Head Trauma as a Risk Factor for Alzheimer's Disease: A Collaborative Re-Analysis of Case-Control Studies

Abstract

A re-analysis of the data from 11 case-control studies was performed to investigate the association between head trauma and Alzheimer's disease (AD). To increase comparability of studies, exposures were limited to head trauma with loss of consciousness (hereafter referred to as 'head trauma') and comparisons were restricted to community (versus hospital) controls. Test for heterogeneity across studies was negative; consequently, data were pooled in subsequent analyses. The pooled relative risk for head trauma was 1.82 (95% confidence interval: 1.26-2.67). Stratified analyses showed stronger associations in cases without a positive family history of dementia and in males (versus females). Adjustment of the pooled relative risk for family history of dementia, education and alcohol consumption did not alter significantly the association between head trauma and AD. There was no interaction effect between head trauma and family history of dementia, suggesting that these risk factors operate independently. Mean age of onset was not significantly different in cases with a history of head trauma compared to cases without such a history. The findings of the pooled analysis support an association between reported head trauma and AD.

Traumatic Brain Injury As a Risk Factor for Alzheimer’s Disease: Current Knowledge and Future Directions

“…We discuss the factors that influence the strength and direction of the relationship between TBI and Alzheimer's disease, and the implications of this body of research for patient care and future research. is associated with increased risk for degenerative neurocognitive conditions resulting in dementia [11][12][13][14][15]. AD is by far the most commonly diagnosed subtype of dementia, accounting for up to 80% of all dementia cases [16].…”

Impact of Age on Long-Term Recovery From Traumatic Brain Injury

“…Nonetheless, at least 2 metaanalyses incorporating a number of different study designs have provided partial support for an association between TBI and acceleration or development of later dementia. 23,24 In a longitudinal study, indirect support for this relationship might accrue if older patients with TBI experienced progressive decline after initial recovery compared to younger participants who may be more likely to be stable or continue to recover. The purpose of this study is to determine whether increasing age at injury is associated with a greater risk of progressive functional decline.…”

On the issue of transmissibility of Alzheimer disease

“…Increased stress hormone levels were suggested as one possible causal factor. 47,61 Traumatic brain injury (TBI) may even trigger neuropathologically detectable abnormal tau and amyloid deposition. 62,63 One surely could argue that general anesthesia, TBI or transmissibility between individuals might be the causal factor beneath the observed association.…”