Multimodal neuroimaging biomarkers and subtle cognitive decline in a population-based cohort without dementia

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.

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.

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-β (Aβ) deposition, and [¹⁸F]AV-1451-PET for tau deposition. Neuropsychological evaluations were completed at multiple timepoints up to 11 years prior to neuroimaging. Aβ 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.

Among Aβ(+) 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 Aβ(-) participants, there was an association between tau Braak III/IV and decline on tests of attention/psychomotor speed (p < 0.05).

These findings confirm an Aβ-dependent early AD biomarker pathway, and suggest a possible Aβ-independent, non-AD process underlying subtle cognitive decline in a population-based sample of older adults without dementia.