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Apathy in presymptomatic genetic frontotemporal dementia predicts cognitive decline and is driven by structural brain changes.

Alzheimers Dement. 2020 Dec 14. doi: 10.1002/alz.12252. Epub ahead of print. PMID: 33316852.

Authors/Editors: Malpetti M, Jones PS, Tsvetanov KA, Rittman T, van Swieten JC, Borroni B, Sanchez-Valle R, Moreno F, Laforce R, Graff C, Synofzik M, Galimberti D, Masellis M, Tartaglia MC, Finger E, Vandenberghe R, de Mendonça A, Tagliavini F, Santana I, Ducharme S, Butler CR, Gerhard A, Levin J, Danek A, Otto M, Frisoni GB, Ghidoni R, Sorbi S, Heller C, Todd EG, Bocchetta M, Cash DM, Convery RS, Peakman G, Moore KM, Rohrer JD, Kievit RA, Rowe JB, Genfi OBOTGFI.
Publication Date: 2020


Introduction: Apathy adversely affects prognosis and survival of patients with frontotemporal dementia (FTD). We test whether apathy develops in presymptomatic genetic FTD, and is associated with cognitive decline and brain atrophy.

Methods: Presymptomatic carriers of MAPT, GRN or C9orf72 mutations (N = 304), and relatives without mutations (N = 296) underwent clinical assessments and MRI at baseline, and annually for 2 years. Longitudinal changes in apathy, cognition, gray matter volumes, and their relationships were analyzed with latent growth curve modeling.

Results: Apathy severity increased over time in presymptomatic carriers, but not in non-carriers. In presymptomatic carriers, baseline apathy predicted cognitive decline over two years, but not vice versa. Apathy progression was associated with baseline low gray matter volume in frontal and cingulate regions.

Discussion: Apathy is an early marker of FTD-related changes and predicts a subsequent subclinical deterioration of cognition before dementia onset. Apathy may be a modifiable factor in those at risk of FTD.

Keywords: MRI; apathy; cognitive decline; genetic frontotemporal dementia; longitudinal design; presymptomatic carriers.

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