Public Release: 

Depression is a risk factor rather than early sign of Alzheimer's disease

Rush University Medical Center

A new study by researchers at Rush University Medical Center supports the idea that depression is truly a risk factor for Alzheimer's disease rather than a subtle early sign of its underlying pathology. The study, published in the April issue of the Archives of General Psychiatry, found no evidence of an increase in depressive symptoms during the prodromal phase before the clinical diagnosis of Alzheimer's disease.

Numerous observational studies have found higher levels of depressive symptoms in old age to be associated with increased incidence of Alzheimer's disease and mild cognitive impairment. However, previous studies have not been able to answer the question of whether depressive symptoms actually contribute to the development of dementia (risk factor hypothesis) or are a consequence of the disease (reverse causality hypothesis.)

Robert S. Wilson, PhD, a neuropsychologist at the Rush Alzheimer's Disease Center, and colleagues examined data from the Rush Religious Orders Study, a cohort of 917 older Catholic clergy without dementia at study onset, to examine the change in depressive symptoms of Alzheimer's disease before and after the emergence of the cognitive symptoms of the disease.

For up to 13 years, the study participants underwent annual clinical evaluations that included assessment of depressive symptoms, cognitive testing, and clinical classification of mild cognitive impairment (MCI) and Alzheimer's disease. During the study period, 190 participants developed Alzheimer's disease.

Consistent with earlier findings in the Rush Religious Orders Study, having more depressive symptoms at baseline was associated with increased incidence of Alzheimer's disease and MCI.

However, the study found that those who developed Alzheimer's disease showed no increase in depressive symptoms before clinical diagnosis. Researchers were able to observe patients during a mean of approximately four years before the onset of dementia. Additionally, researchers saw no increase in depression during the three to four years preceding the onset of MCI, which antedates the onset of dementia by several years.

"If depressive symptoms are a consequence of dementia or a reaction to declining function, depressive symptoms would likely increase at some point before dementia is clinically evident," said Wilson. "We observed no such increase."

The study also found that even after the diagnosis of Alzheimer's disease was made there was no general increase in depression, but rather an increase that was confined to individuals with certain personality traits.

"Depressive symptoms may be associated with distinctive changes in the brain that somehow reduce neural reserve, which is the brain's ability to tolerate the pathology associated with Alzheimer's disease," said Wilson. "Understanding how depression contributes to the development of Alzheimer's disease may suggest new approaches to disease prevention."


The research was supported by grants from the National Institutes on Aging, which leads the Federal effort to support and conduct basic, clinical, and social and behavioral studies on aging and on Alzheimer's disease. The Rush Alzheimer's Disease Center is one of 29 NIA-supported Alzheimer's Disease Centers across the United States. For more information on the Rush Alzheimer's Disease Center, visit

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