Head injury and risk of Alzheimer's disease by apolipoprotein E genotype.
Level 4 - case-series / case-control
Case-control study
PubMed 9290497 · doi:10.1093/oxfordjournals.aje.a009290
What was done
Researchers conducted a case-control study between 1987 and 1995 among enrollees of a Seattle-based health maintenance organization. They assessed prior head injury involving loss of consciousness via proxy informants for 349 patients with probable Alzheimer's disease and 342 age- and sex-matched control subjects. In a genotyped subgroup of 230 cases and 309 controls, they evaluated whether the risk associated with head injury varied by presence of the APOE-epsilon 4 allele.
What was found
Prior head injury with loss of consciousness was reported in 32 of 349 cases and 16 of 342 controls, reflecting an elevated risk of Alzheimer's disease (OR = 2.1, 95% CI 1.1–3.8). Stratified by sex, elevated risk was present in men (OR = 4.2, 95% CI 1.5–11.5) but not women (OR = 1.1, 95% CI 0.5–2.6). In the genotyped subset, the association did not differ significantly by APOE-epsilon 4 status: OR = 3.1 (95% CI 0.7–14.6) for individuals with at least one e4 allele versus OR = 2.0 (95% CI 0.8–5.2) for those without e4.
Why it matters
These findings suggest that head trauma with loss of consciousness acts as an independent risk factor for Alzheimer's disease rather than synergistically amplifying risk in carriers of the APOE-epsilon 4 genotype.
Limits
Head injury history was collected retrospectively from proxy informants, introducing potential recall bias. Head injury with loss of consciousness was relatively rare in the sample (32 cases and 16 controls), leading to wide confidence intervals in stratified analyses. Genotyping was available for only a subset of participants (230 cases and 309 controls).
Cited by
- contradicts Individuals with traumatic brain injury who carry the APOE4 allele have a 10 to 20 times increased risk of developing Alzheimer's disease depending on allele count.