Frontiers in Aging Neuroscience · Nov 9, 2026
Longitudinal Hippocampal Atrophy and Entorhinal Thinning Across Cognitive Trajectories in Older Adults
By Xuedong Yang, Li Li, Rong Deng et al.
Background: Cognitive trajectories in later life are heterogeneous. We assessed whether participants with dementia at all eligible visits and participants in the converted trajectory had faster longitudinal hippocampal volume loss and entorhinal cortical thinning than participants without dementia in OASIS-2. Methods: OASIS-2 scans were processed using FreeSurfer 7.4.1 longitudinal pipelines with participant-specific templates. Participants with at least two scans that passed technical and anatomical quality control were included. Bilateral hippocampal volume and entorhinal cortical thickness were analyzed using random-intercept linear mixed-effects models adjusted for time, cognitive trajectory, their interaction, baseline age, sex, and education; hippocampal models additionally adjusted for baseline estimated total intracranial volume. Participants without dementia served as the reference group. False-discovery-rate correction was applied within endpoint families. Results: The analysis included 355 visits from 143 participants. Compared with participants without dementia, participants with dementia showed faster annual loss of left hippocampal volume (beta, -29.84 mm3/year; 95% CI, -42.03 to -17.64; q=2.18e-06), right hippocampal volume (beta, -29.44 mm3/year; 95% CI, -41.63 to -17.26; q=2.18e-06), left entorhinal thickness (beta, -0.0220 mm/year; 95% CI, -0.0365 to - 0.00745; q=0.00300), and right entorhinal thickness (beta, -0.0264 mm/year; 95% CI, -0.0417 to -0.0111; q=0.00143). Among the 14 participants in the Converted trajectory, bilateral hippocampal loss was faster, whereas entorhinal estimates were less robust across sensitivity analyses. Secondary whole-cortex analyses showed distributed trajectory-related cortical differences. Conclusions: In this OASIS-2 cohort, participants with dementia showed faster bilateral hippocampal volume loss and entorhinal cortical thinning than participants without dementia. Participants in the converted trajectory also showed faster bilateral hippocampal loss, whereas entorhinal estimates were less robust across sensitivity analyses.