Effects of a stage-specific cognitive intervention on brain metabolism in patients with aMCI and mild AD

Objectives Cognitive intervention was found to be beneficial in pts with MCI and AD, but the effect of cognitive training on brain metabolism is unexplored. We used FDG-PET to test for metabolic effects of a six month stage-specific cognitive intervention program in pts with aMCI and mild AD.

Methods 21 pts with aMCI- and 15 with mild AD syndrome (20 m, 74 yrs) were randomly assigned either to a cognitive intervention group (CIG), receiving weekly sessions of cognitive intervention, or to an active control group (ACG), which met monthly and received pencil and paper exercises for self-study. Groups were matched for syndrome, age-, gender-, APO E4 status, education and degree of cognitive impairment. All pts underwent resting-state FDG-PET and extensive neuropsychological testing at baseline and after 6 months. Normalized FDG-PET images were analyzed using voxel-based SPM5 approaches to determine longitudinal changes and group-by-time interactions (p< 0.001). Changes in global cognitive status were determined by multivariate analyses of covariance with MMSE and ADAS-cog scores as dependent measures (p<0.05).

Results There was a trend towards global cognitive improvement in the whole CIG (p=0.06), reaching significance for the aMCI subgroup. ACG showed widespread bilateral declines in FDG uptake in parieto- and occipito- temporal cortices, while CIG showed discrete decline only in left inferior occipital gyrus. Group by time analyses revealed for the whole CIG attenuation of metabolic decline in right inferior-/ middle temporal gyrus, and right middle frontal gyrus, while for the aMCI subgroup attenuation effects were strongest and occurred in left superior temporal gyrus and anterior cingulate gyrus.

Conclusions A six-month stage-specific cognitive intervention program in pts with aMCI and mild AD imparted cognitive benefits, which could be linked for the first time to an attenuated metabolic decline in regions typically affected by neurodegenerative AD