Alzheimer's & Dementia最新文献

Introduction: Amyloid-targeting therapies for Alzheimer's disease require regular MRI monitoring for amyloid-related imaging abnormalities (ARIA). 3D scans are more sensitive but time intensive; ultra-fast implementations could improve access and reduce burden.

Methods: Eighty scans from 20 participants were acquired with standard 2D fluid-attenuated inversion recovery (FLAIR) and T2*-gradient recalled echo (T2*-GRE), or accelerated Wave-controlled aliasing in parallel imaging (Wave-CAIPI) 3D FLAIR and susceptibility-weighted imaging (SWI) at 3 T. Two neuroradiologists graded ARIA-E (edema/effusion) and ARIA-H (hemosiderin deposits). Bayesian models estimated sensitivity, specificity, severity agreement, and interchangeability between acquisitions.

Results: Accelerated sequences reduced acquisition time by up to 56%. Four participants had ARIA-E and microbleeds; five had microbleeds alone. Sensitivity and specificity for ARIA-E were identical (1.00; 0.94-0.95); severity was comparable. Replacing standard with accelerated FLAIR did not decrease severity agreement (interchangeability 1.4; 95% highest-density interval [HDI] -3.6% to 5.4%). Fast SWI showed higher microbleed severity gradings.

Discussion: Wave-CAIPI offers fast high-resolution FLAIR acquisitions with comparable performance for ARIA-E monitoring. Wave-CAIPI SWI provides high-quality scans that may aid ARIA-H interpretation.

Introduction: Associations of adherence to and changes in Mediterranean (MedDiet) and Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) diets with cognitive outcomes are unclear.

Methods: We prospectively followed 86,740 women (Nurses' Health Study, 1980-2023) and 43,500 men (Health Professionals Follow-Up Study, 1986-2023). Diet was assessed repeatedly using food frequency questionnaires. Dementia cases were identified from self-reported physician diagnoses and death records. Cognitive function was assessed by telephone tests, and subjective cognitive decline (SCD) was self-reported.

Results: Participants in the highest versus lowest MedDiet and MIND categories had 21% (hazard ratio [HR] = 0.79, 95% confidence interval [CI]: 0.73-0.84) and 14% (HR = 0.86, 95% CI: 0.81-0.91) lower dementia risk, respectively. Higher adherence was associated with 0.75 to 1.59 fewer years of cognitive aging, and 40% to 42% lower risk of SCD. Similar inverse associations were observed for improved adherence over 4 or 8 years.

Discussion: Adherence to Mediterranean and MIND diets was associated with cognitive benefits.

Background: Apolipoprotein E (APOE) alleles are well-established genetic risk factors for Alzheimer's disease (AD), but their effects on AD biomarkers (amyloid beta [Aβ]42/40, phosphorylated tau [p-tau]181, neurofilament light chain [NfL], and glial fibrillary acidic protein [GFAP]) may vary across populations due to ancestry-, age-, and sex-related differences. We hypothesized that these effects vary across Hispanic/Latino background groups with distinct ancestral admixture.

Methods: We analyzed ε2 and ε4 allele associations with AD biomarkers using survey-weighted linear regression models, adjusting for demographic covariates. Secondary analyses examined genetic analysis group- and ancestry-specific effects.

Results: ε4 was associated with lower Aβ42/40 and higher p-tau181and GFAP levels, but not with NfL, suggesting its role in Aβ and tau deposition and neuroinflammation. ε4 associations were stronger in those with higher European and lower African ancestry.

Discussion: These findings expand on prior studies suggesting that genetic ancestry modifies APOE-associated AD risk in Hispanic/Latino populations and highlight the importance of capturing ancestry-based heterogeneity in AD biomarker research.

Introduction: Alzheimer's disease (AD), a neurodegenerative disease, involves early alterations in the gut microbiota. Bile acids (BAs), which are metabolites produced by the microbiota, may impact brain function through the gut-brain axis.

Methods: By reference to multimodal datasets from the Chinese Preclinical Alzheimer's Disease Study (n = 1397) and the Alzheimer's Disease Neuroimaging Initiative (n = 1275), we analyzed differences in BA levels and their associations with AD biomarkers.

Results: Lithocholic acid (LCA) -family BAs are associated with the amyloid-β status. Longitudinal changes in BA levels correlated with amyloid and tau pathologies. LCA and the deoxycholic acid (DCA) family exhibited predictive value with respect to AD pathology. Imaging transcriptomic analyses suggested that BAs modulated amyloid pathology through multiple mechanisms.

Discussion: DCA- and LCA-family BAs were proposed as molecular bridges that connect age signatures with AD pathology. They represent a new avenue for the development of biomarkers and therapeutic interventions.

Introduction: We aimed to define the genetic architecture and regulatory mechanisms of Alzheimer's disease (AD) -related plasma biomarkers in an East Asian population.

Methods: Genome-wide association studies (GWAS) of plasma phosphorylated tau at threonine 217 (pTau217), pTau181, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were performed in 1,972 individuals from the Korea-Registries to Overcome and Accelerate Dementia Research (K-ROAD) cohort. Results were integrated with Korean single-nucleus transcriptomics, AD-relevant brain quantitative trait loci resources, and summary-based Mendelian randomization (SMR) and colocalization analyses.

Results: Genome-wide significant loci were identified for all biomarkers, including DACT1-DAAM1 (pTau217), KCNJ3 (pTau181), KLHDC4 (NfL), SLC10A7 (GFAP), and PPP4R2 (composite score). Strong associations at the apolipoprotein E locus were observed across biomarkers. Integrative analyses implicated DACT1 as a key regulatory mediator of pTau217, particularly in oligodendrocytes.

Discussion: These findings link ancestry-relevant AD biomarker genetics to brain regulatory mechanisms and support integrative causal analyses.