Joyce R. Chong, Yuek Ling Chai, Amelia T. Y. Yam, S. Hilal, Henri Vrooman, Narayanaswamy Venketasubramanian, K. Blennow, Henrik Zetterberg, N. Ashton, Christopher P Chen, Mitchell Kim Peng Lai
Abstract INTRODUCTION While elevated blood glial fibrillary acidic protein (GFAP) has been associated with brain amyloid pathology, whether this association occurs in populations with high cerebral small vessel disease (CSVD) concomitance remains unclear. METHODS Using a Singapore‐based cohort of cognitively impaired subjects, we assessed associations between plasma GFAP and neuroimaging measures of brain amyloid and CSVD, including white matter hyperintensities (WMH). We also examined the diagnostic performance of plasma GFAP in detecting brain amyloid beta positivity (Aβ+). RESULTS When stratified by WMH status, elevated brain amyloid was associated with higher plasma GFAP only in the WMH– group (β = 0.383; P < 0.001). The diagnostic performance of plasma GFAP in identifying Aβ+ was significantly higher in the WMH– group (area under the curve [AUC] = 0.896) than in the WMH+ group (AUC = 0.712, P = 0.008). DISCUSSION The biomarker utility of plasma GFAP in detecting brain amyloid pathology is dependent on the severity of concomitant WMH. Highlight Glial fibrillary acidic protein (GFAP)’s association with brain amyloid is unclear in populations with high cerebral small vessel disease (CSVD). Plasma GFAP was measured in a cohort with CSVD and brain amyloid. Plasma GFAP was better in detecting amyloid in patients with low CSVD versus high CSVD. Biomarker utility of GFAP in detecting brain amyloid depends on the severity of CSVD.
{"title":"Association of plasma GFAP with elevated brain amyloid is dependent on severity of white matter lesions in an Asian cognitively impaired cohort","authors":"Joyce R. Chong, Yuek Ling Chai, Amelia T. Y. Yam, S. Hilal, Henri Vrooman, Narayanaswamy Venketasubramanian, K. Blennow, Henrik Zetterberg, N. Ashton, Christopher P Chen, Mitchell Kim Peng Lai","doi":"10.1002/dad2.12576","DOIUrl":"https://doi.org/10.1002/dad2.12576","url":null,"abstract":"Abstract INTRODUCTION While elevated blood glial fibrillary acidic protein (GFAP) has been associated with brain amyloid pathology, whether this association occurs in populations with high cerebral small vessel disease (CSVD) concomitance remains unclear. METHODS Using a Singapore‐based cohort of cognitively impaired subjects, we assessed associations between plasma GFAP and neuroimaging measures of brain amyloid and CSVD, including white matter hyperintensities (WMH). We also examined the diagnostic performance of plasma GFAP in detecting brain amyloid beta positivity (Aβ+). RESULTS When stratified by WMH status, elevated brain amyloid was associated with higher plasma GFAP only in the WMH– group (β = 0.383; P < 0.001). The diagnostic performance of plasma GFAP in identifying Aβ+ was significantly higher in the WMH– group (area under the curve [AUC] = 0.896) than in the WMH+ group (AUC = 0.712, P = 0.008). DISCUSSION The biomarker utility of plasma GFAP in detecting brain amyloid pathology is dependent on the severity of concomitant WMH. Highlight Glial fibrillary acidic protein (GFAP)’s association with brain amyloid is unclear in populations with high cerebral small vessel disease (CSVD). Plasma GFAP was measured in a cohort with CSVD and brain amyloid. Plasma GFAP was better in detecting amyloid in patients with low CSVD versus high CSVD. Biomarker utility of GFAP in detecting brain amyloid depends on the severity of CSVD.","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":"140761757","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 Introduction The distribution of voxel‐ and connection‐based white matter hyperintensity (WMH) patterns in early‐onset Alzheimer's disease (EOAD) and late‐onset Alzheimer's disease (LOAD), as well as factors associated with these patterns, remain unclear. Method We analyzed the WMH distribution patterns in EOAD and LOAD at the voxel and connection levels, each compared with their age‐matched cognitively unimpaired participants. Linear regression assessed the independent effects of amyloid and vascular risk factors on WMH distribution patterns in both groups. Results Patients with EOAD showed increased WMH burden in the posterior region at the voxel level, and in occipital region tracts and visual network at the connection level, compared to controls. LOAD exhibited extensive involvement across various brain areas in both levels. Amyloid accumulation was associated WMH distribution in the early‐onset group, whereas the late‐onset group demonstrated associations with both amyloid and vascular risk factors. Discussion EOAD showed posterior‐focused WMH distribution pattern, whereas LOAD was with a wider distribution. Amyloid accumulation was associated with connection‐based WMH patterns in both early‐onset and late‐onset groups, with additional independent effects of vascular risk factors in late‐onset group. Highlights Both early‐onset Alzheimer's disease (EOAD) and late‐onset AD (LOAD) showed increased white matter hyperintensity (WMH) volume compared with their age‐matched cognitively unimpaired participants. EOAD and LOAD exhibited distinct patterns of WMH distribution, with EOAD showing a posterior‐focused pattern and LOAD displaying a wider distribution across both voxel‐ and connection‐based levels. In both EOAD and LOAD, amyloid accumulation was associated with connection‐based WMH patterns, with additional independent effects of vascular risk factors observed in LOAD.
{"title":"Distinct patterns of voxel‐ and connection‐based white matter hyperintensity distribution and associated factors in early‐onset and late‐onset Alzheimer's disease","authors":"Hui Hong, Yutong Chen, Weiran Liu, Xiao Luo, Minming Zhang","doi":"10.1002/dad2.12585","DOIUrl":"https://doi.org/10.1002/dad2.12585","url":null,"abstract":"Abstract Introduction The distribution of voxel‐ and connection‐based white matter hyperintensity (WMH) patterns in early‐onset Alzheimer's disease (EOAD) and late‐onset Alzheimer's disease (LOAD), as well as factors associated with these patterns, remain unclear. Method We analyzed the WMH distribution patterns in EOAD and LOAD at the voxel and connection levels, each compared with their age‐matched cognitively unimpaired participants. Linear regression assessed the independent effects of amyloid and vascular risk factors on WMH distribution patterns in both groups. Results Patients with EOAD showed increased WMH burden in the posterior region at the voxel level, and in occipital region tracts and visual network at the connection level, compared to controls. LOAD exhibited extensive involvement across various brain areas in both levels. Amyloid accumulation was associated WMH distribution in the early‐onset group, whereas the late‐onset group demonstrated associations with both amyloid and vascular risk factors. Discussion EOAD showed posterior‐focused WMH distribution pattern, whereas LOAD was with a wider distribution. Amyloid accumulation was associated with connection‐based WMH patterns in both early‐onset and late‐onset groups, with additional independent effects of vascular risk factors in late‐onset group. Highlights Both early‐onset Alzheimer's disease (EOAD) and late‐onset AD (LOAD) showed increased white matter hyperintensity (WMH) volume compared with their age‐matched cognitively unimpaired participants. EOAD and LOAD exhibited distinct patterns of WMH distribution, with EOAD showing a posterior‐focused pattern and LOAD displaying a wider distribution across both voxel‐ and connection‐based levels. In both EOAD and LOAD, amyloid accumulation was associated with connection‐based WMH patterns, with additional independent effects of vascular risk factors observed in LOAD.","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":"140790094","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}
E. Schworer, B. Handen, Melissa E. Petersen, S. O'Bryant, Jamie C. Peven, D. Tudorascu, Laisze Lee, S. Krinsky-McHale, C. Hom, Isabel Clare, Bradley T. Christian, N. Schupf, Joseph H. Lee, Elizabeth Head, M. Mapstone, Ira T. Lott, B. Ances, Shahid H. Zaman, Adam M. Brickman, F. Lai, H. D. Rosas, S. Hartley
Abstract INTRODUCTION People with Down syndrome (DS) have a 75% to 90% lifetime risk of Alzheimer's disease (AD). AD pathology begins a decade or more prior to onset of clinical AD dementia in people with DS. It is not clear if plasma biomarkers of AD pathology are correlated with early cognitive and functional impairments in DS, and if these biomarkers could be used to track the early stages of AD in DS or to inform inclusion criteria for clinical AD treatment trials. METHODS This large cross‐sectional cohort study investigated the associations between plasma biomarkers of amyloid beta (Aβ)42/40, total tau, and neurofilament light chain (NfL) and cognitive (episodic memory, visual–motor integration, and visuospatial abilities) and functional (adaptive behavior) impairments in 260 adults with DS without dementia (aged 25–81 years). RESULTS In general linear models lower plasma Aβ42/40 was related to lower visuospatial ability, higher total tau was related to lower episodic memory, and higher NfL was related to lower visuospatial ability and lower episodic memory. DISCUSSION Plasma biomarkers may have utility in tracking AD pathology associated with early stages of cognitive decline in adults with DS, although associations were modest. Highlights Plasma Alzheimer's disease (AD) biomarkers correlate with cognition prior to dementia in Down syndrome. Lower plasma amyloid beta 42/40 was related to lower visuospatial abilities. Higher plasma total tau and neurofilament light chain were associated with lower cognitive performance. Plasma biomarkers show potential for tracking early stages of AD symptomology.
{"title":"Cognitive and functional performance and plasma biomarkers of early Alzheimer's disease in Down syndrome","authors":"E. Schworer, B. Handen, Melissa E. Petersen, S. O'Bryant, Jamie C. Peven, D. Tudorascu, Laisze Lee, S. Krinsky-McHale, C. Hom, Isabel Clare, Bradley T. Christian, N. Schupf, Joseph H. Lee, Elizabeth Head, M. Mapstone, Ira T. Lott, B. Ances, Shahid H. Zaman, Adam M. Brickman, F. Lai, H. D. Rosas, S. Hartley","doi":"10.1002/dad2.12582","DOIUrl":"https://doi.org/10.1002/dad2.12582","url":null,"abstract":"Abstract INTRODUCTION People with Down syndrome (DS) have a 75% to 90% lifetime risk of Alzheimer's disease (AD). AD pathology begins a decade or more prior to onset of clinical AD dementia in people with DS. It is not clear if plasma biomarkers of AD pathology are correlated with early cognitive and functional impairments in DS, and if these biomarkers could be used to track the early stages of AD in DS or to inform inclusion criteria for clinical AD treatment trials. METHODS This large cross‐sectional cohort study investigated the associations between plasma biomarkers of amyloid beta (Aβ)42/40, total tau, and neurofilament light chain (NfL) and cognitive (episodic memory, visual–motor integration, and visuospatial abilities) and functional (adaptive behavior) impairments in 260 adults with DS without dementia (aged 25–81 years). RESULTS In general linear models lower plasma Aβ42/40 was related to lower visuospatial ability, higher total tau was related to lower episodic memory, and higher NfL was related to lower visuospatial ability and lower episodic memory. DISCUSSION Plasma biomarkers may have utility in tracking AD pathology associated with early stages of cognitive decline in adults with DS, although associations were modest. Highlights Plasma Alzheimer's disease (AD) biomarkers correlate with cognition prior to dementia in Down syndrome. Lower plasma amyloid beta 42/40 was related to lower visuospatial abilities. Higher plasma total tau and neurofilament light chain were associated with lower cognitive performance. Plasma biomarkers show potential for tracking early stages of AD symptomology.","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":"140759156","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}
Luwen Cao, Kunmei Han, Li Lin, J. Hing, Vincent Ooi, Nick Huang, Junhong Yu, Ted Kheng Siang Ng, Lei Feng, Rathi Mahendran, E. Kua, Zhiming Bao
Abstract INTRODUCTION Patients with Alzheimer's disease present with difficulty in lexical retrieval and reversal of the concreteness effect in nouns. Little is known about the phenomena before the onset of symptoms. We anticipate early linguistic signs in the speech of people who suffer from amnestic mild cognitive impairment (MCI). Here, we report the results of a corpus‐linguistic approach to the early detection of cognitive impairment. METHODS One hundred forty‐eight English‐speaking Singaporeans provided natural speech data, on topics of their choice; 74 were diagnosed with single‐domain MCI (38 amnestic, 36 non‐amnestic), 74 cognitively healthy. The recordings yield 267,310 words, which are tagged for parts of speech. We calculate the per‐minute word counts and concreteness scores of all tagged words, nouns, and verbs in the dataset. RESULTS Compared to controls, subjects with amnestic MCI produce fewer but more abstract nouns. Verbs are not affected. DISCUSSION Slower retrieval of nouns and the reversal of the concreteness effect in nouns are manifested in natural speech and can be detected early through corpus‐based analysis. Highlights Reversal of the concreteness effect is manifested in patients with Alzheimer's disease (AD) and semantic dementia. The paper reports a corpus‐based analysis of natural speech by people with amnestic and non‐amnestic mild cognitive impairment (MCI) and cognitively healthy controls. People with amnestic MCI produce fewer and more abstract nouns than people with non‐amnestic MCI and healthy controls. Verbs appear to be unaffected. The imageability problem can be detected in natural everyday speech by people with amnestic MCI, which carries a higher risk of conversion to AD.
{"title":"Reversal of the concreteness effect can be detected in the natural speech of older adults with amnestic, but not non‐amnestic, mild cognitive impairment","authors":"Luwen Cao, Kunmei Han, Li Lin, J. Hing, Vincent Ooi, Nick Huang, Junhong Yu, Ted Kheng Siang Ng, Lei Feng, Rathi Mahendran, E. Kua, Zhiming Bao","doi":"10.1002/dad2.12588","DOIUrl":"https://doi.org/10.1002/dad2.12588","url":null,"abstract":"Abstract INTRODUCTION Patients with Alzheimer's disease present with difficulty in lexical retrieval and reversal of the concreteness effect in nouns. Little is known about the phenomena before the onset of symptoms. We anticipate early linguistic signs in the speech of people who suffer from amnestic mild cognitive impairment (MCI). Here, we report the results of a corpus‐linguistic approach to the early detection of cognitive impairment. METHODS One hundred forty‐eight English‐speaking Singaporeans provided natural speech data, on topics of their choice; 74 were diagnosed with single‐domain MCI (38 amnestic, 36 non‐amnestic), 74 cognitively healthy. The recordings yield 267,310 words, which are tagged for parts of speech. We calculate the per‐minute word counts and concreteness scores of all tagged words, nouns, and verbs in the dataset. RESULTS Compared to controls, subjects with amnestic MCI produce fewer but more abstract nouns. Verbs are not affected. DISCUSSION Slower retrieval of nouns and the reversal of the concreteness effect in nouns are manifested in natural speech and can be detected early through corpus‐based analysis. Highlights Reversal of the concreteness effect is manifested in patients with Alzheimer's disease (AD) and semantic dementia. The paper reports a corpus‐based analysis of natural speech by people with amnestic and non‐amnestic mild cognitive impairment (MCI) and cognitively healthy controls. People with amnestic MCI produce fewer and more abstract nouns than people with non‐amnestic MCI and healthy controls. Verbs appear to be unaffected. The imageability problem can be detected in natural everyday speech by people with amnestic MCI, which carries a higher risk of conversion to AD.","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":"140796730","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}
C. Crump, W. Sieh, Barbara G Vickrey, Alexis C Edwards, J. Sundquist, Kristina Sundquist
Abstract INTRODUCTION Depression is a risk factor and possible prodromal symptom of Alzheimer's disease (AD), but little is known about subsequent risk of developing depression in persons with AD. METHODS National matched cohort study was conducted of all 129,410 persons diagnosed with AD and 390,088 with all‐cause dementia during 1998–2017 in Sweden, and 3,900,880 age‐ and sex‐matched controls without dementia, who had no prior depression. Cox regression was used to compute hazard ratios (HRs) for major depression through 2018. RESULTS Cumulative incidence of major depression was 13% in persons with AD and 3% in controls. Adjusting for sociodemographic factors and comorbidities, risk of major depression was greater than two‐fold higher in women with AD (HR, 2.21; 95% confidence interval [CI], 2.11–2.32) or men with AD (2.68; 2.52–2.85), compared with controls. Similar results were found for all‐cause dementia. DISCUSSION Persons diagnosed with AD or related dementias need close follow‐up for timely detection and treatment of depression. Highlights In a large cohort, women and men with AD had >2‐fold subsequent risk of depression. Risks were highest in the first year (>3‐fold) but remained elevated ≥3 years later. Risk of depression was highest in persons aged ≥85 years at AD diagnosis. Persons with AD need close follow‐up for detection and treatment of depression.
{"title":"Risk of depression in persons with Alzheimer's disease: A national cohort study","authors":"C. Crump, W. Sieh, Barbara G Vickrey, Alexis C Edwards, J. Sundquist, Kristina Sundquist","doi":"10.1002/dad2.12584","DOIUrl":"https://doi.org/10.1002/dad2.12584","url":null,"abstract":"Abstract INTRODUCTION Depression is a risk factor and possible prodromal symptom of Alzheimer's disease (AD), but little is known about subsequent risk of developing depression in persons with AD. METHODS National matched cohort study was conducted of all 129,410 persons diagnosed with AD and 390,088 with all‐cause dementia during 1998–2017 in Sweden, and 3,900,880 age‐ and sex‐matched controls without dementia, who had no prior depression. Cox regression was used to compute hazard ratios (HRs) for major depression through 2018. RESULTS Cumulative incidence of major depression was 13% in persons with AD and 3% in controls. Adjusting for sociodemographic factors and comorbidities, risk of major depression was greater than two‐fold higher in women with AD (HR, 2.21; 95% confidence interval [CI], 2.11–2.32) or men with AD (2.68; 2.52–2.85), compared with controls. Similar results were found for all‐cause dementia. DISCUSSION Persons diagnosed with AD or related dementias need close follow‐up for timely detection and treatment of depression. Highlights In a large cohort, women and men with AD had >2‐fold subsequent risk of depression. Risks were highest in the first year (>3‐fold) but remained elevated ≥3 years later. Risk of depression was highest in persons aged ≥85 years at AD diagnosis. Persons with AD need close follow‐up for detection and treatment of depression.","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":"140765194","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}
Sofia Toniolo, Sijia Zhao, A. Scholcz, B. Amein, A. Ganse-Dumrath, A. Heslegrave, Sian Thompson, Sanjay Manohar, Henrik Zetterberg, Masud Husain
Abstract INTRODUCTION A major limitation in Alzheimer's disease (AD) research is the lack of the ability to measure cognitive performance at scale—robustly, remotely, and frequently. Currently, there are no established online digital platforms validated against plasma biomarkers of AD. METHODS We used a novel web‐based platform that assessed different cognitive functions in AD patients (N = 46) and elderly controls (N = 53) who were also evaluated for plasma biomarkers (amyloid beta 42/40 ratio, phosphorylated tau ([p‐tau]181, glial fibrillary acidic protein, neurofilament light chain). Their cognitive performance was compared to a second, larger group of elderly controls (N = 352). RESULTS Patients with AD were significantly impaired across all digital cognitive tests, with performance correlating with plasma biomarker levels, particularly p‐tau181. The combination of p‐tau181 and the single best‐performing digital test achieved high accuracy in group classification. DISCUSSION These findings show how online testing can now be deployed in patients with AD to measure cognitive function effectively and related to blood biomarkers of the disease. Highlights This is the first study comparing online digital testing to plasma biomarkers. Alzheimer's disease patients and two independent cohorts of elderly controls were assessed. Cognitive performance correlated with plasma biomarkers, particularly phosphorylated tau (p‐tau)181. Glial fibrillary acidic protein and neurofilament light chain, and less so the amyloid beta 42/40 ratio, were also associated with performance. The best cognitive metric performed at par to p‐tau181 in group classification.
{"title":"Relationship of plasma biomarkers to digital cognitive tests in Alzheimer's disease","authors":"Sofia Toniolo, Sijia Zhao, A. Scholcz, B. Amein, A. Ganse-Dumrath, A. Heslegrave, Sian Thompson, Sanjay Manohar, Henrik Zetterberg, Masud Husain","doi":"10.1002/dad2.12590","DOIUrl":"https://doi.org/10.1002/dad2.12590","url":null,"abstract":"Abstract INTRODUCTION A major limitation in Alzheimer's disease (AD) research is the lack of the ability to measure cognitive performance at scale—robustly, remotely, and frequently. Currently, there are no established online digital platforms validated against plasma biomarkers of AD. METHODS We used a novel web‐based platform that assessed different cognitive functions in AD patients (N = 46) and elderly controls (N = 53) who were also evaluated for plasma biomarkers (amyloid beta 42/40 ratio, phosphorylated tau ([p‐tau]181, glial fibrillary acidic protein, neurofilament light chain). Their cognitive performance was compared to a second, larger group of elderly controls (N = 352). RESULTS Patients with AD were significantly impaired across all digital cognitive tests, with performance correlating with plasma biomarker levels, particularly p‐tau181. The combination of p‐tau181 and the single best‐performing digital test achieved high accuracy in group classification. DISCUSSION These findings show how online testing can now be deployed in patients with AD to measure cognitive function effectively and related to blood biomarkers of the disease. Highlights This is the first study comparing online digital testing to plasma biomarkers. Alzheimer's disease patients and two independent cohorts of elderly controls were assessed. Cognitive performance correlated with plasma biomarkers, particularly phosphorylated tau (p‐tau)181. Glial fibrillary acidic protein and neurofilament light chain, and less so the amyloid beta 42/40 ratio, were also associated with performance. The best cognitive metric performed at par to p‐tau181 in group classification.","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":"140778141","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}
Louise N Pivac, B. Brown, Kelsey R. Sewell, J. Doecke, V. Villemagne, V. Doré, M. Weinborn, H. Sohrabi, S. Gardener, R. Bucks, Simon M. Laws, K. Taddei, P. Maruff, Colin L. Masters, Christopher C. Rowe, Ralph N. Martins, S. Rainey-Smith
Abstract INTRODUCTION This study investigated whether self‐reported sleep quality is associated with brain amyloid beta (Aβ) accumulation. METHODS Linear mixed effect model analyses were conducted for 189 cognitively unimpaired (CU) older adults (mean ± standard deviation 74.0 ± 6.2; 53.2% female), with baseline self‐reported sleep data, and positron emission tomography‐determined brain Aβ measured over a minimum of three time points (range 33.3–72.7 months). Analyses included random slopes and intercepts, interaction for apolipoprotein E (APOE) ε4 allele status, and time, adjusting for sex and baseline age. RESULTS Sleep duration <6 hours, in APOE ε4 carriers, and sleep efficiency <65%, in the whole sample and APOE ε4 non‐carriers, is associated with faster accumulation of brain Aβ. DISCUSSION These findings suggest a role for self‐reported suboptimal sleep efficiency and duration in the accumulation of Alzheimer's disease (AD) neuropathology in CU individuals. Additionally, poor sleep efficiency represents a potential route via which individuals at lower genetic risk may progress to preclinical AD. Highlights In cognitively unimpaired older adults self‐report sleep is associated with brain amyloid beta (Aβ) accumulation. Across sleep characteristics, this relationship differs by apolipoprotein E (APOE) genotype. Sleep duration <6 hours is associated with faster brain Aβ accumulation in APOE ε4 carriers. Sleep efficiency < 65% is associated with faster brain Aβ accumulation in APOE ε4 non‐carriers. Personalized sleep interventions should be studied for potential to slow Aβ accumulation.
{"title":"Suboptimal self‐reported sleep efficiency and duration are associated with faster accumulation of brain amyloid beta in cognitively unimpaired older adults","authors":"Louise N Pivac, B. Brown, Kelsey R. Sewell, J. Doecke, V. Villemagne, V. Doré, M. Weinborn, H. Sohrabi, S. Gardener, R. Bucks, Simon M. Laws, K. Taddei, P. Maruff, Colin L. Masters, Christopher C. Rowe, Ralph N. Martins, S. Rainey-Smith","doi":"10.1002/dad2.12579","DOIUrl":"https://doi.org/10.1002/dad2.12579","url":null,"abstract":"Abstract INTRODUCTION This study investigated whether self‐reported sleep quality is associated with brain amyloid beta (Aβ) accumulation. METHODS Linear mixed effect model analyses were conducted for 189 cognitively unimpaired (CU) older adults (mean ± standard deviation 74.0 ± 6.2; 53.2% female), with baseline self‐reported sleep data, and positron emission tomography‐determined brain Aβ measured over a minimum of three time points (range 33.3–72.7 months). Analyses included random slopes and intercepts, interaction for apolipoprotein E (APOE) ε4 allele status, and time, adjusting for sex and baseline age. RESULTS Sleep duration <6 hours, in APOE ε4 carriers, and sleep efficiency <65%, in the whole sample and APOE ε4 non‐carriers, is associated with faster accumulation of brain Aβ. DISCUSSION These findings suggest a role for self‐reported suboptimal sleep efficiency and duration in the accumulation of Alzheimer's disease (AD) neuropathology in CU individuals. Additionally, poor sleep efficiency represents a potential route via which individuals at lower genetic risk may progress to preclinical AD. Highlights In cognitively unimpaired older adults self‐report sleep is associated with brain amyloid beta (Aβ) accumulation. Across sleep characteristics, this relationship differs by apolipoprotein E (APOE) genotype. Sleep duration <6 hours is associated with faster brain Aβ accumulation in APOE ε4 carriers. Sleep efficiency < 65% is associated with faster brain Aβ accumulation in APOE ε4 non‐carriers. Personalized sleep interventions should be studied for potential to slow Aβ accumulation.","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":"140756825","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}
Lisa V. Graves, W. Tarraf, Kevin A. González, M. Bondi, Linda C. Gallo, Carmen R. Isasi, Martha L Daviglus, Melissa Lamar, Donglin Zeng, Jianwen Cai, Hector M. González
Abstract Introduction We investigated cognitive profiles among diverse, middle‐aged and older Hispanic/Latino adults in the Study of Latinos–Investigation of Neurocognitive Aging (SOL‐INCA) cohort using a cross‐sectional observational study design. Methods Based on weighted descriptive statistics, the average baseline age of the target population was 56.4 years, slightly more than half were women (54.6%), and 38.4% reported less than a high school education. We used latent profile analysis of demographically adjusted z scores on SOL‐INCA neurocognitive tests spanning domains of verbal memory, language, processing speed, and executive function. Results Statistical fit assessment indices combined with clinical interpretation suggested five profiles: (1) a Higher Global group performing in the average‐to‐high‐average range across all cognitive and instrumental activity of daily living (IADL) tests (13.8%); (2) a Higher Memory group with relatively high performance on memory tests but average performance across all other cognitive/IADL tests (24.6%); (3) a Lower Memory group with relatively low performance on memory tests but average performance across all other cognitive/IADL tests (32.8%); (4) a Lower Executive Function group with relatively low performance on executive function and processing speed tests but average‐to‐low‐average performance across all other cognitive/IADL tests (16.6%); and (5) a Lower Global group performing low‐average‐to‐mildly impaired across all cognitive/IADL tests (12.1%). Discussion Our results provide evidence of heterogeneity in the cognitive profiles of a representative, community‐dwelling sample of diverse Hispanic/Latino adults. Our analyses yielded cognitive profiles that may assist efforts to better understand the early cognitive changes that may portend Alzheimer's disease and related dementias among diverse Hispanics/Latinos. Highlights The present study characterized cognitive profiles among diverse middle‐aged and older Hispanic/Latino adults. Latent profile analysis of neurocognitive test scores was the primary analysis conducted. The target population consists of middle‐aged and older Hispanic/Latino adults enrolled in the Hispanic Community Health Study/Study of Latinos and ancillary Study of Latinos ‐ Investigation of Neurocognitive Aging.
{"title":"Characterizing cognitive profiles in diverse middle‐aged and older Hispanics/Latinos: Study of Latinos‐Investigation of Neurocognitive Aging (HCHS/SOL)","authors":"Lisa V. Graves, W. Tarraf, Kevin A. González, M. Bondi, Linda C. Gallo, Carmen R. Isasi, Martha L Daviglus, Melissa Lamar, Donglin Zeng, Jianwen Cai, Hector M. González","doi":"10.1002/dad2.12592","DOIUrl":"https://doi.org/10.1002/dad2.12592","url":null,"abstract":"Abstract Introduction We investigated cognitive profiles among diverse, middle‐aged and older Hispanic/Latino adults in the Study of Latinos–Investigation of Neurocognitive Aging (SOL‐INCA) cohort using a cross‐sectional observational study design. Methods Based on weighted descriptive statistics, the average baseline age of the target population was 56.4 years, slightly more than half were women (54.6%), and 38.4% reported less than a high school education. We used latent profile analysis of demographically adjusted z scores on SOL‐INCA neurocognitive tests spanning domains of verbal memory, language, processing speed, and executive function. Results Statistical fit assessment indices combined with clinical interpretation suggested five profiles: (1) a Higher Global group performing in the average‐to‐high‐average range across all cognitive and instrumental activity of daily living (IADL) tests (13.8%); (2) a Higher Memory group with relatively high performance on memory tests but average performance across all other cognitive/IADL tests (24.6%); (3) a Lower Memory group with relatively low performance on memory tests but average performance across all other cognitive/IADL tests (32.8%); (4) a Lower Executive Function group with relatively low performance on executive function and processing speed tests but average‐to‐low‐average performance across all other cognitive/IADL tests (16.6%); and (5) a Lower Global group performing low‐average‐to‐mildly impaired across all cognitive/IADL tests (12.1%). Discussion Our results provide evidence of heterogeneity in the cognitive profiles of a representative, community‐dwelling sample of diverse Hispanic/Latino adults. Our analyses yielded cognitive profiles that may assist efforts to better understand the early cognitive changes that may portend Alzheimer's disease and related dementias among diverse Hispanics/Latinos. Highlights The present study characterized cognitive profiles among diverse middle‐aged and older Hispanic/Latino adults. Latent profile analysis of neurocognitive test scores was the primary analysis conducted. The target population consists of middle‐aged and older Hispanic/Latino adults enrolled in the Hispanic Community Health Study/Study of Latinos and ancillary Study of Latinos ‐ Investigation of Neurocognitive 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":"140768925","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}
F. Kumfor, G. Wei, Nola Ries, Hayley Bennett, M. D'Mello, C. Kaizik, Olivier Piguet, John R. Hodges
Abstract INTRODUCTION Some people with dementia develop changes in behaviour and cognition that may lead to interactions with police or the legal system. However, large, prospective case–control studies examining these behaviours are lacking. METHODS One hundred and forty‐four people with dementia and 53 controls completed the Misdemeanours and Transgressions Screener. RESULTS Criminal risk behaviours were reported in: 65.6% of behavioural‐variant frontotemporal dementia, 46.2% of right‐lateralised semantic dementia, and 27.0% of Alzheimer's disease patients. In 19.1% of patients these behaviours led to contact with police or authority figures. Compared to controls, people with dementia showed higher rates of physical assault (p = 0.024), financial/professional recklessness (p = 0.009), and inappropriate behaviours (p = 0.052). DISCUSSION Criminal risk behaviours are common across dementia subtypes and may be one of the first clinical signs of frontotemporal dementia. Further research to understand how to balance risk minimisation with an individual's liberties as well as the inappropriate criminalisation of people with dementia is needed. Highlights The Misdemeanours and Transgressions Screener is a new tool to assess criminal risk behaviours. Forty‐seven percent of patients with dementia show criminal risk behaviour after dementia onset. Behaviours included verbal abuse, traffic violations, physical assault. New onset of criminal risk behaviours >50 years is a clinical sign for frontotemporal dementia.
{"title":"Examining the propensity and nature of criminal risk behaviours in frontotemporal dementia syndromes and Alzheimer's disease","authors":"F. Kumfor, G. Wei, Nola Ries, Hayley Bennett, M. D'Mello, C. Kaizik, Olivier Piguet, John R. Hodges","doi":"10.1002/dad2.12577","DOIUrl":"https://doi.org/10.1002/dad2.12577","url":null,"abstract":"Abstract INTRODUCTION Some people with dementia develop changes in behaviour and cognition that may lead to interactions with police or the legal system. However, large, prospective case–control studies examining these behaviours are lacking. METHODS One hundred and forty‐four people with dementia and 53 controls completed the Misdemeanours and Transgressions Screener. RESULTS Criminal risk behaviours were reported in: 65.6% of behavioural‐variant frontotemporal dementia, 46.2% of right‐lateralised semantic dementia, and 27.0% of Alzheimer's disease patients. In 19.1% of patients these behaviours led to contact with police or authority figures. Compared to controls, people with dementia showed higher rates of physical assault (p = 0.024), financial/professional recklessness (p = 0.009), and inappropriate behaviours (p = 0.052). DISCUSSION Criminal risk behaviours are common across dementia subtypes and may be one of the first clinical signs of frontotemporal dementia. Further research to understand how to balance risk minimisation with an individual's liberties as well as the inappropriate criminalisation of people with dementia is needed. Highlights The Misdemeanours and Transgressions Screener is a new tool to assess criminal risk behaviours. Forty‐seven percent of patients with dementia show criminal risk behaviour after dementia onset. Behaviours included verbal abuse, traffic violations, physical assault. New onset of criminal risk behaviours >50 years is a clinical sign for frontotemporal 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":"140785373","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 INTRODUCTION Recent Alzheimer's disease (AD) clinical trials have used cerebrospinal fluid (CSF) biomarker levels for screening and enrollment. Preliminary evidence suggests that AD risk is related to impaired renal function. The impact of kidney function on commonly used AD biomarkers remains unknown. METHODS Participants in studies conducted at the Goizueta Alzheimer's Disease Research Center (N = 973) had measurements of serum creatinine and CSF AD biomarkers. General linear models and individual data were used to assess the relationships between biomarkers and eGFR. RESULTS Lower estimated glomerular filtration rate (eGFR) was associated with lower amyloid beta (Aβ)42/tau ratio (p < 0.0001) and Aβ42 (p = 0.002) and higher tau (p < 0.0001) and p‐tau (p = 0.0002). The impact of eGFR on AD biomarker levels was more robust in individuals with cognitive impairment (all p‐values were < 0.005). DISCUSSION The association between eGFR and CSF AD biomarkers has a significant impact that varies by cognitive status. Future studies exploring this impact on the pathogenesis of AD and related biomarkers are needed. Highlights There is a significant association between Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers and both estimated glomerular filtration rate (eGFR) and mild cognitive impairment (MCI). Kidney function influences CSF biomarker levels in individuals with normal cognitive function and those with MCI. The impact of kidney function on AD biomarker levels is more pronounced in individuals with cognitive impairment. The variation in CSF tau levels is independent of cardiovascular factors and is likely directly related to kidney function. Tau may have a possible role in both kidney and cognitive function.
摘要 引言 最近的阿尔茨海默病（AD）临床试验使用脑脊液（CSF）生物标志物水平进行筛查和入组。初步证据表明，阿尔茨海默病风险与肾功能受损有关。肾功能对常用的 AD 生物标志物的影响尚不清楚。方法 戈伊祖塔阿尔茨海默病研究中心（Goizueta Alzheimer's Disease Research Center）的研究参与者（N = 973）测量了血清肌酐和脑脊液 AD 生物标志物。一般线性模型和个体数据用于评估生物标志物与 eGFR 之间的关系。结果 肾小球滤过率（eGFR）越低，淀粉样β（Aβ）42/tau比值（p < 0.0001）和Aβ42（p = 0.002）越低，tau（p < 0.0001）和p-tau（p = 0.0002）越高。eGFR对AD生物标志物水平的影响在认知障碍患者中更为明显（所有p值均小于0.005）。讨论 eGFR 与脑脊液 AD 生物标志物之间的关联具有显著影响，且因认知状况而异。今后需要开展研究，探讨这种关系对 AD 发病机制和相关生物标志物的影响。要点 阿尔茨海默病（AD）脑脊液（CSF）生物标志物与估计肾小球滤过率（eGFR）和轻度认知障碍（MCI）之间存在明显的关联。肾功能会影响认知功能正常者和 MCI 患者的 CSF 生物标志物水平。肾功能对注意力缺失症生物标志物水平的影响在认知障碍患者中更为明显。CSF tau水平的变化与心血管因素无关，可能与肾功能直接相关。Tau可能对肾脏和认知功能都有影响。
{"title":"Alzheimer's disease cerebrospinal fluid biomarkers and kidney function in normal and cognitively impaired older adults","authors":"I. Hajjar, Reem Neal, Zhiyi Yang, James Lah","doi":"10.1002/dad2.12581","DOIUrl":"https://doi.org/10.1002/dad2.12581","url":null,"abstract":"Abstract INTRODUCTION Recent Alzheimer's disease (AD) clinical trials have used cerebrospinal fluid (CSF) biomarker levels for screening and enrollment. Preliminary evidence suggests that AD risk is related to impaired renal function. The impact of kidney function on commonly used AD biomarkers remains unknown. METHODS Participants in studies conducted at the Goizueta Alzheimer's Disease Research Center (N = 973) had measurements of serum creatinine and CSF AD biomarkers. General linear models and individual data were used to assess the relationships between biomarkers and eGFR. RESULTS Lower estimated glomerular filtration rate (eGFR) was associated with lower amyloid beta (Aβ)42/tau ratio (p < 0.0001) and Aβ42 (p = 0.002) and higher tau (p < 0.0001) and p‐tau (p = 0.0002). The impact of eGFR on AD biomarker levels was more robust in individuals with cognitive impairment (all p‐values were < 0.005). DISCUSSION The association between eGFR and CSF AD biomarkers has a significant impact that varies by cognitive status. Future studies exploring this impact on the pathogenesis of AD and related biomarkers are needed. Highlights There is a significant association between Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers and both estimated glomerular filtration rate (eGFR) and mild cognitive impairment (MCI). Kidney function influences CSF biomarker levels in individuals with normal cognitive function and those with MCI. The impact of kidney function on AD biomarker levels is more pronounced in individuals with cognitive impairment. The variation in CSF tau levels is independent of cardiovascular factors and is likely directly related to kidney function. Tau may have a possible role in both kidney and cognitive function.","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":"140773088","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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