👤 Maryam Bemanalizadeh

Alzheimer's disease (AD) is characterized by amyloid-β (Aβ) accumulation and brain atrophy; however, the assocation between plasma Aβ biomarkers and regional neurodegeneration remains unclear. We investigated whether plasma Aβ42, Aβ40, and the Aβ42/40 ratio are associated with temporal lobe atrophy measured using tensor-based morphometry (TBM) in cognitively healthy controls (HC) and participants with mild cognitive impairment (MCI). We analyzed longitudinal MRI and plasma biomarkers data from 29 participants from ADNI (HC = 14, MCI = 15) with imaging and blood samples available at baseline, 24 months, and 48 months. TBM Jacobian maps were summarized within temporal lobe regions of interest (ROIs). Associations between plasma Aβ measures and TBM-derived atrophy were examined with linear mixed-effects models, adjusting for age, sex, and APOE ε4 status, with false-discovery-rate correction. Participants with MCI showed greater temporal lobe atrophy compared with HC people, with significantly lower TBM values at follow-up. Plasma Aβ42, Aβ40, and Aβ42/40 levels showed no consistent or robust differences between diagnostic groups. After covariate adjustment and FDR correction, no plasma Aβ-TBM associations were significant at baseline or 24 months. At 48 months, positive associations were identified between Aβ42 and temporal lobe atrophy (measure 2) in HC participants (β = 0.70, p = 0.046) and between Aβ40 and measure 2 in participants with MCI (β = 0.60, p = 0.036). In contrast, a negative association was observed between the Aβ42/40 and temporal lobe atrophy (measure 2) in MCI group (β = -0.53, p = 0.049). TBM captured greater temporal lobe atrophy in participants with MCI compared with HC. Plasma amyloids showed only limited and inconsistent associations with temporal lobe atrophy over time. These findings suggest that plasma Aβ measures alone may not reliably reflect longitudinal regional neurodegeneration in early AD. Show less

White matter hyperintensity (WMH), indicative of cerebral small vessel disease, has emerged as a potential biomarker for cognitive decline in Alzheimer's disease (AD). However, their predictive role across specific cognitive domains within the AD spectrum remains unclear. This study investigates the relationship between WMH volume and cognitive performance in memory, executive function, and language across the AD continuum. A cross-sectional analysis was conducted using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), comprising 557 participants categorized into cognitively normal (CN; n = 158), mild cognitive impairment (MCI; n = 334), and Alzheimer's dementia (AD; n = 65) groups. Cognitive function was assessed using composite scores for memory (ADNI-MEM), executive function (ADNI-EF), and language (ADNI-LAN). WMH volume was quantified through validated Bayesian segmentation of MRI data. Associations between cognitive scores and WMH volume, adjusted for age, gender, APOE ε4 status, and vascular risk factors, were evaluated via multiple linear regression analyses. WMH volume showed numerically progressive increases from CN to MCI and AD groups; however, between-group differences did not reach statistical significance. Within the MCI group, significant negative associations emerged between WMH volume and memory (β=-0.13, adjusted p = 0.045) and language scores (β=-0.12, adjusted p = 0.045). Conversely, these relationships were absent in both the CN and AD groups. WMH volume relates specifically to declines in memory and language abilities, particularly in individuals with MCI. These results support using WMH measurements as early markers to identify cognitive decline in AD, potentially helping to guide earlier diagnosis and treatment decisions. Show less