Yi-Ci Zhang,Xue-Ting Zhang,Peng-Yue Chen,Zi-Yue Zhou,Mao-Qing Huang,Kai-Wen He
INTRODUCTIONSleep-wake disturbances frequently occur at early stages of Alzheimer's disease (AD) and accelerate disease progression, but the underlying neural mechanisms are not fully understood.METHODSWe examined sleep-wake behavior and locus coeruleus (LC) activity in young 5xFAD mice using electrophysiology and pharmacological approaches targeting adrenergic signaling and potassium channels.RESULTS5xFAD mice displayed dark phase-specific hyperarousal and impaired brain state transitions by 2 months of age. LC neurons exhibited increased tonic firing due to impaired Kv4 and Kv7 potassium channel conductance, resulting from soluble amyloid beta (Aβ)-induced disruption of α2A adrenergic receptor regulation. Pharmacological activation of α2A adrenergic receptors restored Kv4/7 function and normalized LC excitability. Local administration of guanfacine (α2A agonist) or retigabine (Kv7 modulator) significantly rescued sleep-wake disturbances.DISCUSSIONThese findings identify LC hyperexcitability as a mechanistic driver of early sleep disruption in AD and implicate α2A receptors and Kv7 channels as promising therapeutic targets for early intervention.
{"title":"Impaired adrenergic regulation of Kv channels underlies LC hyperactivity and early-onset sleep disruption in AD-like amyloidogenic mice.","authors":"Yi-Ci Zhang,Xue-Ting Zhang,Peng-Yue Chen,Zi-Yue Zhou,Mao-Qing Huang,Kai-Wen He","doi":"10.1002/alz.71127","DOIUrl":"https://doi.org/10.1002/alz.71127","url":null,"abstract":"INTRODUCTIONSleep-wake disturbances frequently occur at early stages of Alzheimer's disease (AD) and accelerate disease progression, but the underlying neural mechanisms are not fully understood.METHODSWe examined sleep-wake behavior and locus coeruleus (LC) activity in young 5xFAD mice using electrophysiology and pharmacological approaches targeting adrenergic signaling and potassium channels.RESULTS5xFAD mice displayed dark phase-specific hyperarousal and impaired brain state transitions by 2 months of age. LC neurons exhibited increased tonic firing due to impaired Kv4 and Kv7 potassium channel conductance, resulting from soluble amyloid beta (Aβ)-induced disruption of α2A adrenergic receptor regulation. Pharmacological activation of α2A adrenergic receptors restored Kv4/7 function and normalized LC excitability. Local administration of guanfacine (α2A agonist) or retigabine (Kv7 modulator) significantly rescued sleep-wake disturbances.DISCUSSIONThese findings identify LC hyperexcitability as a mechanistic driver of early sleep disruption in AD and implicate α2A receptors and Kv7 channels as promising therapeutic targets for early intervention.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"389 1","pages":"e71127"},"PeriodicalIF":14.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073330","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}
INTRODUCTIONThe apolipoprotein E ε4 (APOE ε4) allele is a major genetic risk factor for Alzheimer's disease, but its relevance to cognition in intracranial atherosclerosis (ICAS) remains unclear. We investigated the association between APOE ε4 and cognition in ICAS.METHODSBaseline data from a multicenter cohort were analyzed. Patients with radiologically confirmed ICAS underwent APOE genotyping, plasma biomarker assays, magnetic resonance imaging assessment of cerebral small vessel disease (CSVD) and brain atrophy, and standardized cognitive testing.RESULTSAmong 409 patients (mean age 60 years, 55% male), 16% carried APOE ε4. Carriers showed more frequent cognitive impairment (63% vs 48%), greater stenosis burden, and lower plasma amyloid beta (Aβ)42/40 ratios, whereas other Alzheimer's biomarkers, CSVD burden, and atrophy scores showed no difference. After adjustment, APOE ε4remained associated with cognitive impairment (odds ratio [OR] 1.86). The association was pronounced in women (OR 4.43) but absent in men.DISCUSSIONAPOE ε4 is linked to cognitive impairment in ICAS, particularly in women, through mechanisms beyond Alzheimer's pathology.HIGHLIGHTSIn patients with ICAS, cognitive impairment was more prevalent in carriers than in non-carriers. Carriers showed greater stenosis burden and lower plasma Aβ42/40 ratios. After full adjustment (stroke, CSVD, and AD biomarkers), APOE ε4 remained associated with cognitive impairment. Female carriers had substantially higher odds of cognitive impairment.
{"title":"APOE4 and cognition in intracranial atherosclerosis: beyond Alzheimer's pathology.","authors":"Anqi Cheng,Yinxi Zou,Linwen Liu,Hebo Wang,Zhibing Ai,Shiwen Wu,Qianqian Si,Yiyang Liu,Huanyu Zhou,Haoyao Guo,Qiuyu Yu,Zijue Wang,Mingli Li,Caiyan Liu,Weihai Xu","doi":"10.1002/alz.71087","DOIUrl":"https://doi.org/10.1002/alz.71087","url":null,"abstract":"INTRODUCTIONThe apolipoprotein E ε4 (APOE ε4) allele is a major genetic risk factor for Alzheimer's disease, but its relevance to cognition in intracranial atherosclerosis (ICAS) remains unclear. We investigated the association between APOE ε4 and cognition in ICAS.METHODSBaseline data from a multicenter cohort were analyzed. Patients with radiologically confirmed ICAS underwent APOE genotyping, plasma biomarker assays, magnetic resonance imaging assessment of cerebral small vessel disease (CSVD) and brain atrophy, and standardized cognitive testing.RESULTSAmong 409 patients (mean age 60 years, 55% male), 16% carried APOE ε4. Carriers showed more frequent cognitive impairment (63% vs 48%), greater stenosis burden, and lower plasma amyloid beta (Aβ)42/40 ratios, whereas other Alzheimer's biomarkers, CSVD burden, and atrophy scores showed no difference. After adjustment, APOE ε4remained associated with cognitive impairment (odds ratio [OR] 1.86). The association was pronounced in women (OR 4.43) but absent in men.DISCUSSIONAPOE ε4 is linked to cognitive impairment in ICAS, particularly in women, through mechanisms beyond Alzheimer's pathology.HIGHLIGHTSIn patients with ICAS, cognitive impairment was more prevalent in carriers than in non-carriers. Carriers showed greater stenosis burden and lower plasma Aβ42/40 ratios. After full adjustment (stroke, CSVD, and AD biomarkers), APOE ε4 remained associated with cognitive impairment. Female carriers had substantially higher odds of cognitive impairment.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"81 1","pages":"e71087"},"PeriodicalIF":14.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146088919","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}
Darcy Wear,Christopher Daniel Morrone,Dominic Simpson,Fang Liu,Syed Abid Hussaini,Wai Haung Yu
INTRODUCTIONSleep impairments likely contribute to Alzheimer's pathology, though specific contributions to disease progression are incompletely understood. We propose that autophagic impairment is associated with chronic sleep disruption and examine how sleep loss and stress influence disease development, including having impacts on proteostasis, cognition, and neural circuitry.METHODSWe sleep-disrupted 6-month-old APPNL-G-F mice for 2 weeks and behaviorally assessed sleep recovery, nesting, stress, and cognition. Subsequently, we analyzed markers of Alzheimer's pathology, stress, neuroinflammation, and proteostasis in hippocampal and subcortical brain regions.RESULTSSleep-deprived mice had altered sleep-related behaviors, increased stress, and signs of disease-acceleration including sex-dependent neurodegeneration, proteinopathy, and changes to autophagy and the neuroinflammatory response.DISCUSSIONChronic sleep disruption accelerates the pathological cascade of Alzheimer's, including cognitive impairment and Alzheimer's pathology in a sex-dependent manner. This work enhances our understanding of the sleep-stress-Alzheimer's relationship, including sex-based differences, and may point to a novel therapeutic avenue to limit Alzheimer's progression.
{"title":"Sex-specific acceleration of Alzheimer's pathogenesis by chronic sleep-deprivation.","authors":"Darcy Wear,Christopher Daniel Morrone,Dominic Simpson,Fang Liu,Syed Abid Hussaini,Wai Haung Yu","doi":"10.1002/alz.71099","DOIUrl":"https://doi.org/10.1002/alz.71099","url":null,"abstract":"INTRODUCTIONSleep impairments likely contribute to Alzheimer's pathology, though specific contributions to disease progression are incompletely understood. We propose that autophagic impairment is associated with chronic sleep disruption and examine how sleep loss and stress influence disease development, including having impacts on proteostasis, cognition, and neural circuitry.METHODSWe sleep-disrupted 6-month-old APPNL-G-F mice for 2 weeks and behaviorally assessed sleep recovery, nesting, stress, and cognition. Subsequently, we analyzed markers of Alzheimer's pathology, stress, neuroinflammation, and proteostasis in hippocampal and subcortical brain regions.RESULTSSleep-deprived mice had altered sleep-related behaviors, increased stress, and signs of disease-acceleration including sex-dependent neurodegeneration, proteinopathy, and changes to autophagy and the neuroinflammatory response.DISCUSSIONChronic sleep disruption accelerates the pathological cascade of Alzheimer's, including cognitive impairment and Alzheimer's pathology in a sex-dependent manner. This work enhances our understanding of the sleep-stress-Alzheimer's relationship, including sex-based differences, and may point to a novel therapeutic avenue to limit Alzheimer's progression.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"117 1","pages":"e71099"},"PeriodicalIF":14.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146089110","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}
Caroline Dallaire-Théroux, Helena L Denis, Rosalie Cottez, Cyntia Tremblay, Amélie Provencher, Josue Valentin-Escalera, Manon Leclerc, Andreanne Loiselle, Marine Tournissac, Olivier Potvin, Sylvie Belleville, Anne Gangloff, Frederic Picard, Henrik Zetterberg, Frédéric Calon
Introduction: Metabolic disorders are risk factors for Alzheimer's disease (AD), although underlying mechanisms remain unclear. We investigated the relationship between peripheral metabolic markers - adiponectin, fibroblast growth factor 21 (FGF-21), and insulin-like growth factor binding protein 2 (IGFBP-2) - and AD.
Methods: Participants with subjective cognitive decline (SCD), mild cognitive impairment (MCI), AD, and cognitively healthy (CH) controls were from the Consortium for the Early Identification of Alzheimer's Disease-Quebec cohort (n = 287). Serum adiponectin, FGF-21, and IGFBP-2 concentrations were measured, compared between groups, and assessed for associations with clinical, cognitive, biochemical, and magnetic resonance imaging (MRI) data.
Results: Metabolic dysfunction was linked to lower adiponectin and IGFBP-2, but higher FGF-21. Both FGF-21 and IGFBP-2 increased with age and were inversely associated with cognitive performance. IGFBP-2 was elevated at SCD stage and correlated with plasma tau phosphorylated at threonine 181 and amygdala atrophy. Adiponectin was unrelated to cognition.
Discussion: These findings suggest that IGFBP-2 and, to a lesser extent, FGF-21 may serve as early biomarkers of cognitive impairment, reflecting intricate links between peripheral dysmetabolism and AD.
{"title":"Distinct alterations of adiponectin, fibroblast growth factor 21 (FGF-21), and insulin-like growth factor binding protein 2 (IGFBP-2) link dysmetabolism with cognitive decline across the Alzheimer's disease spectrum.","authors":"Caroline Dallaire-Théroux, Helena L Denis, Rosalie Cottez, Cyntia Tremblay, Amélie Provencher, Josue Valentin-Escalera, Manon Leclerc, Andreanne Loiselle, Marine Tournissac, Olivier Potvin, Sylvie Belleville, Anne Gangloff, Frederic Picard, Henrik Zetterberg, Frédéric Calon","doi":"10.1002/alz.71097","DOIUrl":"10.1002/alz.71097","url":null,"abstract":"<p><strong>Introduction: </strong>Metabolic disorders are risk factors for Alzheimer's disease (AD), although underlying mechanisms remain unclear. We investigated the relationship between peripheral metabolic markers - adiponectin, fibroblast growth factor 21 (FGF-21), and insulin-like growth factor binding protein 2 (IGFBP-2) - and AD.</p><p><strong>Methods: </strong>Participants with subjective cognitive decline (SCD), mild cognitive impairment (MCI), AD, and cognitively healthy (CH) controls were from the Consortium for the Early Identification of Alzheimer's Disease-Quebec cohort (n = 287). Serum adiponectin, FGF-21, and IGFBP-2 concentrations were measured, compared between groups, and assessed for associations with clinical, cognitive, biochemical, and magnetic resonance imaging (MRI) data.</p><p><strong>Results: </strong>Metabolic dysfunction was linked to lower adiponectin and IGFBP-2, but higher FGF-21. Both FGF-21 and IGFBP-2 increased with age and were inversely associated with cognitive performance. IGFBP-2 was elevated at SCD stage and correlated with plasma tau phosphorylated at threonine 181 and amygdala atrophy. Adiponectin was unrelated to cognition.</p><p><strong>Discussion: </strong>These findings suggest that IGFBP-2 and, to a lesser extent, FGF-21 may serve as early biomarkers of cognitive impairment, reflecting intricate links between peripheral dysmetabolism and AD.</p>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"22 2","pages":"e71097"},"PeriodicalIF":11.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12865228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146103401","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}
Lianlian Du, Lei Yu, Tianhao Wang, Patricia A Boyle, Lisa L Barnes, David X Marquez, David A Bennett
Introduction: We estimated the lifetime risk of incident dementia and mild cognitive impairment (MCI) from ages 55-105 and examined differences by sex and race.
Methods: Data were drawn from five harmonized longitudinal cohort studies at the Rush Alzheimer's Disease Center, including 4611 participants for dementia and 3915 for MCI. Diagnoses were based on annual clinical evaluations. Lifetime risk was estimated using nonparametric cumulative incidence curves by age conditional on being alive and event-free at the index age, accounting for competing mortality and delayed study entry, stratified by sex and race.
Results: Lifetime risk from age 55 was 43% (95% confidence interval [CI]: 38%-47%) for dementia and 62% (95% CI: 57%-67%) for MCI. Female participants had higher risks than male participants, and racial differences were modest.
Discussion: These findings extend lifetime risk estimation beyond age 90 among diverse older adults and provide MCI estimates, emphasizing equity-focused prevention and public health strategies to reduce cognitive impairment.
Highlights: Lifetime risk (cumulative incidence) of dementia and mild cognitive impairment (MCI) was estimated from ages 55 to 105 using nonparametric cumulative incidence models accounting for competing risk of death and left truncation. The estimated lifetime risk was 43% for incident dementia and 62% for MCI, with risk rising steeply after age 75 and appearing to level off at the oldest ages. Women and Black participants showed higher lifetime risks, partly reflecting mortality and selective survival dynamics. Exploratory analyses suggested elevated risks among Latino participants and those with a history of stroke. These findings extend lifetime risk estimation beyond age 90 and highlight the need for equitable, culturally informed dementia prevention and monitoring strategies.
{"title":"Lifetime risk of incident dementia and incident mild cognitive impairment in older adults.","authors":"Lianlian Du, Lei Yu, Tianhao Wang, Patricia A Boyle, Lisa L Barnes, David X Marquez, David A Bennett","doi":"10.1002/alz.71173","DOIUrl":"10.1002/alz.71173","url":null,"abstract":"<p><strong>Introduction: </strong>We estimated the lifetime risk of incident dementia and mild cognitive impairment (MCI) from ages 55-105 and examined differences by sex and race.</p><p><strong>Methods: </strong>Data were drawn from five harmonized longitudinal cohort studies at the Rush Alzheimer's Disease Center, including 4611 participants for dementia and 3915 for MCI. Diagnoses were based on annual clinical evaluations. Lifetime risk was estimated using nonparametric cumulative incidence curves by age conditional on being alive and event-free at the index age, accounting for competing mortality and delayed study entry, stratified by sex and race.</p><p><strong>Results: </strong>Lifetime risk from age 55 was 43% (95% confidence interval [CI]: 38%-47%) for dementia and 62% (95% CI: 57%-67%) for MCI. Female participants had higher risks than male participants, and racial differences were modest.</p><p><strong>Discussion: </strong>These findings extend lifetime risk estimation beyond age 90 among diverse older adults and provide MCI estimates, emphasizing equity-focused prevention and public health strategies to reduce cognitive impairment.</p><p><strong>Highlights: </strong>Lifetime risk (cumulative incidence) of dementia and mild cognitive impairment (MCI) was estimated from ages 55 to 105 using nonparametric cumulative incidence models accounting for competing risk of death and left truncation. The estimated lifetime risk was 43% for incident dementia and 62% for MCI, with risk rising steeply after age 75 and appearing to level off at the oldest ages. Women and Black participants showed higher lifetime risks, partly reflecting mortality and selective survival dynamics. Exploratory analyses suggested elevated risks among Latino participants and those with a history of stroke. These findings extend lifetime risk estimation beyond age 90 and highlight the need for equitable, culturally informed dementia prevention and monitoring strategies.</p>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"22 2","pages":"e71173"},"PeriodicalIF":11.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12865328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146103414","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}
Dustin B Hammers,Ani Eloyan,Maryanne Thangarajah,Alexander Taurone,Sujuan Gao,Laurel Beckett,Kala Kirby,Jeffrey L Dage,Kelly Nudelman,Paul Aisen,Rema Reman,Prashanthi Vemuri,Renaud La Joie,Alexandra Touroutoglou,Alireza Atri,David Clark,Gregory S Day,Ranjan Duara,Neill R Graff-Radford,Lawrence S Honig,David T Jones,Joseph C Masdeu,Mario F Mendez,Kyle Womack,Erik Musiek,Chiadi U Onyike,Meghan Riddle,Ian Grant,Emily Rogalski,Erik C B Johnson,Steven Salloway,Sharon J Sha,Raymond Scott Turner,Thomas S Wingo,David A Wolk,Maria C Carrillo,Bradford C Dickerson,Gil D Rabinovici,Liana G Apostolova, ,
INTRODUCTIONRecent work has identified unique cognitive profiles for early-onset Alzheimer's disease (EOAD) relative to late-onset Alzheimer's disease (LOAD), however, examination has been limited in determining whether the association between age and cognitive severity at presentation also differs across conditions.METHODSA series of linear spline regression models was conducted across baseline cognitive data from 325 EOAD and 314 LOAD participants, after accounting for education, sex, and apolipoprotein ε4 status.RESULTSSignificant differences existed in the relationship between baseline age and cognitive performance between EOAD and LOAD samples for Processing Speed/Attention, Executive Functioning, and Episodic Immediate Memory. Younger participants from both EOAD and LOAD groups performed disproportionately worse on non-amnestic cognitive domains, with this occurring to a greater extent in EOAD than LOAD.DISCUSSIONIn the age of disease-modifying treatments, results highlight the importance of assessing for cognitive declines in individuals starting much earlier than age 65.HIGHLIGHTSEarly-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD) participants each displayed cognitive impairments relative to same-aged peers across most domains. Both groups displayed positive relationships between impairment among non-amnestic cognitive domains and baseline age. This relationship displayed a significantly greater effect in EOAD than LOAD, with domains of Processing Speed/Attention and Executive Functioning skills being the most pronounced. Of those participants developing AD, age displayed a disproportionate impact on their symptom onset.
{"title":"Relationship between age and severity of cognitive impairment at diagnosis for early-onset and late-onset Alzheimer's disease: Comparison of LEADS and ADNI.","authors":"Dustin B Hammers,Ani Eloyan,Maryanne Thangarajah,Alexander Taurone,Sujuan Gao,Laurel Beckett,Kala Kirby,Jeffrey L Dage,Kelly Nudelman,Paul Aisen,Rema Reman,Prashanthi Vemuri,Renaud La Joie,Alexandra Touroutoglou,Alireza Atri,David Clark,Gregory S Day,Ranjan Duara,Neill R Graff-Radford,Lawrence S Honig,David T Jones,Joseph C Masdeu,Mario F Mendez,Kyle Womack,Erik Musiek,Chiadi U Onyike,Meghan Riddle,Ian Grant,Emily Rogalski,Erik C B Johnson,Steven Salloway,Sharon J Sha,Raymond Scott Turner,Thomas S Wingo,David A Wolk,Maria C Carrillo,Bradford C Dickerson,Gil D Rabinovici,Liana G Apostolova, , ","doi":"10.1002/alz.71160","DOIUrl":"https://doi.org/10.1002/alz.71160","url":null,"abstract":"INTRODUCTIONRecent work has identified unique cognitive profiles for early-onset Alzheimer's disease (EOAD) relative to late-onset Alzheimer's disease (LOAD), however, examination has been limited in determining whether the association between age and cognitive severity at presentation also differs across conditions.METHODSA series of linear spline regression models was conducted across baseline cognitive data from 325 EOAD and 314 LOAD participants, after accounting for education, sex, and apolipoprotein ε4 status.RESULTSSignificant differences existed in the relationship between baseline age and cognitive performance between EOAD and LOAD samples for Processing Speed/Attention, Executive Functioning, and Episodic Immediate Memory. Younger participants from both EOAD and LOAD groups performed disproportionately worse on non-amnestic cognitive domains, with this occurring to a greater extent in EOAD than LOAD.DISCUSSIONIn the age of disease-modifying treatments, results highlight the importance of assessing for cognitive declines in individuals starting much earlier than age 65.HIGHLIGHTSEarly-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD) participants each displayed cognitive impairments relative to same-aged peers across most domains. Both groups displayed positive relationships between impairment among non-amnestic cognitive domains and baseline age. This relationship displayed a significantly greater effect in EOAD than LOAD, with domains of Processing Speed/Attention and Executive Functioning skills being the most pronounced. Of those participants developing AD, age displayed a disproportionate impact on their symptom onset.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"31 1","pages":"e71160"},"PeriodicalIF":14.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073051","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}
Morgan Daven,David M Bass,Nicole Deaner,R John Sawyer,Leslie Evertson,David B Reuben,
In 2023, the Alzheimer's Association launched the Dementia Care Navigation (DCN) Roundtable, a diverse group of dementia experts to provide strategic guidance to organizations implementing person- and family-centered DCN services. Three initial areas to enhance DCN and its implementation were identified: (1) improving the quality of DCN by further defining navigator duties, roles, and care pathways; (2) establishing standards for DCN training to ensure quality, consistency, and person- and family-centeredness; and (3) developing a sustainable business case to ensure its financial viability. The roundtable clarified navigator responsibilities, encouraged the use of community partners as DCN providers, and aligned DCN services with Medicare's Guiding and Improved Dementia Experience GUIDE model. The roundtable recommended that all team members undergo training to acquire the necessary knowledge to provide effective and compassionate care. Building a sustainable business case requires demonstrating both financial and non-financial value, engaging payers, and aligning DCN with healthcare performance metrics. HIGHLIGHTS: Recommendations were based on the GUIDE model and 7 Essential Principles of DCN. Dementia care team members should have defined roles across care delivery domains. Dementia care navigators should be trained in person- and family-centered care. A sustainable business case should demonstrate financial and non-financial value.
{"title":"A framework for implementing high-quality dementia care navigation: recommendations from the Alzheimer's Association Dementia Care Navigation Roundtable.","authors":"Morgan Daven,David M Bass,Nicole Deaner,R John Sawyer,Leslie Evertson,David B Reuben, ","doi":"10.1002/alz.71102","DOIUrl":"https://doi.org/10.1002/alz.71102","url":null,"abstract":"In 2023, the Alzheimer's Association launched the Dementia Care Navigation (DCN) Roundtable, a diverse group of dementia experts to provide strategic guidance to organizations implementing person- and family-centered DCN services. Three initial areas to enhance DCN and its implementation were identified: (1) improving the quality of DCN by further defining navigator duties, roles, and care pathways; (2) establishing standards for DCN training to ensure quality, consistency, and person- and family-centeredness; and (3) developing a sustainable business case to ensure its financial viability. The roundtable clarified navigator responsibilities, encouraged the use of community partners as DCN providers, and aligned DCN services with Medicare's Guiding and Improved Dementia Experience GUIDE model. The roundtable recommended that all team members undergo training to acquire the necessary knowledge to provide effective and compassionate care. Building a sustainable business case requires demonstrating both financial and non-financial value, engaging payers, and aligning DCN with healthcare performance metrics. HIGHLIGHTS: Recommendations were based on the GUIDE model and 7 Essential Principles of DCN. Dementia care team members should have defined roles across care delivery domains. Dementia care navigators should be trained in person- and family-centered care. A sustainable business case should demonstrate financial and non-financial value.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"82 1","pages":"e71102"},"PeriodicalIF":14.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073053","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}
Alejandra O Morcillo-Nieto, Mateus Rozalem-Aranha, Lucia Maure-Blesa, Íñigo Rodríguez-Baz, José Enrique Arriola-Infante, Maria Franquesa-Mullerat, Sara E Zsadanyi, Lídia Vaqué-Alcázar, José Allende Parra, Zili Zhao, Javier Arranz, Laura Videla, Isabel Barroeta, Laura Del Hoyo Soriano, Bessy Benejam, Susana Fernández, Aida Sanjuan Hernandez, Lucia Pertierra, Sandra Giménez, Daniel Alcolea, Olivia Belbin, Alberto Lleó, María Carmona-Iragui, Juan Fortea, Alexandre Bejanin
Introduction: White matter hyperintensities (WMH) are common in Down syndrome (DS), yet their longitudinal evolution and associations with Alzheimer's disease (AD) remain unclear.
Methods: Longitudinal MRI study, including 80 DS adults and 53 euploid controls. WMH were segmented on serial FLAIR using a longitudinal pipeline. We assessed the effects of demographic, genetic factors, AD clinical stage, AD-related fluid, and cerebrovascular biomarkers on annual WMH volume changes.
Results: In DS, annual WMH changes were relatively stable until age 40, and then exhibited fluctuations, with a significant decrease at the group level. Declines were larger in symptomatic cases, particularly in periventricular and fronto-parieto-occipital regions. Higher baseline WMH and microbleeds presence related to greater WMH reduction. Visual ratings and adjustment for white matter volume supported the robustness of the results.
Discussion: WMH trajectories were heterogeneous in DS and declined over time with AD symptoms. This unexpected reduction may reflect different underlying pathological processes, including neurodegeneration or neuroinflammation.
{"title":"Temporal dynamics of white matter hyperintensities related to Alzheimer's disease in adults with Down syndrome.","authors":"Alejandra O Morcillo-Nieto, Mateus Rozalem-Aranha, Lucia Maure-Blesa, Íñigo Rodríguez-Baz, José Enrique Arriola-Infante, Maria Franquesa-Mullerat, Sara E Zsadanyi, Lídia Vaqué-Alcázar, José Allende Parra, Zili Zhao, Javier Arranz, Laura Videla, Isabel Barroeta, Laura Del Hoyo Soriano, Bessy Benejam, Susana Fernández, Aida Sanjuan Hernandez, Lucia Pertierra, Sandra Giménez, Daniel Alcolea, Olivia Belbin, Alberto Lleó, María Carmona-Iragui, Juan Fortea, Alexandre Bejanin","doi":"10.1002/alz.71157","DOIUrl":"https://doi.org/10.1002/alz.71157","url":null,"abstract":"<p><strong>Introduction: </strong>White matter hyperintensities (WMH) are common in Down syndrome (DS), yet their longitudinal evolution and associations with Alzheimer's disease (AD) remain unclear.</p><p><strong>Methods: </strong>Longitudinal MRI study, including 80 DS adults and 53 euploid controls. WMH were segmented on serial FLAIR using a longitudinal pipeline. We assessed the effects of demographic, genetic factors, AD clinical stage, AD-related fluid, and cerebrovascular biomarkers on annual WMH volume changes.</p><p><strong>Results: </strong>In DS, annual WMH changes were relatively stable until age 40, and then exhibited fluctuations, with a significant decrease at the group level. Declines were larger in symptomatic cases, particularly in periventricular and fronto-parieto-occipital regions. Higher baseline WMH and microbleeds presence related to greater WMH reduction. Visual ratings and adjustment for white matter volume supported the robustness of the results.</p><p><strong>Discussion: </strong>WMH trajectories were heterogeneous in DS and declined over time with AD symptoms. This unexpected reduction may reflect different underlying pathological processes, including neurodegeneration or neuroinflammation.</p>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"22 2","pages":"e71157"},"PeriodicalIF":11.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117537","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}
Samuel N Lockhart, Courtney L Sutphen, Jordan Tanley, Fernando Gonzalez-Ortiz, Przemysław R Kac, Mohamad Habes, Susan R Heckbert, Nicholas J Ashton, Michelle M Mielke, Robert Koeppe, Marc D Rudolph, Kiran K Solingapuram Sai, Christopher T Whitlow, Kevin D Hiatt, Suzanne Craft, Thomas C Register, Kathleen M Hayden, Stephen R Rapp, Bonnie C Sachs, Henrik Zetterberg, Kaj Blennow, Thomas K Karikari, Timothy M Hughes
Introduction: Little is known about how Alzheimer's disease (AD) plasma biomarkers relate to cerebral small vessel disease (cSVD) neuroimaging biomarkers.
Methods: The study involved 251 Wake Forest Multi-Ethnic Study of Atherosclerosis (MESA) Exam 6 participants with plasma AD biomarkers, magnetic resonance imaging, amyloid positron emission tomography (PET), and adjudicated cognitive status. Multivariable models examined cross-sectional relationships between plasma and neuroimaging biomarkers, considering comorbidities.
Results: Lower amyloid beta (Aβ) 42/Aβ40 and higher glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and phosphorylated tau at threonine 217 (p-tau217) were associated with greater neurodegeneration. Lower plasma Aβ42/Aβ40 and higher p-tau217 and p-tau231 were associated with greater Aβ PET deposition. NfL was positively associated with white matter hyperintensities (WMH) and white matter (WM) free water. P-tau measures were positively associated with WM free water. Lower Aβ42/Aβ40 was associated with the presence of microbleeds. GFAP was positively associated with WMH.
Discussion: We observed expected associations of plasma biomarkers with cognitive status and imaging biomarkers. GFAP, NfL, p-tau181, p-tau217, and p-tau231 are associated with cSVD in addition to AD-related pathology.
{"title":"Plasma and neuroimaging biomarkers of small vessel disease and Alzheimer's disease in a diverse cohort: MESA.","authors":"Samuel N Lockhart, Courtney L Sutphen, Jordan Tanley, Fernando Gonzalez-Ortiz, Przemysław R Kac, Mohamad Habes, Susan R Heckbert, Nicholas J Ashton, Michelle M Mielke, Robert Koeppe, Marc D Rudolph, Kiran K Solingapuram Sai, Christopher T Whitlow, Kevin D Hiatt, Suzanne Craft, Thomas C Register, Kathleen M Hayden, Stephen R Rapp, Bonnie C Sachs, Henrik Zetterberg, Kaj Blennow, Thomas K Karikari, Timothy M Hughes","doi":"10.1002/alz.71131","DOIUrl":"10.1002/alz.71131","url":null,"abstract":"<p><strong>Introduction: </strong>Little is known about how Alzheimer's disease (AD) plasma biomarkers relate to cerebral small vessel disease (cSVD) neuroimaging biomarkers.</p><p><strong>Methods: </strong>The study involved 251 Wake Forest Multi-Ethnic Study of Atherosclerosis (MESA) Exam 6 participants with plasma AD biomarkers, magnetic resonance imaging, amyloid positron emission tomography (PET), and adjudicated cognitive status. Multivariable models examined cross-sectional relationships between plasma and neuroimaging biomarkers, considering comorbidities.</p><p><strong>Results: </strong>Lower amyloid beta (Aβ) 42/Aβ40 and higher glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and phosphorylated tau at threonine 217 (p-tau217) were associated with greater neurodegeneration. Lower plasma Aβ42/Aβ40 and higher p-tau217 and p-tau231 were associated with greater Aβ PET deposition. NfL was positively associated with white matter hyperintensities (WMH) and white matter (WM) free water. P-tau measures were positively associated with WM free water. Lower Aβ42/Aβ40 was associated with the presence of microbleeds. GFAP was positively associated with WMH.</p><p><strong>Discussion: </strong>We observed expected associations of plasma biomarkers with cognitive status and imaging biomarkers. GFAP, NfL, p-tau181, p-tau217, and p-tau231 are associated with cSVD in addition to AD-related pathology.</p>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"22 2","pages":"e71131"},"PeriodicalIF":11.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12865319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146103402","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}
Mohsen Sedighi, Mohammad Hasan Shahabi, Alireza Amanollahi, Khurshid Alam, Soudabeh Shemehsavar, Zahra Shirzadi, Serena Sabatini, Ahmad R. Khatoonabadi, Matthew Prina, Akram A. Hosseini, Claire V. Burley, Jennifer Dunne, Simin Mahinrad, Iman Dajani, Ralph N. Martins, Blossom C. M. Stephan, Ali Chaari, Hamid R. Sohrabi
Data on dementia epidemiology in the Middle East and North Africa (MENA) region is limited. This systematic review and meta‐analysis examined dementia prevalence across MENA. Databases were searched up to October 2024. Analyses were stratified by country and sex. Pooled prevalence was estimated using a random‐effects model with a 95% confidence interval (CI). Fifty‐two studies on the selected countries met inclusion criteria, covering 87,219 individuals with dementia from a total population of 1,045,908. The pooled prevalence was 12.16% (95% CI: 9.61–14.96) for the region and the Israel had the highest prevalence (17.00%), followed by Iran (13.20%), Turkey (11.40%), Saudi Arabia (8.34%), and Egypt (6.86%). Dementia was more common in women than men (13.84% vs. 8.69%). Dementia is prevalent in MENA, with significant variation across countries. The region's aging population highlights the need for ongoing monitoring of dementia trends.
{"title":"Prevalence of dementia in selected Middle East and North Africa (MENA) countries: A systematic review and meta‐analysis","authors":"Mohsen Sedighi, Mohammad Hasan Shahabi, Alireza Amanollahi, Khurshid Alam, Soudabeh Shemehsavar, Zahra Shirzadi, Serena Sabatini, Ahmad R. Khatoonabadi, Matthew Prina, Akram A. Hosseini, Claire V. Burley, Jennifer Dunne, Simin Mahinrad, Iman Dajani, Ralph N. Martins, Blossom C. M. Stephan, Ali Chaari, Hamid R. Sohrabi","doi":"10.1002/alz.71109","DOIUrl":"https://doi.org/10.1002/alz.71109","url":null,"abstract":"Data on dementia epidemiology in the Middle East and North Africa (MENA) region is limited. This systematic review and meta‐analysis examined dementia prevalence across MENA. Databases were searched up to October 2024. Analyses were stratified by country and sex. Pooled prevalence was estimated using a random‐effects model with a 95% confidence interval (CI). Fifty‐two studies on the selected countries met inclusion criteria, covering 87,219 individuals with dementia from a total population of 1,045,908. The pooled prevalence was 12.16% (95% CI: 9.61–14.96) for the region and the Israel had the highest prevalence (17.00%), followed by Iran (13.20%), Turkey (11.40%), Saudi Arabia (8.34%), and Egypt (6.86%). Dementia was more common in women than men (13.84% vs. 8.69%). Dementia is prevalent in MENA, with significant variation across countries. The region's aging population highlights the need for ongoing monitoring of dementia trends.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"33 1","pages":"e71109"},"PeriodicalIF":14.0,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146070254","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}
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