Depression, Anxiety Plus Amyloid Pathology Elevates MCI Risk

Researchers have uncovered a positive synergistic interaction between Alzheimer's pathology and neuropsychiatric symptoms.

VANCOUVER, British Columbia – The presence of beta amyloid deposits, together with depression or anxiety, appears to elevate the risk of incident mild cognitive impairment (MCI) in cognitively normal adults.

While previously recognized as independent risk factors for cognitive impairment, the effects of the interaction between the characteristic plaques and neuropsychiatric symptoms have not been explored. 

In order to examine the potential interaction and its effect on patient outcomes, researchers led by Yonas Geda, MD, of the Mayo Clinic, in Rochester, Minnesota, conducted a prospective cohort study from the Mayo Clinic Study of Aging. In total, the researchers analyzed outcomes from 950 cognitively normal participants aged 50 years and older for a median of 28 months or to diagnosis of incident MCI. The findings from the study were presented at the 2016 annual meeting of the American Academy of Neurology (AAN).

Patients underwent positron emission tomography with Pittsburgh compound B (PiB-PET) imaging and were evaluated based on the Beck Depression Inventory II (BDI-II) and Beck Anxiety Inventory (BAI). Participants were classified as PiB-positive (≥1.4) or PiB-negative (<1.4) based on global cortical-to-cerebellar ratio cut-point. Depression was indicated as a BDI-II score ≥13, and anxiety was indicated with a BAI score ≥10. Cognitive diagnosis was determined by an expert consensus panel.

After adjusting for age, sex, and education, the researchers found that participants who were PiB-positive and depressed had a more than 3-fold increased risk of MCI (hazard ratio [HR] 3.56; 95% confidence interval [CI], 1.46-8.63) compared with controls. Those who were PiB-positive and anxious had a more than 5-fold increased risk for MCI (HR, 5.38; 95% CI, 2.35-12.3]) compared with controls. Positive interaction between both beta amyloid and depression and beta-amyloid and anxiety was statistically significant (P=.032 and P=.034, respectively).

The results indicate that both depression and anxiety should be considered targets for intervention in presymptomatic Alzheimer’s disease.

Click here for more coverage from the 68th Annual Meeting of the American Academy of Neurology, April 15-21, 2016, in Vancouver, British Columbia, Canada.


Neureiter J, Krell-Roesch J, Pink A, et al. Amyloid-β, neuropsychiatric symptoms and the risk of incident mild cognitive impairment: a prospective cohort study. Presented at: The 68th Annual Meeting of the American Academy of Neurology; April 15-21, 2016; Vancouver, British Columbia, Canada. Abstract S35.003.