Depression in older adults is often treated as a separate mental health problem, but new research suggests that changes in the brain may sometimes begin before obvious memory difficulties appear.
Scientists have found a link between the buildup of the protein tau and increasing depressive symptoms in older people whose thinking and memory were still normal.
The study was led by Teodora Markova of Brandeis University and colleagues and was published in JNeurosci, the journal of the Society for Neuroscience. The researchers examined information collected through the Alzheimer’s Disease Neuroimaging Initiative, a major long-term project studying brain aging and Alzheimer’s disease.
Alzheimer’s disease is best known for causing memory loss, confusion, and problems with thinking. However, changes in mood and behavior can also occur, sometimes years before a person receives a diagnosis.
Researchers are therefore interested in whether emotional changes during later life can provide clues about what is happening inside the brain. Depression is especially important because it is common among older adults and can have many possible causes.
Tau is a protein that normally helps support nerve cells in the brain. In Alzheimer’s disease, tau can change and collect abnormally inside brain cells, eventually forming structures that interfere with normal cell function.
These abnormal tau changes are one of the main biological signs scientists study when investigating Alzheimer’s disease. Another well-known brain change involves the buildup of a protein called amyloid.
For the new research, the team studied older men and women with different levels of cognitive health. Some participants had normal memory, attention, and thinking abilities, while others had mild cognitive impairment or Alzheimer’s disease.
Participants underwent repeated brain imaging designed to detect tau. They also completed questionnaires that measured depressive symptoms during several visits, allowing researchers to compare changes in mood with changes in tau over time.
The researchers found an interesting pattern among people whose cognitive abilities were still intact. Participants with faster tau buildup also tended to experience a faster increase in depressive symptoms over time.
Higher tau levels could also help predict higher scores on the depression measure in cognitively healthy participants. The order of the changes suggested that tau accumulation occurred before the rise in depressive symptoms.
This raises the possibility that early tau-related brain changes may contribute to mood changes before clear problems with memory or thinking develop. It does not mean that depression in an older person is necessarily an early sign of Alzheimer’s disease.
Depression has many causes, including stressful life events, loneliness, physical illness, sleep problems, medication effects, and other biological and psychological factors. Most importantly, an association between tau and depressive symptoms does not prove that tau directly caused the symptoms.
The researchers also found that the pattern was not present in participants who already had mild cognitive impairment or Alzheimer’s disease. This difference suggests that the relationship between tau and mood may be particularly relevant during an earlier stage of brain aging.
Once cognitive impairment develops, many other brain changes may be occurring at the same time. These changes could make the relationship between a single protein and depressive symptoms much harder to detect.
The findings may eventually help scientists improve methods for identifying people at increased risk of neurodegenerative disease. Tracking changes in mood over several years could potentially add useful information alongside memory testing, brain scans, blood tests, and other measures.
However, depression questionnaires cannot diagnose Alzheimer’s disease. Someone developing depressive symptoms should not assume that they are experiencing Alzheimer’s-related brain changes, and routine depression screening should continue to focus on helping people receive appropriate care.
Markova said future research should follow participants for longer periods. This would allow scientists to see whether people with early tau buildup and increasing depressive symptoms are more likely to later develop memory problems or clinically significant depression.
Researchers also want to compare mood changes with other ways of tracking Alzheimer’s disease. Combining several types of information may eventually provide a clearer picture of who is at risk and when disease-related changes begin.
The study has several strengths, including repeated brain scans and repeated measures of depressive symptoms. Following the same people over time is more informative than looking at tau and mood only once because it allows researchers to examine how both change together.
Still, the findings should be viewed as an early clue rather than a clinical test. The study shows a relationship in cognitively healthy older adults, but further research is needed to determine whether depressive changes can reliably predict future Alzheimer’s disease.
Overall, the research adds to the idea that Alzheimer’s-related changes may begin long before obvious memory loss. Mood could be one part of that early picture, but it will need to be considered together with brain biology, cognitive testing, medical history, and many other factors.
Source: Brandeis University.
