CSF biomarker and PIB-PET–derived beta-amyloid signature predicts metabolic, grey matter and cognitive changes in nondemented subjects

Abstract

Beta-amyloid (Ab) is a histopathological hallmark of Alzheimer’s disease dementia, but high levels of Ab 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 Ab levels, as assessed with cerebrospinal fluid and molecular positron emission tomography (PET)--based biomarkers of Ab. In subjects with mild cognitive impairment, increased brain Ab 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 Ab and cognitive decline. In contrast, elderly cognitively healthy controls (HC) with high Ab levels showed only a faster medial temporal lobe and precuneus volume decline compared with HC with low Ab. In conclusion, the current results suggest not only that both functional and volumetric brain changes are associated with high Ab years before the onset of dementia but also that HC with substantial Ab levels show higher Ab pathology resistance, lack other pathologies that condition neurotoxic effects of Ab, or accumulated Ab for a shorter time period.