Cognitive Indicators of Preclinical Behavioral Variant Frontotemporal Dementia in MAPT Carriers
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OBJECTIVES: The cognitive indicators of preclinical behavioral variant Frontotemporal Dementia (bvFTD) have not been identified. To investigate these indicators, we compared cross-sectional performance on a range of cognitive measures in 12 carriers of pathogenic MAPT mutations not meeting diagnostic criteria for bvFTD (i.e., preclinical) versus 32 demographically-matched familial non-carriers (n = 44). Studying preclinical carriers offers a rare glimpse into emergent disease, environmentally and genetically contextualized through comparison to familial controls. METHODS: Evaluating personnel blinded to carrier status administered a standardized neuropsychological battery assessing attention, speed, executive function, language, memory, spatial ability, and social cognition. Results from mixed effect modeling were corrected for multiplicity of comparison by the false discovery rate method, and results were considered significant at p < .05. To control for potential interfamilial variation arising from enrollment of six families, family was treated as a random effect, while carrier status, age, gender, and education were treated as fixed effects. RESULTS: Group differences were detected in 17 of 31 cognitive scores and spanned all domains except spatial ability. As hypothesized, carriers performed worse on specific measures of executive function, and social cognition, but also on measures of attention, speed, semantic processing, and memory storage and retrieval. CONCLUSIONS: Most notably, group differences arose on measures of memory storage, challenging long-standing ideas about the absence of amnestic features on neuropsychological testing in early bvFTD. Current findings provide important and clinically relevant information about specific measures that may be sensitive to early bvFTD, and advance understanding of neurocognitive changes that occur early in the disease. (JINS, 2019, 25, 184-194).
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Some of these linguistic deficits may occur preclinically in each of these neurodegenerative disorders.
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- Authors
- Cheran, G., Wu, L., Lee, S., Manoochehri, M., Cines, S., Fallon, E., Lynch, T., Heidebrink, J., Paulson, H., Goldman, J., Huey, E., & Cosentino, S.
- Affiliations
- Columbia University (US)
- Fairleigh Dickinson University (US)
- University of Michigan (US)
- New York State Psychiatric Institute (US)
- Corresponding author
- Cosentino, Stephanie
- ORCID
- Venue
- Journal of the International Neuropsychological Society
- Publisher
- Cambridge University Press (CUP)
- Published
- 2018-11-21
- Volume
- 25
- Issue
- 2
- Pages
- 184-194
- ISSN
- 1355-6177 (ISSN-L)
- 1469-7661
- PMC
- PMC6374161
- OpenAlex
- W2901056969
- Cited by
- 29
- References
- 43
- Citations by year
- 2026: 2 · 2025: 3 · 2023: 6 · 2022: 6 · 2021: 6 · 2020: 4 · 2019: 2
- FWCI
- 2.34
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of the International Neuropsychological Society (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR000040)
- National Institute on Aging (P30AG053760, U01AG016976, K01AG051348)
- National Institute of Neurological Disorders and Stroke (R01NS076837, U24NS095871)
- National Center for Research Resources (UL1RR024156)
- National Center for Advancing Translational Sciences
- 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, tauopathy, cognitive indicators, executive function, social cognition, memory impairment, attention and processing speed, neuropsychological assessment
- MeSH terms
- Adult, Aged, Attention, Cross-Sectional Studies, Family, Female, Heterozygote, Humans, Male, Memory, Memory Disorders, Middle Aged, Reaction Time, Social Perception, Cohort Studies, tau Proteins, Executive Function, Frontotemporal Dementia, Prodromal Symptoms
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