FRONTOTEMPORAL DEMENTIA - COMPREHENSIVE INSIGHTS INTO PATHOGENESIS, DIAGNOSIS, AND INNOVATIVE TREATMENTS

Abstract

Frontotemporal dementia (FTD) is a clinically and genetically diverse group of neurodegenerative disorders predominantly affecting the frontal and anterior temporal lobes, leading to progressive changes in behavior, language, and executive function. FTD is the most common cause of young-onset dementia and third overall among degenerative dementias, with a prevalence of 15–22 per 100,000 and an incidence of 2.7–4.1 per 100,000. The core clinical syndromes include the behavioral variant (bvFTD), semantic and nonfluent primary progressive aphasias (svPPA, nfvPPA), and overlap with motor disorders such as progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). Genetic mutations, especially C9orf72, GRN, and MAPT, are responsible for most familial cases and involve proteinopathies with TDP-43, tau, and FUS proteins. Biomarkers (e.g., neurofilament light chain, progranulin) and neuroimaging are used to improve detection and differentiate subtypes, although reliable biomarkers are lacking. Management is largely supportive, with a combination of non-pharmacological therapies (e.g., exercise, speech and occupational strategies, behavioral tactics, caregiver education) and pharmacotherapy for neuropsychiatric symptoms. Clinical trials explore gene therapies and disease-modifying drugs, indicating a move towards personalized medicine. Despite major advances, obstacles persist for early detection and effective therapies, underlining the need for sustained multidisciplinary research in FTD.