Traumatic Brain Injury Tied to Accelerated Alzheimer's Risk

Pauline Anderson

November 12, 2020

Abdalla Z. Mohamed

Patients with a history of traumatic brain injury (TBI) are at increased risk for dementia-related pathology, including more amyloid deposition and less cortical thickness, compared to those without TBI, new research suggests.

Results showed that TBI accelerated the onset of cognitive impairment by about 4 years.

The study is believed to be the first to investigate the effect of TBI history on Alzheimer's disease (AD) pathology in those at high risk for the disease, lead investigator Abdalla Z. Mohamed, PhD candidate, Functional Neuroimaging and Brain Injury Laboratory, Queensland Brain Institute, University of Queensland, Brisbane, Australia, noted.

"Close monitoring of patients post-TBI may allow for early prevention strategies and early intervention to improve the quality of life of those suspected to be on the Alzheimer's disease continuum," Mohamed told Medscape Medical News.

The findings were presented at the virtual Alzheimer's Association International Conference Neuroscience Next (AAIC-NN) meeting.

An Important Risk Factor

Among individuals older than 65 years, AD is the most common cause of dementia. And AD is the second leading cause of death in Australia, but so far, the search for effective treatments to prevent or slow the development of AD has been "unfruitful," Mohamed said.

Major symptoms of AD often present at an advanced stage of the disease. However, expression of its main pathological features, including the accumulation of β-amyloid (Aβ) plaques, tau tangles, and neural loss, may begin years to decades before the onset of obvious clinical symptoms.

Identifying early biomarkers and pathologies in those at risk for AD "might enable timely interventions that alter or mitigate against the course of the disease," said Mohamed.

TBI has emerged as an important risk factor for AD. Experiencing a moderate TBI more than doubles the risk for dementia, and a severe TBI is associated with a 4.5 times greater risk for dementia, Mohamed noted.

However, the mechanism underlying this association is poorly understood, he added.

For the current study, investigators downloaded 241 datasets from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The data were collected from 14 different sites in North America.

The researchers divided the datasets into groups based on having or not having a self-reported history of TBI (mild, moderate, or severe, including concussion) and stratified them by clinical dementia rating (CDR) score using neuropsychological testing. A CDR score of 0 was considered "normal" and a score of 0.5 or greater signified that the participants had signs of dementia.

Patients were also stratified using PET imaging with florbetapir to assess amyloid status.

After excluding amyloid-negative participants, the study included 155 patients over age 65.

Researchers quantified group differences in cortical morphometry using the standard uptake value ratio (SUVr) method. In all analyses, they corrected for age, gender, education, and APOE-4 status.

Plaque Build-Up

Results showed a number of differences between the participants with TBI and those without. Participants with TBI had increased cortical amyloid deposition and those with TBI plus signs of dementia had an onset of cognitive impairment about 4 years earlier.

In amyloid-positive patients, those with TBI had increased amyloid deposition at locations following the same amyloid pathology as patients with AD. In addition, the TBI group had reduced cortical thickness.

"While this study doesn't directly shed light on the mechanisms tying TBI to AD, it clearly shows that increased Aβ-plaque build-up in the brain triggered by a traumatic brain injury plays an important role in the development of the pathology and symptoms associated with AD," Mohamed said. 

The investigators then tried to reduce the contribution of differences in cognitive status by comparing participants with dementia (17 with a history of TBI, 17 without a history of TBI) matched for Mini-Mental State Examination (MMSE) scores.

This analysis showed increased amyloid deposition (cortical SUVr 1.65 vs 1.51; P = .05) in the TBI group, as well as earlier onset of cognitive impairment (64.8 years vs 68.8 years; P < .001).

A New Piece of the Puzzle

Commenting on the study for Medscape Medical News, Heather Snyder, PhD, vice president of medical and scientific operations, Alzheimer's Association, said it sheds new light on how TBI "may make a person more vulnerable to increased risk" for AD.

What is especially interesting about the study is that it's taking work in this area "a step further in trying to understand what might be some of the biology that's at play," said Snyder, who was not involved with the research.

She added this is one of the larger studies of its kind and included "a fairly decent number of participants."

The US Center for Disease Control and Prevention estimates that about 1.5 million Americans experience a TBI every year; and TBI may affect the immune system as well as changes in tau protein, one of the hallmarks of AD, Snyder said.

Exactly how those intersect and "how that plays out in elevated amyloid" in this study "is really an interesting question," she added.

However, while this study adds a new piece to the AD puzzle, "understanding the full puzzle is ultimately what's going to tell us who is at greater risk," said Snyder.

The study was funded by the Motor Accident Insurance Commission in Queensland. Data collection and sharing for the project was funded by the ADNI.

AAIC-NN. Presented November 10, 2020. Poster 48713.

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