Frontotemporal dementia. How to deal with its diagnostic complexity?

Introduction: Frontotemporal dementia (FTD) encompasses a group of heterogeneous neurodegenerative disorders. Aside from genetic cases, its diagnosis is challenging, particularly in the early stages when symptoms are ambiguous, and structural neuroimaging does not reveal characteristic patterns. Areas covered: The authors performed a comprehensive literature search through MEDLINE, Scopus, and Web of Science databases to gather evidence to aid the diagnostic process for suspected FTD patients, particularly in early phases, even in sporadic cases, ranging from established to promising tools. Blood-based biomarkers might help identify very early neuropathological stages and guide further evaluations. Subsequently, neurophysiological measures reflecting functional changes in cortical excitatory/inhibitory circuits, along with functional neuroimaging assessing brain network, connectivity, metabolism, and perfusion alterations, could detect specific changes associated to FTD even decades before symptom onset. As the neuropathological process advances, cognitive-behavioral profiles and atrophy patterns emerge, distinguishing specific FTD subtypes. Expert opinion: Emerging disease-modifying therapies require early patient enrollment. Therefore, a diagnostic paradigm shift is needed–from relying on typical cognitive and neuroimaging profiles of advanced cases to widely applicable biomarkers, primarily fluid biomarkers, and, subsequently, neurophysiological and functional neuroimaging biomarkers where appropriate. Additionally, exploring subjective complaints and behavioral changes detected by home-based technologies might be crucial for early diagnosis.