Multimodal Neuroimaging Biomarkers and Subtle Cognitive Decline in a Population-Based Cohort Without Dementia
Journal of Alzheimer's disease : JAD（2025）
Univ Pittsburgh | Eastern Virginia Med Sch
Abstract
Background The relationship between subtle cognitive decline and Alzheimer's disease (AD) pathology as measured by biomarkers in settings outside of specialty memory clinics is not well characterized. Objective To investigate how subtle longitudinal cognitive decline relates to neuroimaging biomarkers in individuals drawn from a population-based study in an economically depressed, small-town area in southwestern Pennsylvania, USA. Methods A subset of participants without dementia (N = 115, age 76.53 years +/- 6.25) from the Monongahela Youghiogheny Healthy Aging Team (MYHAT) study completed neuroimaging including magnetic resonance imaging (MRI) measures of AD-signature region cortical thickness and white matter hyperintensities (WMH), Pittsburgh compound B (PiB)-positron emission tomography (PET) for amyloid-beta (A beta) deposition, and [F-18]AV-1451-PET for tau deposition. Neuropsychological evaluations were completed at multiple timepoints up to 11 years prior to neuroimaging. A beta positivity was determined using a regional approach. We used linear mixed models to examine neuroimaging biomarker associations with retrospective cognitive slopes in five domains and a global cognitive composite. Results Among A beta(+) participants (38%), there were associations between (i) tau Braak III/IV and language decline (p < 0.05), (ii) cortical thickness and both memory decline (p < 0.001) and global cognitive decline (p < 0.01), and (iii) WMH and decline in executive function (p < 0.05) and global cognition (p < 0.05). Among A beta(-) participants, there was an association between tau Braak III/IV and decline on tests of attention/psychomotor speed (p < 0.05). Conclusions These findings confirm an A beta-dependent early AD biomarker pathway, and suggest a possible A beta-independent, non-AD process underlying subtle cognitive decline in a population-based sample of older adults without dementia.
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Key words
aging,Alzheimer's disease,biomarkers,cognition,neuropsychology
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