PITTSBURGH, Aug. 7, 2014 - People who develop depression and mild cognitive impairment (MCI) after age 65 are more likely to have biological and brain imaging markers that reflect a greater vulnerability for accelerated brain aging, according to a study conducted by researchers at the University of Pittsburgh School of Medicine. The findings were published online in Molecular Psychiatry.

Older adults with major depression have double the risk of developing dementia in the future compared with those who have never had the mood disorder, said senior investigator Meryl A. Butters, Ph.D., associate professor of psychiatry, Pitt School of Medicine. But there's no clear explanation for why a treatable mood disorder like depression leads to increased risk for dementia, a progressive brain disease. Until now, most studies have examined only one or two biomarkers to get at this question.

"Our study represents a significant advance because it provides a more comprehensive and integrated view of the neurobiological changes related to mild cognitive impairment in late-life," she said. "Better understanding of the neurobiology of cognitive impairment in depression can provide new targets for developing more specific treatments, not only for its prevention and treatment, but also for its down-stream negative outcomes, including the development of dementia and related disorders."

The team collected blood samples from 80 older adults in remission after being treated for major depression, 36 of whom had MCI and 44 with normal cognitive function. Their blood was tested for 242 proteins involved in biologic pathways associated with cancer, cardiovascular diseases, and metabolic disorders as well as psychiatric and neurodegenerative disorders. The researchers also performed PET and MRI brain scans on the participants to look for indicators of cerebrovascular disease, brain atrophy or shrinkage, and beta-amyloid, which is the protein that makes up the brain plaques associated with Alzheimer's disease.

The MCI group was more likely to have differences in the biologic activity of 24 proteins that are involved in the regulation of immune and inflammatory pathways, intracellular signaling, cell survival, and protein and lipid balance.

Brain scans revealed a greater propensity for cerebrovascular disease - for example, small strokes - in the MCI group, but there was no difference in the amount of beta-amyloid deposition.

"If you take these results altogether, they suggest that people with depression and cognitive impairment may be more vulnerable to accelerated brain aging, which in turn puts them at risk for developing dementia," Dr. Butters said. "Ultimately, if we can understand what happens in the brain when people are depressed and suffer cognitive impairment, we can then develop strategies to slow or perhaps stop the impairment from progressing to dementia."

Next steps include assessing the protein panel in older people with normal cognitive function who have not experienced depression.

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Co-authors of the study include Etienne Sibille, Ph.D., Ying Ding, Ph.D., George Tseng, Ph.D., Howard Aizenstein, M.D., Ph.D., Frances Lotrich, M.D., Ph.D., James T. Becker, Ph.D., Oscar L. Lopez, M.D., Michael T. Lotze M.D., William E. Klunk M.D., Ph.D., and Charles F. Reynolds, M.D., all of the University of Pittsburgh; and the first author is Breno S. Diniz, M.D., Ph.D., now of the Federal University of Minas Gerais, Brazil.

The project was funded by National Institutes of Health grants MH080240, MH90333 (ACISR for Late Life Depression Prevention and Treatment), AG05133 (Alzheimer Disease Research Center), MH09456; CA047904-22S1, CA160417, CA181450; the John A. Hartford Foundation Center of Excellence in Geriatric Psychiatry; and the Brazilian Intramural Research Program.

About the University of Pittsburgh School of Medicine

As one of the nation's leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1998. In rankings recently released by the National Science Foundation, Pitt ranked fifth among all American universities in total federal science and engineering research and development support.