Head injury as a risk factor for Alzheimer's disease: the evidence 10 years on; a partial replication

Abstract

Objective: To determine, using a systematic review of case-control studies, whether head injury is a significant risk factor for Alzheimer's disease. We sought to replicate the findings of the meta-analysis of Mortimer et al (1991). Methods: A predefined inclusion criterion specified case-control studies eligible for inclusion. A comprehensive and systematic search of various electronic databases, up to August 2001, was undertaken. Two independent reviewers screened studies for eligibility. Fifteen case-control studies were identified that met the inclusion criteria, of which seven postdated the study of Mortimer et al. The most convincing evidence to date in support of an association between head injury and Alzheimer's disease is the meta-analysis by Mortimer et al of seven case-control studies conducted before 1991. 5 In this study, the raw data for each case-control study were collected directly from the original authors. Mortimer et al reported a relative risk of 1.82 (95% confidence interval (CI) 1.26 to 2.67) for head injury with a loss of consciousness. 5 The relative risk, when adjusted for a family history of dementing illness, education, and alcohol consumption, remained significant but was only true for males (2.67, 95% CI 1.64 to 4.41) and not females (0.85, 95% CI 0.43 to 1.70).In view of the equivocal findings from Mortimer et al's study, 5 and knowing that further case-control studies have been reported, we aimed to replicate the findings of Mortimer et al using a systematic review of case-control studies conducted in the past 10 years. We also sought to review the evidence for a relation between APOE status and head injury as risk factors for Alzheimer's disease. We have primarily relied on the data presented in published papers and, consequently, were unable to analyse covariate risk factors such as alcohol consumption, family history of dementing illness, and education. METHODS Inclusion criteriaThis study identified case-control studies that reported on head injury, or the interaction between head injury and APOE status, as risk factors for Alzheimer's disease. The inclusion criteria were developed on the basis of a comprehensive review of the literature, and consideration of the criteria used by Mortimer et al, 5 in order to identify the major sources of potential bias and the measures taken in an attempt to minimise such bias. Seven factors were identified as essential requirements for entry into this study:(1) Head injury with loss of consciousness: We were interested in head injury of a severity that occurs infrequently and that is likely to produce neurological effect. Therefore, we required that studies defined head trauma in terms of the presence of loss of consciousness. By excluding lesser head injuries, studies should be less exposed to recall bias and less likely to find an association that merely reflects a consequence of the prodrome of the dementia. No time restriction was placed on the period of unconsciousness.(2) Matching of case and control subjects: Two different types o...

Long-Term Cognitive Correlates of Traumatic Brain Injury across Adulthood and Interactions with APOE Genotype, Sex, and Age Cohorts

“…Furthermore, oestrogen therapy has been found to improve outcomes following cerebral ischemia and TBI in experimental models (Roof & Hall, 2000;Stein, 2001). Previous reports also indicate greater history of TBI amongst males with Alzheimer's disease, but not in females (Fleminger et al, 2003;Mortimer et al, 1991). While our study suggests that cognitive outcomes are poorer for older females with TBI history, it is not clear whether this will trigger or exacerbate pathological decline and dementia.…”

A Novel, Ultrasensitive Assay for Tau: Potential for Assessing Traumatic Brain Injury in Tissues and Biofluids

“…15,35 Epidemiological evidence, which includes the appearance of fibrillary Ab plaques in the brain several years following a single sTBI, suggests that TBI may be an risk factor for the development of AD and may accelerate the pathophysiological processes leading to AD. 3,[7][8][9]83 Although there exists a causal connection, there are clinical and histopathological differences between AD and TBI, 8 including the distribution of P-tau immunoreactive NFTs, suggesting that the neurophysiological and neuropathological mechanisms leading to the increased risk for neurodegenerative diseases following TBI are highly complex.…”

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.…”