A new study sheds light on the relationship between late-life depression, its treatment with antidepressant medicines, and deterioration in cognitive function.

Over 10% of adults over age 60 are thought to have symptoms consistent with a diagnosis of major depressive disorder (MDD). MDD in this population is often called late-life depression. MDD is recognized as a risk factor for dementia, and, importantly, it is among the risk factors that can potentially be modified with existing therapies, including drug and talk therapies.

As noted in a recent review article, depression in later life is underdiagnosed and under-treated. The DSM-5 diagnostic manual defines major depressive disorder by the presence of depressed mood or marked loss of interest or pleasure in activities along with five of the following symptoms: changes in appetite or weight (5% total body weight), sleep, energy, concentration, and psychomotor activity, feelings of inappropriate guilt or worthlessness and recurrent thoughts of death or suicide.

Dementia risk associated with MDD is present in those who become depressed early in life, but the risk is thought to be greater in those whose symptoms develop after age 50 or 60. Almost all patients with late-life depression have some degree of cognitive impairment, with up to 40% meeting diagnostic criteria for mild cognitive impairment, according to the team that conducted the new study. Cognitive domains affected in late-life depression, they note, include attention, processing speed (taking in and responding to information), learning and memory, and executive function. Executive function issues have been linked in past studies with lower likelihood of antidepressant response or remission.

Still, in older adults in particular, existing evidence on the impact of antidepressant treatment on cognitive function in late-life depression has been inconsistent, and, says the research team, “difficult to interpret.” As a result, treatment guidelines have not been able to make specific recommendations.

Led by Nicholas J. Ainsworth, M.D., of the Centre for Addiction and Mental Health (CAMH) at the University of Toronto, Canada, the team, reporting in the American Journal of Psychiatry, was able to “quantify for the first time the degree to which pharmacotherapy of late-life depression improves cognitive function in the short term.” The study also “establishes a link between the resolution of depressive symptoms and cognitive improvement in late-life depression.”

Tarek K. Rajji, M.D., and Daniel M. Blumberger, M.D., both of whom received 2010 BBRF Young Investigator grants and are affiliated with CAMH and the University of Toronto, were members of the team.

The researchers conducted a systematic review and meta-analysis of past studies involving antidepressant drug therapy for adults 50 and over with late-life depression (the average age of participants was over 65). A meta-analysis is one that combines the statistical results of multiple prior studies, thus increasing their collective statistical power. The primary and secondary outcomes of interest in the team’s analyses were, respectively, changes in cognitive test scores from baseline to post-treatment in the studies under review; and associations between changes in depressive symptoms and scores on cognitive tests.

Twenty-two studies met criteria established by the team; these were used in the analyses in various ways, depending on the degree to which they were statistically or descriptively comparable in various respects. In 13 of 19 comparable studies, an improvement was noted in at least one cognitive test at the conclusion of drug therapy. Improvements in depressive symptoms were associated with improvement in cognitive scores in six of seven relevant studies. In another phase of the review, a meta-analysis that encompassed eight studies (a combined 493 participants) revealed “a statistically significant improvement in memory and learning,” although not in other cognitive domains, following treatment of late-life depression with antidepressant drugs.

Based on the results of their review, the team concluded that “antidepressant treatment of late-life depression appears to be associated with some improvements in cognition, with meta-analysis evidence in the [specific cognitive] domain of memory and learning.” There was also “qualitative evidence supporting an association between a reduction in depressive symptoms and an improvement in cognitive function.” This, the team stressed, “emphasizes the importance of effective treatment of late-life depression.” Indeed, they said, “our findings strongly support assertive treatment of late-life depression to target full remission, which appears to lead to improved cognitive outcomes.”

Although the evidence for improvement in memory and learning following antidepressant therapy was statistically strongest, it is possible, the researchers aid, that some cognitive domains may be more susceptible to improvement than others. For those showing less improvement, for instance executive function, “it is possible that other therapeutic modalities such as psychotherapy may be useful as alternative or adjunctive treatment strategies.”

Finally, a portion of the team’s analysis generated evidence suggesting that among antidepressant medicines, SSRIs (selective serotonin reuptake inhibitors) and particularly sertraline (Zoloft) “may be of particular benefit for optimizing cognitive outcomes” in later-life major depression patients. This result may, however, be related to the fact that that drug has been studied in the context of cognitive function more than others; other SSRIs, they said, may also have a positive impact on aspects of cognition in late-life major depression patients.