O3‐07‐02: WHITE MATTER BURDEN IN CLINICALLY NORMAL OLDER ADULTS MEDIATES THE RELATIONSHIP BETWEEN AMYLOID BURDEN AND MEMORY FREE RECALL BUT NOT CUED RECALL

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Clinical lore suggests that poor cued recall in addition to poor free recall is associated with memory storage loss and therefore worrisome for an Alzheimer's disease etiology. Our goal was to investigate the relationship between free and cued memory retrieval, beta-amyloid (Aβ) deposition and white matter hyperintensity (WMH) volume in clinically normal (CN) individuals We studied baseline data of 184 CN older adults (mean age=73.6, age range 65-90) participating in the Harvard Aging Brain study. Participants obtained a CDR of 0 and performed above education-adjusted cut-offs on Logical Memory IIa (WMS-R) and the MMSE. Participants underwent MRI and C 11 PiB-PET imaging to derive a global beta-amyloid (A b) index and white matter hyperintensity (WMH) volume. A memory Free Recall (FR) score was computed by averaging sample-derived z-scores on free recall trials of the Selective Reminding Test, the Memory Capacity Test, and the Free and Cued Selective Reminding Test. Likewise, a Cued Recall/Recognition (CR) score was computed using cued recall or recognition scores on these same tests. Lower verbal IQ, male sex, and greater Aβ deposition was associated with lower FR [F(4,170)= 10.113, p<.001 adj. R 2 = .167] and lower CR [F(4,178)= 4.529, p<.01 adj. R 2 = .072] while greater WMH volume was related to worse FR but unrelated to CR. Age was not related to performance in either model. Further analysis indicated that the relationship between Aβ deposition and FR was mediated by WMH volume. The standardized regression coefficient between Aβ and Free Recall (Beta=-.16, p<.05) mildly but significantly decreased when controlling for WM burden (Beta=-.12, p>.05). The other conditions of mediation were also met: Aβ was a significant predictor of FR and of WMH volume (Beta=.17, p<.05), and WMH volume was a significant predictor of FR while controlling for Aβ deposition (Beta=-.21, p<.05). In clinically normal older adults, greater Aβ deposition is associated with worse memory performance on both free and cued memory recall paradigms. Interestingly, white matter burden mediates the relationship between Aβ deposition on free but not cued recall, suggesting that free retrieval may be vulnerable to multiple age-related pathologies.

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