Neuropsychiatric Symptoms in Frontotemporal Dementia: A Comparative Analysis of Sporadic and Genetic Forms

Objectives. Behavioral and Psychological Symptoms of Dementia (BPSD) are frequently observed in patients with frontotemporal dementia (FTD), including both sporadic (sFTD) and genetic forms associated with MAPT, GRN, and C9ORF72 mutations. Despite growing interest, few studies have systematically compared the neuropsychiatric phenotype across these variants. This study aimed to: (1) compare the frequency and severity of BPSD in sFTD and genetically determined FTD (MAPT, GRN, C9ORF72); (2) identify distinguishing features in the neuropsychiatric profiles among these groups at the time of diagnosis. Materials. The sample included patients diagnosed with behavioral variant FTD (bvFTD), followed at the Regional Neurogenetics Centre of Lamezia Terme. Participants were divided into four groups: sFTD, MAPT, GRN, and C9ORF72 mutation carriers. Clinical, cognitive, and neuropsychiatric data were retrospectively collected, with a focus on BPSD as measured by the Neuropsychiatric Inventory (NPI). Methods The presence, frequency, and severity of 12 neuropsychiatric domains were assessed using the NPI, administered to caregivers at diagnosis. Statistical analyses included chi-square tests for categorical variables and ANCOVA to control for confounding factors (age at diagnosis, education, disease duration, gender, and FTD variant subtype). Results. Significant differences emerged between the four groups for apathy (χ² = 10.8, p < 0.013), with higher frequencies observed in GRN (85.7%) and C9ORF72 (84.6%) patients, compared to MAPT (72.7%) and sFTD (52.7%). C9ORF72 patients showed the highest prevalence of social withdrawal (50%) and generalized seizures (10%), which were absent in MAPT carriers. GRN mutations were associated with greater distractibility, while MAPT patients showed more frequent agraphia. These findings suggest mutation-specific neuropsychiatric profiles. Discussion The results underscore the influence of genetic mutations on the clinical expression of BPSD in FTD. While apathy was the most common symptom across all groups—consistent with its inclusion in bvFTD diagnostic criteria—its prevalence was significantly higher in GRN and C9ORF72 carriers. Specific symptoms, such as distractibility and social withdrawal, also varied depending on genetic status. Conclusions This study highlights distinct neuropsychiatric patterns among sFTD and genetic forms of FTD. Identifying these differences may improve early diagnosis and guide more personalized therapeutic strategies tailored to genetic subtype.