Predicting Depression and Alzheimer Disease Through Major Depressive Disorder Risk Factors

Individuals with depression may be at a greater risk to develop late-onset Alzheimer disease, but a new study suggests depression onset may help predict Alzheimer disease.

Depression is a common comorbidity for patients with late-onset Alzheimer disease, and individuals with depression are at greater risk to develop late-onset Alzheimer disease.1,2 Although the genetic heterogeneity of depression cooccurrence with late-onset Alzheimer disease and genetic etiologies predisposing the comorbid conditions are largely unknown, previous research suggests interactions between the 2 conditions.

Using statistics from a genome-wide association study, investigators created polygenic risk scores (PRS) using datasets from the Religious Orders Society and Rush Memory and Aging Project (ROSMAP, n = 1708) and National Alzheimer’s Coordinating Center (NACC, n = 10,256) as discovery and validation cohorts. The data were used to assess the PRS performance in predicting depression onset in patients with late-onset Alzheimer disease.

Standalone models showed marginal results for predicting depression onset in both ROSMAP (AUC = 0.540) and NACC (AUC = 0.527). Full models—with baseline age, sex, education, and APOEε4 allele count—showed improved prediction of depression onset in both ROSMAP (AUC: 0.606) and NACC (AUC: 0.581). In time-to-event analysis, standalone PRS models showed significant effects in ROSMAP (P = 0.0051), but not in NACC cohort. Full models showed significant performance in predicting depression in late-onset Alzheimer disease for both datasets (P < 0.001 for all).

“This study provided new insights into the genetic factors contributing to depression onset in [late-onset Alzheimer disease] and advanced our knowledge of the genetics underlying the heterogeneity of depression in [late-onset Alzheimer disease],” said the authors.

As individuals with depression are more likely to develop late-onset Alzheimer disease, this suggests treating depression may delay development of Alzheimer disease. Further studies needed to confirm and replicate findings.


1. Upadhya S, Liu H, Luo S, et al. Polygenic risk score effectively predicts depression onset in Alzheimer’s disease based on major depressive disorder risk variants. Front Neurosci. 2022;16:827447.

2. Lyketsos CG, Carrillo MC, Ryan JM, et al. Neuropsychiatric symptoms in Alzheimer’s disease. Alzheimers Dement. 2011;7(5):532-539.