Clinical phenotypes of behavioral variant frontotemporal dementia by age at onset

Abstract

AbstractBackgroundBehavioral variant frontotemporal dementia (bvFTD) is generally considered a young‐onset dementia, although late‐onset is not uncommon. BvFTD knows a large clinical variability and an age range varying from 21 to 85 years of age at onset. This heterogeneity challenges diagnostics, patient management and trial cohort design. While several studies indicate clinical differences regarding age at onset, no biomarker validated cohort studies with updated clinical criteria have been performed. We aimed to examine behavior, cognition and mortality over the full age spectrum in a cohort of bvFTD patients with neuroimaging, genetic or histopathological confirmation and exclusion of positive Alzheimer’s disease biomarkers.MethodIn total, 321 patients with a clinical diagnosis of probable or definite bvFTD from the Amsterdam Dementia Cohort were included and grouped into quartiles by age‐at‐diagnosis. Neuropsychiatric symptoms were assessed with the Neuropsychiatric Inventory and the Geriatric Depression Scale. Cognitive functioning was assessed with a neuropsychological test battery. Data on mortality was obtained from the Dutch municipal register. Continuous associations of clinical features with age‐at‐diagnosis, group differences between age quartiles, and mortality risk were examined in two models (M1: unadjusted, M2: adjusted for sex).ResultAge‐at‐diagnosis ranged between 26‐85 years and established quartiles with mean ages of 52±6, 60±2, 66±2 and 74±3 years. In the total sample, 44.2% exceeded an age of 65 years at time of diagnosis, 50% were deceased at time of analysis and mean survival time from date of diagnosis was 4±3 years. Earlier age‐at‐diagnosis was associated with more severe behavioral symptoms of primarily euphoria, apathy and depression, while later age‐at‐diagnosis was associated with more memory deficits. This was mainly explained by the youngest subgroup. Unexpectedly, mortality risk was not associated with age‐at‐diagnosis and was equal within age quartiles (Figure 1).ConclusionIn bvFTD, symptom profile is associated with age‐at‐diagnosis. This should be taken into account with regard to diagnostics, patient management and trial design. Furthermore, our findings suggest that late disease onset and memory deficits are more frequent in bvFTD than generally thought.