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Prognostic importance of apathy in syndromes associated with frontotemporal lobar degeneration.

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Lansdall, Claire J 
Coyle-Gilchrist, Ian TS 
Vázquez Rodríguez, Patricia 
Wilcox, Alicia 
Wehmann, Eileen 


OBJECTIVE: To determine the influence of apathy, impulsivity, and behavioral change on survival in patients with frontotemporal dementia, progressive supranuclear palsy, and corticobasal syndrome. METHODS: We assessed 124 patients from the epidemiologic PiPPIN (Pick's Disease and Progressive Supranuclear Palsy, Prevalence and Incidence) study. Patients underwent detailed baseline cognitive and behavioral assessment focusing on apathy, impulsivity, and behavioral change. Logistic regression identified predictors of death within 2.5 years from assessment, including age, sex, diagnosis, cognition, and 8 neurobehavioral profiles derived from a principal component analysis of neuropsychological and behavioral measures. RESULTS: An apathetic neurobehavioral profile predicted death (Wald statistic = 8.119, p = 0.004, Exp(B) = 2.912, confidence interval = >1 [1.396-6.075]) and was elevated in all patient groups. This profile represented apathy, weighted strongly to carer reports from the Apathy Evaluation Scale, Neuropsychiatric Inventory, and Cambridge Behavioral Inventory. Age at assessment, sex, and global cognitive impairment were not significant predictors. Differences in mortality risk across diagnostic groups were accounted for by their neuropsychiatric and behavioral features. CONCLUSIONS: The relationship between apathy and survival highlights the need to develop more effective and targeted measurement tools to improve its recognition and facilitate treatment. The prognostic importance of apathy suggests that neurobehavioral features might be useful to predict survival and stratify patients for interventional trials. Effective symptomatic interventions targeting the neurobiology of apathy might ultimately also improve prognosis.



Aged, Aged, 80 and over, Apathy, Female, Frontotemporal Dementia, Frontotemporal Lobar Degeneration, Humans, Impulsive Behavior, Logistic Models, Male, Middle Aged, Principal Component Analysis, Prognosis, Supranuclear Palsy, Progressive, Survival Rate

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Ovid Technologies (Wolters Kluwer Health)
Wellcome Trust (103838/Z/14/Z)
James S McDonnell Foundation (220020289)
Evelyn Trust (46722)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
Medical Research Council (MR/M009041/1)
Medical Research Council (MR/M024873/1)
The study was funded by the NIHR Cambridge Biomedical Research Centre, Cambridge Home and EU Scholarship Scheme, James F McDonnell Foundation, Wellcome Trust (103838), Medical Research Council, and Evelyn Trust. We would like to acknowledge the support of all the patients, and their relatives, who agreed to participate in this study, and the PSP Association (UK), and FTD Support Group (UK) for promoting the study, and the NIHR Biomedical Research Centre’s Cambridge Brain Bank.