New Evidence That Depression May Be An Early Sign of Alzheimer’s


The link between depression and dementia is something researchers have been aware of and studying for some time now, and according to a study led by Harvard Medical School researchers, mild depression may be one of the first clinical signs of the neurodegenerative disease Alzheimer’s.

"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.

What Gatchel refers to are amyloid-beta plaques, which are considered to be the primary pathological characteristics of Alzheimer’s as well as having a presence in increasing symptoms of depression and decreasing cognition early in life. 

The researchers gathered data from 276 older adults — 164 women and 112 men, mostly in their early 70s — in the Harvard Aging-Brain study, a long-running study that tracks the early stages of cognitive decline in individuals. In their particular sample group, each individual suffered from nothing more than mild depression at the beginning of the study. By measuring PET scan data for as much as seven years in their subjects, researchers were able to track baseline amyloid deposits with the greatest increase in depression and the greatest decline in depression resulting in people who had the highest levels of amyloid deposits at the beginning of the study period. Their resulting hypothesis is pretty straightforward and highly positive if correct: “depression and cognitive decline could share the same pathological process in preclinical cases of Alzheimer's disease.” This means effectively treating depression may also be one of the most effective ways to treat the earliest stages of Alzheimer’s. 

"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.” 

While researchers have long since believed in the correlation between depression and declining cognitive diseases in older adults, this study is one of the first to uncover that the link is fueled by cortical amyloid in unimpaired people.  

“Our findings add to a growing body of literature supporting an association between concurrent changes in depression and cognition, providing some of the first focused evidence of this association in preclinical AD defined based on amyloid PET neuroimaging,” the researchers wrote in their findings published in JAMA Network Open. “Results support depressive symptoms as among the earliest changes related to AD pathological burden and cognitive decline. They underscore the importance of close monitoring of older adults with depressive symptoms in clinical settings and the need for further study of the potential utility of targeting these symptoms in preclinical AD intervention studies aimed at mitigating cognitive decline.”

Of course, researchers noted that the presence of cortical amyloid and depression in unimpaired people is not a guarantee of the eventual development of Alzheimer’s. They studied other factors like brain metabolism and volume of the hippocampus, the part of the brain that helps us form memories and maintain information. They found that tau-mediated neurodegeneration, hypertension, hypercortisolemia, and inflammation may also be ingredients in the perfect recipe for Alzheimer’s. 

“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,” said Gatchel. “This is an area we will continue to actively study.”

Almost ironically, a study published within the past year in the Journal of Clinical Psychiatry revealed that we’re actually likelier to avoid depression in our later years. As we get older, statistics would argue that we can expect to find more happiness and wellbeing. In the meantime, we are most likely to struggle with stress, anxiety, and depression in our earlier adult years. 

“There’s this idea that old age is bad, it’s all gloom and doom and older people are usually depressed, grumpy and unhappy,” says study author Dr. Dilip Jeste, a geriatric psychiatrist and director of the Center on Healthy Aging at the University of California, San Diego.

The data was analyzed and collected from a sample of 1,546 people from ages 21 to 99 in San Diego. Participants were asked about their physical, cognitive and mental health in both a phone interview and a long survey that was filled out. Questions covered topics like happy and satisfied with life participants were, as well as how depressed, anxious or stressed they were.

People in their 20s and 30s reported having the highest levels of depression, anxiety, and stress, as well as the lowest levels of happiness, satisfaction, and wellbeing. But while older people experience greater levels of deterioration in physical health, they were found to be the healthiest mentally and emotionally— more specifically, the 60s are going to be the height of your mental and emotional wellbeing, according to this study. 

While the data was revealing about mental health, it didn’t control for the progression or digression of happiness or stress, anxiety, and depression in all these specific individuals throughout their lives. The belief that the study may not have accounted for how answers may have changed through an individual’s life. But overall, “as they got older, it looks like things started getting better for them,” Jeste says. “It suggests that with age, there’s a progressive improvement in mental health. It is conceivable that the changes in societal functioning because of progressive globalization, technology development, increased competition for higher education and for better-paying jobs and changing roles of women in the society are likely to impact young women and men more than they might affect older people,” Jeste adds. “Any relatively rapid changes tend to bring in stress for the people most affected.”

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