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Head Injury Tied to Long-term Cognitive Decline, Dementia Risk

Nancy A. Melville
November 05, 2018

A history of head injury is common in the United States and is associated with steeper long-term cognitive decline and a greater risk for dementia over the following 20 years than not having a head injury, new research suggests.

Although head injury is known to be associated with short-term cognitive impairment and incident dementia, research on the longer-term cognitive effects has been lacking. For the current analysis, investigators assessed data from participants in the ongoing Atherosclerosis Risk in Communities (ARIC) trial.

"Our study adds to the literature by providing evidence from a large cohort of more than 13,000 individuals followed for a median of 20 years that head injury is common, nearly 25% in this population, and is associated with greater long-term cognitive decline and increased risk of incident dementia," lead author Andrea L. C. Schneider, MD, PhD, Johns Hopkins University, Baltimore, Maryland, told Medscape Medical News.

The findings were presented here at ANA 2018: the 143rd Annual Meeting of the American Neurological Association.

20 Years of Data

ARIC is an ongoing prospective cohort study of more than 15,000 adults aged 45 to 65 years from four US communities. The new analysis included the 13,192 participants who were in the study at its first cognitive assessment, which was conducted from 1990 to 1992. The results of this assessment were considered baseline for the current analysis.

To evaluate the participants' prospective cognitive function over time, a global cognitive Z score was used to represent the results of three cognitive assessments measured during the course of the study, at baseline, from 1996 to 1998, and from 2011 to 2013.

During a median follow-up of 20 years, 24% of the participants experienced at least one head injury, determined on the basis of self-report and emergency department/hospitalization ICD-9 codes. These injuries ranged from mild concussion, with or without loss of consciousness, to moderate/severe traumatic brain injury.

After adjusting for factors such as age, sex, race, hypertension, and stroke, results showed that decreases in cognitive decline were observed in both the participants who had had head injuries and those who had not. Those sustaining at least one or more head injuries showed significantly greater cognitive decline (-1.00; 95% confidence interval [CI], -1.06 to -0.95) than those who had not had a head injury (-0.87; 95% CI, -0.91 to -0.83; difference, -0.13).

In clinical terms, the increased decline for those with head injury "is equivalent to a person without head injury being approximately 4 years older at study baseline," Schneider noted.

There were 1295 cases of incident dementia overall, determined by using neuropsychological tests, telephone interviews, and hospitalization/death certificate codes. These included 895 patients among those without head injury and 400 patients who had had a head injury.

The median time from head injury to dementia in the head injury group was 17 years. The participants who experienced a head injury showed an increased risk for incident dementia (hazard ratio [HR], 1.54; 95% CI, 1.37 to 1.74) after a multivariate adjustment for key risk factors.

Of those with head injuries, 25% had had more than one head injury. In addition, a dose-response association was observed, such that a greater number of head injuries was associated with greater cognitive decline and incident dementia risk (P < .001).

In response to a question from the audience, Schneider underscored that the study did adjust for patients'apolipoprotein E (APOE) genotype, which significantly increases the risk for Alzheimer's disease.

"We did look at the effect of APOE genotype but did not see any effect on modification for either cognitive decline or dementia," she said.

Second Study

As reported in a research letter by Schneider and her team that was published in September in the New England Journal of Medicine, the prevalence of head injury in the United States from 2011 to 2014 was 16%. The investigators used a nationally representative sample from the National Health and Nutrition Examination Survey, which included data from these years for community-dwelling US adults aged 40 years and older.

Estimates from the data suggested a higher risk among men (20.0%) than women (12%) and among non-Hispanic white respondents (18.0%) than non-Hispanic black respondents (8.9%).

Risk factors associated with head injury included smoking, fair to poor health, sleep disorders, heavy alcohol consumption, a history of stroke, and depressive symptoms.

"Approximately 23 million US adults 40 years of age or older reported a history of head injury with loss of consciousness," the authors write.

"The high prevalence of head injury in the general population and its links with neurologic and psychiatric conditions suggest that research into the causes and consequences of head injury in the general population and in subgroups would be valuable," they add.

The findings from the new study further add to the understanding of the long-term effects of those injuries, said senior author Rebecca Gottesman, MD, PhD, professor of neurology at Johns Hopkins University.

The research letter study "shows the incredibly high frequency of even mild head injury in the US; and now this new study suggests that these minor injuries are associated with steeper cognitive decline compared to those who don't have head injuries," Gottesman told Medscape Medical News.

'Confirms and Extends Other Work'

Asked to comment, Ramon Diaz-Arrastia, MD, PhD, associate director for clinical research in the Center for Neurodegeneration and Repair at the University of Pennsylvania, Philadelphia, agreed that the study contributes important new data on the longer-term effects of head injury.

"I think the work is terrific and both confirms and extends on other work on this issue that has been emerging over the past several years," he told Medscape Medical News.

"It is clear now that there is a modest increased risk of late-life dementia in those who have suffered a traumatic brain injury in early or midlife. The increased relative risk is modest, in the range of 1.5 to 2 times, but since late-life dementia is so common, the absolute numbers are quite large," he said.

Further research is needed to better understand the specific mechanisms behind the longer-lasting cognitive effects, Diaz-Arrasta added.

"What remains to be determined is, what is the pathophysiology of this TBI [traumatic brain injury]–associated dementia?" he asked. "Is it an acceleration of Alzheimer's type pathology? Or is it something else related to vascular pathology, inflammation, Lewy bodies, etc?"

Dr Schneider has received funding from the National Institutes of Health's National Institute of Neurological Disorders and Stroke. Dr Gottesman is an associate editor of the journal Neurology. Dr Diaz-Arrasta has disclosed no relevant financial relationships.

Reviewed on 11/5/2018

SOURCE: Medscape, November 05, 2018. ANA 2018: 143rd Annual Meeting of the American Neurological Association. Abstract 187, presented October 21, 2018.

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