Depression and Risk of Alzheimer's Disease: A Mendelian Randomization Study.

INTRODUCTION/

BACKGROUND

Recent studies show that depression often occurs years before Alzheimer's disease onset in many older adults. However, it is unclear whether this link reflects a causal relationship.

MATERIALS AND

METHODS

Summary statistics from Genome-Wide Association Studies (GWAS) of depression and Alzheimer's disease were utilized. Data associated with broad depression included up to 407,746 Europeans, and data associated with major depression disorder included up to 480,359 Europeans; the corresponding Alzheimer's disease associations from consortia included up to 488,285 European participants in the UK Biobank. Two-sample Mendelian randomization analyses served as our primary approach, with additional three-sample analyses performed to validate the findings.

RESULTS

In the sample of 407,746 participants, genetically predicted levels of broad depression showed no significant association with Alzheimer's disease risk (odds ratio, 1.00007; p = 0.908). As for the sample of 480,359 participants associated with major depressive disorder, the result was consistent (odds ratio, 0.99918, p = 0.138) with findings from broad depression. Secondary analyses present consistent results with primary findings. Statistically significant bias from pleiotropy or genetic confounding was not detected in sensitivity analyses.

DISCUSSION: The study's findings do not support a causal role of depression in AD and are more consistent with depression reflecting early disease processes or shared mechanisms.

CONCLUSION

This study's Mendelian randomization approach revealed no causal relationship between depression and Alzheimer's disease, consistent with depression reflecting early disease manifestations rather than a direct causal factor, and hinting at possible shared pathological processes in both conditions.