onset of ischemic stroke or transient ischemic attack (TIA) does not improve outcomes, according to data presented at the International Stroke Conference sponsored by the American Heart Association. Results suggest that GTN causes adverse effects in patients with intracerebral hemorrhage (ICH), but this observation is not definitive, according to the researchers. Study results were published online ahead of print Feb. 6 in the Lancet.

Nitric oxide is a regulatory molecule that has vasoactive effects and promotes blood pressure reduction. Vascular levels of nitric oxide are low in stroke, which suggests that the molecule may be a target for stroke treatment. GTN, a nitric oxide donor, lowered blood pressure and improved functional outcome among patients with acute stroke in the phase 2 Rapid Intervention with GTN in Hypertensive Stroke Trial (RIGHT).

Philip Bath, MD, Stroke Association Professor of Stroke Medicine at the University of Nottingham (England), and colleagues conducted the RIGHT-2 study to evaluate the safety and efficacy of GTN when administered early after onset of suspected stroke. Paramedics randomized patients in equal groups to a GTN patch or a sham patch in the ambulance. Three more patches were administered in the hospital on the following days. Active and sham patches looked similar and had no writing on them, thus ensuring effective blinding upon administration. Investigators followed up patients by telephone at 90 days to assess the modified Rankin Scale score and markers of disability, mood, cognition, and quality of life.

Eligible participants were adults who had dialed emergency services, independently or with assistance, because of a possible stroke. They had a Face, Arm, Speech, Time (FAST) score of 2 or 3, were within 4 hours of onset, and had a systolic blood pressure greater than 120 mm Hg. Patients from nursing homes, those with hypoglycemia, those who were unconscious, and those with a witnessed seizure were excluded.

Dr. Bath and colleagues planned to enroll 850 patients from five ambulance services in 30 hospitals across the United Kingdom. Data were to be examined through an intention-to-treat analysis. During the trial, however, the investigators observed that the rate of stroke mimics was 26%, rather than the 12% that they had anticipated. To ensure the proper power for the study, the investigators increased the sample size to 1,149 patients. They also changed the planned data analysis from intention-to-treat to hierarchical analysis. Specifically, the researchers planned to perform the primary analysis in patients with stroke or TIA. If the results were positive, then they would perform a standard intention-to-treat analysis.

More than 99% of patients received the first patch. Approximately 57% of the population received the first two patches. One reason for this decrease in adherence was that many patients were discharged from the hospital with a TIA or a stroke mimic. Participants’ average age was 72. The median time from onset to randomization was 71 minutes, and the median time to treatment was 73 minutes. Participants’ mean systolic blood pressure was 162 mm Hg. Approximately 60% of the patients had a FAST score of 3. About 50% of participants had ischemic stroke, 13% had ICH, 10% had TIA, and 26% had stroke mimics.

At 1 hour after treatment initiation, systolic blood pressure decreased by 6.2 mm Hg and diastolic blood pressure decreased by 2.7 mm Hg among patients who received GTN, compared with controls. At one day, the differences were 5.2 mm Hg and 2.5 mm Hg, respectively, in treated patients, compared with controls. Blood pressure became similar between groups thereafter, “in part because of the tachyphylaxis that we know happens with GTN,” said Dr. Bath.

The researchers found no evidence of an effect of GTN on functional outcome at 90 days in participants with stroke or transient ischemic attack. The adjusted common odds ratio of poor outcome was 1.25 in the GTN group, compared with the control group (95 % confidence interval, 0.97-1.60; P = .083). “We were close to getting a negative trial,” said Dr. Bath.

Subgroup analyses revealed differences in outcome according to the time to randomization. GTN had a negative effect in patients treated within 1 hour of onset. Results were neutral, but tended to be negative, in patients treated between 1 and 2 hours of onset. Results were neutral, but tended to be positive, among patients treated at more than 2 hours after onset. There was no difference between groups in the rate of mortality.

One of the study’s limitations was its single-blind design. In addition, the trial was conducted in a single country, and the investigators changed the protocol after it was initiated. “We had a higher-than-expected [stroke] mimic rate, although I’m reassured by most experts that ... this is probably about right,” said Dr. Bath.

A potential reason for the neutral results is the negative effect that GTN had among patients with ICH, said Dr. Bath. “In that very early first hour, we are of course breaking a law that we learned in medical school, which is that the first part of hemostasis is spasm. We gave an antispasmodic: a vasodilator,” he added. “That is speculation.”

The trial was funded by the British Heart Foundation. Dr. Bath declared a modest ownership interest in Platelet Solutions and consultant or advisory board positions with Moleac, DiaMedica, Phagenesis, Nestle, and ReNeuron. The other investigators declared no conflicts of interest.

[email protected]

SOURCE: Bath PM et al. ISC 2019, Abstract LB2.

HONOLULU – Administering glyceryl trinitrate (GTN) early after onset of ischemic stroke or transient ischemic attack (TIA) does not improve outcomes, according to data presented at the International Stroke Conference sponsored by the American Heart Association. Results suggest that GTN causes adverse effects in patients with intracerebral hemorrhage (ICH), but this observation is not definitive, according to the researchers. Study results were published online ahead of print Feb. 6 in the Lancet.

Nitric oxide is a regulatory molecule that has vasoactive effects and promotes blood pressure reduction. Vascular levels of nitric oxide are low in stroke, which suggests that the molecule may be a target for stroke treatment. GTN, a nitric oxide donor, lowered blood pressure and improved functional outcome among patients with acute stroke in the phase 2 Rapid Intervention with GTN in Hypertensive Stroke Trial (RIGHT).

Philip Bath, MD, Stroke Association Professor of Stroke Medicine at the University of Nottingham (England), and colleagues conducted the RIGHT-2 study to evaluate the safety and efficacy of GTN when administered early after onset of suspected stroke. Paramedics randomized patients in equal groups to a GTN patch or a sham patch in the ambulance. Three more patches were administered in the hospital on the following days. Active and sham patches looked similar and had no writing on them, thus ensuring effective blinding upon administration. Investigators followed up patients by telephone at 90 days to assess the modified Rankin Scale score and markers of disability, mood, cognition, and quality of life.

Eligible participants were adults who had dialed emergency services, independently or with assistance, because of a possible stroke. They had a Face, Arm, Speech, Time (FAST) score of 2 or 3, were within 4 hours of onset, and had a systolic blood pressure greater than 120 mm Hg. Patients from nursing homes, those with hypoglycemia, those who were unconscious, and those with a witnessed seizure were excluded.

Dr. Bath and colleagues planned to enroll 850 patients from five ambulance services in 30 hospitals across the United Kingdom. Data were to be examined through an intention-to-treat analysis. During the trial, however, the investigators observed that the rate of stroke mimics was 26%, rather than the 12% that they had anticipated. To ensure the proper power for the study, the investigators increased the sample size to 1,149 patients. They also changed the planned data analysis from intention-to-treat to hierarchical analysis. Specifically, the researchers planned to perform the primary analysis in patients with stroke or TIA. If the results were positive, then they would perform a standard intention-to-treat analysis.

More than 99% of patients received the first patch. Approximately 57% of the population received the first two patches. One reason for this decrease in adherence was that many patients were discharged from the hospital with a TIA or a stroke mimic. Participants’ average age was 72. The median time from onset to randomization was 71 minutes, and the median time to treatment was 73 minutes. Participants’ mean systolic blood pressure was 162 mm Hg. Approximately 60% of the patients had a FAST score of 3. About 50% of participants had ischemic stroke, 13% had ICH, 10% had TIA, and 26% had stroke mimics.

At 1 hour after treatment initiation, systolic blood pressure decreased by 6.2 mm Hg and diastolic blood pressure decreased by 2.7 mm Hg among patients who received GTN, compared with controls. At one day, the differences were 5.2 mm Hg and 2.5 mm Hg, respectively, in treated patients, compared with controls. Blood pressure became similar between groups thereafter, “in part because of the tachyphylaxis that we know happens with GTN,” said Dr. Bath.

The researchers found no evidence of an effect of GTN on functional outcome at 90 days in participants with stroke or transient ischemic attack. The adjusted common odds ratio of poor outcome was 1.25 in the GTN group, compared with the control group (95 % confidence interval, 0.97-1.60; P = .083). “We were close to getting a negative trial,” said Dr. Bath.

Subgroup analyses revealed differences in outcome according to the time to randomization. GTN had a negative effect in patients treated within 1 hour of onset. Results were neutral, but tended to be negative, in patients treated between 1 and 2 hours of onset. Results were neutral, but tended to be positive, among patients treated at more than 2 hours after onset. There was no difference between groups in the rate of mortality.

One of the study’s limitations was its single-blind design. In addition, the trial was conducted in a single country, and the investigators changed the protocol after it was initiated. “We had a higher-than-expected [stroke] mimic rate, although I’m reassured by most experts that ... this is probably about right,” said Dr. Bath.

A potential reason for the neutral results is the negative effect that GTN had among patients with ICH, said Dr. Bath. “In that very early first hour, we are of course breaking a law that we learned in medical school, which is that the first part of hemostasis is spasm. We gave an antispasmodic: a vasodilator,” he added. “That is speculation.”

The trial was funded by the British Heart Foundation. Dr. Bath declared a modest ownership interest in Platelet Solutions and consultant or advisory board positions with Moleac, DiaMedica, Phagenesis, Nestle, and ReNeuron. The other investigators declared no conflicts of interest.

[email protected]

SOURCE: Bath PM et al. ISC 2019, Abstract LB2.

HONOLULU – Administering glyceryl trinitrate (GTN) early after onset of ischemic stroke or transient ischemic attack (TIA) does not improve outcomes, according to data presented at the International Stroke Conference sponsored by the American Heart Association. Results suggest that GTN causes adverse effects in patients with intracerebral hemorrhage (ICH), but this observation is not definitive, according to the researchers. Study results were published online ahead of print Feb. 6 in the Lancet.

Nitric oxide is a regulatory molecule that has vasoactive effects and promotes blood pressure reduction. Vascular levels of nitric oxide are low in stroke, which suggests that the molecule may be a target for stroke treatment. GTN, a nitric oxide donor, lowered blood pressure and improved functional outcome among patients with acute stroke in the phase 2 Rapid Intervention with GTN in Hypertensive Stroke Trial (RIGHT).

Philip Bath, MD, Stroke Association Professor of Stroke Medicine at the University of Nottingham (England), and colleagues conducted the RIGHT-2 study to evaluate the safety and efficacy of GTN when administered early after onset of suspected stroke. Paramedics randomized patients in equal groups to a GTN patch or a sham patch in the ambulance. Three more patches were administered in the hospital on the following days. Active and sham patches looked similar and had no writing on them, thus ensuring effective blinding upon administration. Investigators followed up patients by telephone at 90 days to assess the modified Rankin Scale score and markers of disability, mood, cognition, and quality of life.

Eligible participants were adults who had dialed emergency services, independently or with assistance, because of a possible stroke. They had a Face, Arm, Speech, Time (FAST) score of 2 or 3, were within 4 hours of onset, and had a systolic blood pressure greater than 120 mm Hg. Patients from nursing homes, those with hypoglycemia, those who were unconscious, and those with a witnessed seizure were excluded.

Dr. Bath and colleagues planned to enroll 850 patients from five ambulance services in 30 hospitals across the United Kingdom. Data were to be examined through an intention-to-treat analysis. During the trial, however, the investigators observed that the rate of stroke mimics was 26%, rather than the 12% that they had anticipated. To ensure the proper power for the study, the investigators increased the sample size to 1,149 patients. They also changed the planned data analysis from intention-to-treat to hierarchical analysis. Specifically, the researchers planned to perform the primary analysis in patients with stroke or TIA. If the results were positive, then they would perform a standard intention-to-treat analysis.

More than 99% of patients received the first patch. Approximately 57% of the population received the first two patches. One reason for this decrease in adherence was that many patients were discharged from the hospital with a TIA or a stroke mimic. Participants’ average age was 72. The median time from onset to randomization was 71 minutes, and the median time to treatment was 73 minutes. Participants’ mean systolic blood pressure was 162 mm Hg. Approximately 60% of the patients had a FAST score of 3. About 50% of participants had ischemic stroke, 13% had ICH, 10% had TIA, and 26% had stroke mimics.

At 1 hour after treatment initiation, systolic blood pressure decreased by 6.2 mm Hg and diastolic blood pressure decreased by 2.7 mm Hg among patients who received GTN, compared with controls. At one day, the differences were 5.2 mm Hg and 2.5 mm Hg, respectively, in treated patients, compared with controls. Blood pressure became similar between groups thereafter, “in part because of the tachyphylaxis that we know happens with GTN,” said Dr. Bath.

The researchers found no evidence of an effect of GTN on functional outcome at 90 days in participants with stroke or transient ischemic attack. The adjusted common odds ratio of poor outcome was 1.25 in the GTN group, compared with the control group (95 % confidence interval, 0.97-1.60; P = .083). “We were close to getting a negative trial,” said Dr. Bath.

Subgroup analyses revealed differences in outcome according to the time to randomization. GTN had a negative effect in patients treated within 1 hour of onset. Results were neutral, but tended to be negative, in patients treated between 1 and 2 hours of onset. Results were neutral, but tended to be positive, among patients treated at more than 2 hours after onset. There was no difference between groups in the rate of mortality.

One of the study’s limitations was its single-blind design. In addition, the trial was conducted in a single country, and the investigators changed the protocol after it was initiated. “We had a higher-than-expected [stroke] mimic rate, although I’m reassured by most experts that ... this is probably about right,” said Dr. Bath.

A potential reason for the neutral results is the negative effect that GTN had among patients with ICH, said Dr. Bath. “In that very early first hour, we are of course breaking a law that we learned in medical school, which is that the first part of hemostasis is spasm. We gave an antispasmodic: a vasodilator,” he added. “That is speculation.”

The trial was funded by the British Heart Foundation. Dr. Bath declared a modest ownership interest in Platelet Solutions and consultant or advisory board positions with Moleac, DiaMedica, Phagenesis, Nestle, and ReNeuron. The other investigators declared no conflicts of interest.

[email protected]

SOURCE: Bath PM et al. ISC 2019, Abstract LB2.

The estimated prevalence of multiple sclerosis (MS) as of 2010 is the highest to date, according to an analysis of administrative health claims (AHC) datasets and 2010 U.S. Census data.

“Our findings suggest that there has been a steady rise in the prevalence of MS over the past 5 decades, that the prevalence of MS remains higher for women than men, and that a north-south geographic gradient still persists,” wrote lead author Mitchell T. Wallin, MD, of Georgetown University, Washington, and his coauthors. The study was published in Neurology.

To determine adult cases of MS, Dr. Wallin and colleagues applied a validated algorithm to private, military, and public AHC datasets. Data from the 2010 U.S. Census were also used to standardize age and sex. In total, 125 million people over 18 years of age were captured in the study, nearly 45% of the U.S. population.

After adjustment, the 2010 prevalence for MS cumulated over 10 years was 309.2 per 100,000 adults (95% confidence interval, 308.1-310.1). This represented a total of 727,344 people with MS. The female to male ratio was 2.8, with a prevalence of 450.1 per 100,000 (95% CI, 448.1-451.6) for women versus a prevalence of 159.7 (95% CI, 158.7-160.6) for men. The age group with the highest estimated prevalence was 55-64 years old, and the prevalence in northern regions of the United States was statistically significantly higher than in southern regions.

The limitations of this study included not including children, the Indian Health Service, the U.S. prison system, or undocumented U.S. residents in the prevalence estimates. However, the authors did note that “these segments of the population are relatively small or, in the case of children, would contribute few cases.” In addition, they were unable to acquire more than 3 years of data for all insurance pools because of high costs.

The study was funded by a grant from the National Multiple Sclerosis Society. The authors reported numerous disclosures, including receiving consulting fees, researching funding, and grant support from various government agencies, foundations, and pharmaceutical companies.

SOURCE: Wallin MT et al. Neurology. 2019 Feb 15. doi: 10.1212/WNL.0000000000007035.

The estimated prevalence of multiple sclerosis (MS) as of 2010 is the highest to date, according to an analysis of administrative health claims (AHC) datasets and 2010 U.S. Census data.

“Our findings suggest that there has been a steady rise in the prevalence of MS over the past 5 decades, that the prevalence of MS remains higher for women than men, and that a north-south geographic gradient still persists,” wrote lead author Mitchell T. Wallin, MD, of Georgetown University, Washington, and his coauthors. The study was published in Neurology.

To determine adult cases of MS, Dr. Wallin and colleagues applied a validated algorithm to private, military, and public AHC datasets. Data from the 2010 U.S. Census were also used to standardize age and sex. In total, 125 million people over 18 years of age were captured in the study, nearly 45% of the U.S. population.

After adjustment, the 2010 prevalence for MS cumulated over 10 years was 309.2 per 100,000 adults (95% confidence interval, 308.1-310.1). This represented a total of 727,344 people with MS. The female to male ratio was 2.8, with a prevalence of 450.1 per 100,000 (95% CI, 448.1-451.6) for women versus a prevalence of 159.7 (95% CI, 158.7-160.6) for men. The age group with the highest estimated prevalence was 55-64 years old, and the prevalence in northern regions of the United States was statistically significantly higher than in southern regions.

The limitations of this study included not including children, the Indian Health Service, the U.S. prison system, or undocumented U.S. residents in the prevalence estimates. However, the authors did note that “these segments of the population are relatively small or, in the case of children, would contribute few cases.” In addition, they were unable to acquire more than 3 years of data for all insurance pools because of high costs.

The study was funded by a grant from the National Multiple Sclerosis Society. The authors reported numerous disclosures, including receiving consulting fees, researching funding, and grant support from various government agencies, foundations, and pharmaceutical companies.

SOURCE: Wallin MT et al. Neurology. 2019 Feb 15. doi: 10.1212/WNL.0000000000007035.

The estimated prevalence of multiple sclerosis (MS) as of 2010 is the highest to date, according to an analysis of administrative health claims (AHC) datasets and 2010 U.S. Census data.

“Our findings suggest that there has been a steady rise in the prevalence of MS over the past 5 decades, that the prevalence of MS remains higher for women than men, and that a north-south geographic gradient still persists,” wrote lead author Mitchell T. Wallin, MD, of Georgetown University, Washington, and his coauthors. The study was published in Neurology.

To determine adult cases of MS, Dr. Wallin and colleagues applied a validated algorithm to private, military, and public AHC datasets. Data from the 2010 U.S. Census were also used to standardize age and sex. In total, 125 million people over 18 years of age were captured in the study, nearly 45% of the U.S. population.

After adjustment, the 2010 prevalence for MS cumulated over 10 years was 309.2 per 100,000 adults (95% confidence interval, 308.1-310.1). This represented a total of 727,344 people with MS. The female to male ratio was 2.8, with a prevalence of 450.1 per 100,000 (95% CI, 448.1-451.6) for women versus a prevalence of 159.7 (95% CI, 158.7-160.6) for men. The age group with the highest estimated prevalence was 55-64 years old, and the prevalence in northern regions of the United States was statistically significantly higher than in southern regions.

The limitations of this study included not including children, the Indian Health Service, the U.S. prison system, or undocumented U.S. residents in the prevalence estimates. However, the authors did note that “these segments of the population are relatively small or, in the case of children, would contribute few cases.” In addition, they were unable to acquire more than 3 years of data for all insurance pools because of high costs.

The study was funded by a grant from the National Multiple Sclerosis Society. The authors reported numerous disclosures, including receiving consulting fees, researching funding, and grant support from various government agencies, foundations, and pharmaceutical companies.

SOURCE: Wallin MT et al. Neurology. 2019 Feb 15. doi: 10.1212/WNL.0000000000007035.

Here are 5 articles from the March issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):

1. Endometriosis surgery: Women can expect years-long benefits

To take the posttest, go to: https://bit.ly/2Ez8mdu
Expires January 3, 2019

2. Cerebral small vessel disease progression linked to MCI in hypertensive patients

To take the posttest, go to: https://bit.ly/2ExDV7o
Expires January 4, 2019

3. Adult atopic dermatitis is fraught with dermatologic comorbidities

To take the posttest, go to: https://bit.ly/2Vl7E9a
Expires January 11, 2019

4. Antidepressants tied to greater hip fracture incidence in older adults

To take the posttest, go to: https://bit.ly/2GRfMeH
Expires January 4, 2019

5. Researchers exploring ways to mitigate aging’s impact on diabetes

To take the posttest, go to: https://bit.ly/2tFxF7v
Expires January 8, 2019

Here are 5 articles from the March issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):

1. Endometriosis surgery: Women can expect years-long benefits

To take the posttest, go to: https://bit.ly/2Ez8mdu
Expires January 3, 2019

2. Cerebral small vessel disease progression linked to MCI in hypertensive patients

To take the posttest, go to: https://bit.ly/2ExDV7o
Expires January 4, 2019

3. Adult atopic dermatitis is fraught with dermatologic comorbidities

To take the posttest, go to: https://bit.ly/2Vl7E9a
Expires January 11, 2019

4. Antidepressants tied to greater hip fracture incidence in older adults

To take the posttest, go to: https://bit.ly/2GRfMeH
Expires January 4, 2019

5. Researchers exploring ways to mitigate aging’s impact on diabetes

To take the posttest, go to: https://bit.ly/2tFxF7v
Expires January 8, 2019

Here are 5 articles from the March issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):

1. Endometriosis surgery: Women can expect years-long benefits

To take the posttest, go to: https://bit.ly/2Ez8mdu
Expires January 3, 2019

2. Cerebral small vessel disease progression linked to MCI in hypertensive patients

To take the posttest, go to: https://bit.ly/2ExDV7o
Expires January 4, 2019

3. Adult atopic dermatitis is fraught with dermatologic comorbidities

To take the posttest, go to: https://bit.ly/2Vl7E9a
Expires January 11, 2019

4. Antidepressants tied to greater hip fracture incidence in older adults

To take the posttest, go to: https://bit.ly/2GRfMeH
Expires January 4, 2019

5. Researchers exploring ways to mitigate aging’s impact on diabetes

To take the posttest, go to: https://bit.ly/2tFxF7v
Expires January 8, 2019

DALLAS – The time is right to bring big data and high-horsepower computation to the thorniest problems in multiple sclerosis (MS) research, said Jennifer Graves, MD, who cochaired the closing session at the meeting held by the Americas Committee for Research and Treatment in Multiple Sclerosis. The session focused on harnessing machine learning, deep learning, and the newest noninvasive observational techniques to move research and clinical care forward.

“We’ve reached a point in MS research where we’re hitting some stumbling blocks. And a lot of those stumbling blocks are related to how well and how precisely we can measure phenotype in MS. The reason that’s important is that our next frontier is treating progressive MS – and what that requires is finding things that let us know what’s happening at the biological level, so that we can screen drugs faster. We can’t afford to have 3- to 5-year clinical trials. ... Because our patients can’t wait,” said Dr. Graves, an associate professor of neuroscience at the University of California, San Diego.

“We can use all sorts of big data sources, whether it’s the rich imaging data we get on patients when they go into the MRI scanner, whether it’s wearable sensors,” or even newer technology, Dr. Graves said. “We can use technology to give us the sensitivity that we’ve been missing.”

Wearable technology, including accelerometers, can track physical activity that tracks with outcomes in MS, she added. As the tech armament increases, so will data available for analysis and correlation.

However, the key to progress will be to focus on technology that measures change over time. “This is the key: sensitivity to change over time. A lot of things can be associated with disability,” said Dr. Graves, but the key is tracking what changes in an individual patient with disease progression, “so that we can detect treatment effects or side effects.”

[email protected]

DALLAS – The time is right to bring big data and high-horsepower computation to the thorniest problems in multiple sclerosis (MS) research, said Jennifer Graves, MD, who cochaired the closing session at the meeting held by the Americas Committee for Research and Treatment in Multiple Sclerosis. The session focused on harnessing machine learning, deep learning, and the newest noninvasive observational techniques to move research and clinical care forward.

“We’ve reached a point in MS research where we’re hitting some stumbling blocks. And a lot of those stumbling blocks are related to how well and how precisely we can measure phenotype in MS. The reason that’s important is that our next frontier is treating progressive MS – and what that requires is finding things that let us know what’s happening at the biological level, so that we can screen drugs faster. We can’t afford to have 3- to 5-year clinical trials. ... Because our patients can’t wait,” said Dr. Graves, an associate professor of neuroscience at the University of California, San Diego.

“We can use all sorts of big data sources, whether it’s the rich imaging data we get on patients when they go into the MRI scanner, whether it’s wearable sensors,” or even newer technology, Dr. Graves said. “We can use technology to give us the sensitivity that we’ve been missing.”

Wearable technology, including accelerometers, can track physical activity that tracks with outcomes in MS, she added. As the tech armament increases, so will data available for analysis and correlation.

However, the key to progress will be to focus on technology that measures change over time. “This is the key: sensitivity to change over time. A lot of things can be associated with disability,” said Dr. Graves, but the key is tracking what changes in an individual patient with disease progression, “so that we can detect treatment effects or side effects.”

[email protected]

DALLAS – The time is right to bring big data and high-horsepower computation to the thorniest problems in multiple sclerosis (MS) research, said Jennifer Graves, MD, who cochaired the closing session at the meeting held by the Americas Committee for Research and Treatment in Multiple Sclerosis. The session focused on harnessing machine learning, deep learning, and the newest noninvasive observational techniques to move research and clinical care forward.

“We’ve reached a point in MS research where we’re hitting some stumbling blocks. And a lot of those stumbling blocks are related to how well and how precisely we can measure phenotype in MS. The reason that’s important is that our next frontier is treating progressive MS – and what that requires is finding things that let us know what’s happening at the biological level, so that we can screen drugs faster. We can’t afford to have 3- to 5-year clinical trials. ... Because our patients can’t wait,” said Dr. Graves, an associate professor of neuroscience at the University of California, San Diego.

“We can use all sorts of big data sources, whether it’s the rich imaging data we get on patients when they go into the MRI scanner, whether it’s wearable sensors,” or even newer technology, Dr. Graves said. “We can use technology to give us the sensitivity that we’ve been missing.”

Wearable technology, including accelerometers, can track physical activity that tracks with outcomes in MS, she added. As the tech armament increases, so will data available for analysis and correlation.

However, the key to progress will be to focus on technology that measures change over time. “This is the key: sensitivity to change over time. A lot of things can be associated with disability,” said Dr. Graves, but the key is tracking what changes in an individual patient with disease progression, “so that we can detect treatment effects or side effects.”

[email protected]