Patterns and Trajectories of Behavioral and Neuropsychiatric Symptoms in Frontotemporal Dementia and Primary Progressive Aphasia

BACKGROUND AND OBJECTIVES: Behavioral and neuropsychiatric symptoms are common in frontotemporal dementia (FTD) and primary progressive aphasia (PPA). However, little is known about their patterns, time course, and association with brain atrophy. We, therefore, aimed to describe behavioral and neuropsychiatric phenotypes in patients with FTD and PPA, leveraging a hypothesis-free/data-driven approach. METHODS: We included participants diagnosed with behavioral variant FTD (bvFTD) or PPA according to Rascovsky and Gorno-Tempini criteria from the German Center for Neurodegenerative Diseases Clinical Registry Study of Neurodegenerative Diseases-FTD prospective multicenter observational cohort study. Symptoms were assessed using the Neuropsychiatric Inventory-Questionnaire. Principal component analysis (PCA) was used to delineate symptom groups. Subsequently, frequency and severity across diagnostic groups were examined. We applied linear mixed-effects models to describe the longitudinal evolution of symptoms. Associations with MRI-assessed atrophy were investigated using linear regression models. RESULTS: = 0.021) indicated a progressive increase in symptom severity in men over time. Furthermore, we found robust neuroanatomical correlations of passive behavioral symptoms with subcortical and bilateral frontal and cingulate cortical atrophy. DISCUSSION: Our findings demonstrate that behavioral and neuropsychiatric symptoms are prevalent in both bvFTD and PPA. Their severity depends on the disease duration, phenotypic group, and sex. This detailed understanding of symptomatology is crucial for optimizing patient care, diagnostic evaluations, and the design of clinical trials. Limitations comprise the lack of neuropathologic validation and the limited availability of MRI data.