According to findings published in The American Journal of Psychiatry, elevated amyloid beta levels are associated with anxious-depressive symptoms in older individuals with normal cognition. These results support the theory that neuropsychiatric symptoms may act as early indicators of preclinical Alzheimer disease.

Researchers extracted data from the Harvard Aging Brain Study cohort and conducted an observational study of 270 cognitively normal older adults over 5 years. Patients underwent Pittsburgh compound B (PiB) positron emission tomography imaging at baseline to ascertain cortical amyloid beta levels. Participants were also assessed annually for depression using the Geriatric Depression Scale (GDS). In addition to a total GDS score, researchers calculated an average score for each of 3 clusters of GDS items: anxiety-concentration, apathy-anhedonia, and dysphoria.

Researchers investigated PiB binding as a predictor of GDS score and found that higher PiB binding by time was associated with steeper rates of increase in total GDS score over time (regression coefficient 0.65; 95% CI, 0.02-1.28; P =.04). Higher PiB binding also predicted a steeper increase in anxiety-concentration scores (regression coefficient 0.04; 95% CI, 0.007-0.067; P =.015), although not in apathy-anhedonia or dysphoria scores. These results suggest that anxious-depressive symptoms specifically may be the most useful early marker of preclinical Alzheimer disease.

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Screening criteria restricted the study population to those with low baseline GDS scores, thus limiting the applicability of these findings to individuals with relatively good mental health. Researchers also recommended longitudinal follow-up to ascertain whether escalating depression symptoms eventually give rise to cognitive impairment or Alzheimer disease.


Donovan NJ, Locascio JJ, Marshall GA, et al. Longitudinal association of amyloid beta and anxious-depressive symptoms in cognitively normal older adults [published online January 12, 2018]. Am J Psychiatry. doi:10.1176/appi.ajp.2017.17040442