CSF Biomarker and PIB-PET-Derived Beta-Amyloid Signature Predicts Metabolic, Gray Matter, and Cognitive Changes in Nondemented Subjects

Beta-amyloid (A beta) is a histopathological hallmark of Alzheimer's disease dementia, but high levels of A beta in the brain can also be found in a substantial proportion of nondemented subjects. Here we investigated which 2-year rate of brain and cognitive changes are present in nondemented subjects with high and low A beta levels, as assessed with cerebrospinal fluid and molecular positron emission tomography (PET)-based biomarkers of A beta. In subjects with mild cognitive impairment, increased brain A beta levels were associated with significantly faster cognitive decline, progression of gray matter atrophy within temporal and parietal brain regions, and a trend for a faster decline in parietal Fludeoxyglucose (FDG)-PET metabolism. Changes in gray matter and FDG-PET mediated the association between A beta and cognitive decline. In contrast, elderly cognitively healthy controls (HC) with high A beta levels showed only a faster medial temporal lobe and precuneus volume decline compared with HC with low A beta. In conclusion, the current results suggest not only that both functional and volumetric brain changes are associated with high A beta years before the onset of dementia but also that HC with substantial A beta levels show higher A beta pathology resistance, lack other pathologies that condition neurotoxic effects of A beta, or accumulated A beta for a shorter time period.