Frontotemporal dementia (FTD) is a neurodegenerative disorder with a heterogeneous profile. It is a highly heritable disorder with an autosomal dominant pattern of inheritance. The three most...Show moreFrontotemporal dementia (FTD) is a neurodegenerative disorder with a heterogeneous profile. It is a highly heritable disorder with an autosomal dominant pattern of inheritance. The three most common mutations are found in the microtubule-associated protein tau (MAPT) gene, progranulin (GRN) gene and hexanucleotide repeat expansion in the chromosome 9 open reading frame 72 (C9orf72) gene. Sensitive outcome measures in early stage genetic FTD are necessary for upcoming disease-modifying therapeutic trials. It is known that social cognition declines in genetic mutation carriers of FTD. The Dutch version of the Social Norms Questionnaire (SNQ-NL) measures the degree to which subjects understand and identify accepted social norms and is able to differentiate FTD patients from healthy controls. The aim of this study was to identify if the SNQ-NL can already indicate social cognitive changes in the presymptomatic phase of FTD. We examined group differences between patients with FTD (n = 34), presymptomatic mutation carriers (n = 55), prodromal mutation carriers (n = 20), and control participants (n = 51) in Total score, Break errors and Overadhere errors of the SNQ-NL, associations with other cognitive functions, and longitudinal data in a subset were further explored. Results showed that the SNQ-NL Total Score and Overadhere errors differed between patients and the other participant groups, but not between presymptomatic or prodromal mutation carriers and control participants. Differences between patients and the other participant groups were also found for the SNQ-NL Direct/indirect ratio. The SNQ-NL Total score and Overadhere scores significantly correlated with cognitive flexibility, theory of mind and confrontation naming. None of the SNQ-NL variables correlated significantly with emotion recognition. No interaction effect is found between groups over time for one of the SNQ-NL variables. In conclusion, present results showed that the SNQ-NL can differentiate between FTD patients, presymptomatic and prodromal mutation carriers. No evidence is found for the SNQ-NL as an indicator of social cognitive changes in the presymptomatic phase of genetic FTD.Show less
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
