CSF tau markers are associated with fine memory discrimination in older adults with amnestic MCI in the EXERT trial.

Background: Cognitive assessments sensitive to the integrity of the medial temporal lobe, an area vulnerable to early tau deposition, may serve as a low‐cost, effective marker of underlying tau burden in older adults at risk of Alzheimer's dementia. The current post hoc analyses from the EXERT study examined the relationship between CSF phosphorylated tau181 (p‐tau181), total tau (t‐tau), hippocampal volume, and cognitive performance on three distinct memory assessments in older adults with amnestic mild cognitive impairment (aMCI). Method: The study used baseline data from 41 older adults with aMCI in the EXERT trial who consented to lumbar puncture and had CSF data available (mean age = 74.10±11.98 years, mean education = 16.24±2.39 years, 61% female). P‐tau181 and t‐tau levels were quantified using Lumipulse from CSF samples. Structural brain images were processed using NeuroQuant. Hippocampal volume measures were averaged across hemispheres and adjusted for intracranial volume. Memory measures included the computerized Cogstate Behavioral Pattern Separation of Objects task (BPSO; fine memory discrimination), the Auditory Verbal Learning Test (AVLT; long delay free recall), and the Logical Memory test (delayed recall). Linear regression models were adjusted for age, sex, and education. Result: Lower CSF p‐tau181 was significantly associated with better fine memory discrimination (β = ‐0.11, SE = 0.03, p<0.01). Lower CSF t‐tau was significantly associated with better fine memory discrimination (β = ‐0.09, SE = 0.03, p = 0.01). Larger hippocampal volume was significantly associated with better fine memory discrimination (β = 0.08, SE = 0.02, p<0.01), better AVLT delayed recall (β = 1.69, SE = 0.32, p<0.01), and better Logical Memory delayed recall (β = 1.69, SE = 0.40, p<0.01). Neither p‐tau181 or t‐tau were significantly associated with AVLT delayed recall or Logical Memory delayed recall. Conclusion: Fine memory discrimination measured via the computerized BPSO test was associated with CSF p‐tau181, CSF t‐tau, and hippocampal volume, while more traditional verbal memory tests of list learning and story recall were associated only with hippocampal volume. The BPSO test may be a sensitive indicator of early pathology in individuals with aMCI with underlying tau burden. EXERT was supported by the Alzheimer's Disease Cooperative Study (ADCS) and funded by the National Institutes of Health Grant U19 AG010483. [ABSTRACT FROM AUTHOR]