Clinical study explores relationship between depression and dementia

In recent years, researchers have studied the link between depression and dementia. Depression can affect different aspects of cognition such as attention, executive function and memory. Some researchers believe that depression may even be an early symptom of Alzheimer’s disease.

But there is conflicting evidence yet about how these two conditions are related or the biological mechanisms that may be involved.

“Depression is considered a modifiable risk factor of dementia, but it’s not yet known how it is related,” says Patrick Salwierz, a master’s student at the University of Toronto’s Tanz Centre for Neurodegenerative Diseases, supervised by Associate Professor Carmela Tartaglia.

“One theory even suggests that the accumulation of misfolded amyloid-beta protein seen in Alzheimer’s disease may also lead to depression, but there is no conclusive evidence that this is the case,” says Salwierz, who is also a medical student at Queen’s University.

Salwierz and Tartaglia recently led a small clinical study, published in GeroScience, that examined the relationship between a patient’s past history of depression and dementia. The researchers did not find a direct link, suggesting that the association is complex and depression is likely a heterogeneous condition. The study lays the groundwork for a larger study that may help to explain how the two conditions are connected.

Salwierz’s interest in depression and dementia dates back several years, to when he worked as a research analyst at the Centre for Addiction and Mental Health.

In 2021, he began to investigate associations between the two conditions with Tartaglia, an associate professor at the Temerty Faculty of Medicine and clinician-scientist at the Krembil Brain Institute, University Health Network (UHN).

In their recent publication, they used clinical data from 126 patients at the UHN memory clinic who had cognitive decline. They gathered information from the patients about their history of depression, and they analyzed the patients’ cerebrospinal fluid and MRI brain scans, looking for biological factors and brain white matter injury that could link depression and neurodegeneration, particularly Alzheimer’s disease.

Using real world data from the clinic, Salwierz says, means the study better represents the general population of dementia patients.

“People who sign up to participate in research studies are generally less diverse and have better access to health care, and the inclusion criteria usually results in a homogenous sample that doesn’t necessarily reflect the broader population of dementia patients,” says Salwierz. “Being able to use a clinic sample that better reflects the general population was a real strength of our study.”

When the team examined the results, they could not find a clear relationship between a patient’s history of depression and dementia. They did not see a significant difference in the biomarkers of Alzheimer's disease, the age that dementia began, cognitive scores and other measures between patients with and without a history of depression.

“The same thing that is a strength of the clinic sample, its heterogeneity, also makes the results hard to tease out,” says Salwierz. “Patients have different types of dementia or depression, different lifestyle factors, and a broad range of biomarkers, and we didn’t see a clear relationship among them.”

These results provide valuable information that the relationship between past depression and dementia is complex and that there may be different types of depression. The team has already started a larger project looking at a similar question with the goal of replicating their results and furthering the investigation of past depression and neurodegenerative disease.

“Recognizing the heterogeneity within depression is crucial, and advancing our understanding of its relationship to dementia requires the application of precision medicine, including biomarkers, to this psychiatric disorder. This approach can help us identify distinct subtypes of depression,” explains Tartaglia.

Taking part in a clinical study while pursuing medical education has also been a valuable learning experience for Salwierz.

“Working at the Tanz, we have a level of intellectual freedom to pursue important questions in neurodegenerative disease,” he says. “We’re surrounded by other labs, which facilitates collaboration with other teams and fields, and I appreciate those opportunities as I start my career.”