Predicting functional decline in behavioural variant frontotemporal dementia
Open accessAbstract
Behavioural variant frontotemporal dementia is characterized by a change in comportment. It is associated with considerable functional decline over the course of the illness albeit with sometimes dramatic variability among patients. It is unknown whether any baseline features, or combination of features, could predict rate of functional decline in behavioural variant frontotemporal dementia. The aim of this study was to investigate the effects of different baseline clinical, neuropsychological, neuropsychiatric, genetic and anatomic predictors on the rate of functional decline as measured by the Clinical Dementia Rating Sum of Boxes scale. We identified 86 subjects with behavioural variant frontotemporal dementia that had multiple serial Clinical Dementia Rating Sum of Boxes assessments (mean 4, range 2-18). Atlas-based parcellation was used to generate volumes for specific regions of interest at baseline. Volumes were utilized to classify subjects into different anatomical subtypes using the advanced statistical technique of cluster analysis and were assessed as predictor variables. Composite scores were generated for the neuropsychological domains of executive, language, memory and visuospatial function. Behaviours from the brief questionnaire form of the Neuropsychiatric Inventory were assessed. Linear mixed-effects regression modelling was used to determine which baseline features predict rate of future functional decline. Rates of functional decline differed across the anatomical subtypes of behavioural variant frontotemporal dementia, with faster rates observed in the frontal dominant and frontotemporal subtypes. In addition, subjects with poorer performance on neuropsychological tests of executive, language and visuospatial function, less disinhibition, agitation/aggression and night-time behaviours at presentation, and smaller medial, lateral and orbital frontal lobe volumes showed faster rates of decline. In many instances, the effect of the predictor variables observed across all subjects was also preserved within anatomical subtypes. Furthermore, some of the predictor variables improved our prediction of rate of functional decline after anatomical subtype was taken into account. In particular, age at onset was a highly significant predictor but only after adjusting for subtype. We also found that although some predictor variables, for example gender, Mini-Mental State Examination score, and apathy/indifference, did not affect the rate of functional decline; these variables were associated with the actual Clinical Dementia Rating Sum of Boxes score estimated for any given time-point. These findings suggest that in behavioural variant frontotemporal dementia, rate of functional decline is driven by the combination of anatomical pattern of atrophy, age at onset, and neuropsychiatric characteristics of the subject at baseline.
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Associations between NPI/CUSPAD and disease severity were inconsistent, and the evidence as a bvFTD-specific progression marker was insufficient.
“While parts of AD-oriented neuropsychiatric scales, such as the NPI and the Columbia University Scale for Psychopathology in Alzheimer’s Disease (CUSPAD), predicted cognitive and functional decline in FTD (2.5 years) (Santacruz Escudero et al., 2019), associations with disease severity were inconsistent (Josephs et al., 2011; Kazui et al., 2016; Ranasinghe et al., 2016) and the evidence as bvFTD-s”
From The pursuit for markers of disease progression in behavioral variant frontotemporal dementia: a scoping review to optimize outcome measures for clinical trials (2024) · cites this paper as Josephs et al., 2011
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- Authors
- Josephs, K. A., Whitwell, J. L., Weigand, S. D., Senjem, M. L., Boeve, B. F., Knopman, D. S., Smith, G. E., Ivnik, R. J., Jack, C. R., & Petersen, R. C.
- Affiliations
- Mayo Clinic (US)
- ORCID
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-01-20
- Volume
- 134
- Issue
- 2
- Pages
- 432-448
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- PMC
- PMC3030765
- OpenAlex
- W2117776733
- Cited by
- 56
- References
- 52
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 2 · 2022: 4 · 2021: 4 · 2020: 2 · 2019: 1 · 2018: 5 · 2017: 2 · 2016: 5 · 2015: 3 · 2014: 5 · 2013: 6 · 2012: 5
- FWCI
- 4.38
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Brain (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Dana Foundation
- Mayo Foundation for Medical Education and Research (AG16574)
- National Institutes of Health (AG11378, R01 AG11378, AG16574)
- National Institute on Aging (R01AG11378, R21-AG38736, P50‐AG16574, U01AG06786, U01AG006786, R21AG038736, R01AG011378, R01AG037491, P50AG016574)
- National Institute on Deafness and Other Communication Disorders (R01DC010367)
- National Center for Research Resources (C06RR018898)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (K12HD049078, K12 HD 49078)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- behavioral variant frontotemporal dementia, functional decline, CDR-SB, frontal lobe atrophy, age of onset, neuropsychiatric symptoms, disinhibition, executive function, frontal lobe volume, predictors of decline, disease progression
- MeSH terms
- Progranulins, Adult, Aged, Aged, 80 and over, Atrophy, Female, Frontal Lobe, Humans, Male, Middle Aged, Mutation, Neuropsychological Tests, Psychiatric Status Rating Scales, tau Proteins, Age of Onset, Disease Progression, Intercellular Signaling Peptides and Proteins, Apolipoprotein E4, Frontotemporal Dementia
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