Castranio EL, Varghese M, Argyrousi EK
… +26 more, Tripathi K, Huang Y, Asada A, Söderberg L, Bresnahan E, Lerner D, Garretti F, Zhang H, van de Loo J, Stimpson CD, Talty R, Glabe C, Levy E, Wang M, Ilkov M, Suzuki T, Ando K, Zhang B, Lannfelt L, Guérin B, Lubell WD, Rahimipour S, Dickstein DL, Gandy S, Arancio O, Ehrlich ME
Alzheimers Dement
· 2026 Jun · PMID 42261875
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BACKGROUND: APP ("Dutch") transgenic mice develop aging-related learning deficits and accumulate endogenously generated non-fibrillar aggregates (NFAs) of amyloid beta (Aβ) and amyloid precursor protein α-carboxy termina...BACKGROUND: APP ("Dutch") transgenic mice develop aging-related learning deficits and accumulate endogenously generated non-fibrillar aggregates (NFAs) of amyloid beta (Aβ) and amyloid precursor protein α-carboxy terminal fragments. NFA-Aβ correlates with synaptic loss and memory deficits more closely than does fibrillar Aβ. METHODS: We assessed the physiological, transcriptomic, ultrastructural, histological, and metabolic changes associated with the accumulation of NFA of Dutch Aβ in brains of APP mice. RESULTS: Aging-related accumulation of NFA-Aβ in APP mice was revealed by A11 immunohistochemistry and cyclic D,L-α-peptide-fluorescein-5-isothiocyanate microscopy. Presynaptic termini of APP mice developed physiological abnormalities in post-tetanic potentiation, synaptic fatigue, synaptic vesicle replenishment, and an aging-related reduction in mitochondrial complex I activity. Single-cell RNA sequencing showed that excitatory neurons exhibited an altered transcriptomic profile involving "protein translation" and "oxidative phosphorylation." DISCUSSION: Accumulation of NFA-Aβ alters neuronal metabolism but does not activate inflammation. Depletion of all forms of Aβ may be required to eliminate Aβ toxicity with anti-amyloid antibodies.
Jarvis I, Besser L, Finlay J
… +13 more, Hystad P, Lane KJ, Hunter RF, James P, Jiménez MP, Nieuwenhuijsen M, van den Bosch M, Van Riper D, Lee J, Doiron D, Brook J, Adar SD, Brauer M
Alzheimers Dement
· 2026 Jun · PMID 42252512
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Urban greenspace has been associated with improved cognition and reduced Alzheimer's disease (AD) and AD-related dementias (ADRD) risk, but findings remain mixed, study quality varies, and evidence is largely cross-secti...Urban greenspace has been associated with improved cognition and reduced Alzheimer's disease (AD) and AD-related dementias (ADRD) risk, but findings remain mixed, study quality varies, and evidence is largely cross-sectional. To advance the field, we offer guidance to select and apply greenspace exposure measures in AD/ADRD research. Our interdisciplinary expert working group synthesized existing knowledge and developed consensus-based recommendations through collaborative discussion. In this paper, we outline hypothesized pathways, summarize data sources and measurement approaches, and propose criteria and recommendations to select and apply greenspace exposure measures in research. Based on hypothesized pathways, we recommend tree canopy cover for stress reduction, attention restoration, and improved mental health; parks for increased physical and social activity; and greenness for reduced harmful exposures, highlighting the Normalized Difference Vegetation Index as capturing multiple pathways. We also identify future research priorities to advance understanding of greenspace-AD/ADRD associations and support more rigorous, comparable, and policy-relevant evidence.
Chen K, Pineau E, Koletar M
… +7 more, Trevisiol A, He JS, Hill M, Goubran M, Sled J, McLaurin J, Stefanovic B
Alzheimers Dement
· 2026 Jun · PMID 42252511
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INTRODUCTION: While Alzheimer's disease (AD) typically elicits progressive cognitive decline, some individuals with significant AD pathology maintain cognition. Understanding the neuronal underpinnings of such cognitive...INTRODUCTION: While Alzheimer's disease (AD) typically elicits progressive cognitive decline, some individuals with significant AD pathology maintain cognition. Understanding the neuronal underpinnings of such cognitive resilience would propel the development of interventions for delaying dementia. METHODS: We used Barnes Maze testing to identify cognitively resilient 13-month-old TgF344-AD rats (established AD) and their non-transgenic littermates, followed by Neuropixels recording from 8500 neurons during repeated somatosensory stimulation, and culminating in post mortem tau and amyloid load quantifications. RESULTS: Cognitively resilient TgF344-AD rats recruited fewer neurons and displayed more stable neuronal representations during repeated stimulations in cortical excitatory and hippocampal inhibitory ensembles, with reduced excitatory spike burstiness and a distinct pattern of functional synaptic connectivity. These associations existed independently of amyloid levels. DISCUSSION: For the first time, our study revealed neuronal population-level hallmarks of maintained cognition that may serve as a novel neurophysiological biomarker of cognitive resilience and a target for stabilizing cognition.
Alzheimers Dement
· 2026 Jun · PMID 42252510
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INTRODUCTION: Sleep disruption is an early feature of Alzheimer's disease (AD), but the cellular mechanisms linking amyloid pathology to sleep loss remain unclear. METHODS: Electroencephalography/electromyography (EEG/EM...INTRODUCTION: Sleep disruption is an early feature of Alzheimer's disease (AD), but the cellular mechanisms linking amyloid pathology to sleep loss remain unclear. METHODS: Electroencephalography/electromyography (EEG/EMG) recordings, quantitative EEG analysis, and sleep deprivation were performed in APPswe/PSEN1dE9 (APP/PS1) mice at different stages of pathology relative to normal aging. Amyloid burden and microglial density were quantified with whole-brain light-sheet microscopy. CSF1R-mediated microglial depletion explored effects of microglia on sleep loss. RESULTS: Amyloid plaques caused non-rapid eye movement (NREM) sleep loss that did not worsen with increased plaque burden. Aging reduced REM sleep and eliminated sleep rebound. Amyloid pathology was associated with cortical hyperexcitability, network desynchrony, and microglial expansion extending beyond plaque-bearing regions into thalamocortical and white matter networks governing sleep-wake dynamics. Microglial depletion restored > 2 hours of sleep per day without altering amyloid burden. DISCUSSION: Microglia are a causal, reversible driver of amyloid-associated sleep loss, positioning sleep and EEG-based metrics as sensitive biomarkers of presymptomatic AD.
Dewenter A, Bürger K, Janowitz D
… +18 more, Paulus M, Nuscher B, Hirsch F, Gesierich B, Steward A, Frontzkowski L, Roemer-Cassiano SN, Zhu Z, Biel D, Klonowski M, Biechele G, Stoecklein S, Ewers M, Duering M, Tiedt S, Brendel M, Franzmeier N, Alzheimer's Disease Neuroimaging Initiative (ADNI)
Alzheimers Dement
· 2026 Jun · PMID 42252508
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INTRODUCTION: We investigated how plasma biomarkers (phosphorylated tau 217 [ptau], glial fibrillary acidic protein [GFAP], neurofilament light chain [NfL]) relate to imaging markers of small vessel disease (SVD) and Alz...INTRODUCTION: We investigated how plasma biomarkers (phosphorylated tau 217 [ptau], glial fibrillary acidic protein [GFAP], neurofilament light chain [NfL]) relate to imaging markers of small vessel disease (SVD) and Alzheimer's disease (AD), and cognition in memory clinic patients. METHODS: 76 memory clinic patients underwent plasma biomarker assessment, neuropsychological testing, and 3T MRI. SVD burden was assessed using white matter hyperintensity (WMH) volume, mean skeletonized mean diffusivity (MSMD), and fiber density. AD-related neurodegeneration was captured by AD-signature cortical thickness and fiber-bundle cross-section. Findings were validated in 41 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants with amyloid-/tau-positron emission tomography (PET). RESULTS: Associations varied between biomarkers. NfL showed strongest associations with SVD burden, ptau with AD-related neurodegeneration, while GFAP was linked to both. SVD markers were associated with processing speed, whereas AD markers were most associated with memory. DISCUSSION: NfL relates to SVD burden, while ptau remains most sensitive to AD-related biomarkers. GFAP's dual associations suggest overlapping biological processes. Together, coexisting SVD should be considered when interpreting plasma biomarkers in memory clinic patients.
Cary GA, Keegan S, Wiley JC
… +8 more, Gockley J, Butler RR, Longo FM, Levey AI, Greenwood AK, Leal K, Carter GW, Emory‐Sage‐SGC‐JAX TREAT‐AD Center
Alzheimers Dement
· 2026 Jun · PMID 42252507
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INTRODUCTION: Alzheimer's disease (AD) is a complex neurodegenerative disorder with numerous known risk factors. Identification of which genetic factors are causal drivers is difficult due to the long disease prodrome in...INTRODUCTION: Alzheimer's disease (AD) is a complex neurodegenerative disorder with numerous known risk factors. Identification of which genetic factors are causal drivers is difficult due to the long disease prodrome in an inaccessible organ. The application of integrative, systems-level approaches are crucial for addressing this complexity. METHODS: Sixteen biological domain specific interaction networks were derived from the top AD risk-enriched proteins within each domain. Weighted key driver analysis (wKDA) identified influential hub nodes within each network. RESULTS: Distinct processes and drivers were identified within each domain's network. Domains including structural stabilization, endolysosome, and lipid metabolism were especially influential. Integrating key drivers across domains identified consistent drivers such as CTNNB1, ACSL1, and ALDH3A2, suggesting fundamental roles contributing to AD risk. DISCUSSION: This highly integrative network-based approach identified context-dependent drivers and enabled the inference of interactions between domains. The identified drivers suggest potential targets for future therapeutic development.
Dittrich A, Arslan B, Skillbäck T
… +7 more, Rydén L, Kvartsberg H, Gobom J, Blennow K, Zetterberg H, Kern S, Skoog I
Alzheimers Dement
· 2026 Jun · PMID 42252493
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INTRODUCTION: High-risk plasma p-tau217 levels predict amyloid-β pathology in Alzheimer's disease, but little is known about the prevalence and temporal dynamics in the general population. METHODS: Participants from the...INTRODUCTION: High-risk plasma p-tau217 levels predict amyloid-β pathology in Alzheimer's disease, but little is known about the prevalence and temporal dynamics in the general population. METHODS: Participants from the Gothenburg H70 Birth Cohort Study in Sweden were examined (n = 1157) and re-examined after 5-7 years (n = 771). Prevalence and 5-7 year transition of high-risk plasma p-tau217 status was determined among community-dwelling 70-year-olds. RESULTS: High-risk plasma p-tau217 prevalence was 3.6% at age 70 and 7.0% at age 75-77 years. Eighty-nine percent remained low-risk and 4% converted to high-risk at follow-up. Prevalence of dementia at follow-up was 1.7% if remaining in the low-risk group and 21.4% if transitioning to the high-risk group. Prevalence of dementia among participants staying in the high-risk group was 16.7% at follow-up. DISCUSSION: Individuals with low-risk plasma p-tau217 were unlikely to transition over 5-7 years. However, transitioning to a higher risk-category was associated with a higher prevalence of cognitive disability.
Colbeth HL, Roscoe JN, Corrada MM
… +5 more, Meunier CC, George KM, Glymour MM, Gilsanz P, Whitmer RA
Alzheimers Dement
· 2026 Jun · PMID 42252490
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INTRODUCTION: Midlife hypertension is a well-established predictor of late-life cognitive decline; however, few population-representative estimates of this association exist among oldest-old cohorts. METHODS: LifeAfter90...INTRODUCTION: Midlife hypertension is a well-established predictor of late-life cognitive decline; however, few population-representative estimates of this association exist among oldest-old cohorts. METHODS: LifeAfter90 (LA90) is an ethnoracially diverse cohort of individuals aged 90+ linked to midlife multiphasic health check-ups (MHC). We assessed executive function, semantic memory, and verbal memory at age 90+. We used stabilized inverse probability of censoring weights and linear regression to estimate the association between midlife hypertension and cognitive function in the MHC target population. RESULTS: After weighting, LA90 participants (n = 307) were similar to the MHC population on race/ethnicity, hypertension, and education. Midlife hypertension was not associated with executive function (β = 0.03, [95% confidence interval [CI]: -0.24, 0.31]) and verbal memory (β = -0.10 [95% CI: -0.37, 0.16]). Midlife hypertension was associated with poorer semantic memory (β = -0.19 [95% CI: -0.44, 0.06]). DISCUSSION: People with midlife hypertension averaged lower semantic memory using population-representative models, suggesting that it may have sustained impact on learning and memory in those aged 90+.
Farombi T, Azzi T, Legaz A
… +34 more, Aguillón D, Avila-Funes JA, Behrens MI, Bruno M, Cardona JF, Custodio N, Delgado C, Pina-Escudero S, Galofre MDPG, Maito M, Magrath-Guimet N, Miller JB, Matallana D, de Oliveira MO, Rocatti G, Resende EPF, Slachevsky A, Takada L, Wen O, Zapata-Restrepo LM, Lawlor B, Yaffe K, Hu K, Miller B, Possin K, Yokoyama JS, Fittipaldi S, García AM, Larzabal HH, Santamaria-Garcia H, Tagliazzuchi E, Duran-Aniotz C, Ibanez A, Migeot J
Alzheimers Dement
· 2026 Jun · PMID 42251497
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INTRODUCTION: Adverse social conditions across the life course influence brain aging and dementia, yet their compounded impact on clinical phenotypes remains underexplored, particularly in Latin America, where social ine...INTRODUCTION: Adverse social conditions across the life course influence brain aging and dementia, yet their compounded impact on clinical phenotypes remains underexplored, particularly in Latin America, where social inequality and dementia burden are high. METHODS: We studied 3941 individuals from six Latin American countries, including cognitively unimpaired controls (CU), Alzheimer's disease (AD), and frontotemporal lobar degeneration (FTLD). A life-course questionnaire captured eight domains of social vulnerability, used to derive a social vulnerability index and latent vulnerability profiles. Brain health was characterized across 37 cognitive, functional, mental health, and dementia severity indicators. RESULTS: Higher vulnerability was mostly associated with executive and memory deficits in CU, cognitive and functional impairment in AD, and social cognition and neuropsychiatric symptoms in FTLD. Multidimensional brain health was affected across groups. DISCUSSION: Compounded social vulnerability is a key determinant of clinical expression in aging and dementia, underscoring the need for life-course-informed and equity-oriented dementia models.
Fonseca LM, Lila E, Shojaie A
… +14 more, Chhatwal J, Forlenza O, Beeri MS, Krinsky-McHale S, Cohen AD, Christian BT, Head E, Mapstone M, Handen B, Ances BM, Grabowski T, Chaytor NS, Zaman S, Alzheimer's Biomarkers Consortium‐ Down Syndrome (ABC‐DS) Investigators
Alzheimers Dement
· 2026 Jun · PMID 42251495
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INTRODUCTION: Adults with Down syndrome (DS) are at risk for Alzheimer's disease (AD), yet identifying the preclinical phase remains challenging. Intraindividual cognitive variability (IICV) may be a sensitive marker of...INTRODUCTION: Adults with Down syndrome (DS) are at risk for Alzheimer's disease (AD), yet identifying the preclinical phase remains challenging. Intraindividual cognitive variability (IICV) may be a sensitive marker of early AD-related changes but remains understudied in DS. METHODS: Adults from the Alzheimer's Biomarker Consortium-DS (ABC-DS) study (N = 460, mean age 43.3 years; 45.7% female) were included. Generalized linear models examined whether baseline IICV predicted incident mild cognitive impairment (MCI)/dementia, cognitive decline, and amyloid and tau positron emission tomography outcomes, adjusting for demographics, intellectual disability, apolipoprotein E ε4, site, assessment interval, and mean cognitive performance, with Bonferroni correction. RESULTS: Greater IICV predicted incident MCI/dementia (odds ratio = 4.63 to 5.13, p < 0.05), greater amyloid burden, early tau accumulation, and higher tau across Braak stages, independent of mean cognition. Exploratory analyses suggested sex-specific interactions with tau outcomes. DISCUSSION: IICV is a sensitive marker of dementia risk and cognitive resilience in DS, with potential utility for secondary prevention and trial enrichment.
Guan DX, Ismail Z, McLeod GA
… +3 more, Marzoughi S, Smith EE, Ganesh A
Alzheimers Dement
· 2026 Jun · PMID 42251494
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INTRODUCTION: Imaging-based cerebral small vessel disease (CSVD) summary scores quantify CSVD burden. This study characterized CSVD scores and assessed their cognitive associations in older adults with various neurodegen...INTRODUCTION: Imaging-based cerebral small vessel disease (CSVD) summary scores quantify CSVD burden. This study characterized CSVD scores and assessed their cognitive associations in older adults with various neurodegenerative diseases and cognitive profiles. METHODS: Baseline data from 958 Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) study participants were analyzed (19.4% cognitively normal, 14.9% subjective cognitive decline, 40.3% mild cognitive impairment, 25.4% dementia). MRI markers of cerebral vascular injury (lacunes, microbleeds, white matter hyperintensities [WMHs], and enlarged perivascular spaces) were visually rated, and a cumulative CSVD score was generated. Cognition was measured using the Montreal Cognitive Assessment (MoCA), Clinical Dementia Rating-Sum of Boxes (CDR-SB), and a composite neuropsychological battery test z-score. RESULTS: Higher CSVD scores were associated with greater Hachinski ischemic scores, poorer MoCA performance, worse CDR-SB, and lower composite z-scores. Associations were strongest for cognitive domains of executive function, attention, and learning. DISCUSSION: CSVD burden may further contribute to poorer cognition across neurodegenerative conditions and cognitive profiles.
Mammel AE, Gonzalez-Ortiz F, Mousavi A
… +9 more, Hallett K, Encarnacion M, Biehl D, Gill P, Ismael S, Fowler C, Doecke JD, Ward L, Frykman H
Alzheimers Dement
· 2026 Jun · PMID 42251493
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INTRODUCTION: The extent to which non-pathological aging influences plasma biomarkers remains unclear. Here, we investigate factors influencing plasma p-tau217 levels in cognitively unimpaired (CU), amyloid-beta-negative...INTRODUCTION: The extent to which non-pathological aging influences plasma biomarkers remains unclear. Here, we investigate factors influencing plasma p-tau217 levels in cognitively unimpaired (CU), amyloid-beta-negative (Aβ-) individuals. METHODS: Plasma p-tau217 was measured in CU Aβ- positron emission tomography-negative (PET-) participants using two immunoassays (ALZpath n = 360 and LUMIPULSE G1200 n = 73). Associations between p-tau217 and age groups (60-69, 70-79, and 80+ years), apolipoprotein E (APOE) genotype, and gender were evaluated. RESULTS: ALZpath plasma p-tau217 showed a non-pathological age-related increase (p < 0.001), and increased percentage within the intermediate zone with age. Lumipulse p-tau217 showed an increase in the percentage of subjects with positive results with age, however, this trend was not significant (p > 0.05). Men had higher levels of p-tau217 only with the ALZpath assay (p = 0.02; Lumipulse: p = 0.81). No significant associations were found between p-tau217 and APOE genotype. DISCUSSION: Our results highlight the importance of incorporating age and sex into the interpretation of plasma p-tau217 particularly in preclinical stages.
Huang Z, Qiu G, Shi C
… +6 more, Chen R, Xue E, Wang Z, Xu DR, Ao X, Wang Y
Alzheimers Dement
· 2026 Jun · PMID 42251492
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INTRODUCTION: The WW-FINGERS network has demonstrated the efficacy of multidomain non-pharmaceutical interventions (NPIs) but left their real-world implementation largely unexplored, prompting this study in Changxing Cou...INTRODUCTION: The WW-FINGERS network has demonstrated the efficacy of multidomain non-pharmaceutical interventions (NPIs) but left their real-world implementation largely unexplored, prompting this study in Changxing County to identify key determinants and develop actionable strategies for community-based delivery. METHODS: An embedded mixed-methods retrospective evaluation using the Consolidated Framework for Implementation Research (CFIR) was conducted. Data from 42 stakeholders across six communities were analyzed via a hybrid deductive-inductive approach and coincidence analysis (CNA). Strategies were matched using the ERIC compendium and refined by a stakeholder panel. RESULTS: We identified 202 determinants, revealing six core facilitator themes (e.g., policy-academia-community synergy) and six barrier themes(e.g., unsustainable funding). CNA delineated potential pathways. Three strategy bundles were finalized: Capacity Building, Collaborative Network Building, and an AI-enabled digital platform. DISCUSSION: This study provides a practical, theory-informed framework for implementing complex NPIs, bridging the science-to-practice gap in dementia prevention. The AI-enabled platform offers a forward-looking approach for sustained delivery.
Wec A, Wu M, Scerpella D
… +7 more, Zhang Z, Peereboom D, Colburn JL, Nothelle SK, Green AR, Wolff JL, Powell DS
Alzheimers Dement
· 2026 Jun · PMID 42243620
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INTRODUCTION: The Medicare Annual Wellness Visit (AWV) may improve timely detection of Alzheimer's disease and related dementias (ADRD), yet little is known about the frequency of follow-up on patient-reported memory con...INTRODUCTION: The Medicare Annual Wellness Visit (AWV) may improve timely detection of Alzheimer's disease and related dementias (ADRD), yet little is known about the frequency of follow-up on patient-reported memory concerns during the AWV. METHODS: We use electronic medical record (EMR) data from an academic health system to examine EMR-documented follow-up actions for patients with newly reported memory concerns on the AWV health risk assessment, including formal cognitive assessment or specialist referrals. RESULTS: The 1411 patients with newly reported memory concerns were predominantly white (70%) and female (63%), with an average age of 78 (SD 7.5). At the AWV, few patients received a cognitive assessment (5.4%; n = 76), specialist referral (2.1%; n = 30), or both (0.4%; n = 6). In adjusted analyses, we did not observe statistically significant differences by sociodemographic characteristics. DISCUSSION: This EMR-based study highlights an opportunity to better leverage the AWV to improve ADRD detection and care.
Tsuda Y, Madokoro Y, Suzuki K
… +8 more, Ooba T, Sato T, Uchida Y, Nagai-Arakawa I, Saito T, Hara H, Hida H, Matsukawa N
Alzheimers Dement
· 2026 Jun · PMID 42233314
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INTRODUCTION: Whether cholinergic activity in the septohippocampal network affects cognitive dysfunction via hippocampal cholinergic neurostimulating peptide (HCNP) in Alzheimer's pathogenesis remains unclear. METHODS: A...INTRODUCTION: Whether cholinergic activity in the septohippocampal network affects cognitive dysfunction via hippocampal cholinergic neurostimulating peptide (HCNP) in Alzheimer's pathogenesis remains unclear. METHODS: An Alzheimer's pathogenesis by mutation in amyloid-beta precursor protein gene (App) knock-in (KI) and HCNP precursor protein conditional knockout (HCNP-pp cKO) mouse model was generated, exhibiting both cholinergic dysfunction and amyloid pathogenesis. Theta power-related cholinergic function and long-term potentiation (LTP) were evaluated in App KI/HCNP-pp cKO mice. Molecules associated with the cholinergic/glutamatergic neurons, amyloid beta (Aβ), and inflammation were examined. RESULTS: Reduced HCNP levels enhanced cognitive impairment, inhibiting theta power and LTP, although without accompanying pathological changes or inflammation. Decreased N-methyl-D-aspartate receptor subunit 2A (NR2A), choline acetyltransferase (ChAT), and Vesicular acetylcholine transporter (VAChT) levels were observed in the hippocampus and ChAT in the medial septal nucleus (MSN) of App KI/HCNP-pp cKO mice. DISCUSSION: Cholinergic dysfunction in HCNP-pp cKO mice exacerbates cognitive dysfunction in App KI mice. The obtained mouse models are expected to be used to investigate cholinergic dysfunction and amyloid pathogenesis in AD.
Shihadeh L, Rosselli M, Conniff J
… +13 more, Asken B, Goytizolo A, Barker W, Matusz EF, Collie A, Coombes SA, Armstrong M, Velez-Uribe I, Adjouadi M, Smith GE, Duara R, DeKosky SD, Loewenstein DA
Alzheimers Dement
· 2026 Jun · PMID 42233291
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INTRODUCTION: This study aimed to investigate whether sleep quality predicts cognitive/functional decline, and whether Alzheimer's disease (AD) pathology modifies these relationships. METHODS: The Pittsburgh Sleep Qualit...INTRODUCTION: This study aimed to investigate whether sleep quality predicts cognitive/functional decline, and whether Alzheimer's disease (AD) pathology modifies these relationships. METHODS: The Pittsburgh Sleep Quality Index was administered to 326 older adults (113 cognitively normal, 192 mild cognitive impairment, 21 dementia; mean age = 66.4 ± 8.0 years) enrolled in the 1Florida Alzheimer's Disease Research Center. The Clinical Dementia Rating Sum of Boxes (CDR-SB) assessed cognitive/functional decline at baseline and over time. Moderators included hippocampal volume (HV), amyloid beta (Aβ) positron emission tomography, and plasma phosphorylated tau (p-tau)217. RESULTS: Cross-sectionally, longer sleep duration and later wake time were associated with worse CDR-SB, with stronger associations observed among individuals with higher Aβ and p-tau217 levels, and smaller HV. Longitudinally, prolonged sleep duration was associated with faster cognitive decline, particularly in individuals with elevated Aβ or p-tau217 levels and smaller hippocampal volumes at baseline. DISCUSSION: Prolonged sleep duration and later wake times predicted worsening cognitive performance, and these effects were strengthened by greater AD pathology.
Han HR, Perrin N, Yun JY
… +6 more, Min D, Kwon SC, Joo J, Cho JY, Kim S, Lee HB
Alzheimers Dement
· 2026 Jun · PMID 42233272
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BACKGROUND: Linkage to medical services enables timely diagnosis and treatment, yet racial/ethnic minority older adults with limited English proficiency (LEP) face substantial barriers. We tested Preparing Healthy Aging...BACKGROUND: Linkage to medical services enables timely diagnosis and treatment, yet racial/ethnic minority older adults with limited English proficiency (LEP) face substantial barriers. We tested Preparing Healthy Aging through Dementia Literacy Education and Navigation (PLAN), a language-concordant community health worker (CHW)-led intervention, to improve dementia linkage among Korean American (KA) older adults with undiagnosed probable dementia and to assess caregiver outcomes. METHODS: In a community-based randomized trial, 287 older adult-caregiver dyads were followed for 6 months. Trained Korean-speaking CHWs delivered a 1-h dementia literacy education session plus phone navigation. The primary outcome was linkage to medical services, verified through clinic documentation. Secondary outcomes included caregiver psychosocial measures. RESULTS: PLAN increased linkage to medical services versus control (16.7% vs 0%, chi-squared [df = 1] = 24.05, p < 0.001). Caregiver outcomes were largely unchanged, with self-efficacy favoring control. DISCUSSION: This language-concordant CHW model achieved verified community-to-clinic linkage at 6 months. Longer follow-up and testing across diverse LEP communities are needed to assess diagnosis, treatment initiation, and caregiver trajectories.
Heikal SA, Khedr EM, Fawi G
… +11 more, Othman M, Elsheikh NG, Tawfik HM, Hassanin HI, ElFarrash S, Salama S, Ali EM, Ibrahim A, Qayaty A, Moustafa SA, Salama M
Alzheimers Dement
· 2026 Jun · PMID 42233255
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BACKGROUND: Dementia prevention targets modifiable factors from high-income cohorts, but most studies conflate dementia status and cognitive performance, distinct outcomes with potentially different outcomes. This distin...BACKGROUND: Dementia prevention targets modifiable factors from high-income cohorts, but most studies conflate dementia status and cognitive performance, distinct outcomes with potentially different outcomes. This distinction is critical to disentangle in resource-constrained low- and middle-income countries, where resource prioritization requires context-specific evidence. METHODS: Cross-sectional analysis of 660 adults with dementia/mild cognitive impairment from the Egyptian Dementia Network registry (2022 to 2025). Parallel logistic/linear regression models identified factors associated with dementia status versus continuous Mini-Mental State Examination (MMSE) scores, comparing determinants across outcomes. RESULTS: The mean age of participants was 68 years, 51% were male, and 81% had a primary education. Multivariable models showed only college education (odds ratio [OR] 0.30, 95% confidence interval [CI]: 0.10 to 0.86) and social inactivity (OR 3.00, 95% CI: 1.27 to 7.08) associated with dementia status. Eight factors (age, diabetes, hypertension, cholesterol, family history, apolipoprotein ε4, body mass index, and sex; all p < 0.05) strongly predicted MMSE but not diagnosis. DISCUSSION: Dementia diagnosis and cognitive performance show mechanistically distinct cross-sectional associations. LMICs should prioritize education/social engagement for dementia prevention, framing vascular-metabolic management as cognitive maintenance.