Clinician‐reported features in MBI/MCI and early dementia in genetic FTLD

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AbstractBackgroundFrontotemporal dementia (FTD) can present with significant phenotypic heterogeneity. Most cases of sporadic FTD do not present for diagnosis until functional impairment is evident, making it difficult to identify and characterize the earliest features of FTD. Focusing on participants from families with known FTD‐causing pathogenic mutations allows for the characterization of the earliest features of FTD in genetic carriers.MethodThe ARTFL and LEFFTDS consortia (AG063911, AG045390, NS092089, AG016976) are joint, multi‐center cohort studies of patients with FTLD, including symptomatic and asymptomatic family members. For this study, a subset of ARTFL/LEFFTDS participants from families with known genetic mutations were selected if they were determined by a study physician to have (a) a phenotype of Mild Behavioral / Cognitive Impairment (MBI/MCI) and CDR®+NACC‐FTLD = 0.5 (44 participants, 19 C9orf72, 12 GRN, 13 MAPT mutations), or (b) CDR®+NACC‐FTLD = 1 (33 participants, 16 C9orf72, 10 GRN, 7 MAPT mutations). We examined the NACC Uniform Data Set (UDS) B9F form, bvFTD criteria. Pearson chi‐squared tests compared the frequency of identified bvFTD features between MBI/MCI and bvFTD participants.ResultThe most common bvFTD diagnostic criteria features questionably or definitely present in the 44 MBI/MCI participants were Apathy and Disinhibition, both at 30% (Within the early FTLD group: Apathy at 70% and Disinhibition at 72%). Neuropsychological testing deficits consistent with bvFTD were present in 27% (72%), and loss of empathy in 25% (72%). Impaired daily functioning was next at 16% (81%), Ritualistic behaviors were observed in 7%, (36%) and Hyperorality in 5% (33%). Chi‐squared tests revealed significant differences between the two groups for all features, with the largest numerical and statistical difference in impaired daily functioning.ConclusionApathy and Disinhibition were the most common neuropsychiatric symptoms noted in FLTD MBI/MCI. Development of impairments in daily functioning best distinguished the MBI/MCI and FTLD groups. This may be related to the requirement of functional impairment for the diagnosis of dementia. The relative frequency of different features in early dementia of genetic FTLD is similar to that reported in sporadic bvFTD. As more longitudinal data is collected, within‐subject assessment of the development of features in genetic bvFTD over time will be instructive.