Alzheimer's & Dementia最新文献

Introduction: This study longitudinally examined 154 magnetic resonance imaging (MRI) biomarkers in cognitively normal (CN) individuals to identify structural brain changes most strongly associated with subsequent cognitive impairment (SI).

Methods: We analyzed 509 Baltimore Longitudinal Study of Aging participants (age ≥ 50, CN at baseline) with longitudinal cognitive and 3T MRI (T1/T2-weighted scans and diffusion tensor imaging) data. MRI biomarker associations with SI status were analyzed, adjusting for confounders and stratifying by sex and amyloid beta (Aβ) status.

Results: Participants who developed SI over 4.6 years' follow-up showed greater longitudinal changes in white matter (WM) integrity, particularly in the corpus callosum, cingulum bundle, and inferior fronto-occipital fasciculus, compared to CN-stable. To a lesser degree, we also observed temporal thinning and atrophy linked to SI. These associations were amplified among males and amyloid-positive individuals.

Discussion: Longitudinal alterations in WM microstructural integrity were most strongly associated with future impairment, highlighting the importance of early WM changes in the development of MCI and dementia.

Introduction: Evidence is limited on preferences of persons with cognitive decline and their care partners (CPs) regarding care. Our aim was to identify preferences and preference evolution for transitions in supportive care.

Methods: We conducted a discrete choice experiment (DCE) (repeated measures baseline, 6-months) with older adults with mild cognitive impairment or mild to moderate dementia and CPs. Tasks were anchored to health states describing progressive memory and function decline. Split-sample mixed logit models estimated part-worth utilities.

Results: Baseline DCEs were completed by 131 cognitively impaired older adults and 137 CPs; 118 and 132 completed 6-month DCEs. At both timepoints, respondents preferred in-home care with moderate support when considering moderate or severe cognitive impairment. As impairment worsened, the acceptability of assisted living increased, especially among CPs.

Discussion: Persons with cognitive decline engaged in future-oriented decisions. Preferences were stable across time for both samples, and assisted living was more acceptable for CPs.

Introduction: Knowledge of modifiable factors influencing age at onset (AAO) of Alzheimer's disease (AD) remains limited. This study utilizes genetic information to uncover such factors.

Methods: Using 43 exposure genome-wide association studies (GWAS) summary statistics, we calculated corresponding polygenic scores (PGS) for 9219 AD cases and 10,345 controls from the Alzheimer's Disease Genetic Consortium (ADGC). Linear mixed model and survival analyses were performed to identify exposure-PGS associated with AAO. Top exposures were cross-evaluated using PGS from the PGS Catalog and Mendelian randomization (MR) for causal relationships.

Results: Eight exposures showed significant exposure-PGS associations with AAO of AD. Higher educational attainment, better cognitive performance, and greater relative fat intake were associated with later AAO; whereas the remaining were linked to earlier onset. MR analysis indicated a causal relationship between AAO and educational attainment, cardiovascular disease, and type 2 diabetes (T2D).

Discussion: The eight modifiable factors, particularly educational attainment, cardiovascular disease, and T2D, may facilitate early intervention to delay the onset of AD.

Highlights: We screened 43 modifiable factors for their association with the age at onset (AAO) of Alzheimer's disease (AD) using polygenic scores (PGS) as the proxy for the exposure. Higher educational attainment, better cognitive performance, and greater relative fat intake were linked to later AAO, suggesting an enhanced resilience against AD. Type 2 diabetes, cardiovascular disease, major coronary heart disease, and increased low-density lipoprotein (LDL) -cholesterol and total cholesterol are associated with earlier AAO. Mendelian randomization analysis revealed causal effects of educational attainment, type 2 diabetes, and cardiovascular disease on AAO of AD.