ArticleJournal of neurology2026
Impact of awareness of genetic status on cognitive, behavioral, and neuropsychiatric outcomes in genetic frontotemporal dementia.
Article in Journal of neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundPrior research on genetic frontotemporal dementia (FTD) has examined the psychological impact of predictive testing, leaving other effects of genetic awareness largely unexplored. This study examined whether genetic awareness is associated with cognitive, behavioral, and neuropsychiatric outcomes in individuals from genetic FTD families.
methodsFrom a longitudinal genetic cohort study, we included 228 individuals (age 18-70 years) from families with different underlying pathogenic variants. 99 individuals were aware of their genetic status, of which 75 pathogenic variant carriers and 24 non-carriers. 129 individuals were unaware of their genetic status, of which 56 carriers and 73 non-carriers. 26 individuals became aware of their genetic status mid-study. We compared baseline and longitudinal cognitive, behavioral, and neuropsychiatric outcomes between the aware and unaware groups, and explored differences in longitudinal slopes before and after becoming aware of the genetic status.
resultsCross-sectionally, genetic awareness is associated with the anxiety subdomain of the NPI-Q, but not after FDR correction. Longitudinally, awareness of genetic status was associated with decline in verbal learning, recall, and semantic fluency in carriers. Non-carriers who learned their status mid-study reported fewer depressive symptoms post-disclosure, but depressive symptoms increased over time.
conclusionAwareness of genetic status is associated with faster cognitive decline and greater behavioral and neuropsychiatric symptoms in aware carriers of FTD variants. These findings suggest that genetic awareness is an important factor to consider during personalized guidance and monitoring in clinical trials. Future studies should aim for larger sample sizes to further explore potential effects in genetic subgroups.
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