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Depression interacts with allostatic load to accelerate cognitive decline, study finds

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The new research provides evidence that markers of inflammation, lipid metabolism and body composition play a key role in predicting the likelihood of cognitive decline among depressed middle-aged adults. published work, psychoneuroendocrinologyfound that a history of depression interacted with allostatic load to predict a decline in cognitive performance.

Allostatic load is a measure of the cumulative damage that occurs as a result of chronic stress. It includes factors such as high blood pressure and high levels of inflammation. Managing the allostatic load is essential to maintaining health. Many studies have shown that having a high allostatic load is associated with lower cognitive performance. This previous study, however, did not assess depression, leaving open questions about the nature of the combined effects of allostatic burden and depression on cognition.

“Cognitive changes are common in depression, but the risk of cognitive decline over time is not equal among individuals with depression,” said George Perlman of the University of Toronto and Sunnybrook Research Institute, lead author of the new study. “We wanted to know what put some people at greater risk. In the field of psychoneuroendocrinology, the allostatic load is a kind of “theory of everything” proposed to explain the long-term impact of environmental and psychological stress on overall health.

“We evaluated whether depression, allostatic load, or a combination of the two predict cognitive decline. We studied middle-aged people and followed them for 9 years, because currently cognitive changes may predispose to dementia.”

Researchers analyzed data from Mid-Life in the United States (MIDUS), a national longitudinal study of health and well-being that recruited nearly 7,000 people aged 25-74 in 1995. The study found “behavioral, psychological, and social factors in explaining age-related differences in health and well-being in a national sample of Americans.

More importantly, the study collected a second wave of data from 2004 to 2009 and a third wave of data from 2013 to 2014, which included both physiological assessments and cognitive tests. The researchers zeroed in on 815 participants with depression, physiological, and cognitive data. They calculated allostatic load scores based on 24 biomarkers from blood samples, urine samples, body measurements, and electrocardiographic recordings.

Perlman and colleagues found that depression and allostatic load interactively predicted cognitive decline, but not independently. In other words, a high allostatic load was associated with cognitive decline in participants with depression, but not in participants without depression.

“People with both depression and a high allostatic load were most vulnerable to cognitive decline in midlife,” Perlman told PsyPost. “In a way, the somatic wear and tear on the body along with depression ‘picked up’ to accelerate cognitive decline. Future studies looking for ways to preserve cognitive function may focus on those most at risk, namely individuals with both depression and markers of high allostatic load, such as inflammation and vascular risk factors.

Cognitive tests included assessments of executive function and episodic memory. When examining individual physiological areas, the researchers found that inflammation was the largest moderator.

“Allostatic load is often estimated as a combination of physiological disturbances such as inflammation, metabolic dysfunction, blood pressure changes, and autonomic dysfunction,” Perlman said. “When we looked at these components individually, inflammation was the main culprit predicting declines in overall cognitive performance when present alongside depression.”

None of these physiological disturbances predicted episodic memory declines in people with or without depression. But the researchers uncovered some specific biomarkers that smooth out the declines in executive function.

“Decreases in brain functions such as speed, information processing, attention, sequencing, and general thinking ability (i.e. executive function) were especially seen in people with both allostatic load and depression,” Perlman said. “For the decline in executive function, it was lipid metabolism (ie, cholesterol and triglycerides) and body composition (BMI and waist-to-hip ratio) that showed the strongest interactions. These metabolic factors are known to be particularly bad for blood vessels.”

“The cognitive outcomes and risk factors identified may suggest vascular dysfunction affecting the brain in people with depression. Neuroimaging studies can be useful for examining areas such as the white matter and prefrontal cortex that are often affected by vascular disease.”

However, as with any study, the findings contain some caveats.

“Although the study followed people for 9 years, longer follow-ups of larger groups will be needed to determine whether the interactions we found predict event dementia,” Perlman told PsyPost. It will also be important to know whether the risk is related to Alzheimer’s disease, vascular dementia, or a mix of the two, which is the most common culprit.”

“The main limitation of this study is demographic; 93% of the study group were white. This analysis should be repeated in non-white populations and populations outside of North America if we want to know whether these findings generalize to all middle-aged people.”

“We would like to thank the researchers and staff of the Midlife study in the United States for providing the data and for all their friendly guidance from start to finish,” said Perlman.

“Depression interacts with allostatic load to predict cognitive decline in middle age,” authored by George Perlman, Hugo Cogo-Moreira, Che-Yuan Wu, Nathan Herrmann, and Walter Swardfager.