Background: Epidemiological studies linking traumatic brain injury (TBI) and Alzheimer's disease and related conditions (ADRC), including Parkinson's disease, Lewy Body dementia, Frontotemporal dementia, and amyotrophic lateral sclerosis, have yielded conflicting results. These discrepant findings reflect methodological variation in defining TBI, classifying injury severity, and studying clinical cohorts not representative of the broader population. The epidemiology of TBI in military and civilian populations is dominated by the least severe injuries, exposing the greatest number of individuals to potential risk for developing ADRC, yet most previous analysis studying the connection between TBI and ADRC do not include this category of injury severity. The most accurate and reliable study design to determine whether the occurrence of TBI increases risk for the development of ADRC is to identify incident TBI events by medical record review within a defined population and classify each by injury severity, identify matched referents within that same population, and follow both cohorts over time to observe incidence rates of ADRC. The Mayo Clinic has been at the forefront of population-based epidemiological research related to both TBI and ADRC and has a unique capability to study their association.Hypothesis: We hypothesize that individuals in the population with a confirmed TBI will not be at increased risk of developing ADRC compared to age- and sex-matched referents without a TBI, after controlling for non-head injuries.Specific Aims: Specific Aim 1: Increase the size of the existing incident cohort of individuals aged 30 years and older who experience TBI between 1985 and 1999 in the population of Olmsted County, Minnesota. Specific Aim 2: Classify each TBI event by injury severity and determine the number of TBI events per individual. Specific Aim 3: Match, by age and sex, each individual with a confirmed TBI to a population-based referent without a TBI and account for non-head trauma. Specific Aim 4: Longitudinally determine whether TBI, including number of events and severity, is associated with subsequent risk of ADRC after accounting for non-head trauma.Research Strategy: All aims will utilize the Rochester Epidemiology Project (REP) medical records linkage system. The proposed epidemiological analysis is a population-based medical record review study. Aims 1-3 will expand the existing REP TBI cohort of 812 individuals aged 30 years and older who met record-review TBI criteria between 1985 and 2000 and age- and sex-matched individuals without a TBI during this timeframe. Aim 4 will determine diagnoses of ADRC among the expanded cohort and will also determine whether TBI increases the risk of ADRC within the population. Trained abstractors will complete the medical record abstraction, and we estimate that at the conclusion of this study we will have identified and confirmed at least 2,235 individuals aged 30 and older with any severity of TBI and age- and sex-matched them to 2,235 population-based individuals without a TBI. Median follow-up on these individuals is approximately 15 years. Individuals will be followed from the date of the index TBI event forward until the earliest date of (a) the first clinical diagnosis of an ADRC; (b) the last medical visit in Olmsted County; or (c) death. The risk of an ADRC in those with a TBI event will be compared directly to those without a TBI event using Cox proportional hazards models and adjusting for non-head trauma.
|Effective start/end date||9/15/15 → 9/14/18|
- Congressionally Directed Medical Research Programs: $794,377.00