Traumatic Brain Injury and Risk of Alzheimer’s Disease and Related Dementias in the Population

Article type: Research Article

Authors: Mielke, Michelle M.^{a; b; *} | Ransom, Jeanine E.^a | Mandrekar, Jay^a | Turcano, Pierpaolo^c | Savica, Rodolfo^d | Brown, Allen W.^e

Affiliations: [a] Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA | [b] Department of Epidemiology and Prevention, Wake Forest University School of Medicine, Winston-Salem, NC, USA | [c] Department of Neurology, Mayo Clinic, Jacksonville, FL, USA | [d] Department of Neurology, Mayo Clinic, Rochester, MN, USA | [e] Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN, USA

Correspondence: [*] Correspondence to: Dr. Michelle M. Mielke, Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest University School of Medicine, 525 Vine, 5th floor, Winston-Salem, NC 27101, USA. E-mail: mmielke@wakehealth.edu.

Abstract: Background:Epidemiological studies examining associations between traumatic brain injury (TBI) and Alzheimer’s disease and related dementias (ADRD) have yielded conflicting results, which may be due to methodological differences. Objective:To examine the relationship between the presence and severity of TBI and risk of ADRD using a population-based cohort with medical record abstraction for confirmation of TBI and ADRD. Methods:All TBI events among Olmsted County, Minnesota residents aged > 40 years from 1985–1999 were confirmed by manual review and classified by severity. Each TBI case was randomly matched to two age-, sex-, and non-head injury population-based referents without TBI. For TBI events with non-head trauma, the Trauma Mortality Prediction Model was applied to assign an overall measure of non-head injury severity and corresponding referents were matched on this variable. Medical records were manually abstracted to confirm ADRD diagnosis. Cox proportional hazards models examined the relationship between TBI and severity with risk of ADRD. Results:A total of 1,418 residents had a confirmed TBI (865 Possible, 450 Probable, and 103 Definite) and were matched to 2,836 referents. When combining all TBI severities, the risk of any ADRD was significantly higher for those with a confirmed TBI compared to referents (HR = 1.32, 95% CI: 1.11, 1.58). Stratifying by TBI severity, Probable (HR = 1.42, 95% CI: 1.05, 1.92) and Possible (HR = 1.29, 95% CI: 1.02–1.62) TBI was associated with an increased risk of ADRD, but not Definite TBI (HR = 1.22, 95% CI: 0.68, 2.18). Conclusion:Our analyses support including TBI as a potential risk factor for developing ADRD.

Keywords: Alzheimer’s disease, dementia, epidemiology, Parkinson’s disease, population, traumatic brain injury

DOI: 10.3233/JAD-220159

Journal: Journal of Alzheimer's Disease, vol. 88, no. 3, pp. 1049-1059, 2022