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Structural brain changes have been described in both mild cognitive impairment (MCI) and Alzheimer's disease (AD). However, less is known about whether structural changes are detectable earlier, in the asymptomatic phase. Using voxel-based morphometry (VBM) and shape analyses of magnetic resonance imaging (MRI) data, we investigated structural brain differences between groups of healthy subjects, stratified by subsequent diagnoses of MCI or AD during a 10-year follow-up. Images taken at baseline, at least 4 years before any cognitive symptoms, showed that subjects with future cognitive impairment (preclinical AD and MCI) had reduced brain volume in medial temporal lobes, posterior cingulate/precuneus, and orbitofrontal cortex, compared with matched subjects who remained cognitively healthy for 10 years (HC). For only those subjects later diagnosed as AD, significantly greater atrophy at baseline was detected in the right medial temporal lobe, which was also confirmed by shape analysis of the right hippocampus in these subjects. Our results demonstrate that structural brain changes occur years before clinical cognitive decline in AD and are localized to regions affected by AD neuropathology.

Original publication




Journal article


Neurobiol Aging

Publication Date





825.e25 - 825.e36


Age Factors, Aged, Aged, 80 and over, Alzheimer Disease, Analysis of Variance, Brain, Brain Mapping, Cognitive Dysfunction, Disease Progression, Female, Humans, Image Processing, Computer-Assisted, Longitudinal Studies, Magnetic Resonance Imaging, Male, Mental Status Schedule, Neuropsychological Tests, Statistics as Topic