Homocysteine levels do not impact cognitive profile in frontotemporal dementia.

Oscar Prata, Veronica Cherubini, Valentina Ranaldi, Sara Baldinelli, Chiara Fiori, Pamela Rosettani, Azzurra Biagiotti, Sofia Belcecchi, Mauro Silvestrini, Alessio Toraldo, Simona Luzzi

Journal: Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 2026;47(1):148

PMID: 41524819

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Abstract

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.

Address: Department of Experimental and Clinical Medicine, Polytechnic University of Marche, Via Conca 1, Ancona, Italy.; Clinical Psychology Operative Unit, Azienda Ospedaliero Universitaria delle Marche, Via Conca 1, Ancona, Italy.; Neurological Unit, Azienda Ospedaliero Universitaria delle Marche, Via Conca 1, Ancona, Italy.; Department of Experimental and Clinical Medicine, Polytechnic University of Marche, Via Conca 1, Ancona, Italy.; Neurological Unit, Azienda Ospedaliero Universitaria delle Marche, Via Conca 1, Ancona, Italy.; Department of Brain and Behavioural Sciences, University of Pavia, Viale Golgi 19, Pavia, Italy.; Milan Center for Neuroscience (NeuroMI), Piazza dell'Ateneo Nuovo 1, Milano, Italy.; Department of Experimental and Clinical Medicine, Polytechnic University of Marche, Via Conca 1, Ancona, Italy. [email protected].; Neurological Unit, Azienda Ospedaliero Universitaria delle Marche, Via Conca 1, Ancona, Italy. [email protected].; Cognitive and Behavioural Unit, Department of Experimental and Clinical Medicine, Marche Polytechnic University, Azienda Ospedaliero Universitaria delle Marche, Via Conca, 1, Torrette di Ancona, Italy. [email protected].

DOI: 10.1007/s10072-025-08701-x

MeSH Terms: Humans, Homocysteine, Male, Female, Frontotemporal Dementia, Cross-Sectional Studies, Middle Aged, Aged, Neuropsychological Tests, Cognition