K. Samra, Georgia Peakman, Amy Macdougall, A. Bouzigues, C. Greaves, R. Convery, J. V. van Swieten, L. Jiskoot, H. Seelaar, F. Moreno, R. Sánchez-Valle, R. Laforce, Caroline Graff, M. Masellis, M. Tartaglia, James B. Rowe, B. Borroni, E. Finger, M. Synofzik, Daniela Galimberti, R. Vandenberghe, A. de Mendonça, Christopher R. Butler, Alexander Gerhard, S. Ducharme, I. Ber, Pietro Tiraboschi, Isabel Santana, F. Pasquier, J. Levin, M. Otto, S. Sorbi, J. Rohrer, L. Russell
Abstract INTRODUCTION We aimed to expand the range of the frontotemporal dementia (FTD) phenotypes assessed by the Clinical Dementia Rating Dementia Staging Instrument plus National Alzheimer's Coordinating Center Behavior and Language Domains (CDR plus NACC FTLD). METHODS Neuropsychiatric and motor domains were added to the standard CDR plus NACC FTLD generating a new CDR plus NACC FTLD‐NM scale. This was assessed in 522 mutation carriers and 310 mutation‐negative controls from the Genetic Frontotemporal dementia Initiative (GENFI). RESULTS The new scale led to higher global severity scores than the CDR plus NACC FTLD: 1.4% of participants were now considered prodromal rather than asymptomatic, while 1.3% were now considered symptomatic rather than asymptomatic or prodromal. No participants with a clinical diagnosis of an FTD spectrum disorder were classified as asymptomatic using the new scales. DISCUSSION Adding new domains to the CDR plus NACC FTLD leads to a scale that encompasses the wider phenotypic spectrum of FTD with further work needed to validate its use more widely. Highlights The new Clinical Dementia Rating Dementia Staging Instrument plus National Alzheimer's Coordinating Center Behavior and Language Domains neuropsychiatric and motor (CDR plus NACC FTLD‐NM) rating scale was significantly positively correlated with the original CDR plus NACC FTLD and negatively correlated with the FTD Rating Scale (FRS). No participants with a clinical diagnosis in the frontotemporal dementia spectrum were classified as asymptomatic with the new CDR plus NACC FTLD‐NM rating scale. Individuals had higher global severity scores with the addition of the neuropsychiatric and motor domains. A receiver operating characteristic analysis of symptomatic diagnosis showed nominally higher areas under the curve for the new scales.
{"title":"Extending the phenotypic spectrum assessed by the CDR plus NACC FTLD in genetic frontotemporal dementia","authors":"K. Samra, Georgia Peakman, Amy Macdougall, A. Bouzigues, C. Greaves, R. Convery, J. V. van Swieten, L. Jiskoot, H. Seelaar, F. Moreno, R. Sánchez-Valle, R. Laforce, Caroline Graff, M. Masellis, M. Tartaglia, James B. Rowe, B. Borroni, E. Finger, M. Synofzik, Daniela Galimberti, R. Vandenberghe, A. de Mendonça, Christopher R. Butler, Alexander Gerhard, S. Ducharme, I. Ber, Pietro Tiraboschi, Isabel Santana, F. Pasquier, J. Levin, M. Otto, S. Sorbi, J. Rohrer, L. Russell","doi":"10.1002/dad2.12571","DOIUrl":"https://doi.org/10.1002/dad2.12571","url":null,"abstract":"Abstract INTRODUCTION We aimed to expand the range of the frontotemporal dementia (FTD) phenotypes assessed by the Clinical Dementia Rating Dementia Staging Instrument plus National Alzheimer's Coordinating Center Behavior and Language Domains (CDR plus NACC FTLD). METHODS Neuropsychiatric and motor domains were added to the standard CDR plus NACC FTLD generating a new CDR plus NACC FTLD‐NM scale. This was assessed in 522 mutation carriers and 310 mutation‐negative controls from the Genetic Frontotemporal dementia Initiative (GENFI). RESULTS The new scale led to higher global severity scores than the CDR plus NACC FTLD: 1.4% of participants were now considered prodromal rather than asymptomatic, while 1.3% were now considered symptomatic rather than asymptomatic or prodromal. No participants with a clinical diagnosis of an FTD spectrum disorder were classified as asymptomatic using the new scales. DISCUSSION Adding new domains to the CDR plus NACC FTLD leads to a scale that encompasses the wider phenotypic spectrum of FTD with further work needed to validate its use more widely. Highlights The new Clinical Dementia Rating Dementia Staging Instrument plus National Alzheimer's Coordinating Center Behavior and Language Domains neuropsychiatric and motor (CDR plus NACC FTLD‐NM) rating scale was significantly positively correlated with the original CDR plus NACC FTLD and negatively correlated with the FTD Rating Scale (FRS). No participants with a clinical diagnosis in the frontotemporal dementia spectrum were classified as asymptomatic with the new CDR plus NACC FTLD‐NM rating scale. Individuals had higher global severity scores with the addition of the neuropsychiatric and motor domains. A receiver operating characteristic analysis of symptomatic diagnosis showed nominally higher areas under the curve for the new scales.","PeriodicalId":516929,"journal":{"name":"Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140773238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Down syndrome (DS) is caused by a third copy of chromosome 21. Alzheimer's disease (AD) is a neurodegenerative condition characterized by the deposition of amyloid‐beta (Aβ) plaques and neurofibrillary tangles in the brain. Both disorders have elevated Aβ, tau, dysregulated immune response, and inflammation. In people with DS, Hsa21 genes like APP and DYRK1A are overexpressed, causing an accumulation of amyloid and neurofibrillary tangles, and potentially contributing to an increased risk of AD. As a result, people with DS are a key demographic for research into AD therapeutics and prevention. The molecular links between DS and AD shed insights into the underlying causes of both diseases and highlight potential therapeutic targets. Also, using biomarkers for early diagnosis and treatment monitoring is an active area of research, and genetic screening for high‐risk individuals may enable earlier intervention. Finally, the fundamental mechanistic parallels between DS and AD emphasize the necessity for continued research into effective treatments and prevention measures for DS patients at risk for AD. Genetic screening with customized therapy approaches may help the DS population in current clinical studies and future biomarkers.
摘要 唐氏综合征（DS）是由 21 号染色体的第三个拷贝引起的。阿尔茨海默病（AD）是一种神经退行性疾病，其特征是淀粉样β（Aβ）斑块和神经纤维缠结在大脑中沉积。这两种疾病都有 Aβ、tau 增高、免疫反应失调和炎症等症状。在 DS 患者中，APP 和 DYRK1A 等 Hsa21 基因过度表达，导致淀粉样蛋白和神经纤维缠结的积累，并有可能导致 AD 风险的增加。因此，DS患者是研究注意力缺失症治疗和预防的关键人群。DS和AD之间的分子联系揭示了这两种疾病的根本原因，并突出了潜在的治疗目标。此外，利用生物标志物进行早期诊断和治疗监测也是一个活跃的研究领域，而对高危人群进行基因筛查则可以实现早期干预。最后，DS 和 AD 在基本机理上的相似性强调了继续研究针对有 AD 风险的 DS 患者的有效治疗和预防措施的必要性。在当前的临床研究和未来的生物标志物研究中，基因筛查和定制治疗方法可能会对 DS 患者有所帮助。
{"title":"From understanding to action: Exploring molecular connections of Down syndrome to Alzheimer's disease for targeted therapeutic approach","authors":"Sonal Sukreet, M. Rafii, R. Rissman","doi":"10.1002/dad2.12580","DOIUrl":"https://doi.org/10.1002/dad2.12580","url":null,"abstract":"Abstract Down syndrome (DS) is caused by a third copy of chromosome 21. Alzheimer's disease (AD) is a neurodegenerative condition characterized by the deposition of amyloid‐beta (Aβ) plaques and neurofibrillary tangles in the brain. Both disorders have elevated Aβ, tau, dysregulated immune response, and inflammation. In people with DS, Hsa21 genes like APP and DYRK1A are overexpressed, causing an accumulation of amyloid and neurofibrillary tangles, and potentially contributing to an increased risk of AD. As a result, people with DS are a key demographic for research into AD therapeutics and prevention. The molecular links between DS and AD shed insights into the underlying causes of both diseases and highlight potential therapeutic targets. Also, using biomarkers for early diagnosis and treatment monitoring is an active area of research, and genetic screening for high‐risk individuals may enable earlier intervention. Finally, the fundamental mechanistic parallels between DS and AD emphasize the necessity for continued research into effective treatments and prevention measures for DS patients at risk for AD. Genetic screening with customized therapy approaches may help the DS population in current clinical studies and future biomarkers.","PeriodicalId":516929,"journal":{"name":"Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140795405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abigail Dove, Jie Guo, Jiao Wang, D. L. Vetrano, Sakura Sakakibara, E. Laukka, David A. Bennett, Weili Xu
Abstract INTRODUCTION The presence of multiple cardiometabolic diseases (CMDs) has been linked to increased dementia risk, but the combined influence of CMDs on cognition and brain structure across the life course is unclear. METHODS In the UK Biobank, 46,562 dementia‐free participants completed a cognitive test battery at baseline and a follow‐up visit 9 years later, at which point 39,306 also underwent brain magnetic resonance imaging. CMDs (diabetes, heart disease, and stroke) were ascertained from medical records. Data were analyzed using age‐stratified (middle age [< 60] versus older [≥ 60]) mixed‐effects models and linear regression. RESULTS A higher number of CMDs was associated with significantly steeper global cognitive decline in older (β = –0.008; 95% confidence interval: −0.012, −0.005) but not middle age. Additionally, the presence of multiple CMDs was related to smaller total brain volume, gray matter volume, white matter volume, and hippocampal volume and larger white matter hyperintensity volume, even in middle age. DISCUSSION CMDs are associated with cognitive decline in older age and poorer brain structural health beginning already in middle age. Highlights We explored the association of CMDs with cognitive decline and brain MRI measures. CMDs accelerated cognitive decline in older (≥60y) but not middle (<60) age. CMDs were associated with poorer brain MRI parameters in both middle and older age. Results highlight the connection between CMDs and cognitive/brain aging.
{"title":"Cardiometabolic disease, cognitive decline, and brain structure in middle and older age","authors":"Abigail Dove, Jie Guo, Jiao Wang, D. L. Vetrano, Sakura Sakakibara, E. Laukka, David A. Bennett, Weili Xu","doi":"10.1002/dad2.12566","DOIUrl":"https://doi.org/10.1002/dad2.12566","url":null,"abstract":"Abstract INTRODUCTION The presence of multiple cardiometabolic diseases (CMDs) has been linked to increased dementia risk, but the combined influence of CMDs on cognition and brain structure across the life course is unclear. METHODS In the UK Biobank, 46,562 dementia‐free participants completed a cognitive test battery at baseline and a follow‐up visit 9 years later, at which point 39,306 also underwent brain magnetic resonance imaging. CMDs (diabetes, heart disease, and stroke) were ascertained from medical records. Data were analyzed using age‐stratified (middle age [< 60] versus older [≥ 60]) mixed‐effects models and linear regression. RESULTS A higher number of CMDs was associated with significantly steeper global cognitive decline in older (β = –0.008; 95% confidence interval: −0.012, −0.005) but not middle age. Additionally, the presence of multiple CMDs was related to smaller total brain volume, gray matter volume, white matter volume, and hippocampal volume and larger white matter hyperintensity volume, even in middle age. DISCUSSION CMDs are associated with cognitive decline in older age and poorer brain structural health beginning already in middle age. Highlights We explored the association of CMDs with cognitive decline and brain MRI measures. CMDs accelerated cognitive decline in older (≥60y) but not middle (<60) age. CMDs were associated with poorer brain MRI parameters in both middle and older age. Results highlight the connection between CMDs and cognitive/brain aging.","PeriodicalId":516929,"journal":{"name":"Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140793933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nicolas Farina, Esra Hassan, I. Theresia, F. Fitri, Ika Suswanti, T. P. Sani, Sara Evans-Lacko, Sube Banerjee, Y. Turana
Abstract INTRODUCTION Tackling dementia stigma is a policy priority. In Indonesia, we have little insight into the general public's knowledge and attitudes about dementia. METHODS Cross‐sectional study of 4430 Indonesian adults recruited from Jakarta and North Sumatra, Indonesia. Measures included dementia knowledge and attitudes. RESULTS A total of 86.3% (n = 3,803) of adults had not heard of the terms dementia or Alzheimer's disease, and commonly viewed dementia as a normal part of aging. Being older, incorrect knowledge about etiology, not having heard of the terms dementia and/or Alzheimer's disease, having less than primary education, and being from North Sumatra were associated with more negative attitudes (p‐values < 0.05). DISCUSSION Misconceptions and lack of awareness about dementia are common in Indonesia. Attitudes tended not to be negative, but our research highlights factors associated with dementia attitudes. Future research should use this information to better tailor and target potential anti‐stigma strategies. Highlights Most Indonesians had not heard of the terms dementia and/or Alzheimer's disease and thought it was caused by normal aging. The majority of participants held mixed or positive attitudes towards dementia. A series of demographic factors alongside poor awareness were associated with negative attitudes towards dementia.
{"title":"Awareness, attitudes, and beliefs of dementia in Indonesia","authors":"Nicolas Farina, Esra Hassan, I. Theresia, F. Fitri, Ika Suswanti, T. P. Sani, Sara Evans-Lacko, Sube Banerjee, Y. Turana","doi":"10.1002/dad2.12570","DOIUrl":"https://doi.org/10.1002/dad2.12570","url":null,"abstract":"Abstract INTRODUCTION Tackling dementia stigma is a policy priority. In Indonesia, we have little insight into the general public's knowledge and attitudes about dementia. METHODS Cross‐sectional study of 4430 Indonesian adults recruited from Jakarta and North Sumatra, Indonesia. Measures included dementia knowledge and attitudes. RESULTS A total of 86.3% (n = 3,803) of adults had not heard of the terms dementia or Alzheimer's disease, and commonly viewed dementia as a normal part of aging. Being older, incorrect knowledge about etiology, not having heard of the terms dementia and/or Alzheimer's disease, having less than primary education, and being from North Sumatra were associated with more negative attitudes (p‐values < 0.05). DISCUSSION Misconceptions and lack of awareness about dementia are common in Indonesia. Attitudes tended not to be negative, but our research highlights factors associated with dementia attitudes. Future research should use this information to better tailor and target potential anti‐stigma strategies. Highlights Most Indonesians had not heard of the terms dementia and/or Alzheimer's disease and thought it was caused by normal aging. The majority of participants held mixed or positive attitudes towards dementia. A series of demographic factors alongside poor awareness were associated with negative attitudes towards dementia.","PeriodicalId":516929,"journal":{"name":"Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140782273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alejandra Morlett Paredes, W. Tarraf, Kevin A. González, A. Stickel, Lisa V. Graves, David P. Salmon, Sonya Kaur, Linda C. Gallo, C. Isasi, Richard B. Lipton, Melissa Lamar, Zachary T. Goodman, Hector M. González
Abstract INTRODUCTION Executive functioning and processing speed are crucial elements of neuropsychological assessment. To meet the needs of the Hispanic/Latino population, we aimed to provide normative data for the Digit Symbol Substitution (DSS) test. METHODS The target population for the Study of Latinos‐Investigation of Neurocognitive Aging included six heritage backgrounds (n = 6177). Average age was 63.4 ± 8.3 years, 54.5% were female, and mean education was 11.0 ± 4.7 years. Participants were administered the DSS as part of a larger battery. Heritage‐adjusted DSS scores, and percentile cut‐points were created using survey‐adjusted regression and quantile regression models. RESULTS Age, education, sex, heritage, and language preference were associated with DSS scores. DISCUSSION Significant correlates of DSS performance should be considered when evaluating cognitive performance. Representative DSS norms for Hispanics/Latinos will advance assessment and accuracy of neurocognitive disorder diagnosis in clinical practice. To facilitate interpretation, we provide norms to reduce test biases and developed an online dashboard. Highlights Normative data for the Digit Symbol Substitution (DSS) for diverse Hispanic/Latino adults: Results from the Study of Latinos‐Investigation of Neurocognitive Aging (SOL‐INCA) This study is the first to develop norms for the DSS test across four regions of the United States. Factors such as age, education, sex, and Hispanic/Latino heritage and language preference are associated with differences in executive functioning and information processing speed. We created norms and an online dashboard (https://solincalab.shinyapps.io/dsst_shiny/) providing an easily accessible tool to evaluate processing speed and executive functioning in Hispanic/Latino adults.
{"title":"Normative data for the Digit Symbol Substitution for diverse Hispanic/Latino adults: Results from the Study of Latinos‐Investigation of Neurocognitive Aging (SOL‐INCA)","authors":"Alejandra Morlett Paredes, W. Tarraf, Kevin A. González, A. Stickel, Lisa V. Graves, David P. Salmon, Sonya Kaur, Linda C. Gallo, C. Isasi, Richard B. Lipton, Melissa Lamar, Zachary T. Goodman, Hector M. González","doi":"10.1002/dad2.12573","DOIUrl":"https://doi.org/10.1002/dad2.12573","url":null,"abstract":"Abstract INTRODUCTION Executive functioning and processing speed are crucial elements of neuropsychological assessment. To meet the needs of the Hispanic/Latino population, we aimed to provide normative data for the Digit Symbol Substitution (DSS) test. METHODS The target population for the Study of Latinos‐Investigation of Neurocognitive Aging included six heritage backgrounds (n = 6177). Average age was 63.4 ± 8.3 years, 54.5% were female, and mean education was 11.0 ± 4.7 years. Participants were administered the DSS as part of a larger battery. Heritage‐adjusted DSS scores, and percentile cut‐points were created using survey‐adjusted regression and quantile regression models. RESULTS Age, education, sex, heritage, and language preference were associated with DSS scores. DISCUSSION Significant correlates of DSS performance should be considered when evaluating cognitive performance. Representative DSS norms for Hispanics/Latinos will advance assessment and accuracy of neurocognitive disorder diagnosis in clinical practice. To facilitate interpretation, we provide norms to reduce test biases and developed an online dashboard. Highlights Normative data for the Digit Symbol Substitution (DSS) for diverse Hispanic/Latino adults: Results from the Study of Latinos‐Investigation of Neurocognitive Aging (SOL‐INCA) This study is the first to develop norms for the DSS test across four regions of the United States. Factors such as age, education, sex, and Hispanic/Latino heritage and language preference are associated with differences in executive functioning and information processing speed. We created norms and an online dashboard (https://solincalab.shinyapps.io/dsst_shiny/) providing an easily accessible tool to evaluate processing speed and executive functioning in Hispanic/Latino adults.","PeriodicalId":516929,"journal":{"name":"Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140354095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Renée C. Groechel, Albert C. Liu, Chelsea Liu, D. Knopman, S. Koton, Anna M. Kucharska‐Newton, P. Lutsey, Thomas H. Mosley, Priya Palta, A. R. Sharrett, Keenan A Walker, Dean F. Wong, Rebecca F. Gottesman
Abstract INTRODUCTION This study aimed to assess whether social relationships in mid‐life reduce the risk of dementia related to amyloid burden. METHODS Participants in the Atherosclerosis Risk in Communities (ARIC) study were assessed for social support and isolation (visit 2; 1990–1992). A composite measure, “social relationships,” was generated. Brain amyloid was evaluated with florbetapir positron emission tomography (PET); (visit 5; 2012–2014). Incident dementia cases were identified following visit 5 through 2019 using ongoing surveillance. Relative contributions of mid‐life social relationships and elevated brain amyloid to incident dementia were evaluated with Cox regression models. RESULTS Among 310 participants without dementia, strong mid‐life social relationships were associated independently with lower dementia risk. Elevated late‐life brain amyloid was associated with greater dementia risk. DISCUSSION Although mid‐life social relationships did not moderate the relationship between amyloid burden and dementia, these findings affirm the importance of strong social relationships as a potentially protective factor against dementia.
{"title":"Social relationships, amyloid burden, and dementia: The ARIC‐PET study","authors":"Renée C. Groechel, Albert C. Liu, Chelsea Liu, D. Knopman, S. Koton, Anna M. Kucharska‐Newton, P. Lutsey, Thomas H. Mosley, Priya Palta, A. R. Sharrett, Keenan A Walker, Dean F. Wong, Rebecca F. Gottesman","doi":"10.1002/dad2.12560","DOIUrl":"https://doi.org/10.1002/dad2.12560","url":null,"abstract":"Abstract INTRODUCTION This study aimed to assess whether social relationships in mid‐life reduce the risk of dementia related to amyloid burden. METHODS Participants in the Atherosclerosis Risk in Communities (ARIC) study were assessed for social support and isolation (visit 2; 1990–1992). A composite measure, “social relationships,” was generated. Brain amyloid was evaluated with florbetapir positron emission tomography (PET); (visit 5; 2012–2014). Incident dementia cases were identified following visit 5 through 2019 using ongoing surveillance. Relative contributions of mid‐life social relationships and elevated brain amyloid to incident dementia were evaluated with Cox regression models. RESULTS Among 310 participants without dementia, strong mid‐life social relationships were associated independently with lower dementia risk. Elevated late‐life brain amyloid was associated with greater dementia risk. DISCUSSION Although mid‐life social relationships did not moderate the relationship between amyloid burden and dementia, these findings affirm the importance of strong social relationships as a potentially protective factor against dementia.","PeriodicalId":516929,"journal":{"name":"Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140757310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lara Blömeke, Fabian Rehn, Victoria Kraemer-Schulien, J. Kutzsche, Marlene Pils, T. Bujnicki, P. Lewczuk, J. Kornhuber, S. D. Freiesleben, Luisa-Sophie Schneider, L. Preis, J. Priller, E. Spruth, S. Altenstein, A. Lohse, Anja Schneider, Klaus Fliessbach, Jens Wiltfang, Niels Hansen, A. Rostamzadeh, E. Düzel, W. Glanz, E. Incesoy, M. Butryn, K. Buerger, D. Janowitz, Michael Ewers, Robert Perneczky, B. Rauchmann, Stefan J Teipel, I. Kilimann, Doreen Goerss, C. Laske, M. Munk, C. Sanzenbacher, A. Spottke, Nina Roy-Kluth, Michael T. Heneka, F. Brosseron, Michael Wagner, S. Wolfsgruber, L. Kleineidam, Melina Stark, Matthias C Schmid, Frank Jessen, Oliver Bannach, Dieter Willbold, Oliver Peters
Abstract INTRODUCTION Soluble amyloid beta (Aβ) oligomers have been suggested as initiating Aβ related neuropathologic change in Alzheimer's disease (AD) but their quantitative distribution and chronological sequence within the AD continuum remain unclear. METHODS A total of 526 participants in early clinical stages of AD and controls from a longitudinal cohort were neurobiologically classified for amyloid and tau pathology applying the AT(N) system. Aβ and tau oligomers in the quantified cerebrospinal fluid (CSF) were measured using surface‐based fluorescence intensity distribution analysis (sFIDA) technology. RESULTS Across groups, highest Aβ oligomer levels were found in A+ with subjective cognitive decline and mild cognitive impairment. Aβ oligomers were significantly higher in A+T− compared to A−T− and A+T+. APOE ε4 allele carriers showed significantly higher Aβ oligomer levels. No differences in tau oligomers were detected. DISCUSSION The accumulation of Aβ oligomers in the CSF peaks early within the AD continuum, preceding tau pathology. Disease‐modifying treatments targeting Aβ oligomers might have the highest therapeutic effect in these disease stages. Highlights Using surface‐based fluorescence intensity distribution analysis (sFIDA) technology, we quantified Aβ oligomers in cerebrospinal fluid (CSF) samples of the DZNE‐Longitudinal Cognitive Impairment and Dementia (DELCODE) cohort Aβ oligomers were significantly elevated in mild cognitive impairment (MCI) Amyloid‐positive subjects in the subjective cognitive decline (SCD) group increased compared to the amyloid‐negative control group Interestingly, levels of Aβ oligomers decrease at advanced stages of the disease (A+T+), which might be explained by altered clearing mechanisms
{"title":"Aβ oligomers peak in early stages of Alzheimer's disease preceding tau pathology","authors":"Lara Blömeke, Fabian Rehn, Victoria Kraemer-Schulien, J. Kutzsche, Marlene Pils, T. Bujnicki, P. Lewczuk, J. Kornhuber, S. D. Freiesleben, Luisa-Sophie Schneider, L. Preis, J. Priller, E. Spruth, S. Altenstein, A. Lohse, Anja Schneider, Klaus Fliessbach, Jens Wiltfang, Niels Hansen, A. Rostamzadeh, E. Düzel, W. Glanz, E. Incesoy, M. Butryn, K. Buerger, D. Janowitz, Michael Ewers, Robert Perneczky, B. Rauchmann, Stefan J Teipel, I. Kilimann, Doreen Goerss, C. Laske, M. Munk, C. Sanzenbacher, A. Spottke, Nina Roy-Kluth, Michael T. Heneka, F. Brosseron, Michael Wagner, S. Wolfsgruber, L. Kleineidam, Melina Stark, Matthias C Schmid, Frank Jessen, Oliver Bannach, Dieter Willbold, Oliver Peters","doi":"10.1002/dad2.12589","DOIUrl":"https://doi.org/10.1002/dad2.12589","url":null,"abstract":"Abstract INTRODUCTION Soluble amyloid beta (Aβ) oligomers have been suggested as initiating Aβ related neuropathologic change in Alzheimer's disease (AD) but their quantitative distribution and chronological sequence within the AD continuum remain unclear. METHODS A total of 526 participants in early clinical stages of AD and controls from a longitudinal cohort were neurobiologically classified for amyloid and tau pathology applying the AT(N) system. Aβ and tau oligomers in the quantified cerebrospinal fluid (CSF) were measured using surface‐based fluorescence intensity distribution analysis (sFIDA) technology. RESULTS Across groups, highest Aβ oligomer levels were found in A+ with subjective cognitive decline and mild cognitive impairment. Aβ oligomers were significantly higher in A+T− compared to A−T− and A+T+. APOE ε4 allele carriers showed significantly higher Aβ oligomer levels. No differences in tau oligomers were detected. DISCUSSION The accumulation of Aβ oligomers in the CSF peaks early within the AD continuum, preceding tau pathology. Disease‐modifying treatments targeting Aβ oligomers might have the highest therapeutic effect in these disease stages. Highlights Using surface‐based fluorescence intensity distribution analysis (sFIDA) technology, we quantified Aβ oligomers in cerebrospinal fluid (CSF) samples of the DZNE‐Longitudinal Cognitive Impairment and Dementia (DELCODE) cohort Aβ oligomers were significantly elevated in mild cognitive impairment (MCI) Amyloid‐positive subjects in the subjective cognitive decline (SCD) group increased compared to the amyloid‐negative control group Interestingly, levels of Aβ oligomers decrease at advanced stages of the disease (A+T+), which might be explained by altered clearing mechanisms","PeriodicalId":516929,"journal":{"name":"Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140769721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alison R Huang, George W. Rebok, B. Swenor, Jennifer A. Deal
Abstract BACKGROUND Cognitive training is delivered visually and aurally. It is unknown whether self‐reported sensory difficulty modifies the effects of cognitive training on cognition. METHODS Participants (N = 2788) in the Advanced Cognitive Training for Independent and Vital Elderly Study were randomized to training in memory, reasoning, speed of processing, or control. Differences in the 10‐year effect of cognitive training on cognition by self‐reported vision and hearing difficulty were assessed using linear mixed effect models. RESULTS Benefit (intervention vs. control) of reasoning training was smaller among participants with versus without vision difficulty (difficulty: –0.25, 95% confidence interval: [–0.88, 0.39], no difficulty: 0.58 [0.28, 0.89]). Benefit of memory training was greater for participants with versus without hearing difficulty (difficulty: 0.17 [–0.37, 0.72], no difficulty: –0.20 [–0.65, 0.24]). DISCUSSION Older adults with sensory loss have increased risk for cognitive decline; benefits of cognitive training may be greater for these individuals. Sensory loss should be considered in training design. Highlights Memory training was more beneficial for participants with hearing loss. Participants with vision difficulties did not benefit as much from reasoning training. Low accessibility in design and learned compensation strategies may contribute. Consideration of sensory impairment in study design is needed. Inclusion of older adults with sensory impairment in cognitive training is needed.
{"title":"Vision and hearing difficulty and effects of cognitive training in older adults","authors":"Alison R Huang, George W. Rebok, B. Swenor, Jennifer A. Deal","doi":"10.1002/dad2.12537","DOIUrl":"https://doi.org/10.1002/dad2.12537","url":null,"abstract":"Abstract BACKGROUND Cognitive training is delivered visually and aurally. It is unknown whether self‐reported sensory difficulty modifies the effects of cognitive training on cognition. METHODS Participants (N = 2788) in the Advanced Cognitive Training for Independent and Vital Elderly Study were randomized to training in memory, reasoning, speed of processing, or control. Differences in the 10‐year effect of cognitive training on cognition by self‐reported vision and hearing difficulty were assessed using linear mixed effect models. RESULTS Benefit (intervention vs. control) of reasoning training was smaller among participants with versus without vision difficulty (difficulty: –0.25, 95% confidence interval: [–0.88, 0.39], no difficulty: 0.58 [0.28, 0.89]). Benefit of memory training was greater for participants with versus without hearing difficulty (difficulty: 0.17 [–0.37, 0.72], no difficulty: –0.20 [–0.65, 0.24]). DISCUSSION Older adults with sensory loss have increased risk for cognitive decline; benefits of cognitive training may be greater for these individuals. Sensory loss should be considered in training design. Highlights Memory training was more beneficial for participants with hearing loss. Participants with vision difficulties did not benefit as much from reasoning training. Low accessibility in design and learned compensation strategies may contribute. Consideration of sensory impairment in study design is needed. Inclusion of older adults with sensory impairment in cognitive training is needed.","PeriodicalId":516929,"journal":{"name":"Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140780744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dario Bachmann, Andreas Buchmann, Sandro Studer, A. Saake, Katrin Rauen, Esmeralda Gruber, R. Nitsch, Christoph Hock, A. Gietl, Valerie Treyer
Abstract INTRODUCTION Female sex is associated with increased [18F]‐flortaucipir signal, which may be affected by amyloid pathology, age, and off‐target binding in skull and meninges. METHODS In this cross‐sectional study comprising 52 females and 52 matched males, we examined sex‐related differences in regional tau‐positron emission tomography (PET) with and without considering off‐target binding. We assessed the respective contributions of sex, age, amyloid‐PET burden, and off‐target binding to tau‐PET signal. We explored associations between age at menopause and hormone replacement therapy (HRT) use with regional tau‐PET signals. RESULTS Female sex was associated with increased regional tau both independently and interactively with amyloid, but amyloid‐independent associations were largely reduced when controlling for off‐target binding. Age but not age*sex interactions explained a small but significant amount of tau‐PET signal in temporoparietal regions. Considering the sample size and limited range of amyloid‐PET burden, no clear associations between regional tau‐PET signals and age at menopause or HRT use could be found. DISCUSSION Female sex is associated with increased [18F]‐flortaucipir signal mainly through its interaction with amyloid.
摘要 引言 女性性别与[18F]-flortaucipir信号的增加有关，这可能受到淀粉样病理、年龄以及头骨和脑膜脱靶结合的影响。方法 在这项由 52 名女性和 52 名匹配男性组成的横断面研究中，我们研究了在考虑和不考虑脱靶结合的情况下，区域性 tau 正电子发射断层扫描（PET）与性别相关的差异。我们评估了性别、年龄、淀粉样蛋白-PET负担和脱靶结合对tau-PET信号的贡献。我们还探讨了绝经年龄和使用激素替代疗法（HRT）与区域 tau-PET 信号之间的关系。结果 女性性别与区域性 tau 增高相关，既独立于淀粉样蛋白，也与淀粉样蛋白相互作用，但在控制脱靶结合后，与淀粉样蛋白无关的相关性大大降低。年龄而非年龄*性别的相互作用解释了颞顶叶区域少量但重要的tau-PET信号。考虑到样本量和有限的淀粉样蛋白-PET负担范围，没有发现区域tau-PET信号与绝经年龄或使用HRT之间有明显的关联。讨论 女性性别与[18F]-flortaucipir信号增加有关，主要是通过其与淀粉样蛋白的相互作用。
{"title":"Explaining variability in early stages of [18F]‐flortaucipir tau‐PET binding: Focus on sex differences","authors":"Dario Bachmann, Andreas Buchmann, Sandro Studer, A. Saake, Katrin Rauen, Esmeralda Gruber, R. Nitsch, Christoph Hock, A. Gietl, Valerie Treyer","doi":"10.1002/dad2.12565","DOIUrl":"https://doi.org/10.1002/dad2.12565","url":null,"abstract":"Abstract INTRODUCTION Female sex is associated with increased [18F]‐flortaucipir signal, which may be affected by amyloid pathology, age, and off‐target binding in skull and meninges. METHODS In this cross‐sectional study comprising 52 females and 52 matched males, we examined sex‐related differences in regional tau‐positron emission tomography (PET) with and without considering off‐target binding. We assessed the respective contributions of sex, age, amyloid‐PET burden, and off‐target binding to tau‐PET signal. We explored associations between age at menopause and hormone replacement therapy (HRT) use with regional tau‐PET signals. RESULTS Female sex was associated with increased regional tau both independently and interactively with amyloid, but amyloid‐independent associations were largely reduced when controlling for off‐target binding. Age but not age*sex interactions explained a small but significant amount of tau‐PET signal in temporoparietal regions. Considering the sample size and limited range of amyloid‐PET burden, no clear associations between regional tau‐PET signals and age at menopause or HRT use could be found. DISCUSSION Female sex is associated with increased [18F]‐flortaucipir signal mainly through its interaction with amyloid.","PeriodicalId":516929,"journal":{"name":"Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140077626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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