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Late-Life Depression Associated With Reduced Amyloid Beta Accumulation

September 28, 2020

Contrary to researchers’ expectations, memory loss and accelerated cognitive decline in older adults with major depression are not caused by greater amyloid beta accumulation in the brain, suggests a study published online in Biological Psychiatry.

Researchers collected blood and DNA samples, and also conducted positron emission tomography (PET) brain scans to detect amyloid beta deposits, in 119 older adults with major depression and 119 matched older adult participants without depression. None of the participants had been diagnosed with dementia.

“Surprisingly, we did not observe evidence of increased amyloid deposition in the participants with major depression,” said principal investigator and study lead author Scott Mackin, PhD, a psychiatry professor at the University of California, San Francisco. “Instead, we saw decreased amyloid deposition when we compared the groups in several different ways.”

Just 19.3% of participants with late-life depression had significant amyloid protein deposits, according to the study, compared with 31.1% of participants without late-life depression.

Adjusting Psychopharmacologic Treatment for Geriatric Patients

While older adults with brain amyloid deposits performed worse on memory tests, the finding was true whether or not they had depression. Meanwhile, participants with depression performed worse on cognitive and memory tests than those without depression. 

“Depression had a strong impact on memory performance,” Dr. Mackin said, “independent of amyloid deposition.”

“In the elderly, depression can sometimes be difficult to tease apart from dementia,” said Biological Psychiatry editor John Krystal, MD. “This important study finds that late-life depression was not associated with increased deposition of beta-amyloid in the brain, a hallmark of Alzheimer's disease. This insight is important, because tests— like the PET scans that enable detection of deposited amyloid—may someday play a role in helping doctors to make this distinction.”

—Jolynn Tumolo


Mackin RS, Insel PS, Landau S, et al. Late-life depression is associated with reduced cortical amyloid burden: findings from the Alzheimer’s Disease Neuroimaging Initiative Depression Project. Biological Psychiatry. 2020 July 1;[Epub ahead of print].

Amyloid deposits not associated with depression in the elderly [press release]. Philadelphia, Pennsylvania: Elsevier; September 23, 2020.

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