Neuropsychological profiles in familial frontotemporal dementia

In the last two decades three genetic mutations have been discovered covering most cases of familial frontotemporal dementia (FTD): MAPT, GRN and C9orf72 repeat expansion. Differentiation between different FTD mutations clinically will become more important with forthcoming trials on disease modifying treatments. The aim of the current study is to distinguish between cognitive and/or behavioral profiles in symptomatic FTD patients with a MAPT, GRN or C9orf72 mutation.
In this study we compared neuropsychological and behavioral data of patients diagnosed with familial FTD due to a MAPT (n=26), GRN (n=16) or C9orf72 (n=20) mutation and healthy controls (HC) (n=42). Raw neuropsychological test scores were converted into standardized z-scores, and we calculated composite z-scores for the domains language, attention, executive functioning, social cognition, memory immediate recall, memory delayed recall, memory recognition, working memory and visuo-constructive ability. The presence of 16 behavioral features was scored, suchas disinhibition, apathy, roaming, perseveration, hyperorality, parkinsonism and hallucinations. Between group analyses wereperformed withANCOVA, adjusted for sex, age, education and diseaseduration, and post-hoc t-tests.
All mutation groups showed a cognitive profile of domains language, attention and executive functioning deficits compared to HC. MAPT patients have significant lower scores for the memory domain compared to GRN patients and HC. Concerning behavior, GRN patients presented with the most roaming, MAPT patients with apathy/inertia and in C9orf72 patients hyperorality and language problems were most reported.
These results indicate that we cannot distinguish between FTD due to MAPT, GRN and C9orf72 mutations on the basis of neuropsychological profiles in the symptomatic stage, with subtle differences on the memory domain in MAPT versus GRN mutation carriers. There is a need for other measures distinguishing different FTD mutations clinically, which may be found in behavioral features.