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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 T.S., Vázquez Rodríguez, Patricia, Wilcox, Alicia, Wehmann, Eileen, Robbins, Trevor W., Rowe, James B.·2019·Neurology
DOI 10.1212/wnl.0000000000007249PMC PMC6448451
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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: = 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.

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Figure 1 Boxplot of apathy (component 2) by diagnostic group Patients scored significantly higher than controls on component 2 across diagnostic groups (analysis of variance, least significant difference correction for multiple comparisons, control vs PSP, CBS, bvFTD **p < 0.001, vs PPA *p < 0.05). Component 2 had strong loadings from the carer-rated Apathy Evaluation Scale, Neuropsychiatric Inventory apathy subscore, and Cambridge Behavioral Inventory subscores of everyday skills, self-care, sleep, and motivation. Overall, higher scores on this neurobehavioral component reflected increased endorsement of apathy. bvFTD = behavioral variant frontotemporal dementia; CBS = corticobasal syndrome; PPA = primary progressive aphasia; PSP = progressive supranuclear palsy.
Figure 1 Boxplot of apathy (component 2) by diagnostic group Patients scored significantly higher than controls on component 2 across diagnostic groups (analysis of variance, least significant difference correction for multiple comparisons, control vs PSP, CBS, bvFTD **p < 0.001, vs PPA *p < 0.05). Component 2 had strong loadings from the carer-rated Apathy Evaluation Scale, Neuropsychiatric Inventory apathy subscore, and Cambridge Behavioral Inventory subscores of everyday skills, self-care, sleep, and motivation. Overall, higher scores on this neurobehavioral component reflected increased endorsement of apathy. bvFTD = behavioral variant frontotemporal dementia; CBS = corticobasal syndrome; PPA = primary progressive aphasia; PSP = progressive supranuclear palsy.CC BY · PubMed Central
Figure 2 Kaplan-Meier survival curves showing days since assessment and days since reported symptom onset Survival rates differed significantly between diagnostic groups from PiPPIN assessment (A: log-rank [Mantel-Cox] χ2 = 20.9, df = 3, p < 0.001; pairwise comparisons revealed significant differences for PSP vs PPA χ2 = 17.0, p < 0.001; PSP vs bvFTD χ2 = 6.0, p < 0.05; CBS vs PPA χ2 = 14.0, p < 0.001; and CBS vs bvFTD χ2 = 4.6, p < 0.05), and from onset (B: log-rank [Mantel-Cox] χ2 = 18.0, df = 3, p < 0.001; pairwise comparisons revealed significant differences for PSP vs PPA χ2 = 11.2, p = 0.001; PSP vs bvFTD χ2 = 4.8, p < 0.05; CBS vs PPA χ2 = 13.5, p < 0.001; CBS vs bvFTD χ2 = 5.7, p < 0.05). bvFTD = behavioral variant frontotemporal dementia; CBS = corticobasal syndrome; df = degrees of freedom; PiPPIN = Pick's Disease and Progressive Supranuclear Palsy Prevalence and Incidence; PPA = primary progressive aphasia; PSP = progressive supranuclear palsy.
Figure 2 Kaplan-Meier survival curves showing days since assessment and days since reported symptom onset Survival rates differed significantly between diagnostic groups from PiPPIN assessment (A: log-rank [Mantel-Cox] χ2 = 20.9, df = 3, p < 0.001; pairwise comparisons revealed significant differences for PSP vs PPA χ2 = 17.0, p < 0.001; PSP vs bvFTD χ2 = 6.0, p < 0.05; CBS vs PPA χ2 = 14.0, p < 0.001; and CBS vs bvFTD χ2 = 4.6, p < 0.05), and from onset (B: log-rank [Mantel-Cox] χ2 = 18.0, df = 3, p < 0.001; pairwise comparisons revealed significant differences for PSP vs PPA χ2 = 11.2, p = 0.001; PSP vs bvFTD χ2 = 4.8, p < 0.05; CBS vs PPA χ2 = 13.5, p < 0.001; CBS vs bvFTD χ2 = 5.7, p < 0.05). bvFTD = behavioral variant frontotemporal dementia; CBS = corticobasal syndrome; df = degrees of freedom; PiPPIN = Pick's Disease and Progressive Supranuclear Palsy Prevalence and Incidence; PPA = primary progressive aphasia; PSP = progressive supranuclear palsy.CC BY · PubMed Central

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References 40 · Cited by 66

Metadata

Authors
Lansdall, C. J., Coyle-Gilchrist, I. T. S., Vázquez Rodríguez, P., Wilcox, A., Wehmann, E., Robbins, T. W., & Rowe, J. B.
Affiliations
  • Universität Hamburg (DE)
  • 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.
Corresponding author
Lansdall, Claire J.
ORCID
Venue
Neurology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2019-04-02
Volume
92
Issue
14
Pages
e1547-e1557
ISSN
  • 0028-3878 (ISSN-L)
  • 1526-632X
DOI
10.1212/wnl.0000000000007249
PMC
PMC6448451
OpenAlex
W2912821744
Cited by
66
References
40
Citations by year
2026: 3 · 2025: 15 · 2024: 5 · 2023: 12 · 2022: 9 · 2021: 12 · 2020: 6 · 2019: 4
FWCI
6.17
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Neurology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • UEA Digital Repository (University of East Anglia) (submittedVersion)
  • Apollo (University of Cambridge) (submittedVersion)
  • Apollo
Funders
  • James S. McDonnell Foundation (220020289)
  • Wellcome Trust (103838/Z/14/Z, 103838)
  • PSP Association
  • National Institute for Health and Care Research
  • Cambridge University Hospitals (146281)
  • Evelyn Trust (46722)
  • Medical Research Council (MR/M024873/1, MR/M009041/1)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
  • Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
Keywords
apathy, frontotemporal lobar degeneration, frontotemporal dementia, progressive supranuclear palsy, corticobasal syndrome, Pick's disease, impulsivity, behavior change, survival, mortality prediction, prognostic factors, neuropsychiatric symptoms, neurobehavioral profile
MeSH terms
Aged, Aged, 80 and over, Female, Humans, Impulsive Behavior, Male, Middle Aged, Prognosis, Supranuclear Palsy, Progressive, Survival Rate, Logistic Models, Principal Component Analysis, Frontotemporal Lobar Degeneration, Frontotemporal Dementia, Apathy

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CoChat. (2026). Citation check: Prognostic importance of apathy in syndromes associated with frontotemporal lobar degeneration. https://app.cochat.ai/papers/10.1212/wnl.0000000000007249
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Lansdall, C. J., Coyle-Gilchrist, I. T. S., Vázquez Rodríguez, P., Wilcox, A., Wehmann, E., Robbins, T. W., & Rowe, J. B. (2019). Prognostic importance of apathy in syndromes associated with frontotemporal lobar degeneration. Neurology. https://doi.org/10.1212/wnl.0000000000007249