The Differential Effects of Genetic Mutations in ALS and FTD Genes on Behavioural and Cognitive Changes: A Systematic Review and Meta-Analysis.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are linked by shared genetic mutations and overlapping clinical features, forming a clinical spectrum. This systematic review and meta-analysis analysed 97 studies, including 3212 patients with key ALS/FTD gene mutations, to identify gene-specific behavioural profiles. () mutations were strongly associated with psychotic symptoms and aggression, while () mutations had minimal cognitive effects. () mutations correlated with apathy and hallucinations, () with disinhibition, and () with social impairments. () mutations caused early sleep disturbances, () led to disinhibition, and () was linked to severe aggression. Prodromal cognitive changes in , , and mutations suggested early disease onset. Despite overlapping symptoms and clinical heterogeneity, understanding gene-specific patterns could inform tailored care strategies to enhance the quality of life for ALS and FTD patients. This study calls for refined guidelines integrating genetic behavioural profiles to improve patient and family support.