Scientists have established that depression coexists with dementia in late life and that depression may be an early symptom of the disease.
“We did find that early adulthood and late-life higher depressive symptoms were associated with late-life cognitive impairment in older adults. And that might mean early adulthood depressive symptoms [are] potential risk factors for dementia and should be investigated further.”
Statistics is the grammar of science
Dr. Brenowitz, senior researcher Dr. Kristine Yaffe, and their colleagues pooled data from four large preexisting groups of participants to make a total of around 15,000 people aged 20–89 years.
The four groups are part of ongoing studies investigating risk factors for either cardiovascular disease or body composition and reduced function in older people.
Next, the researchers employed a complex statistical method called imputation. They wanted to understand whether depression in early adulthood is associated with an increased risk of dementia.
Dr. Brenowitz defined imputation as “[t]rying to make associations that would not be otherwise possible.” She explained to MNT:
“Imputation is assigning missing data a value. The idea behind it is: We are missing data from these older adults on their [depressive symptoms as younger adults]. So, we are trying to assign a value to what we think their depressive symptoms were. And, to do that, we need to have data on other [young] people we think are similar: people that are exchangeable.”
Comparing young and old
By comparing young people with older people with similar characteristics, the scientists could make more valid conclusions. To ensure the groups were similar, they compared similar traits, called covariates.
Dr. Brenowitz explained: “We took people that look like each other, based on certain covariates […] — the age is what is different. Also, we included other covariates, such as smoking and cardiovascular risk factors. So we created this model that fits trajectories of depression for all the participants in [the] four different studies.”
Dr. Brenowitz admits there is uncertainty in this unique model, which involves assumptions. However, these methods help scientists avoid excluding important groups of people we wish to understand better.
Brain changes in depression and dementia
Prior work suggests possible mechanisms that make people living with depression more susceptible to dementia.
Individuals with depression exhibit hyperactivity in the area of the brain that stimulates the adrenal glands to produce more glucocorticoids, such as the stress hormone cortisol. Higher cortisol levels can damage the hippocampus, a part of the brain that is important for cognitive function and memory.
Scientists have also identified that people living with Alzheimer’s may experience atrophy of the hippocampus. Dr. Brenowitz clarified for MNT:
“Those with depression exhibit reduced hippocampal volumes. This is thought to be due to increased stress hormones, [and] because the hippocampus is a more susceptible region to health insults […], it is also more susceptible to Alzheimer’s disease.”
She explained that the hippocampus is a “vulnerable region that might be tipped into a nonideal state, where we end up with some sort of volume loss […] that can be independent of Alzheimer’s.”
Dr. Brenowitz continued, “There could already [be] a hit from depression, and then [a person is] more likely to have Alzheimer’s disease or be more susceptible to that pathology.”
Research suggests that other mechanisms that contribute to cognitive decline may also be at work.
Depression may contribute to dementia through vascular disease, increased inflammation, depressed nerve growth factors, or increased accumulation of amyloid — a protein in the brain strongly associated with Alzheimer’s disease.
Chicken vs. egg
The researchers caution that their study estimates associations, not causation, between depression in early adulthood and late-life cognitive impairment.
Depression in early adulthood was not the only factor that increased the risk of dementia in these people. Individuals with more severe depressive symptoms in early adulthood and late life also showed a higher association with more severe cognitive decline.
Dr. Brenowitz recounted:
“In late life, it’s hard to tell the chicken and the egg: Which came first? People who develop dementia often have a trajectory of 20 years of decline, so it’s hard to pinpoint. Is this an early dementia syndrome, or is this due to other risk factors for dementia, such as vascular disease?”
‘Living well is the best revenge.’ – George Herbert
The scientists conclude that early adulthood may be a critical time to modify risk factors for dementia, such as depression. Current interventions in midlife to reduce the likelihood of developing dementia include improving cardiovascular risk and managing diabetes, which may play a role in cognitive impairment.
Dr. Brenowitz acknowledged that the team’s study raises challenging questions. She noted that it remains to be seen whether aggressively addressing midlife risk factors or depressive symptoms in early adulthood will affect rates of late-life cognitive impairment.
“I feel like there is a window in early adulthood where people are starting to get past the feeling that they don’t have to do anything, and they start thinking they should live a [healthier lifestyle]. They start to build good habits that will have an impact not just on cognitive impairment, but also physical and mental health later on.”
– Dr. Willa Brenowitz
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