Eberly SG, Phumsatitpong C, Munro CE
… +3 more, Neylan TC, Kaufer D, Ehrenberg AJ
Alzheimers Dement
· 2026 Jun · PMID 42233253
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Stress is increasingly recognized as an important, modifiable factor for Alzheimer's disease (AD), yet its roles in initiation, progression, and outcomes remain incompletely elucidated. Epidemiologic studies link chronic...Stress is increasingly recognized as an important, modifiable factor for Alzheimer's disease (AD), yet its roles in initiation, progression, and outcomes remain incompletely elucidated. Epidemiologic studies link chronic stress, early-life adversity, and trauma to increased AD risk, while experimental models have uncovered mechanisms by which stress hormones directly drive core AD pathological processes, including amyloid beta and tau aggregation, neuroinflammation, and neurodegeneration. Complicating the relationship, brain structures that regulate the stress response are themselves selectively vulnerable to early degeneration in AD. As these circuits degenerate, interpreting changes in stress biomarkers becomes more challenging, with physiological measures potentially decoupling from perceived stress. Here, we review evidence connecting stress to AD pathophysiology as both a risk factor and a driver, examine how the degeneration of stress neuroendocrine systems accelerates disease progression, and discuss implications for intervention and clinical trial design.
Senador J, Montesinos R, Custodio B
… +7 more, Huilca J, Agüero K, Verastegui G, Bartolo P, Nuñez-Huanca M, Pereira MFA, Custodio N
Alzheimers Dement
· 2026 Jun · PMID 42233248
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INTRODUCTION: In Peru, the Global Deterioration Scale is the only available tool for assessing dementia severity. The Spanish translation and cultural adaptation of the Clinical Dementia Rating (CDR) is used locally but...INTRODUCTION: In Peru, the Global Deterioration Scale is the only available tool for assessing dementia severity. The Spanish translation and cultural adaptation of the Clinical Dementia Rating (CDR) is used locally but requires formal psychometric validation in the Peruvian sociocultural context. METHODS: A total of 1,600 older adults: 902 controls, 271 mild cognitive impairment (MCI), and 427 Alzheimer's disease patients (AD) were assessed to validate two CDR scoring methods: CDR Global Score (CDR-GS) and CDR Sum of Boxes Score (CDR-SB). Discriminative validity, inter-item reliability, and concurrent validity were evaluated using MMSE, RUDAS, PFAQ, and Uniform Data Set (UDS) v3 Neuropsychological Battery. RESULTS: CDR demonstrated high reliability and validity among normal cognition, mild cognitive impairment, and AD. For AD screening, CDR-SB showed 98.2% sensitivity and 99.6% specificity, while CDR-GS demonstrated 99.8% sensitivity and 100% specificity. DISCUSSION: The Peruvian CDR version exhibited good psychometric properties comparable to those reported in Latin American CDR validation studies.
Hsu SL, Lee PL, Chou KH
… +5 more, Kuo CY, Lin CP, Liao YC, Chung CP, Lee YC
Alzheimers Dement
· 2026 Jun · PMID 42230522
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INTRODUCTION: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by cysteine-altering NOTCH3 variants. We examined whether neuroimaging-defined brain age is alt...INTRODUCTION: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by cysteine-altering NOTCH3 variants. We examined whether neuroimaging-defined brain age is altered in CADASIL and its association with disease severity and outcomes. METHODS: A brain-age prediction model was constructed using magnetic resonance imaging from 1482 healthy individuals and applied to 153 individuals with NOTCH3 variants and 30 controls. Brain age gap (BAG) was calculated as predicted minus chronological age. Associations between BAG, imaging markers, and clinical outcomes were analyzed. RESULTS: Individuals with NOTCH3 variants exhibited significantly higher BAG than controls. Higher BAG was associated with greater disease severity, neuroimaging markers - most prominently peak width of skeletonized mean diffusivity - and poorer clinical performance. In addition, BAG showed a partial mediation effect in the association between disease stage and cognitive performance. DISCUSSION: Accelerated brain aging is evident in CADASIL, and the BAG reflects the cumulative microvascular injury burden and may be involved in the pathophysiological pathway linking disease progression to cognitive impairment.
Oberoi A, Cai K, West R
… +8 more, Wadhawan A, Willette A, Simon SS, Tsao J, Gu Y, Fonseca LM, Patel T, Beeri MS
Alzheimers Dement
· 2026 Jun · PMID 42222939
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India's rapidly aging population faces a dementia burden, yet data on factors affecting dementia risk remain limited. A narrative review of studies on dementia prevalence and risk factors in India was conducted using Med...India's rapidly aging population faces a dementia burden, yet data on factors affecting dementia risk remain limited. A narrative review of studies on dementia prevalence and risk factors in India was conducted using Medline, Scopus, and Google Scholar. Findings were synthesized to examine the 14 modifiable risk factors identified by the 2024 Lancet Commission. The Indian dementia research landscape remains dominated by cross-sectional studies. The prevalence of dementia is lower in India than in Western cohorts. However, high prevalence is observed among women, rural dwellers, and individuals with cardiovascular comorbidities, especially diabetes, a condition exhibiting unique metabolic phenotypes within this population. Undocumented alcohol use, air pollution, traumatic brain injuries, loneliness, depression, and sensory deficits are prevalent across India, yet literature linking these exposures to dementia risk lacks empirical research. There is an urgent need for longitudinal studies to identify modifiable risk and protective factors for dementia in the Indian population.
Grenon MB, Cline EN, Jerecic J
… +3 more, Johnson E, Siemers E, Lemere CA
Alzheimers Dement
· 2026 Jun · PMID 42222928
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INTRODUCTION: Immunotherapy targeting amyloid beta (Aβ) is limited by amyloid-related imaging abnormalities (ARIA), hypothesized to result from the direct binding of anti-Aβ monoclonal antibodies (mAbs) to vascular cereb...INTRODUCTION: Immunotherapy targeting amyloid beta (Aβ) is limited by amyloid-related imaging abnormalities (ARIA), hypothesized to result from the direct binding of anti-Aβ monoclonal antibodies (mAbs) to vascular cerebral amyloid angiopathy (CAA), eliciting an immune response. METHODS: Immunofluorescent staining was used to characterize ex vivo plaque and vascular binding of recombinant FDA-approved lecanemab and clinical candidate sabirnetug (ACU193) in 30 min and 24 h fixed APP:hE4 mouse brain tissue. RESULTS: Fixation time was a key factor influencing Aβ antigen labeling with prolonged fixation differentially affecting pan-Aβ and mAb immunoreactivity. Compared with ACU193, lecanemab showed greater cortical plaque and cerebellar vascular labeling and encompassed a larger fraction of total pan-Aβ and β-pleated-sheet-rich signal, reflecting both mAb target abundance and selectivity. DISCUSSION: These findings emphasize that experimental protocols and antibody properties jointly shape the observed mAb binding patterns and highlight differences that may contribute to antibody-specific ARIA risk observed clinically.
Quintero-Cardona P, Tangarife MA, Blandon J
… +3 more, Arango-Lasprilla JC, Ibanez A, Baez S
Alzheimers Dement
· 2026 Jun · PMID 42222927
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Informal caregivers are central to dementia care in Latin America and the Caribbean (LAC), yet determinants of caregiver burden remain insufficiently characterized. We conducted a systematic review and meta-analysis of s...Informal caregivers are central to dementia care in Latin America and the Caribbean (LAC), yet determinants of caregiver burden remain insufficiently characterized. We conducted a systematic review and meta-analysis of studies examining patient- and caregiver-related correlates of burden in LAC. Random-effects models pooled Fisher's z-transformed correlations. Forty studies were included, of which 34 (n = 3,082 caregivers) were meta-analyzed. Higher burden was associated with the patient's neuropsychiatric and depressive symptoms, and caregiver depressive and anxiety symptoms. Better patient cognition and quality of life were associated with lower burden. Meta-regressions showed that higher caregiver education strengthened the association between patient depressive symptoms and burden, and a higher proportion of female caregivers strengthened the association between patient cognition and burden. Findings highlight the role of behavioral and affective symptoms and support culturally grounded, gender-sensitive strategies in LAC. High heterogeneity underscores the need for methodological harmonization and further regional research.
Palatsides EL, Yiallourou S, Himali D
… +14 more, Cavuoto MG, Baril AA, Yang Q, Peloso GM, Ryan J, El Fakhri G, Ghosh S, Thibault E, DeCarli CS, Johnson KA, Beiser AS, Seshadri S, Himali JJ, Pase MP
Alzheimers Dement
· 2026 Jun · PMID 42222915
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INTRODUCTION: Aquaporin-4 (AQP4) is thought to facilitate Alzheimer's disease (AD) protein clearance during sleep. We examined whether AQP4 genetic variation was associated with AD pathology or modified the association b...INTRODUCTION: Aquaporin-4 (AQP4) is thought to facilitate Alzheimer's disease (AD) protein clearance during sleep. We examined whether AQP4 genetic variation was associated with AD pathology or modified the association between sleep duration and AD biomarkers. METHODS: A total of 450 dementia-free participants (mean age = 58 ± 9.9; women = 54%) from the Framingham Heart Study (FHS) with sleep duration measured by self-report and amyloid-β (Aβ) and tau burden quantified using positron emission tomography (PET) were analyzed. RESULTS: AQP4 was not associated with Aβ or tau burden in the overall sample. However, for participants aged less than 60, minor allele carriers displayed lower regional tau burden compared to homozygote majors. AQP4 modified the relationship between short sleep (≤6 hours) and medial temporal tau; short sleep duration was associated with higher medial temporal tau in minor allele carriers, while the opposite was observed in homozygote majors. DISCUSSION: AQP4 genetic variation may influence early tau accumulation and vulnerability to sleep-related AD pathology.
Kim S, Rauet-Tejeda J, Milstein R
… +2 more, Lee J, Llena-Nozal A
Alzheimers Dement
· 2026 Jun · PMID 42222904
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Dementia incurs yearly costs of nearly 1.3 trillion US dollars worldwide, projected to rise significantly in the coming decades due to population aging. This policy review provides an overview of the latest national deme...Dementia incurs yearly costs of nearly 1.3 trillion US dollars worldwide, projected to rise significantly in the coming decades due to population aging. This policy review provides an overview of the latest national dementia strategies, diagnostic guidelines, and treatment guidelines across 38 Organisation for Economic Co-operation and Development countries. Our findings suggest that national dementia policies increasingly emphasize prevention through modifiable risk factors, early diagnosis, and non-pharmacological treatment approaches, progressing toward more coordinated care pathways. Clinical guidelines have evolved to incorporate new research evidence and practices in dementia diagnostics and treatment over the past decade. Despite updates to policy frameworks, we identified a gap between policy and action, with varying degrees of implementation and support for improving diagnosis and adopting new treatments. We identified a series of policy efforts that could be undertaken to enhance the quality of care for people living with dementia.
Porter T, Armstrong AM, O'Brien EK
… +10 more, Doré V, Bourgeat P, Turner M, Maruff P, Rowe CC, Brown BM, Villemagne VL, Rainey-Smith SR, Laws SM, AIBL Research Group
Alzheimers Dement
· 2026 Jun · PMID 42216479
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INTRODUCTION: Variants in the aquaporin-4 gene (AQP4) have been associated with Alzheimer's disease (AD) diagnosis, cognition, and brain amyloid beta (Aβ) and may affect the sleep and Aβ relationship. Their association w...INTRODUCTION: Variants in the aquaporin-4 gene (AQP4) have been associated with Alzheimer's disease (AD) diagnosis, cognition, and brain amyloid beta (Aβ) and may affect the sleep and Aβ relationship. Their association with other AD-related phenotypes/disease progression remain largely unknown. METHODS: Associations between AQP4 variants, self-reported sleep measures, and AD-related phenotypes in cognitively unimpaired individuals with evidence of Aβ accumulation were examined using data from the Australian Imaging, Biomarkers and Lifestyle study. RESULTS: AQP4 variants were directly associated with regional brain volumes, atrophy, and cognition. They were also associated with differences in regional brain volumes and atrophy in interaction with sleep duration, latency, and quality. Finally, AQP4 variants were associated with cognitive decline in interaction with sleep disturbances. DISCUSSION: These findings support a relationship between AQP4 and AD phenotypes, both directly and through their interaction with sleep.
Champetier P, Albero C, Raposo Pereira F
… +12 more, Herzog R, Chaumon M, Houot M, Locatelli M, Kas A, Habert MO, Teichmann M, Epelbaum S, Arnulf I, Oudiette D, Andrillon T, INSIGHT‐preAD group
Alzheimers Dement
· 2026 Jun · PMID 42216470
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INTRODUCTION: Growing evidence supports a critical role of sleep slow waves (SW) in Alzheimer's disease (AD). However, wake SW (sleep-like SW potentially reflecting local intrusions of sleep) remain unexplored in AD. MET...INTRODUCTION: Growing evidence supports a critical role of sleep slow waves (SW) in Alzheimer's disease (AD). However, wake SW (sleep-like SW potentially reflecting local intrusions of sleep) remain unexplored in AD. METHODS: A total of 274 older adults with subjective cognitive decline (SCD) (INSIGHT-preAD cohort, 76.6 ± 3.5 years) underwent (i) positron emission tomography (PET) scans for amyloid (A) and neurodegeneration (N), (ii) high-density resting-state electroencephalogram (EEG) recordings to detect wake SW, and (iii) cognitive assessments. PET biomarkers were reassessed 2 years later. We examined wake SW associations with (1) current A/N status, (2) cognition, and (3) amyloid conversion. RESULTS: A+N-, A-N+, and A+N+ individuals exhibited lower delta wake SW density than A-N- participants. Wake SW amplitude (1) was higher in A+N+ than A-N- individuals, (2) correlated with poorer memory, and (3) predicted A- to A+ conversion (n = 157 A- stable individuals, n = 16 convertors). DISCUSSION: Wake SW represent promising early EEG biomarkers for AD pathology and amyloid conversion, facilitating risk stratification before cognitive decline onset.
Morcillo-Nieto AO, Franquesa-Mullerat M, Zsadanyi SE
… +25 more, Arriola-Infante JE, Vaqué-Alcázar L, Rozalem-Aranha M, Parra JA, Zhao Z, Arranz J, Rodríguez-Baz Í, Maure-Blesa L, Videla L, Barroeta I, Del Hoyo Soriano L, Benejam B, Fernández S, Sanjuan Hernandez A, Pertierra L, Giménez S, Santos-Santos M, Dols-Icardo O, Illán-Gala I, Alcolea D, Belbin O, Lleó A, Carmona-Iragui M, Fortea J, Bejanin A
Alzheimers Dement
· 2026 May · PMID 42212383
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INTRODUCTION: This study investigates the evolution with disease progression and pathological correlates of peak width of skeletonized mean diffusivity (PSMD), a sensitive diffusion magnetic resonance imaging (MRI) marke...INTRODUCTION: This study investigates the evolution with disease progression and pathological correlates of peak width of skeletonized mean diffusivity (PSMD), a sensitive diffusion magnetic resonance imaging (MRI) marker of microvascular white matter (WM) injury, in sporadic Alzheimer's disease (sAD) and Down syndrome (DS)-associated AD (DSAD). METHOD: This cross-sectional study included 150 euploid controls, 118 subjects with sAD, and 228 DS adults (34.65% with symptomatic AD). PSMD was derived from 3T-MRI diffusion tensor imaging. Associations with sociodemographic, clinical stage, cerebrospinal fluid (CSF), and small vessel disease markers were examined. RESULTS: PSMD correlated with age in all groups, showing a stronger association in DS, with alterations apparent 15 years before the population's dementia age at onset. In euploid and DS, higher PSMD correlated with AD severity, CSF-neurofilament light chain (NfL), microbleeds, and WM hyperintensities (WMH). PSMD abnormalities were more frequent than WMH, especially in DS. DISCUSSION: PSMD is a sensitive early biomarker of WM injury across sAD and DSAD, preceding symptom onset and capturing multifactorial disease processes.
Weerawarna PM, Jesudason CD, Lobb KL
… +4 more, Mason ER, Gu X, Chu S, Richardson TI
Alzheimers Dement
· 2026 May · PMID 42210035
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INTRODUCTION: Proline-rich tyrosine kinase 2 (PYK2) and focal adhesion kinase (FAK) are non-receptor tyrosine kinases implicated in Alzheimer's disease (AD), but their functional role in microglia remains understudied. S...INTRODUCTION: Proline-rich tyrosine kinase 2 (PYK2) and focal adhesion kinase (FAK) are non-receptor tyrosine kinases implicated in Alzheimer's disease (AD), but their functional role in microglia remains understudied. Selective pharmacological tools are required for preclinical studies leading to translational therapeutic development. METHODS: We evaluated potent and selective inhibitors described in publications and patents, synthesized or procured representative compounds, and profiled them in kinase assays. In vitro physicochemical and pharmacokinetic (PK) properties were assessed, and functional effects were studied in microglial phagocytosis assays using HMC3 and BV2 microglia cellular models. RESULTS: Biochemical profiling confirmed potent and selective inhibition, consistent with reported data, though assay-dependent differences in apparent selectivity were observed. Most compounds showed favorable physicochemical and PK properties. In HMC3 assay, the PYK2-selective tool compounds showed that strong stimulation of phagocytosis and parallel cell counts declined at non-toxic concentrations. DISCUSSION: This curated set of well-characterized inhibitors provides a validated toolkit to probe PYK2/FAK biology in AD-relevant models.
Khorsand B, Teichrow D, Ghanbarian E
… +6 more, Zheng L, Sajjadi SA, Glover CM, Grill JD, Rabin LA, Ezzati A
Alzheimers Dement
· 2026 May · PMID 42204876
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INTRODUCTION: Amyloid positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers confirm Alzheimer's disease (AD) pathology but are impractical for large-scale screening. Plasma phosphorylated tau at thr...INTRODUCTION: Amyloid positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers confirm Alzheimer's disease (AD) pathology but are impractical for large-scale screening. Plasma phosphorylated tau at threonine 217 (p-tau217), subjective cognitive concerns, and computerized cognitive testing are non-invasive, scalable, and feasible to implement in large populations. We assessed their separate and combined predictive value for cognitive decline. METHODS: We analyzed 1064 cognitively unimpaired adults (ages 65-85 years) from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4; amyloid-positive) and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN; amyloid-negative) studies. Baseline assessments included apolipoprotein E (APOE) ε4 status, hippocampal volume, amyloid PET, plasma p-tau217, Cognitive Function Index (CFI), and Cogstate Computerized Battery (CCB). Cognitive impairment was defined as conversion from a Clinical Dementia Rating Global Score (CDR-GS) of 0 to ≥0.5 over 240 weeks. RESULTS: During the follow-up, 34.1% developed cognitive impairment. Higher p-tau217, higher CFI, and lower CCB were associated with higher odds of converting to CDR-GS >0 across all cohorts. DISCUSSION: P-tau217, CFI, and CCB each independently predict cognitive decline, offering practical, non-invasive tools for early AD risk stratification and trial enrichment.
Alzheimers Dement
· 2026 May · PMID 42204869
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The Alzheimer's Disease Research Centers (ADRC) program, funded by the National Institute on Aging (NIA), is a national network for conducting cutting-edge basic, clinical, and translational Alzheimer's disease (AD) and...The Alzheimer's Disease Research Centers (ADRC) program, funded by the National Institute on Aging (NIA), is a national network for conducting cutting-edge basic, clinical, and translational Alzheimer's disease (AD) and AD-related dementias (ADRD) research. ADRCs collect clinical, biomarker, neuroimaging, and autopsy data on thousands of longitudinally followed research participants and the well-characterized data and samples generated by the ADRCs are readily available to the research community. Beyond conducting research, the primary objectives of the ADRC program are to train the next generation of multidisciplinary AD/ADRD researchers and share information with the public, including the latest findings and opportunities to participate in clinical studies. This article provides an overview of the 40-year history of the ADRC program, from its establishment by Congress in 1984 to now, highlighting the AD/ADRD scientific achievements enabled by the ADRCs, the data, samples, and resources that ADRCs provide, and future directions for the program.
Pierce RM, Scambray KA, Palms JD
… +7 more, Walters M, Sol K, Green N, Lacking SS, Alshiko M, Brickman A, Zahodne LB
Alzheimers Dement
· 2026 May · PMID 42204867
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INTRODUCTION: Racial discrimination (RD) relates to poorer memory, but underlying mechanisms are unclear. METHODS: Participants included 321 Black adults age 55+ from the Michigan Cognitive Aging Project. RD was operatio...INTRODUCTION: Racial discrimination (RD) relates to poorer memory, but underlying mechanisms are unclear. METHODS: Participants included 321 Black adults age 55+ from the Michigan Cognitive Aging Project. RD was operationalized with the Major Experiences of Lifetime Discrimination scale. Subjective memory was measured with the Memory Functioning Questionnaire. Episodic memory was a composite of list learning, story memory, and visual memory tests. White matter hyperintensities (WMHs) were quantified from T2 fluid-attenuated inversion recovery (FLAIR) images. Mediation models examined whether WMHs mediate the associations of racial discrimination on subjective and objective memory. RESULTS: More RD was associated with higher WMH volume. In turn, higher WMH volume was associated with worse objective, but not subjective, memory. Independent of WMH, more RD was associated with worse subjective, but not objective, memory. DISCUSSION: RD is an important intervention target to improve cognitive health equity and reduce WMH burden. RD may influence objective memory through vascular and/or inflammatory mechanisms.
Jiménez DA, Bagnati PM, Flores-Montes RE
… +24 more, Fernández ML, Zuno-Reyes A, Aguillon D, Alaez-Verson C, Becerra-Solano LE, Behrens MI, Branda K, Chrem P, Custodio N, Ducaine W, Dumois-Petersen S, Figuera L, Castaño ML, Longoria EM, Matute E, Sánchez V, Slachevsky A, Sosa AL, Surace E, Takada L, Yaeger L, Ziegemeier E, Guerra JJL, Programa de asesoramiento genético en América Latina (PRAGA)
Alzheimers Dement
· 2026 May · PMID 42204862
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Autosomal dominant Alzheimer's disease (ADAD) represents a small but impactful subset of Alzheimer's cases. Asymptomatic individuals at genetic risk face substantial personal and family implications when considering pred...Autosomal dominant Alzheimer's disease (ADAD) represents a small but impactful subset of Alzheimer's cases. Asymptomatic individuals at genetic risk face substantial personal and family implications when considering predictive testing for known familial variants. Genetic counseling and testing (GCT) frameworks remain limited in Latin America (LatAm). Recommendations for GCT in LatAm were developed through an iterative, multidisciplinary consensus process. Evidence inputs included a structured literature review, site-level recommendations from participating LatAm centers, and a qualitative synthesis of focus groups with experienced investigators. The resulting model includes pre-test evaluation, sample collection, result disclosure, and structured follow-up. Core elements comprise mental health assessment, psychoeducation, exploration of expectations and decision-making needs, guided disclosure with emotional support, and a suggested 3-month post-disclosure reassessment using validated psychological measures. Our framework provides structured guidance for the safe and ethical delivery of GCT for ADAD through a multidisciplinary, culturally informed, and patient-centered approach in LatAm.
Bolton CJ, Dilworth-Anderson P, Steingrimsson J
… +17 more, Thangarajah M, Hanna L, Gatsonis C, Windon C, Carrillo MC, Glavin E, Gareen I, Heston MB, Hillner BE, March A, Rissman RA, Siegel BA, Smith K, Whitmer RA, Weber CJ, Rabinovici GD, Wilkins CH
Alzheimers Dement
· 2026 May · PMID 42200449
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INTRODUCTION: This study leverages a large, diverse cohort to characterize ethnoracial differences in amyloid positron emission tomography (PET) positivity and identify social determinants of health (SDOHs) contributing...INTRODUCTION: This study leverages a large, diverse cohort to characterize ethnoracial differences in amyloid positron emission tomography (PET) positivity and identify social determinants of health (SDOHs) contributing to these differences. METHODS: We assessed differences in amyloid PET positivity by ethnoracial group (Black, Latinx, or all other races/ethnicities [AORE]) among Medicare beneficiaries with cognitive impairment. Secondary analyses associated various SDOHs with amyloid PET positivity. RESULTS: Among 5757 participants (21.7% Black, 20.3% Latinx, 58.1% AORE), we found lower odds of amyloid positivity in Black (odds ratio [OR]: 0.72, 95% confidence interval [CI]: 0.62-0.83) and Latinx (OR: 0.78, 95% CI: 0.67-0.91) compared to AORE. Individuals in the comfortable (OR: 1.22, 95% CI: 1.05-1.42) and distressed (OR: 1.40, 95% CI: 1.08-1.82) Area Deprivation Index (ADI) groups had greater odds of amyloid positivity than individuals in the prosperous group. DISCUSSION: Amyloid PET positivity rates were lower among Black and Latinx individuals and higher among individuals in more deprived ADI categories. This has potential implications for anti-amyloid therapies.
Altschuler F, Castro-Laguardia AM, Canziani V
… +22 more, O'Byrne DF, Hazelton J, Migeot J, Maito M, García AM, Bruno MA, Magrath N, Slachevsky A, Behrens MI, Custodio N, Ávila-Funes JA, Matallana D, Aguillón D, Santamaria-García H, Resende E, Takada L, Brusco LI, Yokoyama JS, Miller B, Ibáñez A, Medel V, Campo CG
Alzheimers Dement
· 2026 May · PMID 42192214
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INTRODUCTION: Cerebral small vessel disease (CSVD) is a key contributor to cognitive impairment and dementia, yet few studies have compared CSVD across dementia variants, particularly in underrepresented populations. MET...INTRODUCTION: Cerebral small vessel disease (CSVD) is a key contributor to cognitive impairment and dementia, yet few studies have compared CSVD across dementia variants, particularly in underrepresented populations. METHODS: In a multicenter cross-sectional study, we analyzed magnetic resonance imaging (MRI) markers of CSVD, including white matter hyperintensities (WMHs), lacunes, and cerebral microbleeds, along with cardiometabolic risk factors and cognitive performance using regression models in 1675 participants (790 healthy controls, 642 with Alzheimer's disease [AD], and 243 with frontotemporal dementia [FTD]) from six Latin American countries. RESULTS: AD showed the greatest CSVD burden, whereas FTD exhibited an intermediate profile driven by elevated WMHs. Blood pressure and smoking were the strongest correlates of WMHs, while diabetes was associated with microbleeds. WMH burden was linked to global and domain-specific cognitive impairment. DISCUSSION: This first large-cohort Latin American study identifies WMHs as a key vascular substrate of cognitive impairment, with AD showing the greatest CSVD burden.
Gaur A, Wong M, Chen JJ
… +8 more, Kang Y, Tahoulas D, Jeor K, Raguram KH, Gallagher D, Rapoport M, Herrmann N, Lanctôt KL
Alzheimers Dement
· 2026 May · PMID 42192211
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INTRODUCTION: Alzheimer's disease (AD) is characterized by synaptopathy, a neuropathological feature that can contribute to underlying cognitive decline. Here, we evaluate potential cerebrospinal fluid (CSF) and blood-ba...INTRODUCTION: Alzheimer's disease (AD) is characterized by synaptopathy, a neuropathological feature that can contribute to underlying cognitive decline. Here, we evaluate potential cerebrospinal fluid (CSF) and blood-based synaptic biomarkers in AD dementia and its earliest clinical stage, mild cognitive impairment (MCI). METHODS: Articles that measured a subset of CSF and/or blood-based synaptic biomarkers in AD dementia, MCI, and/or healthy controls were included. A random-effects model was used to determine standardized mean differences and 95% confidence intervals. RESULTS: In total, 65 study cohorts were included for meta-analysis and 12 for qualitative review. Several CSF (synaptosomal-associated protein 25 [SNAP-25], growth-associated protein 43 [GAP-43], neuronal pentraxin receptor, neuronal pentraxin-1, neuronal pentraxin-2, synaptotagmin-1, syntaxin-1B, and vesicle-associated membrane protein 2) and blood-based (SNAP-25, GAP-43, and synaptotagmin-1) synaptic biomarkers were altered in AD dementia and/or MCI. DISCUSSION: Further evaluation of these identified biomarkers may enrich our understanding of AD pathophysiology and disease trajectory, as well as inform future treatment interventions.