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. 2020 Jun;267(6):1603-1612.
doi: 10.1007/s00415-020-09738-y. Epub 2020 Feb 12.

Cognitive profiles discriminate between genetic variants of behavioral frontotemporal dementia

J M Poos  1   2 , L C Jiskoot  3   4 , S M J Leijdesdorff  5 , H Seelaar  3 , J L Panman  3   6 , E L van der Ende  3 , M O Mol  3 , L H H Meeter  3 , Y A L Pijnenburg  7 , L Donker Kaat  3   8 , F J de Jong  3 , J C van Swieten  3 , J M Papma  3 , E van den Berg  3
Affiliations

Cognitive profiles discriminate between genetic variants of behavioral frontotemporal dementia

J M Poos et al. J Neurol. 2020 Jun.

Erratum in

Abstract

Introduction: Trials to test disease-modifying treatments for frontotemporal dementia are eagerly awaited and sensitive instruments to assess potential treatment effects are increasingly urgent, yet lacking thus far. We aimed to identify gene-specific instruments assessing clinical onset and disease progression by comparing cognitive functioning between bvFTD patients across genetic mutations.

Methods: We examined differences in 7 cognitive domains between bvFTD patients with GRN (n = 20), MAPT (n = 29) or C9orf72 (n = 31) mutations, and non-carriers (n = 24), and described longitudinal (M = 22.6 months, SD = 16.6) data in a subsample (n = 27).

Results: Patients showed overall cognitive impairment, except memory recall, working memory and visuoconstruction. GRN patients performed lower on executive function (mean difference - 2.1; 95%CI - 4.1 to - 0.5) compared to MAPT and lower on attention compared to MAPT (mean difference - 2.5; 95%CI - 4.7 to - 0.3) and C9orf72 (mean difference - 2.4; 95%CI - 4.5 to - 0.3). Only MAPT patients were impaired on delayed recall (mean difference - 1.4; 95%CI - 2.1 to - 0.7). GRN patients declined rapidly on attention and memory, MAPT declined in confrontation naming, whereas C9orf72 patients were globally impaired but remained relatively stable over time on all cognitive domains.

Discussion: This study shows gene-specific cognitive profiles in bvFTD, which underlines the value of neuropsychological tests as outcome measures in upcoming trials for genetic bvFTD.

Keywords: Cognition; FTD; Frontotemporal dementia; Genetic; Neuropsychology.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Within-individual trajectories of cognitive decline on seven cognitive domains. NPA neuropsychological assessment, MAPT microtubule-associated protein tau, GRN progranulin, C9orf72 chromosome 9 open reading frame 72. Raw data for each neuropsychological test were first converted to z-scores by standardization to the baseline data of non-carriers. Composite cognitive domain scores were calculated. Each subplot presents the trajectory on a specific cognitive domain. Data are available in: language (MAPTn = 9; GRNn = 3; C9orf72n = 8); attention and mental processing speed (MAPTn = 8; GRNn = 3; C9orf72n = 8); executive functioning (MAPTn = 9; GRNn = 2; C9orf72n = 8); working memory (MAPTn = 5; GRNn = 2; C9orf72n = 6); memory learning (MAPT n = 7; GRNn = 3; C9orf72n = 8); memory recall (MAPTn = 7; GRNn = 3; C9orf72n = 7); visuoconstruction (MAPTn = 6; GRNn = 2; C9orf72n = 7)
See this image and copyright information in PMC

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