Pub Date : 2024-11-26Epub Date: 2024-11-06DOI: 10.1212/WNL.0000000000210014
Sandro Marini, Tamara N Kimball, Ernst Mayerhofer, Reinier W P Tack, Jasper R Senff, Savvina Prapiadou, Cyprien A Rivier, Jonathan Duskin, Christina Kourkoulis, Guido J Falcone, Nirupama Yechoor, Rudolph E Tanzi, Jonathan Rosand, Sanjula Singh, Livia Parodi, Christopher D Anderson
Background and objectives: The 21-point Brain Care Score (BCS) is an index that ranks behaviors and clinical measurements with the aim of encouraging lifestyle adjustments to lower the incidence of age-related brain disease, including stroke, late-life depression (LLD), and dementia. A higher BCS at baseline is associated with a lower risk of these outcomes. We aimed to investigate whether the associations between BCS and stroke, LLD, and dementia risks are independent of genetic predisposition for these conditions and quantify the effect of healthy lifestyle across genetic risk distributions for these outcomes.
Methods: Using the UK Biobank (UKB) prospective cohort study, we computed baseline BCSs and polygenic scores to estimate genetic predisposition for stroke and LLD and APOE ε allele status to stratify dementia risk. As for outcomes again in UKB, we measured incidence of stroke, LLD, and dementia. We used multivariate Cox proportional hazard models to assess associations between BCS, genetic predisposition, and these outcomes. We also conducted stratified and interaction analyses to estimate the incidence of these outcomes across quartiles of genetic risk and BCS.
Results: We included 368,340 UKB participants (median age 58 years (interquartile range 51-63 years), 46.3% male). Independent of genetic risk, a 5-point increase in BCS corresponded to lowered hazards of stroke (hazard ratio [HR] 0.70, 95% CI 0.68-0.73), LLD (HR 0.65, 95% CI 0.63-0.67), and dementia (HR 0.82, 95% CI 0.78-0.85). Incidences of all 3 outcomes were higher among participants with high genetic risk of these outcomes. However, these increased risks were offset for individuals with a higher BCS (incidence rates per 1,000 person-years were 2.76 vs 1.19 for stroke, 7.34 vs 4.46 for LLD, and 3.64 vs 2.05 for dementia, when comparing low and high BCS).
Discussion: Across different genetic predispositions for stroke, LLD, and dementia, healthier lifestyle behaviors are protective for brain health, demonstrating the nondeterminism of genetic risk. Furthermore, differences in BCS behave as aggregate risk estimators of all 3 outcomes. Further work is needed to prospectively investigate the utility and performance of the BCS as a targeted intervention in populations at elevated genetic risk of age-related brain disease.
背景和目标:21 分护脑评分(BCS)是一项对行为和临床测量进行排名的指数,旨在鼓励人们调整生活方式,以降低中风、晚年抑郁(LLD)和痴呆等老年性脑部疾病的发病率。基线 BCS 越高,发生这些结果的风险越低。我们旨在研究 BCS 与中风、晚年抑郁症和痴呆症风险之间的关联是否与这些疾病的遗传易感性无关,并量化健康生活方式对这些结果的遗传风险分布的影响:利用英国生物库(UKB)前瞻性队列研究,我们计算了基线BCS和多基因评分,以估计中风和LLD的遗传易感性,并计算了APOE ε等位基因状态,以对痴呆风险进行分层。至于结果,我们再次在 UKB 中测量了脑卒中、LLD 和痴呆症的发病率。我们使用多变量 Cox 比例危险模型来评估 BCS、遗传易感性和这些结果之间的关联。我们还进行了分层和交互分析,以估计遗传风险和 BCS 四分位数中这些结果的发生率:我们纳入了 368,340 名 UKB 参与者(中位年龄 58 岁(四分位间范围 51-63 岁),46.3% 为男性)。与遗传风险无关,BCS 每增加 5 分,中风(危险比 [HR] 0.70,95% CI 0.68-0.73)、低密度脂蛋白血症(HR 0.65,95% CI 0.63-0.67)和痴呆(HR 0.82,95% CI 0.78-0.85)的危险性相应降低。在这些结果的高遗传风险参与者中,所有 3 种结果的发生率都较高。然而,这些增加的风险在 BCS 较高的个体中被抵消了(比较低 BCS 和高 BCS,中风的每千人年发病率分别为 2.76 vs 1.19,LLD 的每千人年发病率分别为 7.34 vs 4.46,痴呆的每千人年发病率分别为 3.64 vs 2.05):讨论:在不同的中风、低密度脂蛋白血症和痴呆症遗传倾向中,更健康的生活方式行为对大脑健康具有保护作用,这表明遗传风险具有非决定性。此外,BCS的差异还可作为所有3种结果的总体风险估计因子。需要进一步开展工作,前瞻性地研究 BCS 作为一种有针对性的干预措施,在老年性脑部疾病遗传风险较高的人群中的效用和表现。
{"title":"Health-Related Behaviors and Risk of Common Age-Related Brain Diseases Across Severities of Genetic Risk.","authors":"Sandro Marini, Tamara N Kimball, Ernst Mayerhofer, Reinier W P Tack, Jasper R Senff, Savvina Prapiadou, Cyprien A Rivier, Jonathan Duskin, Christina Kourkoulis, Guido J Falcone, Nirupama Yechoor, Rudolph E Tanzi, Jonathan Rosand, Sanjula Singh, Livia Parodi, Christopher D Anderson","doi":"10.1212/WNL.0000000000210014","DOIUrl":"https://doi.org/10.1212/WNL.0000000000210014","url":null,"abstract":"<p><strong>Background and objectives: </strong>The 21-point Brain Care Score (BCS) is an index that ranks behaviors and clinical measurements with the aim of encouraging lifestyle adjustments to lower the incidence of age-related brain disease, including stroke, late-life depression (LLD), and dementia. A higher BCS at baseline is associated with a lower risk of these outcomes. We aimed to investigate whether the associations between BCS and stroke, LLD, and dementia risks are independent of genetic predisposition for these conditions and quantify the effect of healthy lifestyle across genetic risk distributions for these outcomes.</p><p><strong>Methods: </strong>Using the UK Biobank (UKB) prospective cohort study, we computed baseline BCSs and polygenic scores to estimate genetic predisposition for stroke and LLD and <i>APOE</i> ε allele status to stratify dementia risk. As for outcomes again in UKB, we measured incidence of stroke, LLD, and dementia. We used multivariate Cox proportional hazard models to assess associations between BCS, genetic predisposition, and these outcomes. We also conducted stratified and interaction analyses to estimate the incidence of these outcomes across quartiles of genetic risk and BCS.</p><p><strong>Results: </strong>We included 368,340 UKB participants (median age 58 years (interquartile range 51-63 years), 46.3% male). Independent of genetic risk, a 5-point increase in BCS corresponded to lowered hazards of stroke (hazard ratio [HR] 0.70, 95% CI 0.68-0.73), LLD (HR 0.65, 95% CI 0.63-0.67), and dementia (HR 0.82, 95% CI 0.78-0.85). Incidences of all 3 outcomes were higher among participants with high genetic risk of these outcomes. However, these increased risks were offset for individuals with a higher BCS (incidence rates per 1,000 person-years were 2.76 vs 1.19 for stroke, 7.34 vs 4.46 for LLD, and 3.64 vs 2.05 for dementia, when comparing low and high BCS).</p><p><strong>Discussion: </strong>Across different genetic predispositions for stroke, LLD, and dementia, healthier lifestyle behaviors are protective for brain health, demonstrating the nondeterminism of genetic risk. Furthermore, differences in BCS behave as aggregate risk estimators of all 3 outcomes. Further work is needed to prospectively investigate the utility and performance of the BCS as a targeted intervention in populations at elevated genetic risk of age-related brain disease.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"103 10","pages":"e210014"},"PeriodicalIF":7.7,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-26Epub Date: 2024-10-30DOI: 10.1212/WNL.0000000000210029
Amanda V Gusovsky, Chun Chieh Lin, Kevin Kerber, Evan L Reynolds, Brian C Callaghan, James F Burke
Objectives: To observe medication cost trends for 5 common neurologic conditions.
Methods: We quantified annual out-of-pocket (OOP) and total medication costs for patients seen by a neurologist with epilepsy, multiple sclerosis (MS), Parkinson disease (PD), peripheral neuropathy (PN), and dementia/Alzheimer's disease in a commercial claims database cross-sectionally from 2012 to 2021.
Results: We identified 186,144 patients with epilepsy, 54,676 with MS, 45,909 with PD, 169,127 with PN, and 60,861 with dementia/Alzheimer. OOP costs for MS medications increased each year, by 217% on average. Branded epilepsy medications had higher OOP costs than generics. Decreases ranging from 48% to 80% in annual OOP costs of duloxetine, pregabalin, rasagiline, rivastigmine, and memantine were observed in the years after generic introduction.
Discussion: Preferentially selecting generic medications reduces OOP costs, other than for MS where costs continue to increase. Policy solutions, such as cost caps, are needed.
{"title":"Costs Are Still on the Rise for Commonly Prescribed Branded Neurologic Medications.","authors":"Amanda V Gusovsky, Chun Chieh Lin, Kevin Kerber, Evan L Reynolds, Brian C Callaghan, James F Burke","doi":"10.1212/WNL.0000000000210029","DOIUrl":"https://doi.org/10.1212/WNL.0000000000210029","url":null,"abstract":"<p><strong>Objectives: </strong>To observe medication cost trends for 5 common neurologic conditions.</p><p><strong>Methods: </strong>We quantified annual out-of-pocket (OOP) and total medication costs for patients seen by a neurologist with epilepsy, multiple sclerosis (MS), Parkinson disease (PD), peripheral neuropathy (PN), and dementia/Alzheimer's disease in a commercial claims database cross-sectionally from 2012 to 2021.</p><p><strong>Results: </strong>We identified 186,144 patients with epilepsy, 54,676 with MS, 45,909 with PD, 169,127 with PN, and 60,861 with dementia/Alzheimer. OOP costs for MS medications increased each year, by 217% on average. Branded epilepsy medications had higher OOP costs than generics. Decreases ranging from 48% to 80% in annual OOP costs of duloxetine, pregabalin, rasagiline, rivastigmine, and memantine were observed in the years after generic introduction.</p><p><strong>Discussion: </strong>Preferentially selecting generic medications reduces OOP costs, other than for MS where costs continue to increase. Policy solutions, such as cost caps, are needed.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"103 10","pages":"e210029"},"PeriodicalIF":7.7,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-26Epub Date: 2024-10-28DOI: 10.1212/WNL.0000000000210047
Nara M Michaelson, Eric C Klawiter, Tarun Singhal
{"title":"Journal Club: PET Imaging in Multiple Sclerosis and Its Prognostic Implications.","authors":"Nara M Michaelson, Eric C Klawiter, Tarun Singhal","doi":"10.1212/WNL.0000000000210047","DOIUrl":"https://doi.org/10.1212/WNL.0000000000210047","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"103 10","pages":"e210047"},"PeriodicalIF":7.7,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-26Epub Date: 2024-10-28DOI: 10.1212/WNL.0000000000209668
Emanuele Cerulli Irelli, Barbara Mostacci, Carlo Di Bonaventura
{"title":"Author Response: Predictors of Seizure Recurrence in Women With Idiopathic Generalized Epilepsy Who Switch From Valproate to Another Medication.","authors":"Emanuele Cerulli Irelli, Barbara Mostacci, Carlo Di Bonaventura","doi":"10.1212/WNL.0000000000209668","DOIUrl":"https://doi.org/10.1212/WNL.0000000000209668","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"103 10","pages":"e209668"},"PeriodicalIF":7.7,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-26Epub Date: 2024-10-28DOI: 10.1212/WNL.0000000000210093
Aravind Ganesh, Steven L Galetta
{"title":"Editors' Note: Statin Therapy for Secondary Prevention in Ischemic Stroke Patients With Cerebral Microbleeds.","authors":"Aravind Ganesh, Steven L Galetta","doi":"10.1212/WNL.0000000000210093","DOIUrl":"https://doi.org/10.1212/WNL.0000000000210093","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"103 10","pages":"e210093"},"PeriodicalIF":7.7,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-26Epub Date: 2024-11-04DOI: 10.1212/WNL.0000000000210005
David Bruckman, Ikjae Lee, Jesse D Schold, Benjamin R Claytor, Nicholas J Silvestri, Michael K Hehir, Yuebing Li
Background and objectives: Epidemiologic studies suggest increasing incidence and prevalence of myasthenia gravis (MG) among the elderly population outside the United States. We aimed to provide an estimation of MG incidence and prevalence and their trend among the Medicare Fee-For-Service (FFS)-covered elderly US population.
Methods: We performed a retrospective longitudinal study using Medicare claims data (2006-2019). Study-eligible beneficiaries were aged 65 years and older, had at least 1 month of FFS Part A/B coverage, and were without any health maintenance organization insurance coverage. Study-eligible beneficiaries were aggregated into 2-year periods from 2006-2007 through 2018-2019. MG cases were ascertained using a validated algorithm of 2 MG claims within each 2-year period, from 2 outpatient office visits or a combination of 1 inpatient admission and 1 outpatient office visit, separated by ≥ 28 days. Period prevalence was calculated from MG-ascertained cases divided by FFS Part A/B beneficiaries and reported as cases per 100,000 population. Incident cases were determined among MG prevalent cases if the initial MG claim occurred in that period after a full calendar year since coverage initiation. Incidence was calculated as case counts per 100,000 at-risk beneficiary person-years (PYs) in each period excluding 2006-2007. Trends of prevalence and incidence over time were examined with Poisson regression. All-cause mortality of each 2-year period was calculated.
Results: The period prevalence of MG increased from 81 to 119 per 100,000 FFS A/B population from 2006-2007 to 2018-2019 (p < 0.001). Increasing trends of prevalence were observed in all sex (male/female), age (65-69/70-74/75-79/80+), race/ethnic (African American/Asian/Hispanics of any race/non-Hispanic White/other), and census region (Northeast/Midwest/South/West) subgroups. MG incidence increased from 12.2 to 13.3 per 100,000 PYs from 2008-2009 to 2018-2019 (p < 0.05). Increasing incidence trends were significant in the following subgroups: men and women; all age groups except 75-79 years; White non-Hispanic race; Northeast, Midwest, and South census regions. All-cause mortality among MG beneficiaries was stable from 6.26 deaths per 100 PYs in 2006-2007 to 5.67 in 2018-2019 (p = 0.18).
Discussion: Increasing trends in MG prevalence and incidence in the elderly US population, with variation in rates of certain subgroups, are confirmed in this 14-year period.
{"title":"Epidemiologic Study of Myasthenia Gravis in the Elderly US Population: A Longitudinal Analysis of the Medicare Claims Database, 2006-2019.","authors":"David Bruckman, Ikjae Lee, Jesse D Schold, Benjamin R Claytor, Nicholas J Silvestri, Michael K Hehir, Yuebing Li","doi":"10.1212/WNL.0000000000210005","DOIUrl":"10.1212/WNL.0000000000210005","url":null,"abstract":"<p><strong>Background and objectives: </strong>Epidemiologic studies suggest increasing incidence and prevalence of myasthenia gravis (MG) among the elderly population outside the United States. We aimed to provide an estimation of MG incidence and prevalence and their trend among the Medicare Fee-For-Service (FFS)-covered elderly US population.</p><p><strong>Methods: </strong>We performed a retrospective longitudinal study using Medicare claims data (2006-2019). Study-eligible beneficiaries were aged 65 years and older, had at least 1 month of FFS Part A/B coverage, and were without any health maintenance organization insurance coverage. Study-eligible beneficiaries were aggregated into 2-year periods from 2006-2007 through 2018-2019. MG cases were ascertained using a validated algorithm of 2 MG claims within each 2-year period, from 2 outpatient office visits or a combination of 1 inpatient admission and 1 outpatient office visit, separated by ≥ 28 days. Period prevalence was calculated from MG-ascertained cases divided by FFS Part A/B beneficiaries and reported as cases per 100,000 population. Incident cases were determined among MG prevalent cases if the initial MG claim occurred in that period after a full calendar year since coverage initiation. Incidence was calculated as case counts per 100,000 at-risk beneficiary person-years (PYs) in each period excluding 2006-2007. Trends of prevalence and incidence over time were examined with Poisson regression. All-cause mortality of each 2-year period was calculated.</p><p><strong>Results: </strong>The period prevalence of MG increased from 81 to 119 per 100,000 FFS A/B population from 2006-2007 to 2018-2019 (<i>p</i> < 0.001). Increasing trends of prevalence were observed in all sex (male/female), age (65-69/70-74/75-79/80+), race/ethnic (African American/Asian/Hispanics of any race/non-Hispanic White/other), and census region (Northeast/Midwest/South/West) subgroups. MG incidence increased from 12.2 to 13.3 per 100,000 PYs from 2008-2009 to 2018-2019 (<i>p</i> < 0.05). Increasing incidence trends were significant in the following subgroups: men and women; all age groups except 75-79 years; White non-Hispanic race; Northeast, Midwest, and South census regions. All-cause mortality among MG beneficiaries was stable from 6.26 deaths per 100 PYs in 2006-2007 to 5.67 in 2018-2019 (<i>p</i> = 0.18).</p><p><strong>Discussion: </strong>Increasing trends in MG prevalence and incidence in the elderly US population, with variation in rates of certain subgroups, are confirmed in this 14-year period.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"103 10","pages":"e210005"},"PeriodicalIF":7.7,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-26Epub Date: 2024-11-07DOI: 10.1212/WNL.0000000000210097
Yasmin N Aziz, Joseph P Broderick
{"title":"Understanding Alternatives to Traditional Informed Consent in Acute Stroke Trials.","authors":"Yasmin N Aziz, Joseph P Broderick","doi":"10.1212/WNL.0000000000210097","DOIUrl":"https://doi.org/10.1212/WNL.0000000000210097","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"103 10","pages":"e210097"},"PeriodicalIF":7.7,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}