Depression and Alzheimer’s

Study looks at symptoms in cognitively healthy older individuals

silhouette of elderly person alone

Increasingly, Alzheimer’s disease research has focused on the preclinical stage, when people have biological evidence of Alzheimer’s but either no symptoms or minimal symptoms—the time when interventions might have the potential to prevent future decline of older adults.

Harvard Medical School researchers at Massachusetts General Hospital have shed new light on this area. A new study published in JAMA Network Open indicates that depression symptoms in cognitively healthy older individuals, together with brain amyloid — a biological marker of Alzheimer’s — could trigger changes in memory and thinking over time.

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“Our research found that even modest levels of brain amyloid deposition can impact the relationship between depression symptoms and cognitive abilities,” said Jennifer Gatchel, HMS assistant professor of psychiatry and a geriatric psychiatrist at Mass General and lead author of the study.

“This raises the possibility that depression symptoms could be targets in clinical trials aimed at delaying the progression of Alzheimer’s disease. Further research is needed in this area,” she said.

Past research has shown an association between depression and cognitive deficits in older individuals. This study, however, is among the first to reveal that this association is influenced by the presence of cortical amyloid in unimpaired older adults, even when depression symptoms are mild to moderate.

Data were collected by researchers over a seven-year period from 276 community-dwelling older adults, all participants in the landmark Harvard Aging Brain Study.

Declining cognition

What they discovered was a significant link between worsening depression symptoms and declining cognition over two to seven years that was influenced by Alzheimer’s disease pathology, as measured by PET imaging of brain amyloid.

“Our findings offer evidence that in healthy older adults, depression symptoms together with brain amyloid may be associated with early changes in memory and in thinking,” explained Gatchel.

“Depression symptoms themselves may be among the early changes in the preclinical stages of dementia syndromes. 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,” Gatchel said.

Mass General researchers also learned from their extensive work that not all older adults with depression symptoms and cortical amyloid will experience failing cognition.

Other risk factors investigated by the authors that could modify the relationship between depression and cognition include brain metabolism and volume of the hippocampus, the part of the brain associated with learning and forming of new memories. The authors also noted that other mechanisms, including tau-mediated neurodegeneration, hypertension, hypercortisolemia and inflammation, may be involved and need to be investigated.

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

Adapted from a Mass General news release.

Support for the study includes National Institute on Aging (grants PO1 AGO36694, K24 AG035007 and K23 AG058805), the BrightFocus Foundation, the Alzheimer’s Association, and the Mass General Rappaport Fellowship.

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