Clinical implications of head trauma in frontotemporal dementia and primary progressive aphasia.


Journal

Alzheimer's research & therapy
ISSN: 1758-9193
Titre abrégé: Alzheimers Res Ther
Pays: England
ID NLM: 101511643

Informations de publication

Date de publication:
29 Aug 2024
Historique:
received: 22 03 2024
accepted: 11 08 2024
medline: 31 8 2024
pubmed: 31 8 2024
entrez: 29 8 2024
Statut: epublish

Résumé

Traumatic brain injury (TBI) and repetitive head impacts (RHI) have been linked to increased risk for multiple types of neurodegenerative disease, higher dementia risk, and earlier age of dementia symptom onset, suggesting transdiagnostic implications for later-life brain health. Frontotemporal dementia (FTD) and primary progressive aphasia (PPA) represent a spectrum of clinical phenotypes that are neuropathologically diverse. FTD/PPA diagnoses bring unique challenges due to complex cognitive and behavioral symptoms that disproportionately present as an early-onset dementia (before age 65). We performed a detailed characterization of lifetime head trauma exposure in individuals with FTD and PPA compared to healthy controls to examine frequency of lifetime TBI and RHI and associated clinical implications. We studied 132 FTD/PPA (age 68.9 ± 8.1, 65% male) and 132 sex-matched healthy controls (HC; age 73.4 ± 7.6). We compared rates of prior TBI and RHI (contact/collision sports) between FTD/PPA and HC (chi-square, logistic regression, analysis of variance). Within FTD/PPA, we evaluated associations with age of symptom onset (analysis of variance). Within behavioral variant FTD, we evaluated associations with cognitive function and neuropsychiatric symptoms (linear regression controlling for age, sex, and years of education). Years of participation were greater in FTD/PPA than HC for any contact/collision sport (8.5 ± 6.7yrs vs. 5.3 ± 4.5yrs, p = .008) and for American football (6.2yrs ± 4.3yrs vs. 3.1 ± 2.4yrs; p = .003). Within FTD/PPA, there were dose-dependent associations with earlier age of symptom onset for TBI (0 TBI: 62.1 ± 8.1, 1 TBI: 59.9 ± 6.9, 2 + TBI: 57.3 ± 8.4; p = .03) and years of American football (0yrs: 62.2 ± 8.7, 1-4yrs: 59.7 ± 7.0, 5 + yrs: 55.9 ± 6.3; p = .009). Within bvFTD, those who played American football had worse memory (z-score: -2.4 ± 1.2 vs. -1.4 ± 1.6, p = .02, d = 1.1). Lifetime head trauma may represent a preventable environmental risk factor for FTD/PPA. Dose-dependent exposure to TBI or RHI influences FTD/PPA symptom onset and memory function in bvFTD. Clinico-pathological studies are needed to better understand the neuropathological correlates linking RHI or TBI to FTD/PPA onset and symptoms.

Sections du résumé

BACKGROUND BACKGROUND
Traumatic brain injury (TBI) and repetitive head impacts (RHI) have been linked to increased risk for multiple types of neurodegenerative disease, higher dementia risk, and earlier age of dementia symptom onset, suggesting transdiagnostic implications for later-life brain health. Frontotemporal dementia (FTD) and primary progressive aphasia (PPA) represent a spectrum of clinical phenotypes that are neuropathologically diverse. FTD/PPA diagnoses bring unique challenges due to complex cognitive and behavioral symptoms that disproportionately present as an early-onset dementia (before age 65). We performed a detailed characterization of lifetime head trauma exposure in individuals with FTD and PPA compared to healthy controls to examine frequency of lifetime TBI and RHI and associated clinical implications.
METHODS METHODS
We studied 132 FTD/PPA (age 68.9 ± 8.1, 65% male) and 132 sex-matched healthy controls (HC; age 73.4 ± 7.6). We compared rates of prior TBI and RHI (contact/collision sports) between FTD/PPA and HC (chi-square, logistic regression, analysis of variance). Within FTD/PPA, we evaluated associations with age of symptom onset (analysis of variance). Within behavioral variant FTD, we evaluated associations with cognitive function and neuropsychiatric symptoms (linear regression controlling for age, sex, and years of education).
RESULTS RESULTS
Years of participation were greater in FTD/PPA than HC for any contact/collision sport (8.5 ± 6.7yrs vs. 5.3 ± 4.5yrs, p = .008) and for American football (6.2yrs ± 4.3yrs vs. 3.1 ± 2.4yrs; p = .003). Within FTD/PPA, there were dose-dependent associations with earlier age of symptom onset for TBI (0 TBI: 62.1 ± 8.1, 1 TBI: 59.9 ± 6.9, 2 + TBI: 57.3 ± 8.4; p = .03) and years of American football (0yrs: 62.2 ± 8.7, 1-4yrs: 59.7 ± 7.0, 5 + yrs: 55.9 ± 6.3; p = .009). Within bvFTD, those who played American football had worse memory (z-score: -2.4 ± 1.2 vs. -1.4 ± 1.6, p = .02, d = 1.1).
CONCLUSIONS CONCLUSIONS
Lifetime head trauma may represent a preventable environmental risk factor for FTD/PPA. Dose-dependent exposure to TBI or RHI influences FTD/PPA symptom onset and memory function in bvFTD. Clinico-pathological studies are needed to better understand the neuropathological correlates linking RHI or TBI to FTD/PPA onset and symptoms.

Identifiants

pubmed: 39210451
doi: 10.1186/s13195-024-01553-1
pii: 10.1186/s13195-024-01553-1
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

193

Subventions

Organisme : NIA NIH HHS
ID : P30AG062422
Pays : United States
Organisme : NIA NIH HHS
ID : P30AG062422
Pays : United States
Organisme : NIA NIH HHS
ID : R01AG032289
Pays : United States
Organisme : Larry L. Hillblom Foundation
ID : 2014-A-004-NET

Informations de copyright

© 2024. The Author(s).

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Auteurs

Breton M Asken (BM)

Department of Clinical and Health Psychology, University of Florida, 1Florida Alzheimer's Disease Research Center, Fixel Institute for Neurological Diseases, PO Box 100165, Gainesville, FL, 32610, USA. basken8@phhp.ufl.edu.

Jessica M Bove (JM)

Department of Clinical and Health Psychology, University of Florida, 1Florida Alzheimer's Disease Research Center, Fixel Institute for Neurological Diseases, PO Box 100165, Gainesville, FL, 32610, USA.

Russell M Bauer (RM)

Department of Clinical and Health Psychology, University of Florida, 1Florida Alzheimer's Disease Research Center, Fixel Institute for Neurological Diseases, PO Box 100165, Gainesville, FL, 32610, USA.

Jeremy A Tanner (JA)

Department of Neurology, Biggs Institute for Alzheimer's and Neurodegenerative Diseases South Texas Alzheimer's Disease Research Center, University of Texas Health - San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, 78229, USA.

Kaitlin B Casaletto (KB)

Department of Neurology, Weill Institute for Neurosciences Memory and Aging Center, University of California, San Francisco, UCSF Alzheimer's Disease Research Center, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA.

Adam M Staffaroni (AM)

Department of Neurology, Weill Institute for Neurosciences Memory and Aging Center, University of California, San Francisco, UCSF Alzheimer's Disease Research Center, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA.

Lawren VandeVrede (L)

Department of Neurology, Weill Institute for Neurosciences Memory and Aging Center, University of California, San Francisco, UCSF Alzheimer's Disease Research Center, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA.

Michael L Alosco (ML)

Department of Neurology, Boston University, Boston University Alzheimer's Disease Research Center and CTE Center, 73 E. Concord Street, Boston, MA, 02118, USA.

Jesse B Mez (JB)

Department of Neurology, Boston University, Boston University Alzheimer's Disease Research Center and CTE Center, 73 E. Concord Street, Boston, MA, 02118, USA.

Robert A Stern (RA)

Department of Neurology, Boston University, Boston University Alzheimer's Disease Research Center and CTE Center, 73 E. Concord Street, Boston, MA, 02118, USA.

Bruce L Miller (BL)

Department of Neurology, Weill Institute for Neurosciences Memory and Aging Center, University of California, San Francisco, UCSF Alzheimer's Disease Research Center, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA.

Lea T Grinberg (LT)

Department of Neurology, Weill Institute for Neurosciences Memory and Aging Center, University of California, San Francisco, UCSF Alzheimer's Disease Research Center, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA.

Adam L Boxer (AL)

Department of Neurology, Weill Institute for Neurosciences Memory and Aging Center, University of California, San Francisco, UCSF Alzheimer's Disease Research Center, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA.

Maria Luisa Gorno-Tempini (ML)

Department of Neurology, Weill Institute for Neurosciences Memory and Aging Center, University of California, San Francisco, UCSF Alzheimer's Disease Research Center, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA.

Howie J Rosen (HJ)

Department of Neurology, Weill Institute for Neurosciences Memory and Aging Center, University of California, San Francisco, UCSF Alzheimer's Disease Research Center, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA.

Gil D Rabinovici (GD)

Department of Neurology, Weill Institute for Neurosciences Memory and Aging Center, University of California, San Francisco, UCSF Alzheimer's Disease Research Center, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA.

Joel H Kramer (JH)

Department of Neurology, Weill Institute for Neurosciences Memory and Aging Center, University of California, San Francisco, UCSF Alzheimer's Disease Research Center, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA.

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