Amyloid deposits not associated with depression in the elderly

September 23, 2020

Philadelphia, September 23, 2020 - Depression in elderly people can include symptoms such as memory loss, making it hard to distinguish from the early stages of Alzheimer's disease and other types of dementia. A signature of Alzheimer's is accumulation of a protein called amyloid beta (Aβ) in the brain, which can be detected with brain-imaging technology.

Researchers had suspected that Aβ deposits might also underlie the cognitive decline seen in older people with depression, however a new study from researchers at the University of California, San Francisco (UCSF) has found that abnormal Aβ deposits were actually found in fewer older adults with major depression compared to non-depressed control subjects. The study, appears in Biological Psychiatry, published by Elsevier.

John Krystal, Editor of Biological Psychiatry, said of the work: "In the elderly, depression can sometimes be difficult to tease apart from dementia. 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."

The study included 119 older adults with major depression and 119 non-depressed participants with an average age of 71. All of the depressed participants were enrolled in the Alzheimer's Disease Neuroimaging Initiative's Depression (ADNI-D) Project , a large research collaboration between multiple research agencies and universities. None of the participants in the current study had been diagnosed with dementia. The researchers collected blood and DNA samples from the subjects, and they used positron emission tomography (PET) to detect Aβ deposits in their brains.

"Surprisingly, we did not observe evidence of increased amyloid deposition in the participants with major depression," said Principal Investigator and lead author Scott Mackin, PhD, and professor of Psychiatry at the UCSF Weill Institute for Neurosciences, San Francisco, CA, USA. "Instead, we saw decreased amyloid deposition when we compared the groups in several different ways."

Significant amyloid protein deposits were detected in just 19 percent of participants with depression compared with 31 percent of control subjects.

As expected, subjects with depression performed worse on cognitive and memory tests than non-depressed subjects. In addition, participants with brain amyloid deposits performed worse on the memory tests, but this was true regardless of whether they had depression or not. "Depression had a strong impact on memory performance independent of amyloid deposition," Dr. Mackin said.

Together, the findings indicate that depression is a risk factor for cognitive decline, but that it probably works through some mechanism other than amyloid deposition.

The presence of amyloid deposits did not depend on a patient's history of depression or use of anti-depressant treatments, which, Dr. Mackin said, "would suggest that depressed mood, or depression treatments, are also likely not protective against amyloid deposition."

According to the authors, the findings generated many new questions that will need to be investigated.
Notes for editors

The article is "Late Life Depression is Associated with Reduced Cortical Amyloid Burden: Findings from the ADNI Depression Project," by R. Scott Mackin, Philip S. Insel, Susan Landau, David Bickford, Ruth Morin, Emma Rhodes, Duygu Tosun, Howie J. Rosen, Meryl Butters, Paul Aisen, Rema Raman, Andrew Saykin, Arthur Toga, Clifford Jack, Jr., Robert Koeppe, Michael W. Weiner, Craig Nelson, on behalf of the Alzheimer's Disease Neuroimaging Initiative & the ADNI Depression Project.   ( It appears as an Article in Press in Biological Psychiatry, published by Elsevier.

Copies of this paper are available to credentialed journalists upon request; please contact Rhiannon Bugno at or +1 254 522 9700. Journalists wishing to interview the authors may contact Suzanne Leigh at or 011 415 504 6008.

The authors' affiliations and disclosures of financial and conflicts of interests are available in the article.

John H. Krystal, MD, is Chairman of the Department of Psychiatry at the Yale University School of Medicine, Chief of Psychiatry at Yale-New Haven Hospital, and a research psychiatrist at the VA Connecticut Healthcare System. His disclosures of financial and conflicts of interests are available here.

About Biological Psychiatry

Biological Psychiatry is the official journal of the Society of Biological Psychiatry, whose purpose is to promote excellence in scientific research and education in fields that investigate the nature, causes, mechanisms and treatments of disorders of thought, emotion, or behavior. In accord with this mission, this peer-reviewed, rapid-publication, international journal publishes both basic and clinical contributions from all disciplines and research areas relevant to the pathophysiology and treatment of major psychiatric disorders.

The journal publishes novel results of original research which represent an important new lead or significant impact on the field, particularly those addressing genetic and environmental risk factors, neural circuitry and neurochemistry, and important new therapeutic approaches. Reviews and commentaries that focus on topics of current research and interest are also encouraged.

Biological Psychiatry is one of the most selective and highly cited journals in the field of psychiatric neuroscience. It is ranked 7th out of 155 Psychiatry titles and 12th out of 271 Neurosciences titles in the Journal Citations Reports® published by Clarivate Analytics. The 2019 Impact Factor score for Biological Psychiatry is 12.095.

About Elsevier

Elsevier is a global information analytics business that helps scientists and clinicians to find new answers, reshape human knowledge, and tackle the most urgent human crises. For 140 years, we have partnered with the research world to curate and verify scientific knowledge. Today, we're committed to bringing that rigor to a new generation of platforms. Elsevier provides digital solutions and tools in the areas of strategic research management, R&D performance, clinical decision support, and professional education; including ScienceDirect, Scopus, SciVal, ClinicalKey and Sherpath. Elsevier publishes over 2,500 digitized journals, including The Lancet and Cell, 39,000 e-book titles and many iconic reference works, including Gray's Anatomy. Elsevier is part of RELX, a global provider of information-based analytics and decision tools for professional and business customers.

Media contact

Rhiannon Bugno, Editorial Office
Biological Psychiatry
+1 254 522 9700


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