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The effect of cognitive intervention on brain metabolism in Alzheimer's disease (AD) is largely unexplored. Therefore, we aimed to investigate clinical cognitive parameters and 18FDG PET to test for effects of a cognitive intervention in patients with amnestic mild cognitive impairment (aMCI) or mild AD. Patients with aMCI (n = 24) or mild AD (n = 15) were randomly assigned either to cognitive intervention groups (IGs), receiving weekly sessions of group-based multicomponent cognitive intervention, or active control groups (CGs), receiving pencil-paper exercises for self-study. We obtained resting-state FDG-PET scans and neuropsychological testing at baseline and after six-months. Normalized FDG-PET images were analyzed using voxel-based SPM5 approaches to determine longitudinal changes, group-by-time interactions, and correlations with neuropsychological outcome parameters. Primary global cognitive outcome was determined by analyses of covariance with MMSE and ADAS-cog scores as dependent measures. Both, aMCI and AD subgroups of CGs showed widespread bilateral cortical declines in FDG uptake, while the AD subgroup of IGs showed discrete decline or rather no decline in case of the aMCI subgroup. Group by time analyses revealed strongest attenuation of metabolic decline in the aMCI subgroup of the IGs, involving left superior temporal- and anterior cingulate gyrus. However, correlation analyses revealed only weak non-significant associations between increased FDG uptake and improvement in primary or secondary outcome parameters. Concurrently, there was significant improvement in global cognitive status in the aMCI subgroup of the IGs. A six-month cognitive intervention imparted cognitive benefits in patients with aMCI, which were concurrent with an attenuated decline of glucose metabolism in cortical regions affected by neurodegenerative AD.

Recent studies have shown that patients with Alzheimer's disease (AD) and its possible prodromal stage mild cognitive impairment benefit from cognitive interventions. Few studies so far have used an active control condition and determined effects in different stages of disease. We evaluated a newly developed 6-month group-based multicomponent cognitive intervention in a randomized controlled pilot study on subjects with amnestic mild cognitive impairment (aMCI) and mild AD patients. Forty-three subjects with aMCI and mild AD were recruited. Primary outcome measures were change in global cognitive function as determined by the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and the Mini Mental Status Examination (MMSE). Secondary outcomes were specific cognitive and psychopathological ratings. Thirty-nine patients were randomized to intervention groups (IGs: 12 aMCI, 8 AD) and active control groups (CGs: 12 aMCI, 7 AD). At the end of the study, we found significant improvements in the IG(MCI) compared to the CG(MCI) in the ADAS-cog (p = 0.02) and for the secondary endpoint Montgomery Asberg Depression Rating Scale (MADRS) (p < 0.01) Effects on the MMSE score showed a non-significant trend (p = 0.07). In AD patients, we found no significant effect of intervention on the primary outcome measures. In conclusion, these results suggest that participation in a 6-month cognitive intervention can improve cognitive and non-cognitive functions in aMCI subjects. In contrast, AD patients showed no significant benefit from intervention. The findings in this small sample support the use of the intervention in larger scales studies with an extended follow-up period to determine long-term effects.