In previous work, we found larger nuclear and nucleolar volumes in hippocampus and cingulate regions in asymptomatic individuals with Alzheimer's type pathology (ASYMAD) compared to both older controls and cognitively impaired individuals. More recently, we compared antemortem changes in regional cerebral blood flow in BLSA participants subsequently diagnosed at autopsy as ASYMAD (n=6) with changes in cognitively impaired (CI=6) and normal (CN=7) older individuals. At autopsy, the ASYMAD and CI groups had similar CERAD and Braak scores, similar amounts of beta-amyloid and tau determined with immunohistochemistry in middle frontal (MFG), middle temporal (MTG), and inferior parietal (IP) regions, and more beta-amyloid than CN in precuneus, MFG and IP areas. PET rCBF scans beginning 10 years before death and while all participants were cognitively intact identified similarities and differences in longitudinal rCBF change among groups across a mean 7.2 year interval. Both ASYMAD and CI groups showed similar longitudinal rCBF declines in precuneus, lingual and MTG regions relative to CN. The CI also showed greater rCBF decreases in anterior and posterior cingulate, cuneus and brainstem regions relative to ASYMAD and CN, whereas ASYMAD showed greater relative rCBF increases over time in medial temporal and thalamic regions relative to CI and CN. Our findings provide evidence of early functional alterations that may contribute to cognitive resilience in those who accumulate AD pathology but maintain normal cognition. In a second study, we applied machine learning classifiers to discriminate between cognitively normal individuals who show cognitive decline over time versus those who remain cognitively stable. This study incorporated both MRI and PET resting cerebral blood flow data into the classifier. We showed that functional and structural changes were detected well before (2.3-2.9 years) changes in verbal memory performance. This type of approach will be extended to incorporate additional factors that may protect against cognitive decline and impairment.

National Institute of Health (NIH)
National Institute on Aging (NIA)
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National Institute on Aging
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Resnick, Susan M; Scheltens, Philip (2012) MRI-based biomarkers of preclinical AD: an Alzheimer signature. Neurology 78:80-1
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