Depression Tied to Memory Problems, Smaller Brain Size

Batya Swift Yasgur, MA, LSW

May 15, 2018

Older adults with greater depressive symptoms have more memory problems; more markers of brain aging, such as smaller brain size; and increased vascular brain lesions, new research shows.

Investigators studied over 1000 predominantly Caribbean Hispanic adults (average age, 71 years) and found that a larger number of depressive symptoms was associated with worse episodic memory as well as smaller cerebral volume and more silent infarcts.

"Our research suggests that depression and brain aging may occur simultaneously, and that elevated symptoms of depression may affect brain health through small vessel disease," lead author, Adina Zeki Al Hazzouri, PhD, MS, assistant professor of epidemiology, University of Miami, Florida, told Medscape Medical News.

"Since symptoms of depression can be treated, it may be possible that treatment may also reduce thinking and memory problems," she said.

The study was published online May 9 in Neurology.

Underexplored Population

Evidence suggests that greater depressive symptoms and cognitive dysfunction are "strongly related" in older adults and that both "result in poorer quality of life," the authors write.

Studies of the relationship between greater depressive symptoms and risk for cognitive decline have yielded mixed results.

Additionally, most studies investigating this relationship have been done in non-Hispanic black and white populations, with the association "underexplored" in Hispanic/Latino populations, "despite the increased risk of cognitive impairment in this large subgroup," the authors note.

"Our motivation for conducting the study was that the literature on the relationship between depressive symptoms and brain health is scarce, especially among Hispanics," Zeki Al Hazzouri said.

"With as many as 25% of older adults experiencing depressive symptoms, we felt it was important to better understand the relationship between depression and memory problems," she added.

To investigate the relationship between depressive symptoms, markers of brain aging, cognitive function, and cognitive change in a racially and ethnically diverse population, the researchers used data from the Northern Manhattan Study (NOMAS), a longitudinal, population-based cohort of adults living in the northern Manhattan area of New York City.

The overall study enrolled 3298 participants, 52% of whom were Caribbean Hispanic individuals, and included a "rich data collection" of in-depth neuropsychological assessment and brain imaging.

Participants had to be free of stroke diagnosis, be at least 40 years old, and have resided in northern Manhattan for more than 3 months.

Between 2003 and 2008 (the baseline of the current study), NOMAS participants underwent brain MRI and neuropsychological assessment. This group was required to be stroke free and age 50 years or older.

Participants completed the Center for Epidemiological Studies-Depression (CES-D) scale to assess depressive symptoms. A score of 16 or greater was considered to indicate greater depressive symptoms.

In addition, participants completed a neuropsychological assessment analyzing cognitive function and then were reexamined an average of 5 years later by using a  neuropsychological assessment similar to the one used at baseline.

Participants underwent MRI testing to evaluate total cerebral volume, hippocampal volume, and the presence or absence of subclinical brain infarcts.

Additional in-person evaluations, conducted at the time of MRI assessment, ascertained fasting glucose samples and lipid panels, alcohol consumption, leisure time physical activity, hypertension, type 2 diabetes mellitus, and history of cardiac disease, as well as use of antidepressant medication.

Common Mechanisms?

A final sample of 1111 individuals participated in the study, with a mean (SD) age of 71 (9) years. The analysis exploring 5-year cognitive change included a sample of 858 participants whose cognitive function was assessed at 5-year follow-up.

At baseline, 22% of participants had greater depressive symptoms (CES-D score ≥ 16).

Participants with greater depressive symptoms at baseline were significantly more likely than those without depressive symptoms to be female (74% vs 58%; P < .0001), be uninsured or have Medicaid (56% vs 47%; P < .03), be taking antidepressant medications (21% vs 7%), and have fewer mean years of education (8.69 vs 9.66; P < .02).

Hispanic participants were significantly more likely than white, black, or other participants to have greater depressive symptoms (75% vs 8%, 14%, and 3%, respectively). 

In models that adjusted for sociodemographic, vascular risk factors, and antidepressant medication variables, greater depressive symptoms were significantly associated with worse baseline episodic memory (β  = −0.21 [95% CI, −0.33 to −0.10]; P = .0003).

After adjustment for sociodemographic, behavioral, and vascular risk factor variables, greater depressive symptoms were associated with smaller cerebral parenchymal fraction (β = −0.56 [95% CI, −1.05 to −0.07]; P = .02) and increased odds of subclinical brain infarcts (odds ratio, 1.55 [95% CI, 1.00 - 2.42]; P = .05).

Moreover, after similar adjustments, depressive symptoms were associated with worse episodic memory — an association that remained significant and stable after further adjustment for use of antidepressant medication.

By contrast, greater depressive symptoms were not significantly associated with white matter hyperintensity volume, hippocampal volume, or change in cognition over an average of 5 years.

"In this diverse, stroke-free cohort of older adults, we found significant cross-sectional associations between greater depressive symptoms and episodic memory, but no evidence of association with change in cognition over an average of 5 years," the authors report.

In addition, they state, an association was found between greater depressive symptoms and smaller cerebral volumes, as well as subclinical brain infarcts, which are "a marker of cerebral small vessel disease."

The authors suggest several potential mechanisms for the associations, including the "vascular depression hypothesis," which posits that cerebrovascular disease may contribute to the development of depression, though this relationship may be "bidirectional."

Disease mechanisms "common to both depression and cognitive dysfunction may explain their consistent associations across cohorts, but the temporality of this association is still under debate," they note.

Aim for Remission

Commenting on the study for Medscape Medical News, Charles F. Reynolds III, MD, distinguished professor of psychiatry emeritus, University of Pittsburgh School of Medicine, Pennsylvania, who was not involved with the study, commended it for being "transdisciplinary" because it was conducted by epidemiologists, neuropsychologists, neurologists, and neuroscientists at several institutions who were "writing about a true community sample of midlife and older adults."

Other strengths of the study are that it "provides an interesting and useful contrast to much of the literature that is based largely on clinical samples of help-seeking older adults with depressive illness" and that it includes Hispanic and Caribbean people.

A limitation of the study is that "we do not know which subject upon entry is already in the early stages of dementia, so the finding of an association between depressive symptoms and dementia could actually represent an underlying variable — in other words, early stages of a neurodegenerative disorder," he noted.

Although it is "difficult to draw treatment inferences from an observational study of this kind," one take-home message is that because depression is likely a modifiable risk factor for dementia, it is good to treat depression, and treat it to remission, in order to reduce that source of risk, he said.

The authors add, "Further studies are needed to elucidate the mechanisms between greater depressive symptoms and cognitive function in later life, especially in samples with repeated depressive symptoms and cognitive data."

The study was supported by the National Institutes of Health, the American Heart Association, and the Evelyn F. McKnight Brain Institute. Zeki Al Hazzouri has disclosed no relevant financial relationships. The other authors' disclosures are listed on the original study. Reynolds has disclosed no relevant financial relationships.

Neurology. Published online May 9, 2018. Abstract

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