A cross-sectional analysis found that depressive symptoms were not consistently associated with amyloid pathology in older adults with normal cognition but were linked to a lower likelihood of amyloid pathology in those with mild cognitive impairment.
In the study, published in JAMA Psychiatry, investigators recruited 12,769 participants from the Amyloid Biomarker Study. They pooled data from 49 research centers, population-based studies, and memory clinics across 95 locations. The participants ranged in age from 34 to 100 years, and data was collected between 2012 and 2024.
Among individuals with normal cognition (NC; mean age = 68.6 years, 58.2% female), 9.6% exhibited depressive symptoms and 27.2% had evidence of amyloid pathology. Analysis showed no significant association between depressive symptoms and amyloid pathology (odds ratio [OR] = 1.13, 95% confidence interval [CI] = 0.90–1.40, P = .29).
In contrast, the participants with mild cognitive impairment (MCI; mean age = 70.2 years, 49% female) presented a different pattern. Depressive symptoms were observed in 27.3% of the participants in this group, whereas 55.8% showed amyloid pathology. The investigators found that depressive symptoms were linked to a lower likelihood of amyloid pathology (OR = 0.73, 95% CI = 0.61–0.89, P = .001).
The investigators also explored subgroup effects related to APOE epsilon 4 status—an important genetic risk factor for Alzheimer's disease. Among participants with NC, depressive symptoms were associated with a higher prevalence of amyloid pathology in APOE epsilon 4 noncarriers (mean difference = 5.0%, 95% CI = 1.0–9.0, P = .02) but not in APOE epsilon 4 carriers. This association did not hold in participants with MCI.
"These findings suggest that mechanisms other than amyloid accumulation may underlie the presence of depressive symptomatology in late life," wrote lead study author Wietse A. Wiels, MD, of the Faculty of Medicine and Pharmacy at Vrije Universiteit Brussel in Belgium, and colleagues.
The large-scale data set and harmonized approach provided robust insights into the complex relationship between depressive symptoms and amyloid pathology. Limitations included the study's cross-sectional nature, which precluded causal inference.
The investigators highlighted the need for continued research to explore alternative mechanisms that contribute to depressive symptoms in older adults.
Full disclosures are detailed in the study.
