Why do psychiatric conditions multiply the risk of cognitive decline?
Age is the single biggest risk factor for dementia, with the odds doubling about every five years after age 65. But many things influence those odds for a given individual. Genetic vulnerability is a contributor, as are so-called modifiable risk factors such as smoking, cardiovascular disease, social isolation, and impaired hearing and vision. Certain mental conditions, particularly depression and schizophrenia, have also been linked to dementia. But because depression can itself be a sign of cognitive decline, the causality has been a bit muddy. Earlier this year an analysis of data from New Zealand provided the most convincing evidence to date linking many kinds of mental illness with dementia. That study raises important questions about the reasons for this increased risk and what could be done to reduce it.
The study looks at the health records of 1.7 million New Zealanders born between 1928 and 1967 covering a 30-year period ending in mid-2018. It found that those with a diagnosed mental disorder—such as anxiety disorders, depression or bipolar disorder—had four times the rate of ultimately developing dementia compared with people without such a diagnosis. For those with psychosis such as schizophrenia, it was six times the rate.
Among people who developed dementia, those with a psychiatric disorder were affected 5.6 years earlier, on average.
The study did not examine biological, social, or other reasons for the increased risk, but research on dementia points to several possible explanations. “There might be shared genetic risk factors,” suggests psychologist Leah Richmond-Rakerd of the University of Michigan, lead author of the study. Recent studies have found some overlap in genetic markers associated with Alzheimer’s disease and those linked to bipolar disorder and to major depression. Long-term use of psychiatric medications could also be playing a role in dementia, but Richmond-Rakerd and her co-authors do not think it is a major contributor.
They suspect that a more significant risk factor is the chronic stress associated with having a psychiatric disorder, which may degrade brain health over time. Studies in animals, as well as human autopsy studies, have linked chronic stress to a loss of neural connections in the hippocampus, the brain’s memory center, which is where Alzheimer’s takes a heavy toll. Evidence suggests that stress drives inflammation and immune dysregulation in the body and brain, impacting brain connectivity, says Harvard University neurologist and dementia researcher Steven Arnold. “If you have fewer connections and synapses, to begin with, because of stress, then you can’t afford to lose as many with aging before it starts to show up as what we might call dementia.” In other words, as illustrated by Fatinha Ramos people with mental illnesses may have less “cognitive reserve”— brainpower that is sufficiently robust to withstand normal aging without obvious loss of function.
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