Abstract
IntroductionApathy 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.MethodsPresymptomatic 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.ResultsApathy 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.DiscussionApathy 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.
Highlights
Apathy adversely affects prognosis and survival of patients with frontotemporal dementia (FTD)
Digit Symbol scores were positively associated with gray matter volumes in frontal lobe, temporal lobe, parietal lobe, occipital lobe, cingulate, and central structures, including Total intracranial volume (TIV) and expected symptom onset (EYO) as covariates
In this study we found that apathy progresses significantly in presymptomatic carriers of mutations associated with FTD, and that individual differences in apathy at baseline predict the severity of progressive deterioration of performance on the Digit Symbol test over time
Summary
Apathy adversely affects prognosis and survival of patients with frontotemporal dementia (FTD). The Digit Symbol Substitution test of the Wechsler Adult Intelligence Scale– Revised (WAIS-R) depends on a combination of the components of executive function (working memory, attentional control, and rule sets), in addition to non-executive visuospatial domains and processing speed.[22,23] The Digit Symbol test correlates with other measures of executive function and is sensitive to the presence of cognitive changes in patients with frontal lobe damage and dementia.[20,24,25,26,27,28] We use the Digit Symbol test performance as an index of executive dysfunction in presymptomatic FTD
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