SAN FRANCISCO – Patients with unchecked inflammation, depression, and slow gait make up a “depressed frail phenotype at grave risk of death,” Patrick J. Brown, PhD, said at the 2016 congress of the International Psychogeriatric Association..
“There are multiple pathways into this phenotypic cycle. Depression and slow gait share a bidirectional relationship, and inflammation may indirectly lead to depression because of its impact on mobility,” said Dr. Brown, a clinical psychologist in the department of psychiatry at Columbia University, New York. Clinicians should consider aggressive interventions for older patients with depression and frailty, recognizing that exercise and dietary changes may be “much more relevant” than switching or augmenting antidepressants and other psychotropic medications, which can be especially risky for seniors, he said.
Dr. Patrick J. Brown
Models of psychiatric illness, particularly depression, come from studies of younger adults “and have failed us in geriatric medicine,” Dr. Brown emphasized. About 3%-7% of adults above age 65 years meet criteria for major depressive disorder, and another 15% have “significant but subthreshold” depressive symptoms, but less than half of depressed seniors have responded to antidepressants in controlled trials. High rates of treatment failure in late-life depression suggest that it has diverse etiologies that have to be identified and targeted to improve outcomes, Dr. Brown said. Frailty, characterized by slowed gait, weak grip, and decreased physical activity and energy, resembles and often co-occurs with late-life depression, giving rise to the concept of a “depressed-frail” phenotype at potentially greater risk of imminent death, he added.
To test that idea, Dr. Brown and his associates analyzed 10-year longitudinal data for 3,075 white and African American adults aged 68-80 years who were free from significant disabilities or functional limitations at baseline. These participants were from the Dynamics of Health, Aging, and Body Composition study, which annually measured body composition, gait, grip strength, comorbidities, and other clinical data. Using a method called latent class analysis, the researchers examined trajectories of depression (defined as a score of at least 10 on the Center for Epidemiologic Studies Depression Scale, slow gait (walking speed less than 1.02 meters per second), and inflammation (serum interleukin-6 [IL-6] levels above 3.24 pg/mL) over time. They also used multivariable regression to understand how each of those features correlated with mortality.
The latent class analysis showed that 22% of participants had either rising or consistently high probabilities of inflammation, slow gait, and depression. Slow gait was associated with inflammation (r = 0.40; P less than .001) and depression (r = 0.49; P less than .001). Inflammation was independently associated with mortality (P less than .001), while slow gait was linked to mortality only in participants with depression that worsened over time (P less than .01). Among the 247 patients with a high level of inflammation and slow gait with increasing or a consistently high level of depression, the 10-year mortality was 85%, the highest of any group of patients in the study, Dr. Brown said.
The study also confirmed the overlap between depression and frailty. Depression and inflammation each independently predicted slow gait, with odds ratios of 1.37 (95% confidence interval, 1.17-1.60) and 1.22 (1.05-1.41), respectively. Slow gait also was a significant predictor of depression (OR, 1.27; 1.08-1.50), even after the investigators accounted for age, sex, body mass index, comorbidities, use of anti-inflammatories, and scores on the Modified Mini-Mental State Examination.
These and other recent findings highlight frailty as a physical manifestation of greater biologic aging, Dr. Brown said. Accordingly, researchers are studying whether combatting age-related deterioration can improve outcomes in late-life depression. Specific protocols under study include anaerobic exercise to reverse mitochondrial dysfunction, anti-inflammatories targeting acute phase proteins (C-reactive protein) and cytokines (IL-6 and tumor necrosis factor–alpha), and treatments that augment dopaminergic neurotransmission, he said.
The National Institutes of Health provided funding. Dr. Brown had no relevant financial disclosures.