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Background With upcoming therapeutic interventions for patients with primary progressive aphasia (PPA), instruments for the follow-up of patients are needed to describe disease progression and to evaluate potential therapeutic effects. So far, volumetric brain changes have been proposed as clinical endpoints in the literature, but cognitive scores are still lacking. This study followed disease progression predominantly in language-based performance within 1 year and defined a PPA sum score which can be used in therapeutic interventions. Methods We assessed 28 patients with nonfluent variant PPA, 17 with semantic variant PPA, 13 with logopenic variant PPA, and 28 healthy controls in detail for 1 year. The most informative neuropsychological assessments were combined to a sum score, and associations between brain atrophy were investigated followed by a sample size calculation for clinical trials. Results Significant absolute changes up to 20% in cognitive tests were found after 1 year. Semantic and phonemic word fluency, Boston Naming Test, Digit Span, Token Test, AAT Written language, and Cookie Test were identified as the best markers for disease progression. These tasks provide the basis of a new PPA sum score. Assuming a therapeutic effect of 50% reduction in cognitive decline for sample size calculations, a number of 56 cases is needed to find a significant treatment effect. Correlations between cognitive decline and atrophy showed a correlation up to r = 0.7 between the sum score and frontal structures, namely the superior and inferior frontal gyrus, as well as with left-sided subcortical structures. Conclusion Our findings support the high performance of the proposed sum score in the follow-up of PPA and recommend it as an outcome measure in intervention studies.

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.