We determined the effect of cortical amyloid load using F-florbetapir PET on cognitive performance and gray matter structural integrity derived from MRI in 318 cognitively normally performing older people with subjective memory impairment from the INSIGHT-preAD cohort using multivariate partial least squares regression. Amyloid uptake was associated with reduced gray matter structural integrity in hippocampus, entorhinal and cingulate cortex, middle temporal gyrus, prefrontal cortex, and lentiform nucleus (p < 0.01, permutation test). Higher amyloid load was associated with poorer global cognitive performance, delayed recall and attention (p < 0.05), independently of its effects on gray matter connectivity. These findings agree with the assumption of a two-stage effect of amyloid on cognition, (1) an early direct effect in the preclinical stages of Alzheimer's disease and (2) a delayed effect mediated by downstream effects of amyloid accumulation, such as gray matter connectivity decline.
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