Observational studyThe journal of prevention of Alzheimer's disease2026
Hippocampal microstructure as a measure of cognitive resilience to tau PET burden in older adults.
Observational study in The journal of prevention of Alzheimer's disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- APOE ε4 and amyloid status moderate the associations between sleep, physical activity, and tau-PET burden in cognitively unimpaired older adults.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Tau burden across Braak stages is associated with regionally specific amyloid accumulation.Brain communications · 2026Article
- Longitudinal associations of rest-activity rhythms with executive function, plasma biomarkers, and clinical outcomes in older adults.Frontiers in aging neuroscience · 2026Article
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Authors and funding
9 authors.
Funding
Abstract
backgroundCognitive resilience, the ability to maintain better than expected cognitive function despite neuropathological burden, is a key contributor to clinical outcomes in Alzheimer's disease (AD), though the underlying neurobiological mechanisms remain poorly understood.
objectivesTo determine whether hippocampal volume and microstructure moderate the relationship between early tau pathology and cognitive performance, thereby serving as potential markers of cognitive resilience.
designCross-sectional observational study.
settingParticipant data was obtained from the longitudinal BIOCARD Study, a volunteer-based research cohort.
participantsThe sample included 190 dementia-free adults (mean age = 68 years), comprising 176 cognitively unimpaired individuals and 14 with mild cognitive impairment (MCI). MEASUREMENTS: Hippocampal volume and microstructure (mean diffusivity (MD)) were measured using structural magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI), respectively. Tau pathology was measured using FMK-6240 tau PET imaging across Braak stages I-III. Cognitive performance was indexed using global and domain-specific composite scores. Regression models tested the interactions between hippocampal volume or MD and tau burden, adjusting for demographics, APOE genotype, amyloid status, and diagnostic status.
resultsLower hippocampal MD (indicative of better microstructural integrity) attenuated the negative association between tau burden in Braak stages II-III and both global cognition and episodic memory (ps < 0.010). Logistic regression models indicated that lower hippocampal MD was associated with a weaker relationship between tau burden in Braak stages II-III and the likelihood of MCI diagnosis (ps < 0.050). In contrast, hippocampal volume did not moderate the relationship between tau and any cognitive outcome (ps > 0.250).
conclusionsHippocampal MD may serve as a promising imaging marker of cognitive resilience to early tau pathology, with potential utility for risk stratification and as a target for preventive interventions in AD.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.