Depression may significantly increase the risk of developing dementia later in life, according to a large analysis of global studies involving more than 3 million people.
The analysis combined data from 25 studies to examine how the timing of depression diagnosis—midlife (typically ages 18 to 64) or late life (65 and older)—affects dementia risk. Individuals with late-life depression had nearly double the risk of developing dementia compared to those without depression, with a pooled hazard ratio (HR) of 1.95. Those with midlife depression had a 56% increased risk (HR = 1.56).
Across the 18 studies on late-life depression, more than 900,000 participants and 7,500 dementia cases were included. The 7 studies on midlife depression covered more than 2.5 million individuals and over 270,000 dementia cases. Researchers used random-effects models to account for study differences and found consistent increases in dementia risk across both groups.
In late-life depression, the risk was stronger in studies with shorter follow-up periods, suggesting that some cases may reflect early symptoms—or prodromes—of dementia. Studies with follow-up shorter than 5.6 years reported higher risk estimates than those with longer follow-up.
Still, elevated dementia risk persisted even in studies with extended follow-up, supporting the idea that depression may also be an independent risk factor. Risk estimates were similar regardless of whether depression was identified through self-reports or clinical diagnosis.
Regional analyses showed higher risk estimates in Asian populations, but differences across regions were not statistically significant. Whether studies adjusted for cardiovascular disease, stroke, or genetic factors like APOE did not substantially alter the findings.
While previous research focused largely on late-life depression, this analysis confirmed that midlife depression also poses a significant risk. These findings align with recent public health strategies that emphasize mental health care during midlife as a key step in dementia prevention.
The study highlights the importance of early screening and sustained treatment for depression across the adult lifespan. Although biological pathways remain under investigation, potential mechanisms include chronic inflammation, hormonal changes, vascular dysfunction, and reduced brain plasticity.
Further research is needed to determine whether treating depression can help prevent or delay dementia onset. Standardizing how depression is diagnosed—and incorporating neuroimaging and biomarkers—could improve understanding of its role in cognitive decline.
The authors declared no competing interests.
Source: eClinicalMedicine
