The link between depression and dementia has been noted by researchers and clinicians for several years now. After all, it seems obvious that one would suffer from feelings of depression as one gets older and experiences the earliest stages of cognitive decline. But a growing body of evidence is building to suggest we may have got the causal direction wrong when considering the associations between depression and dementia.

A new study led by Harvard Medical School researchers at Massachusetts General Hospital has found levels of amyloid beta plaques in the brain, the primary pathological characteristic of Alzheimer’s disease, can be directly correlated with both increasing symptoms of depression, and worsening cognition. The hypothesis is that depression and dementia can be symptoms of Alzheimer’s, with mild depression being possibly one of the first clinical signs of the neurodegenerative disease.

“Our research found that even modest levels of brain amyloid deposition can impact the relationship between depression symptoms and cognitive abilities,” says lead author on the study, Jennifer Gatchel.

The new research utilized data from the long-running Harvard Aging Brain Study, providing valuable longitudinal data tracking healthy adults at the earliest stages of cognitive decline. In this instance, data was analyzed from 276 older adults. All the subjects were cognitively unimpaired at the beginning of the study, and suffered from no more than mild depression.

PET scans allowed the researchers to track cortical amyloid levels, with depression and cognition measured for up to seven years. Those subjects with the highest amyloid deposits at the beginning of the study showed the greatest increase in depression and declines in cognition over the subsequent years. The researchers hypothesize depression and cognitive decline could share the same pathological process in preclinical cases of Alzheimer’s disease. And more intriguingly, this means identifying and treating depression in cognitively healthy older adults could be a way to treat the earliest stages of Alzheimer’s disease, slowing any associated cognitive decline.

“Depression symptoms themselves may be among the early changes in the preclinical stages of dementia syndromes,” says Gatchel. “Just as importantly, these stages represent a clinical window of opportunity for closely monitoring at-risk individuals, and for potentially introducing interventions to prevent or slow cognitive decline.”

The researchers do stress that while this study, and others, suggest depression can be one of the earliest signs of Alzheimer’s, there are still a number of factors that influence both depressive symptoms and cognitive decline in later life. So the onset of depression in one’s senior years does not automatically indicate the beginning of Alzheimer’s disease. It’s also still unclear whether pre-existing symptoms of depression can influence amyloid build-up in the brain.

“These findings underscore the fact that depression symptoms are multi-factorial and may actually work synergistically with amyloid and related processes to affect cognition over time in older adults,” concludes Gatchel. “This is an area we will continue to actively study.”