Although the risk of developing dementia doubles in older adults diagnosed with major depression vs those without the disorder, the mechanism is unclear. Most previous studies have examined 1 or 2 biomarkers when investigating this question. However, in the current study, the investigators tested 242 blood-based proteins and also examined structural brain abnormalities. A total of 80 adults with remitted late-life depression were enrolled; 36 had MCI (67% women; mean age, 73.4 years), and 44 had normal cognitive function (87% women; mean age, 72.4 years). Whole-blood samples were taken from all participants and tested for the proteins associated with pathways for cancer, cardiovascular disease, metabolic syndrome, psychiatric disorders, and neurodegenerative disorders.
In addition, positron emission tomography using Pittsburgh compound B (PiB-PET) was used to measure brain amyloid-beta (Aβ) deposition, thought to be involved in Alzheimer’s disease, and MRI scans were used to measure white matter hyperintensity and whole-brain gray matter atrophy volumes. Results showed that the participants who had both depression and MCI had significant “differential expression” of 24 proteins used in the regulation of immune-inflammatory activity (including higher levels of CCL13-MCP-4 and CXCL11-interferon-inducible T-cell alpha chemoattractant), cell survival, protein and lipid homeostasis, and intracellular signaling (all, P < .05). “While people with depression typically have immune-inflammatory abnormalities, those who also had mild cognitive impairment [MCI] had poorer immune-inflammatory control,” added Dr. Butters. This group also had significantly greater white matter hyperintensity volume than the group with normal cognition (0.0201 vs 0.006, respectively; P = .015), signaling cerebrovascular disease. The investigators note that this suggests that MCI in depression may be driven by vascular-related changes. Using “machine learning analysis,” the researchers found that, together, the 3 proteins apolipoprotein AI, interleukin-12, and stem cell factor gave 81.3% accuracy, 75% sensitivity, and 86.4% specificity rates in being able to distinguish the patients with MCI from those without. Mol Psychiatry. Published online August 5, 2014.