Relative risk for Alzheimer disease based on complete family history.
Level 3 - non-randomized controlled study
Retrospective population-based genealogical cohort study linked to death records
PubMed 30867271 · doi:10.1212/WNL.0000000000007231
What was done
Researchers linked a genealogical database of Utah pioneers from the 1800s to Utah death certificates to calculate relative risks (RR) of Alzheimer disease (AD) across specific family history constellations, assessing first-degree (FDR), second-degree (SDR), and third-degree (TDR) relatives.
What was found
AD risk increased with affected FDRs: >=1 FDR had an RR of 1.73 (95% CI 1.59-1.87), >=2 FDRs had an RR of 3.98 (95% CI 3.26-4.82), >=3 FDRs had an RR of 2.48 (95% CI 1.07-4.89), and >=4 FDRs had an RR of 14.77 (95% CI 5.42-32.15). Affected SDRs added risk (FDR = 1 with SDR = 2: RR 21.29, 95% CI 5.80-54.52). Having >=3 affected TDRs in the absence of affected FDRs and SDRs also elevated risk (RR 1.43, 95% CI 1.21-1.68). Men had higher risks than women with equivalent family histories, and risk was elevated with >=1 affected FDR regardless of the relative's age at death, with mixed evidence regarding maternal versus paternal inheritance.
Why it matters
This demonstrates that inherited risk for Alzheimer disease extends into second- and third-degree relatives rather than being confined to immediate family. Collecting multigenerational family histories can improve clinical risk stratification.
Limits
The total sample size and case counts are not reported in the abstract. Outcomes relied on death certificate data, which are vulnerable to misclassification and underreporting of Alzheimer disease. The cohort consists of a historical Utah pioneer population, which may limit generalizability to racially and ethnically diverse modern populations.
Cited by
- context Risk for mental health disorders, Parkinson's disease, and Alzheimer's disease shows stronger maternal than paternal inheritance.