J. Alzheimers Dis. [JOURNAL]
Sun
200 papers
Gut-brain axis crosstalk in patients with Alzheimer's disease and high body mass index: Gut dysbiosis, blood-brain barrier disruption, and neuroinflammation.
Li J, Lian T, Guo P … +12 more , Li J, Qi J, Luo D, Meng Y, He M, Zheng Z, Yue H, Liu Z, Zhang F, Wang R, Zhang W, Zhang W
J Alzheimers Dis · 2026 Jul · PMID 42227185 · Publisher ↗
BackgroundAccumulating evidence indicates that body mass index (BMI) is related to Alzheimer's disease (AD).ObjectiveThis study aimed to investigate the impact of high BMI on cognitive function in AD patients and potenti...
BackgroundAccumulating evidence indicates that body mass index (BMI) is related to Alzheimer's disease (AD).ObjectiveThis study aimed to investigate the impact of high BMI on cognitive function in AD patients and potential mechanisms involving gut dysbiosis, blood-brain barrier (BBB) disruption, and neuroinflammation in brain.MethodsA total of 50 AD patients were recruited and divided into AD with normal BMI (AD-nBMI) and AD with high BMI (AD-hBMI) groups. Cognitive function was assessed, the levels of BBB variables, neuroinflammatory factors, and AD biomarkers in cerebrospinal fluid (CSF) were measured, gut microbiota and metabolites were analyzed using 16S ribosomal ribonucleic acid gene sequencing and gas chromatography-mass spectrometry analysis, and the correlations among gut microbiota and metabolites, BBB variables, and neuroinflammatory factors in CSF were analyzed.ResultsAD-hBMI group exhibited impaired overall cognition, elevated CSF levels of zonula occludens-1 (ZO-1) and occludin (OCLN) (BBB disruption), and increased CSF levels of nitric oxide (NO) and hydroxyl radical (·OH) (neuroinflammation) compared with AD-nBMI group. Correlation analyses revealed that BMI was positively associated with impaired cognition, CSF levels of OCLN and NO in AD patients. AD-hBMI group displayed a unique gut dysbiosis pattern characterized by the alterations in specific metabolite levels. In AD-hBMI group, elevated thioridazine, 4-hydroxybenzaldehyde, and N-acetylleucine were positively correlated with ZO-1 level in CSF, reduced acesulfame and undecanoic acid were negatively correlated with OCLN level in CSF, and elevated (S)-S-methylcysteine sulfoxide was positiveiy correlated with both ZO-1 and OCLN levels in CSF. Elevated thioridazine and medroxyprogesterone were positively correlated with NO level in CSF, and decreased butyric acid was negatively correlated with ·OH level in CSF.ConclusionsHigh BMI may accelerate gut dysbiosis, leading to disrupted BBB, enhanced neuroinflammation, and ultimately accelerated cognitive impairment in AD patients.
Naming performance in bilinguals with Alzheimer's disease and mild cognitive impairment.
Sainz-Pardo M, Hernández M, Suades A … +6 more , Juncadella M, Ortiz-Gil J, Ugas L, Sala I, Lleó A, Calabria M
J Alzheimers Dis · 2026 Jun · PMID 42227174 · Publisher ↗
BackgroundThere is consistent evidence of a disadvantage in bilinguals' speech production compared to monolinguals in healthy individuals, but studies investigating this phenomenon in clinical populations such as mild co...
BackgroundThere is consistent evidence of a disadvantage in bilinguals' speech production compared to monolinguals in healthy individuals, but studies investigating this phenomenon in clinical populations such as mild cognitive impairment (MCI) and Alzheimer's disease (AD) are scarce. Given that both clinical groups are characterized by word-finding difficulties, understanding how bilingualism influences speech production in these populations is essential.ObjectiveTo investigate the effect of bilingualism on dominant-language speech production in individuals with MCI and AD relative to cognitively unimpaired (CU) older adults.MethodsEarly and highly proficient Catalan-Spanish bilinguals (active bilinguals) were compared to Spanish-dominant speakers with low proficiency in Catalan (passive bilinguals) using a picture-naming task. The study included 58 CU older adults, 66 patients with AD, and 124 individuals with MCI. Reaction times, accuracy, and error types were collected in the naming task in each individual's dominant language.ResultsFirst, we observed an advantage for active bilinguals compared to passive bilinguals, as indexed by faster responses, particularly for cognate words. Second, active bilinguals with MCI exhibited a disadvantage, making more naming errors than passive bilinguals with MCI, especially for non-cognates, including a higher incidence of cross-language intrusions and anomia. Third, passive bilinguals with MCI and AD showed more semantic errors than active bilinguals.ConclusionsDisadvantages in naming are discussed in terms of predictions from cognitive and linguistic theories, whereas potential advantages of speaking a second language are considered as a protective factor, consistent with frameworks such as cognitive reserve.
Integrative genomic and transcriptomic analysis identifies microglia-expressed genes with causal links to Alzheimer's disease risk.
Zhao Y, Liu C, Yv K … +2 more , Wang N, Li Z
J Alzheimers Dis · 2026 Jun · PMID 42227173 · Publisher ↗
BackgroundMicroglia play a central role in Alzheimer's disease (AD) pathogenesis, yet it remains unclear whether microglia-related gene expression changes contribute causally to disease risk or reflect downstream respons...
BackgroundMicroglia play a central role in Alzheimer's disease (AD) pathogenesis, yet it remains unclear whether microglia-related gene expression changes contribute causally to disease risk or reflect downstream responses to neurodegeneration.ObjectiveThis study aimed to systematically identify microglia-expressed genes with genetically regulated expression associated with AD risk and to characterize their functional relevance through integrative genomic analyses.MethodsWe compiled 2454 microglia-associated genes from four transcriptomic studies and five expression databases. Using brain cis-eQTL data from PsychENCODE (n = 1387), we performed summary-data-based Mendelian randomization (SMR) and HEIDI tests with AD GWAS data (111,326 cases, 677,663 controls). Significant SMR signals (FDR < 0.05) were evaluated using Bayesian colocalization. Regulatory context was assessed via overlap with PU.1-associated chromatin features, and differential expression was examined using single-nucleus RNA-seq from AD brains.ResultsSMR identified 16 genes whose genetically predicted expression was associated with AD risk (FDR < 0.05), including (OR = 1.10, 95% CI: 1.07-1.13) and (OR = 0.90, 0.86-0.95). Colocalization supported shared causal variants at eight loci (PPH4 > 0.8; e.g., , , ). Most prioritized genes overlapped with PU.1-associated regulatory regions. Single-nucleus RNA-seq confirmed dysregulation of several candidates (e.g., , ) in AD microglia.ConclusionsWe identify microglia-expressed genes with genetic evidence consistent with a potential causal role in AD. These genes are enriched in microglia-specific regulatory elements and exhibit transcriptional alterations in AD, highlighting microglial pathways as potential therapeutic targets.
Setting research priorities around the impact of COVID-19 control measures on people with dementia and caregivers living at home: A 14-country perspective.
Peeters G, Fitzpatrick RL, Mollayeva T … +14 more , Chen Y, de Paula França Resende E, Leon T, Zapata-Restrepo LM, Tituaña K, Tsolaki M, Arshad F, Thapa P, Farombia T, Custodio B, Ntokozo Ngcobo K, O'Sullivan R, Leroi I, STRAP consortium
J Alzheimers Dis · 2026 Jul · PMID 42216674 · Full text
BackgroundThe global impact of COVID-19 restrictions on people with dementia (PWD) living at home and their informal caregivers has been described extensively. However, adoption of this knowledge into policy and practice...
BackgroundThe global impact of COVID-19 restrictions on people with dementia (PWD) living at home and their informal caregivers has been described extensively. However, adoption of this knowledge into policy and practice is limited because of a lack of coordinated, inclusive, and regionally sensitive prioritization.ObjectiveTo establish key regional research priorities for Europe and the Global South.MethodsFollowing consensus-based prioritization methods, we applied a three-step approach: 1) a systematic literature review to derive a list of topics describing how PWD and caregivers were impacted by the COVID-19 restrictions; 2) an online survey distributed to PWD, caregivers and health care professionals (HCP) across 14 countries asking respondents to select the 10 most important topics; and 3) an iterative consultation process with stakeholders from each country to translate the top-ranked topics into a research agenda.ResultsWe identified 51 quantitative and 18 qualitative relevant publications, from which we derived 38 topics. 29 PWD, 110 caregivers and 117 HCP across 14 countries prioritized these topics, which largely overlapped across stakeholder groups and countries. The top ranked priorities cluster into four themes: daily routine and physical function, mental health, disease progression, and access to care. The consultancy process with stakeholders resulted in three lines of research to address these themes: understanding mechanisms, designing and improving education, and information access.ConclusionsThis research agenda offers a roadmap to guide future research and policy aimed at strengthening support for PWD and their caregivers in times of public health crises.
Multimodal machine learning for early risk stratification of post-stroke cognitive impairment.
Zheng X, Zhao P, Wang N … +6 more , Wang X, Dong Z, Gu C, Sun Y, Gu X, Zhou X
J Alzheimers Dis · 2026 May · PMID 42216673 · Publisher ↗
BackgroundPost-stroke cognitive impairment (PSCI) is a major vascular contributor to dementia, significantly impacting long-term recovery and quality of life. Developing accurate prediction models are essential for early...
BackgroundPost-stroke cognitive impairment (PSCI) is a major vascular contributor to dementia, significantly impacting long-term recovery and quality of life. Developing accurate prediction models are essential for early identification and timely intervention in high-risk individuals.ObjectiveTo develop and validate a stacking-based multimodal machine learning model integrating clinical, demographic, and neuroimaging features for early PSCI prediction in acute ischemic stroke (AIS) patients.MethodsIn this retrospective cohort study, 1070 AIS patients admitted to Lianyungang First People's Hospital from January 2020 to August 2023 were included. Demographic, clinical, and neuroimaging data were collected, and cognitive function was assessed 3-6 months post-stroke. PSCI was defined as a z-score ≤ -2.0 in at least one of four cognitive domains. A stacking ensemble model was developed, combining six base algorithms: XGBoost, Gradient Boosting Decision Trees, CatBoost, Support Vector Machine, Logistic Regression, and LightGBM. The final prediction was generated by a meta-model trained on base model outputs.ResultsOf the 1070 patients (mean age 67.4 ± 9.3 years, 61.5% male), 37.2% developed PSCI. The stacking model achieved 98.13% accuracy, 0.9972 AUC, and 0.9744 F1-score in internal validation. External validation showed 81.00% accuracy, 0.9049 AUC, and 0.8780 recall. Key predictors of PSCI included infarct volume, cortical lesions, medial temporal lobe atrophy, and baseline NIHSS score.ConclusionsThis stacking-based multimodal machine learning model demonstrates robust predictive performance for PSCI risk in AIS patients, serving as a reliable tool for early detection that may inform personalized intervention strategies to prevent progression to post-stroke dementia.
Longitudinal amyloid PET changes by cerebrospinal fluid amyloid and tau profiles in individuals with normal cognition: Role of ε4.
Rizzo M, Oomens JE, Jansen WJ … +3 more , Visser PJ, Vos SJB, AMYPAD consortium
J Alzheimers Dis · 2026 May · PMID 42216672 · Publisher ↗
BackgroundIdentifying factors associated with early progression of cortical amyloid deposition is crucial for understanding Alzheimer's disease (AD) pathophysiology, yet these remain unclear.ObjectiveTo investigate the a...
BackgroundIdentifying factors associated with early progression of cortical amyloid deposition is crucial for understanding Alzheimer's disease (AD) pathophysiology, yet these remain unclear.ObjectiveTo investigate the associations of AD cerebrospinal fluid (CSF) biomarkers with early longitudinal amyloid deposition on positron emission tomography (PET), and the impact of ε4 carriership.MethodsWe selected cognitively unimpaired participants with baseline data on CSF amyloid and p-tau181, ε4 carriership, and ≥ 2 consecutive amyloid PET assessments from the AMYPAD-PNHS cohort. Linear mixed models were used to investigate the associations of combinations of amyloid abnormality (A+) and tau abnormality (T+) in CSF (A+T+, A+T-, A-T+, A-T-), without and with stratification for ε4 carriership, with longitudinal global cortical amyloid deposition on PET, measured in Centiloids.ResultsWe included 329 individuals (mean age 63.5 [SD 6.1], 58% female, 49% ε4 carriers). Longitudinally, CSF profiles with abnormal amyloid levels (A+T+, A+T-) showed greater increases in cortical amyloid deposition than profiles with normal amyloid levels (A-T+, A-T-), irrespective of CSF tau abnormality (all p < 0.001). Only for CSF profiles with normal amyloid levels, longitudinal amyloid deposition depended on ε4 carriership, with both A-T+ and A-T- showing increased deposition among ε4 carriers (carriers versus non-carriers: A-T+ p = 0.006, A-T- p = 0.016).ConclusionsIn cognitively unimpaired individuals, longitudinal increase in cortical amyloid deposition was mainly associated with abnormal baseline CSF amyloid rather than tau. ε4 carriership was associated with increased longitudinal cortical amyloid deposition only in individuals with normal baseline CSF amyloid. These findings inform early AD pathological progression and trial design.
Traumatic brain injury and post-traumatic stress disorder on brain imaging markers and cognition in a war veterans population.
Sibilia F, Fotouhi M, Lei X … +6 more , Cabeen RP, Cen S, Choupan J, Hazany S, Sheikh-Bahaei N, Alzheimer's Disease Neuroimaging Initiative
J Alzheimers Dis · 2026 Jul · PMID 42216670 · Full text
BackgroundTraumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) are emerging contributors to the development and progression of dementia.ObjectiveThis study examined how traumatic brain injury and post-t...
BackgroundTraumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) are emerging contributors to the development and progression of dementia.ObjectiveThis study examined how traumatic brain injury and post-traumatic stress disorder relate to cognitive function and neuroimaging markers in U.S. veterans from the Department of Defense Alzheimer's Disease Neuroimaging Initiative (ADNI-DOD).MethodsTBI severity was quantified with a new scoring system, and PTSD symptoms and combat exposure were assessed using the Clinician-Administered PTSD Scale (CAPS) and Combat Exposure Scale (CES). Cognitive performance was evaluated with the Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and Clinical Dementia Rating Sum of Boxes (CDR-SOB). Neuroimaging included amyloid-β (Aβ) and tau positron emission tomography (PET), diffusion tensor imaging (DTI), vascular imaging, and resting-state functional MRI (rs-fMRI).ResultsAs expected, higher Aβ and tau burden were significantly associated with worse cognitive performance on the MMSE, ADAS-Cog, and CDR-SOB. Greater PTSD symptom severity was also linked to poorer cognition measured by all three tests, and higher TBI severity correlated with lower MMSE scores. However, neither TBI severity nor PTSD symptoms were associated with neuroimaging biomarkers of neurodegeneration or vascular damage.ConclusionsThese findings suggest that cognitive impairment in veterans is related to the prior history of TBI and PTSD, but these risk factors may not affect the cognition directly through the accumulation of AD pathologies or vascular injuries. Although these results need further validation by other cohorts who have more recent trauma and wider range of cognitive impairment.
Cannabinoids for Alzheimer's disease: A promising trial, although not yet ready for the prescription pad.
Dos Santos Silva J
J Alzheimers Dis · 2026 May · PMID 42216668 · Publisher ↗
Cury et al. present the first randomized placebo-controlled trial of a low-dose balanced tetrahydrocannabinol-cannabidiol extract targeting cognition in Alzheimer's disease (AD). The study marks a milestone in a field lo...
Cury et al. present the first randomized placebo-controlled trial of a low-dose balanced tetrahydrocannabinol-cannabidiol extract targeting cognition in Alzheimer's disease (AD). The study marks a milestone in a field long dominated by anecdotes and low-certainty evidence. While it demonstrated modest cognitive improvement on the Mini-Mental State Examination, the lack of functional and behavioral outcomes raises questions about real-world benefits. Methodological limitations, including a small sample size and limited power, temper interpretation but highlight the need for larger studies. For clinicians, this trial transforms speculation into evidence-based counseling, promoting informed dialogue while cautioning against premature clinical use of unregulated cannabis products in AD care.
Association of plasma glial fibrillary acidic protein and neurofilament light chain with retinal cell layer thickness: A cross-sectional study of ophthalmic surgical patients.
Prasad M, Pulukuri S, Sampani K … +9 more , Yarala R, Mittal R, Xia W, Stein TD, Aytan N, Chen X, Ness S, Siegel NH, Subramanian ML
J Alzheimers Dis · 2026 May · PMID 42216665 · Publisher ↗
BackgroundRetinal thickness has been associated with neurocognitive conditions such as Alzheimer's disease (AD).ObjectiveRetinal cell layer thickness was evaluated for associations with neurodegenerative protein biomarke...
BackgroundRetinal thickness has been associated with neurocognitive conditions such as Alzheimer's disease (AD).ObjectiveRetinal cell layer thickness was evaluated for associations with neurodegenerative protein biomarkers glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) in plasma, vitreous humor, and aqueous humor.MethodsThis cross-sectional study included 50 patients who underwent vitrectomy and optical coherence tomography imaging of the inner macular ring (IM) and outer macular ring (OM). Associations between inner retinal cell layer thicknesses and GFAP or NfL levels were evaluated with linear regression adjusted for demographic and clinical factors. p-values less than 0.05 and with a false discovery rate less than 10% were considered significant.ResultsHigher plasma GFAP levels were significantly associated with a thinner retinal nerve fiber layer at the superior, nasal, and inferior OM as well as a thinner ganglion cell layer at the superior IM, inferior IM, temporal IM, nasal OM, and temporal OM. Plasma GFAP was also associated with a thinner inner plexiform layer at the nasal IM, inferior IM, temporal IM, nasal OM, and temporal OM. Plasma NfL was negatively associated with GCL thickness only in the superior IM.ConclusionsHigher plasma GFAP levels were associated with thinner inner cell layers, whereas plasma NfL levels showed a more limited association. These findings suggest that systemic astroglial activation may be associated with retinal structural changes.
Bibliometric analysis of natural medicine in the treatment of Alzheimer's disease: Trends, hotspots, and emerging research fields.
Wen T, Zhu T, Zhou LY … +3 more , Ran Z, Chen L, Wang WJ
J Alzheimers Dis · 2026 May · PMID 42216664 · Publisher ↗
BackgroundAlzheimer's disease (AD) is a progressive neurodegenerative disorder whose global prevalence continues to rise, yet treatment options are still limited. Natural medicines, with their potential for multi-target...
BackgroundAlzheimer's disease (AD) is a progressive neurodegenerative disorder whose global prevalence continues to rise, yet treatment options are still limited. Natural medicines, with their potential for multi-target intervention, have become a key direction in AD drug development. However, a systematic overview of research trends in this field based on bibliometric methods is currently lacking.ObjectiveThis study aims to summarize research progress on natural medicines for AD treatment using bibliometric analysis and to identify future research hotspots and trends.MethodsRelevant publications were retrieved from the Web of Science Core Collection. Data visualization and analysis were conducted using VOSviewer, CiteSpace, and R.ResultsA total of 3800 publications were included, involving contributions from 108 countries/regions, 4024 institutions, 18,729 authors, and 706 journals. Publication output showed steady growth, with China and India as the leading contributing countries. Institutions such as the Chinese Academy of Sciences and Kyung Hee University demonstrated high productivity and influence. The research focus has shifted from initial clinical pharmacology and molecular pathology to exploring multi-target mechanisms of natural medicines through network pharmacology and molecular docking. Promising natural agents include Ginkgo biloba, ginseng, curcumin, resveratrol, and Centella asiatica.ConclusionsResearch on natural medicines for AD has progressed steadily over the past two decades, with current emphasis on elucidating multi-target mechanisms using emerging technologies. However, clinical evidence remains limited. Future studies should strengthen multi-omics integration and clinical translation to foster innovative AD prevention and treatment strategies.
A century of coffee and tea research in cognitive health and Alzheimer's disease: Structural, thematic, and translational insights (1911-2025).
Taha MME, Abdelwahab SI, Sahli KA … +5 more , Jeraiby M, Qadri M, Alarifi A, Farasani A, Moshi JM
J Alzheimers Dis · 2026 Jul · PMID 42216624 · Publisher ↗
BackgroundAlthough studies have explored tea and coffee in relation to Alzheimer's disease, no century-scale analysis has jointly examined both within a unified primary-evidence framework.ObjectiveThis study maps the str...
BackgroundAlthough studies have explored tea and coffee in relation to Alzheimer's disease, no century-scale analysis has jointly examined both within a unified primary-evidence framework.ObjectiveThis study maps the structural, thematic, and temporal evolution of coffee and tea research in cognitive aging.MethodsScopus-indexed original English articles (1911-2025) were retrieved using a structured Boolean strategy under PRISMA guidance. Analyses were conducted using Bibliometrix and VOSviewer. Performance metrics, collaboration networks, co-citation mapping, Bradford's Law, co-word clustering, thematic evolution, and overlay visualization were applied to full-period and recent (2021-2025) datasets.ResultsA total of 2873 articles across 1285 sources demonstrated steady annual growth (4.96%) and substantial citation impact (mean 40.17 citations per document). Research productivity was concentrated in high-income countries, led by the United States, United Kingdom, and China, reflecting core-periphery stratification and citation asymmetry. Collaboration networks showed hub dominance with dense transatlantic-Eurasian linkages. Bradford analysis identified a limited core of highly productive journals. Thematic evolution revealed persistent anchoring in Alzheimer's disease, oxidative stress, and neuroprotection, with sustained prominence of coffee, caffeine, tea, and polyphenols. Recent years indicate translational expansion integrating microbiome science and computational methods. Overlay visualization demonstrated temporal stratification, highlighting emerging themes such as gut microbiota and deep learning alongside stable beverage-related cognitive frameworks.ConclusionsCoffee and tea research in cognitive aging has evolved into a mature, mechanistically grounded, and globally stratified field, increasingly integrating translational, microbiome, and computational approaches in dementia-related investigations.
Comparative long-term outcomes of home-based versus institutional care in Alzheimer's disease.
Tan Y, Liu Q, Wu C … +9 more , Zhang C, Yao Q, Li J, Kang Y, Huang B, Gu L, Lu J, Zhu D, Sun M
J Alzheimers Dis · 2026 Jul · PMID 42212579 · Publisher ↗
BackgroundThe decision between home-based (HC) and institutional care (IC) for Alzheimer's disease (AD) is critical for patients, families, and healthcare systems, yet evidence on long-term trade-offs remains insufficien...
BackgroundThe decision between home-based (HC) and institutional care (IC) for Alzheimer's disease (AD) is critical for patients, families, and healthcare systems, yet evidence on long-term trade-offs remains insufficient.ObjectiveThis study comprehensively compare the 5-year clinical, economic, and family-related outcomes between HC and IC for AD patients.MethodsWe conducted a prospective-retrospective cohort study involving 252 AD patients (HC = 124; IC = 128) and their families. Outcomes included cognitive and functional status (using Mini-Mental State Examination and Barthel index), neuropsychiatric symptoms (Neuropsychiatric Inventory), medication adherence (Medication Possession Ratio and Morisky Medication Adherence Scale), healthcare costs, and family impact (Depression, Anxiety and Stress Scales and General Health Questionnaire).ResultsAnalysis revealed a critical dichotomy: HC showed better early cognitive preservation but later accelerated decline, contrasting with IC's stable trajectory. IC demonstrated superior control of harmful behaviors and prevention of consequential events, while HC was associated with more significant medical complications. Medication adherence was sustainably higher in IC but progressively deteriorated in HC. Economically, HC's lower initial direct costs were offset by substantial indirect costs, while IC incurred higher but predictable direct expenditures. Crucially, the psychological and health impact on family progressed substantially in HC but remained low and stable in IC.ConclusionsNo single care model was universally superior. The HC versus IC decision involves strategic trade-offs across clinical, economic, and family domains. These findings advocate for personalized, dynamic care models that facilitate timely transitions, guided by patient needs and family capacity, to optimize long-term outcomes for both patients and their families.
Associations between Alzheimer's disease blood biomarkers and neighborhood disadvantage: A HABS-HD community cohort study.
Miller JB, Rhoads T, Vintimilla R … +6 more , Petersen M, Wong CG, Zhang F, Kind AJ, O'Bryant SE, HABS-HD Study Team
J Alzheimers Dis · 2026 May · PMID 42212447 · Publisher ↗
BackgroundNeighborhood disadvantage has been associated with reduced cognitive reserve, increased risk for cognitive impairment, and greater Alzheimer's disease (AD) neuropathology, with particularly pronounced effects a...
BackgroundNeighborhood disadvantage has been associated with reduced cognitive reserve, increased risk for cognitive impairment, and greater Alzheimer's disease (AD) neuropathology, with particularly pronounced effects among Black and Hispanic/Latino older adults. Blood-based AD biomarkers offer a scalable approach to population-level study of AD risk; however, whether neighborhood-level social determinants influence these biomarkers across diverse populations remains unknown.ObjectiveTo characterize associations between neighborhood disadvantage and AD blood biomarkers in a racially and ethnically diverse community sample of older adults with and without cognitive impairment, and to examine whether these associations differ by race, ethnicity, and cognitive status.MethodsRegression models predicting AD biomarkers (amyloid-β 42/40 ratio, phosphorylated tau-181, total tau, and neurofilament light chain) from demographics and the Area Deprivation Index (ADI) were fit for 1179 Non-Hispanic White, 1264 Hispanic/Latino, and 724 Black adults. Models were stratified by cognitive impairment status and fit separately by race and ethnicity.ResultsAmyloid markers were associated with ADI, but only in cognitively impaired individuals living in highly disadvantaged areas. Total tau was elevated in those from disadvantaged neighborhoods, regardless of cognitive status; however, pTau-181 was not associated with ADI for any group. Significant associations were primarily evident among Black and Hispanic/Latino older adults.ConclusionsThe social exposome is an important factor in AD research, and findings show associations between neighborhood disadvantage and AD blood biomarkers; however, associations are mainly evident among ethnic/racial minority older adults living in moderately to severely disadvantaged neighborhoods. More work is needed to understand these associations.
Evaluation of physical functioning as a marker of brain imaging outcomes in a multiethnic community-based cohort.
Knell G, Meeker KL, Zhou Z … +3 more , Petersen ME, Hall JR, O'Bryant SE
J Alzheimers Dis · 2026 Jul · PMID 42212445 · Publisher ↗
BackgroundPhysical functioning (PF) tests are scalable screening tools for neurodegenerative risk that differ by race and ethnicity, reflecting upstream social inequities. Prior work shows that PF relates to Alzheimer's...
BackgroundPhysical functioning (PF) tests are scalable screening tools for neurodegenerative risk that differ by race and ethnicity, reflecting upstream social inequities. Prior work shows that PF relates to Alzheimer's disease blood biomarkers differentially by race and ethnicity, yet it is unclear if similar associations exist with structural brain outcomes (hyperintensities and brain volumes).ObjectiveThis study evaluated associations between PF and white matter hyperintensity volume (WMH), total brain volume (TBV), and hippocampal volume (HV) and assessed heterogeneity by race and ethnicity.MethodsCognitively normal non-Hispanic Black (n = 420), non-Hispanic white (n = 917), and Hispanic (n = 828) older adults (mean [SD] age = 64.7 [8.4]) from the Healthy Aging Brain Study-Health Disparities cohort completed the Timed Up and Go (TUG) and Short Physical Performance Battery (SPPB). Brain imaging was collected via 3 T magnetic resonance imaging (MRI). Multivariable linear models related PF to brain imaging outcomes (normalized by intracranial volume) and assessed heterogeneity by race and ethnicity.ResultsBonferroni adjusted significant (p < 0.05) associations were observed between WMH and PF (TUG: β = 0.28, 95% CI = 0.17, 0.40; SPPB:β = -0.19, 95% CI = -0.32, -0.07), TBV and PF (TUG: β = -0.50, 95% CI = -0.61, -0.40; SPPB: β = 0.30, 95% CI = 0.18, 0.42), and HV and PF (TUG: β = -0.28, 95% CI = -0.38, -0.18). Associations were generally similar across race and ethnicity groups for TBV and HV.ConclusionsPoorer PF was associated with reduced TBV and HV and greater WMH. Results support PF tests as scalable, non-invasive indicators of brain health in community-based populations.
Adolescent intermittent ethanol exacerbates amyloid-β with age in the dorsal hippocampus of female TgF344-AD rats.
Day SM, Reitz NL, Savage LM
J Alzheimers Dis · 2026 May · PMID 42212444 · Publisher ↗
BackgroundAlcohol misuse increases Alzheimer's disease (ΑD) risk; however, the mechanisms linking these conditions are unknown. In rodents, chronic and acute ethanol increases amyloid-β (Aβ); however, most of those studi...
BackgroundAlcohol misuse increases Alzheimer's disease (ΑD) risk; however, the mechanisms linking these conditions are unknown. In rodents, chronic and acute ethanol increases amyloid-β (Aβ); however, most of those studies have been limited to a single sex or brain region.ObjectiveThis study explored how adolescent intermittent ethanol (AIE), alters Aβ in multiple regions of the brain in female and male TgF344-AD rats as they age.MethodsFrom postnatal days 28-58, female and male TgF344-AD rats were administered either water (CON) or 5.0 g/kg ethanol (AIE; 20% ethanol w/v) via intragastric gavage on a 2-day on/off cycle. In Experiment 1, Aβ was measured in the medial prefrontal cortex, orbitofrontal cortex (OFC), piriform cortex (PC), entorhinal cortex (EC), ventral hippocampus (vHPC), and dorsal hippocampus (dHPC) in 6- and 10-month-old rats. In Experiment 2, in vivo microdialysis was used in 3-month-old female rats to measure how ethanol directly modulates Aβ levels in the dHPC.ResultsIn the OFC, PC, EC, vHPC, and dHPC, Aβ and Aβ was higher in 6-month-old female TgF344-AD rats compared to males. However, at 10 months Aβ and Aβ levels were only elevated in the dHPC of AIE-treated females, compared to all other groups. An acute ethanol challenge at 3 months selectively evoked a sustained increase in interstitial fluid Aβ levels in AIE-treated females.ConclusionsIn aged females, the dHPC is a region sensitive to ethanol-associated Aβ pathology. This may be due to disruptions in Aβ clearance in early life, which may have an additive effect on Aβ aggregation over the lifespan.
U-shaped relationship between hemoglobin glycation index and cognitive outcome in older population in China: A population-based prospective study.
Xiang C, Tang L, Zhao C … +3 more , Zhao Y, Xu X, Zhang Y
J Alzheimers Dis · 2026 May · PMID 42212443 · Publisher ↗
BackgroundThe hemoglobin glycation index (HGI) effectively captures individual variations in glycation, its association with cognitive impairment remains unclear.ObjectiveThe purpose of this study was to investigate the...
BackgroundThe hemoglobin glycation index (HGI) effectively captures individual variations in glycation, its association with cognitive impairment remains unclear.ObjectiveThe purpose of this study was to investigate the relationship between HGI and cognitive impairment risk in the Chinese population.MethodsData from the China Health and Retirement Longitudinal Study (CHARLS) between 2011 and 2015 were analyzed. Cognitive function was assessed using the American Health and Retirement Study's methodology, which included episodic memory and mental status. Multivariate Cox proportional hazards models and restricted cubic splines were used to examine the link between HGI and the likelihood of cognitive impairment, specific cognitive domains included. Moreover, the potential inflection points were investigated using saturation threshold effect analysis, with bootstrap resampling applied for internal validation.ResultsA U-shaped relationship was observed between HGI and the risk of cognitive impairment, as demonstrated by the restricted cubic spline analysis (p for non-linearity <0.001). The primary analysis identified an inflection point at approximately 0.085. Internal validation via bootstrapping yielded a 95% empirical confidence interval of 0.013 to 0.255 for this point. Conversely, HGI levels above 0.085 resulted in a 70.6% increase in the hazard ratio of cognitive impairment (all p < 0.05).ConclusionsIn the Chinese population, our results point to a U-shaped association between HGI and the risk of cognitive impairment, suggesting that both very low and very high HGI levels raise the risk of cognitive impairment, especially execution and memory.
Exploratory study on the synergistic use of plasma neurofilament light chain, phosphorylated Tau181, and retinal examination for assessing the risk of Alzheimer's disease and mild cognitive impairment.
He X, Liu W, Liu R … +5 more , Li B, Xu X, Cheng Y, Li Y, Jiang H
J Alzheimers Dis · 2026 May · PMID 42212442 · Publisher ↗
BackgroundBiomarker detection is crucial for diagnosing Alzheimer's disease (AD). A highly promising approach combines non-invasive fundus imaging of the retinal nerve fiber layer (RNFL) with plasma biomarkers. Combining...
BackgroundBiomarker detection is crucial for diagnosing Alzheimer's disease (AD). A highly promising approach combines non-invasive fundus imaging of the retinal nerve fiber layer (RNFL) with plasma biomarkers. Combining RNFL with plasma neurofilament light chain (pNFL) and phosphorylated Tau181 (P-tau181) may play a significant role in the diagnosis and monitoring of mild cognitive impairment (MCI) and AD.ObjectiveThis study aimed to evaluate the utility of combining RNFL thickness with plasma pNFL and P-tau181 levels for assessing the risk of clinically diagnosed AD.MethodsA total of 143 patients with AD and MCI underwent clinical and cognitive assessments as well as biomarker evaluations (plasma pNFL, P-tau181, RNFL), and receiver operating characteristic (ROC) analysis was finally employed to assess their diagnostic efficacy for clinically diagnosed AD.ResultsSignificant inverse correlations were found between Mini-Mental State Examination scores and pNFL (R = 0.344, p < 0.001) and P-tau181 (R=0.424, p < 0.001). Temporal RNFL thickness was significantly lower in the MCI group versus healthy control (HCs), while the AD group showed intermediate thickness not significantly different from HCs. For AD diagnosis, pNFL achieved the highest area under the curve (AUC=0.748). Combining pNFL with P-tau181 improved the AUC to 0.784, and models further incorporating Apolipoprotein E () ε4 or RNFL thickness similarly showed high accuracy (AUCs=0.785/0.782).ConclusionsElevated levels of pNFL and P-tau181 are independent risk factors for cognitive decline. Combination with fundus examination confers significant diagnostic utility for clinically diagnosed AD.
Biomarkers of angiogenesis in Alzheimer's disease: Systematic review and meta-analysis.
Kapoor A, Nguyen AD, Joyce JL … +4 more , Gaubert A, Duke Han S, Hughes CCW, Nation DA
J Alzheimers Dis · 2026 May · PMID 42212439 · Publisher ↗
BackgroundCerebrovascular dysfunction can contribute to the pathophysiology of Alzheimer's disease (AD) and trigger angiogenesis. To date, no prior systematic review and meta-analysis (SRMA) study has attempted to qualit...
BackgroundCerebrovascular dysfunction can contribute to the pathophysiology of Alzheimer's disease (AD) and trigger angiogenesis. To date, no prior systematic review and meta-analysis (SRMA) study has attempted to qualitatively and quantitatively review existing literature examining angiogenic factors in AD.ObjectiveIn this review, we aimed to identify markers of angiogenesis in biofluids that can differentiate between individuals with AD and healthy older adults, and inform the role of angiogenesis in AD.MethodsUsing Medline (1946 to August 4, 2021), the literature was systematically searched for articles according to PRISMA guidelines. Angiogenesis and AD terms were searched as keywords and mapped to MeSH headings. A total of 18 studies (including 28 dependent effect sizes) were included in the meta-analysis. Hedges' g was selected as the effect size of interest.ResultsA random-effects model including all eligible biofluid studies revealed a small and nonsignificant overall effect size (combined Hedges' g = -0.26, 95% CI [-1.45, 0.92], p = 0.647), with significant heterogeneity (I = 98.6%, p < 0.0001). Moderator analysis revealed no significant difference based on which specific angiogenic biomarker was examined (i.e., vascular endothelial growth factor (VEGF) versus others).ConclusionsVEGF-related marker levels were not significantly different in AD and normal aging. Based on our findings, few studies have examined fibroblast growth factor and platelet-derived growth factor-related markers; however, we believe they warrant further investigation. Identifying novel angiogenic biomarkers could elucidate the role of vascular mechanisms in AD and reveal potential therapeutic targets.
Longitudinal food insecurity patterns and cognitive performance among midlife Latina women: Findings from the CHAMACOS Maternal Cognition Study.
Perez-Rocha Y, Calderon LE, Kogut K … +7 more , Rojas N, Eskenazi B, Warner M, Rojas-Saunero LP, Gunier RB, Ambriz E, Torres JM
J Alzheimers Dis · 2026 May · PMID 42212437 · Publisher ↗
BackgroundAlthough food insecurity (FI) has been linked to cognitive aging, few studies have examined associations in midlife or socioeconomically disadvantaged populations or considered longitudinal FI patterns.Objectiv...
BackgroundAlthough food insecurity (FI) has been linked to cognitive aging, few studies have examined associations in midlife or socioeconomically disadvantaged populations or considered longitudinal FI patterns.ObjectiveTo examine cross-sectional and longitudinal associations between FI and cognitive performance in a prospective cohort of midlife women.MethodsWe analyzed data from 512 women in the CHAMACOS Maternal Cognition Study (2018-2024). FI was measured twice (approximately 3.2 years apart) with the six-item Short Form of the USDA Household Food Security Survey Module (range: 0-6). We categorized FI cross-sectionally (secure, scores of 0-1; insecure, scores 2-6) and longitudinally (persistent security, persistent FI, new FI). Cognitive performance was assessed across multiple domains with the SOL-INCA-AD assessment. We estimated associations using linear regression adjusted for sociodemographic confounders and, among a subset, ɛ4 carrier status.ResultsCross-sectionally, FI was associated with lower global cognition z-scores (β = -0.11, 95% CI: -0.21, -0.01), with similar trends for executive function (β = -0.10, 95% CI: -0.19, 0.01) and memory domains (β = -0.13, 95% CI: -0.29, 0.03). Longitudinally, new FI (versus persistent security) was associated with lower scores across all domains (Global β = -0.19, 95% CI: -0.32, -0.06; Executive function β = -0.15, 95% CI: -0.27, -0.02; Memory β = -0.22, 95% CI: -0.43, -0.01; Verbal fluency β = -0.17, 95% CI: -0.36, 0.02). Persistent FI showed weaker associations.ConclusionsIn this cohort of midlife women, FI and particularly new onset FI were associated with worse cognitive performance after adjusting for sociodemographic and genetic confounders.
Genetically prioritized druggable targets for amyloid-β pathology highlight as a therapeutic candidate in Alzheimer's disease.
Kim JP, Lee H, Kim BH … +6 more , Kang H, Shin D, Yim S, Kim S, Seo SW, Kim HN
J Alzheimers Dis · 2026 May · PMID 42212431 · Publisher ↗
BackgroundAlzheimer's disease (AD) is characterized by a neuropathological cascade that begins with amyloid-β (Aβ) deposition. The recent success of disease-modifying drugs targeting Aβ has demonstrated that modulating a...
BackgroundAlzheimer's disease (AD) is characterized by a neuropathological cascade that begins with amyloid-β (Aβ) deposition. The recent success of disease-modifying drugs targeting Aβ has demonstrated that modulating amyloidopathy can yield clinical benefits, underscoring the need for additional drugs affecting amyloid pathology.ObjectiveTo identify novel drug targets associated with Aβ accumulation in AD using Mendelian randomization (MR) analysis of the druggable genome.MethodsWe performed MR analysis on expression quantitative trait loci (eQTLs) of the druggable genome in relation to Aβ accumulation using summary-data-based MR (SMR). Blood eQTL data were obtained from the eQTLGen consortium, and brain eQTL data from BrainMeta and PsychENCODE, while Aβ positron emission tomography (PET) genome-wide association study data were derived from 11,816 non-Hispanic White participants across 13 cohorts. Co-localization analysis was conducted to enhance the reliability of the MR results, and additional validation was performed using blood and brain protein quantitative trait loci (pQTLs) as instrumental variables.ResultsThe SMR and co-localization analyses revealed causal associations between the druggable genome and Aβ accumulation, with identified in blood eQTL data and , , and identified in brain eQTL data. Further analysis using pQTL data confirmed causal associations for ACE and CR1, with ACE showing a negative association with Aβ PET uptake.ConclusionsThese findings highlight potential target genes for AD treatment, and the protective effect of against amyloid pathology suggests that alternative medications to ACE inhibitors may be preferred for blood pressure management in the context of AD. Overall, our study demonstrates the potential of MR to facilitate drug repurposing for AD.
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