Early Stage Dementia Might Be Predicted by Steadily Increasing Depressive Symptoms in Old Age

In the first long-term analysis of its kind, researchers report that depressive symptoms that progressively increase in older age might better predict the development of dementia than any other type of depression – and may, in fact, represent an early disease stage.

Many studies have linked depressive symptoms with dementia, but failed to take into account that distinct depression courses might represent different underlying mechanisms, with divergent involvement in dementia development.

Researchers at the Erasmus Medical Center in the Netherlands analyzed data from a large population-based study of adults older than 55 years. The study has been ongoing since 1990, and the team identified 3,325 individuals who had symptoms of depression but no signs of dementia. Following these individuals for 11 years allowed the research team to draw a number of depression trajectories: maintaining mild symptoms; moderately severe but transient symptoms followed by full remission; mild symptoms that increased, then remitted; mild symptoms steadily increasing; and chronically severe symptoms.

Among the 3,325 participants, 434 developed dementia, of which a majority — 348 — were diagnosed with Alzheimer’s disease. Instead of comparing risk of dementia to the general population, the research team calculated the risk of dementia among those with continuously mild depressive symptoms, and then compared the other disease trajectories to that.

Findings published in the journal Lancet Psychiatry show that the patients with mild symptoms had a risk of 10 percent. Among other disease trajectories, only patients with steadily increasing depressive symptoms had a higher risk of developing dementia – 22 percent. The risk was particularly high during the first three years.

When researchers restricted outcome to Alzheimer’s disease and censored cases that had suffered stroke, the analysis remained, demonstrating that only the group with increasing depressive symptoms was at higher risk.

The study, “10-year trajectories of depressive symptoms and risk of dementia: a population-based study,” suggests there is no evidence that an isolated depressive episode, even with severe symptoms, has any influence on the development of dementia.

“Depressive symptoms that gradually increase over time appear to better predict dementia later in life than other trajectories of depressive symptoms such as high and remitting, in this study,” senior author Dr. M. Arfan Ikram said in a press release.

“There are a number of potential explanations, including that depression and dementia may both be symptoms of a common underlying cause, or that increasing depressive symptoms are on the starting end of a dementia continuum in older adults. More research is needed to examine this association, and to investigate the potential to use ongoing assessments of depressive symptoms to identify older adults at increased risk of dementia,” he said.

Earlier studies noted that the two conditions share several mechanisms, such as the loss of neurons and neuronal connections, coupled with a lost ability to produce new neurons and a disturbed immune system. This strengthens the case that some forms of depression and dementia might represent different symptoms of a common underlying cause, and suggests that progressively increasing depressive symptoms might, in fact, be an early stage of dementia.

While the study more robustly supports a link between depression and dementia, questions as to how the presence of depressive symptoms alters the risk still remain.

“More studies of depression trajectories over a long period, with inclusion of biological measures, are necessary to understand the link between depression and dementia, in particular the underlying mechanisms,” Dr. Simone Reppermund from the Department of Developmental Disability and Centre for Healthy Brain Aging at the University of New South Wales, Australia, wrote in a comment to the article.

“A focus on lifestyle factors such as physical activity and social networks, and biological risk factors such as vascular disease, neuroinflammation, high concentrations of stress hormones, and neuropathological changes, might bring new treatment and prevention strategies a step closer,” Reppermund said.