Research master thesis | Psychology (research) (MSc)
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Introduction Frontotemporal dementia (FTD) is a young-onset neurodegenerative disorder with treatments still being in development. For trials testing such treatments, sensitive instruments to...Show moreIntroduction Frontotemporal dementia (FTD) is a young-onset neurodegenerative disorder with treatments still being in development. For trials testing such treatments, sensitive instruments to assess treatment effects are essential. This exploratory study aimed to identify such instruments by investigating gene-specific, presymptomatic cognitive decline and the underlying neural mechanisms of this decline. Methods We examined longitudinal cognitive decline using mixed effects models with natural cubic splines in six different domains for carriers of genetic mutations in GRN (n=46), MAPT (n=22), C9orf72 (n=29), and healthy controls (n=84). A voxel-based morphometry analysis was used to correlate cognitive decline to grey matter volume decline for the three mutation carrier groups. Results MAPT and C9orf72 mutation carriers showed a steeper decline on language (χ2(6) = 21.78, p = .001) and memory (χ2(6) = 18.42, p = .005) compared to GRN mutation carriers and controls. Decline in executive functions was associated with larger grey matter volume decline in the left superior and right middle frontal gyrus for C9orf72 mutation carriers and decline in language was associated with larger grey matter volume decline in the right anterior insula for MAPT mutation carriers. Discussion This study provides evidence of gene-specific cognitive decline in presymptomatic genetic mutation carriers of FTD. The findings highlight the importance of both neuropsychological and neuroimaging assessment which can be used as sensitive diagnostic biomarkers to identify and track disease progression in genetic FTD.Show less
