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April 02, 2019; 92 (14) ArticleOpen Access

Prognostic importance of apathy in syndromes associated with frontotemporal lobar degeneration

Claire J. Lansdall, Ian T.S. Coyle-Gilchrist, Patricia Vázquez Rodríguez, Alicia Wilcox, Eileen Wehmann, Trevor W. Robbins, James B. Rowe
First published March 6, 2019, DOI: https://doi.org/10.1212/WNL.0000000000007249
Claire J. Lansdall
From the Departments of Clinical Neurosciences (C.J.L., I.T.S.C.-G., P.V.R., A.W., E.W., J.B.R.) and Psychology (T.W.R.), and Behavioral and Clinical Neuroscience Institute (T.W.R., J.B.R.), University of Cambridge, UK; University Medical Centre Hamburg-Eppendorf (E.W.), University of Hamburg, Germany; and MRC Cognition and Brain Sciences Unit (J.B.R.), Cambridge, UK.
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Ian T.S. Coyle-Gilchrist
From the Departments of Clinical Neurosciences (C.J.L., I.T.S.C.-G., P.V.R., A.W., E.W., J.B.R.) and Psychology (T.W.R.), and Behavioral and Clinical Neuroscience Institute (T.W.R., J.B.R.), University of Cambridge, UK; University Medical Centre Hamburg-Eppendorf (E.W.), University of Hamburg, Germany; and MRC Cognition and Brain Sciences Unit (J.B.R.), Cambridge, UK.
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Patricia Vázquez Rodríguez
From the Departments of Clinical Neurosciences (C.J.L., I.T.S.C.-G., P.V.R., A.W., E.W., J.B.R.) and Psychology (T.W.R.), and Behavioral and Clinical Neuroscience Institute (T.W.R., J.B.R.), University of Cambridge, UK; University Medical Centre Hamburg-Eppendorf (E.W.), University of Hamburg, Germany; and MRC Cognition and Brain Sciences Unit (J.B.R.), Cambridge, UK.
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Alicia Wilcox
From the Departments of Clinical Neurosciences (C.J.L., I.T.S.C.-G., P.V.R., A.W., E.W., J.B.R.) and Psychology (T.W.R.), and Behavioral and Clinical Neuroscience Institute (T.W.R., J.B.R.), University of Cambridge, UK; University Medical Centre Hamburg-Eppendorf (E.W.), University of Hamburg, Germany; and MRC Cognition and Brain Sciences Unit (J.B.R.), Cambridge, UK.
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Eileen Wehmann
From the Departments of Clinical Neurosciences (C.J.L., I.T.S.C.-G., P.V.R., A.W., E.W., J.B.R.) and Psychology (T.W.R.), and Behavioral and Clinical Neuroscience Institute (T.W.R., J.B.R.), University of Cambridge, UK; University Medical Centre Hamburg-Eppendorf (E.W.), University of Hamburg, Germany; and MRC Cognition and Brain Sciences Unit (J.B.R.), Cambridge, UK.
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Trevor W. Robbins
From the Departments of Clinical Neurosciences (C.J.L., I.T.S.C.-G., P.V.R., A.W., E.W., J.B.R.) and Psychology (T.W.R.), and Behavioral and Clinical Neuroscience Institute (T.W.R., J.B.R.), University of Cambridge, UK; University Medical Centre Hamburg-Eppendorf (E.W.), University of Hamburg, Germany; and MRC Cognition and Brain Sciences Unit (J.B.R.), Cambridge, UK.
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James B. Rowe
From the Departments of Clinical Neurosciences (C.J.L., I.T.S.C.-G., P.V.R., A.W., E.W., J.B.R.) and Psychology (T.W.R.), and Behavioral and Clinical Neuroscience Institute (T.W.R., J.B.R.), University of Cambridge, UK; University Medical Centre Hamburg-Eppendorf (E.W.), University of Hamburg, Germany; and MRC Cognition and Brain Sciences Unit (J.B.R.), Cambridge, UK.
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Prognostic importance of apathy in syndromes associated with frontotemporal lobar degeneration
Claire J. Lansdall, Ian T.S. Coyle-Gilchrist, Patricia Vázquez Rodríguez, Alicia Wilcox, Eileen Wehmann, Trevor W. Robbins, James B. Rowe
Neurology Apr 2019, 92 (14) e1547-e1557; DOI: 10.1212/WNL.0000000000007249

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Abstract

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.

Glossary

ALS=
amyotrophic lateral sclerosis;
bvFTD=
behavioral variant frontotemporal dementia;
CBS=
corticobasal syndrome;
df=
degrees of freedom;
FTD=
frontotemporal dementia;
FTLD=
frontotemporal lobar degeneration;
PiPPIN=
Pick's Disease and Progressive Supranuclear Palsy Prevalence and Incidence;
PPA=
primary progressive aphasia;
PSP=
progressive supranuclear palsy;
svPPA=
semantic variant primary progressive aphasia

Footnotes

  • The Article Processing Charge was funded by the Wellcome Trust.

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Received June 14, 2018.
  • Accepted in final form November 21, 2018.
  • Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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