Relationships Between Performance on the Cogstate Brief Battery, Neurodegeneration, and Aβ Accumulation in Cognitively Normal Older Adults and Adults with MCI

We investigated the extent to which decline in memory and working memory in beta-amyloid (A beta) positive non-demented individuals was related to hippocampal atrophy and A beta accumulation over 36 months. Cognitively normal older adults (CN) (n = 178) and adults with mild cognitive impairment (MCI) (n = 49) underwent positron emission tomography neuroimaging, magnetic resonance imaging, and cognitive assessments at baseline, 18- and 36-months. Relative to A beta- CNs, A beta+ CNs and A beta+ MCIs showed greater rates of cognitive decline, A beta accumulation, and hippocampal atrophy. Analysis of interrelationships between these Alzheimer's disease markers in A beta+ CNs and MCIs indicated that rate of A beta accumulation was associated with rate of hippocampal atrophy (beta = -0.05, p = .037), which was in turn associated independently with rate of decline in memory (beta = -0.03, p = .032). This suggests that A beta accumulation precedes any neurodegeneration or clinical symptoms, and that the relationship between A beta and cognitive decline is mediated by hippocampal atrophy.