Homocysteine levels do not impact cognitive profile in frontotemporal dementia.

Background: This study aimed at investigating whether high plasma homocysteine (Hcy) levels affect specific cognitive functions in individuals with Frontotemporal Dementia (FTD). While Hcy is a well-established risk factor for cerebrovascular disorders and Alzheimer’s Disease, its role in other neurodegenerative dementias remains unclear. Furthermore, it is not known whether elevated Hcy levels contribute to a generalized cognitive decline or selectively impair specific cognitive domains. This uncertainty may stem from previous studies predominantly relying on global cognitive assessments rather than detailed domain-specific measures. Methods: In a cross-sectional design, 173 patients with a diagnosis of FTD underwent a comprehensive neuropsychological evaluation assessing key cognitive domains, including memory, language, visuoperception, visuospatial abilities, executive functioning, constructional praxis, and ideomotor praxis. The influence of plasma Hcy levels and other potential risk factors (e.g., cholesterol levels, smoking habits, triglycerides, and the presence of the apolipoprotein E ε4 allele) was analysed. Results: A Generalized Linear Model analysis revealed no significant association between elevated Hcy levels and cognitive performance across domains in the FTD cohort. Conclusions: Hcy levels were not significantly associated with cognitive performance in a large sample of individuals with FTD. If replicated, these findings could challenge the hypothesis that Hcy constitutes a risk factor for FTD.