Active lifestyles moderate clinical outcomes in autosomal dominant frontotemporal degeneration
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Introduction: Leisure activities impact brain aging and may be prevention targets. We characterized how physical and cognitive activities relate to brain health for the first time in autosomal dominant frontotemporal lobar degeneration (FTLD). Methods: A total of 105 mutation carriers (C9orf72/MAPT/GRN) and 69 non‐carriers reported current physical and cognitive activities at baseline, and completed longitudinal neurobehavioral assessments and brain magnetic resonance imaging (MRI) scans. Results: Greater physical and cognitive activities were each associated with an estimated >55% slower clinical decline per year among dominant gene carriers. There was also an interaction between leisure activities and frontotemporal atrophy on cognition in mutation carriers. High‐activity carriers with frontotemporal atrophy (−1 standard deviation/year) demonstrated >two‐fold better cognitive performances per year compared to their less active peers with comparable atrophy rates. Discussion: Active lifestyles were associated with less functional decline and moderated brain‐to‐behavior relationships longitudinally. More active carriers “outperformed” brain volume, commensurate with a cognitive reserve hypothesis. Lifestyle may confer clinical resilience, even in autosomal dominant FTLD.
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In familial frontotemporal dementia mutation carriers, greater intensity of physical and cognitive activities is associated with slower clinical decline and rate of atrophy on MRI.
“Evidence suggests that in familial frontotemporal dementia mutation carriers, greater intensity of physical and cognitive activities are associated with slower clinical decline and rate of atrophy on MRI.80”
From Advances and controversies in frontotemporal dementia: diagnosis, biomarkers, and therapeutic considerations (2022) · cites this paper as [80]
The Results section reports that greater baseline physical and cognitive activity were associated with slower clinical decline in mutation carriers. It does not establish slower MRI-measured atrophy: associations with longitudinal brain-volume change did not reach statistical significance. The reported atrophy interactions concern cognitive performance despite comparable volume loss, not a reduced rate of atrophy. Page numbers were not supplied in our copy. (LLM, conf=0.90)
Experimental — accuracy not yet measuredBeneficial lifestyles confer cognitive reserve, slow progressive neurodegeneration, and ameliorate pathological events and phenotypes of neurodegenerative diseases.
“these beneficial lifestyles are also adapted to confer a cognitive reserve, slow progressive neurodegeneration, and ameliorate pathological events and the phenotypes of neurodegenerative diseases.491”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [491]
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Self-citation
- Authors
- Casaletto, K. B., Staffaroni, A. M., Wolf, A., Appleby, B., Brushaber, D., Coppola, G., Dickerson, B., Domoto‐Reilly, K., Elahi, F. M., Fields, J., Fong, J. C., Forsberg, L., Ghoshal, N., Graff‐Radford, N., Grossman, M., Heuer, H. W., Hsiung, G. ‐., Huey, E. D., Irwin, D., Kantarci, K., Kaufer, D., Kerwin, D., Knopman, D., Kornak, J., Kramer, J. H., Litvan, I., Mackenzie, I. R., Mendez, M., Miller, B., Rademakers, R., Ramos, E. M., Rascovsky, K., Roberson, E. D., Syrjanen, J. A., Tartaglia, M. C., Weintraub, S., Boeve, B., Boxer, A. L., Rosen, H., Yaffe, K., & Study, T. A.
- Affiliations
- University of California, San Francisco (US)
- Case Western Reserve University (US)
- Mayo Clinic (US)
- University of California, Los Angeles (US)
- Harvard University (US)
- University of Washington (US)
- Washington University in St. Louis (US)
- University of Pennsylvania (US)
- University of British Columbia (CA)
- Columbia University (US)
- University of North Carolina at Chapel Hill (US)
- The University of Texas Southwestern Medical Center (US)
- University of California San Diego (US)
- University of Alabama at Birmingham (US)
- University of Toronto (CA)
- Mesulam Center for Cognitive Neurology and Alzheimer's Disease Northwestern University Chicago Illinois USA
- Corresponding author
- Casaletto, K. B.
- ORCID
- Casaletto, K. B.
- Staffaroni, A. M.
- Appleby, B.
- Brushaber, D.
- Coppola, G.
- Dickerson, B.
- Domoto‐Reilly, K.
- Elahi, F. M.
- Fields, J.
- Forsberg, L.
- Ghoshal, N.
- Graff‐Radford, N.
- Grossman, M.
- Heuer, H. W.
- Hsiung, G.‐Y.
- Huey, E. D.
- Irwin, D.
- Kantarci, K.
- Kaufer, D.
- Kerwin, D.
- Kornak, J.
- Kramer, J. H.
- Litvan, I.
- Mackenzie, I. R.
- Mendez, M.
- Miller, B.
- Rademakers, R.
- Ramos, E. M.
- Roberson, E. D.
- Syrjanen, J. A.
- Tartaglia, M. C.
- Boeve, B.
- Boxer, A. L.
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2020-01
- Volume
- 16
- Issue
- 1
- Pages
- 91-105
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC6953618
- OpenAlex
- W3000095436
- Cited by
- 48
- References
- 54
- Citations by year
- 2026: 8 · 2025: 5 · 2024: 6 · 2023: 8 · 2022: 7 · 2021: 9 · 2020: 5
- FWCI
- 5.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Alzheimer s & Dementia (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS; (U01AG045390)
- Advancing Research and Treatment in Frontotemporal Lobar Degeneration (U54NS092089, K23AG058752,, L30AG057123)
- Larry L. Hillblom Fellowship (2017-A-004-FEL)
- 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
- C9orf72
- MeSH terms
- Aged, Atrophy, Cognition, Female, Humans, Leisure Activities, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Exercise, Frontotemporal Lobar Degeneration
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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