Depression Symptoms Help Predict Cognitive Loss in Alzheimer Patients


The association of depression symptoms with cognition and cortical amyloid measurements could lead to better therapies to prevent Alzheimer disease.

Jennifer Gatchel, MD, PhD

Jennifer Gatchel, MD, PhD

The link between concurrent changes in depression and cognition in older adults with increased cortical amyloid could yield better targets in delaying Alzheimer disease (AD) symptoms.

A team, led by Jennifer R. Gatchel, MD, PhD, Harvard Medical School, recently found examining the longitudinal data from the Harvard Aging Brain Study, a cohort study involving 276 patients who were cognitively unimpaired with at most mild depression at study entry, that worsening symptoms over 2 to 7 years in the presence of cortical amyloid was tied to declining cognition.

The study participants, which included 164 women and 112 men with a mean age of 73.5, underwent annual assessments for depression (Geriatric Depression Scale [GDS]), cognition (Preclinical Alzheimer Cognitive Composite [PACC]), and baseline cortical amyloid measurement (Pittsburgh Compound-B positron emission tomography imaging) over a 7-year period.

Approximately 14.9% of the participants reported taking antidepressant medication at baseline, with 8% reporting a history of depression with onset in the past 10 years and 8% reported onset more remotely.

The baseline mean score for depression was 3.0, -.004 for cognition, and 1.16 for cortical amyloid measurements. At the last follow-up, the mean score for depression was 3.9, -.09 for cognition, and the interaction between cortical amyloid and increasing associated with declining cognition (95% CI, −.27-−0.12; P<&thinsp;.001).

“Our findings add to a growing body of literature supporting an association between concurrent changes in depression and cognition, providing some of the first focused evidence of this association in preclinical AD defined based on amyloid PET neuroimaging,” the authors wrote. “Results support depressive symptoms as among the earliest changes related to AD pathological burden and cognitive decline.”

The investigators analyzed the scores using mixed-effects longitudinal models with backward elimination and examined changes in GDS and baseline amyloid as interactive predictors of PACC decline in a linear mixed model with backward elimination, adjusting for age, sex, and education.

PACC and GDS was also inversely associated over the duration of the study in the presence of baseline amyloid. In a mixed-effects model, the team found that the outcome of PACC was predicted by longitudinal GDS and baseline cortical amyloid.

Recent research regarding Alzheimer disease have mainly focused on the preclinical stage, where there is evidence of elevated amyloid and pathological change prior to the development of mild cognitive impairment.

While prevention trials remain ongoing focusing on cognitive outcomes, they do not incorporate depression as an outcome measure.

“The association between mild depressive symptoms and cognition in the presence of in vivo AD pathology in unimpaired older adults has not been clearly established,” the authors wrote. “Better understanding of the associations among depressive symptoms, cognition, and AD pathology is critical to inform prognosis in older adults with depressive symptoms, some of whom may be at risk for cognitive decline.”

Recently, the Cleveland Clinic released their fourth annual “Alzheimer's disease drug development pipeline: 2019,” a comprehensive look at what is currently developed in clinical trials in the US.

The investigators, led by Jeffrey Cummings, MD, ScD, director emeritus of Cleveland Clinic Lou Ruvo Center for Brain Health, identified all pharmacologic Alzheimer trials currently in development from They found 132 agents currently in 156 clinical trials—28 of which are in 42 phase 3 trials; 74 in 83 phase 2 trials; and 30 in 31 phase 1 trials.

The study, “Longitudinal Association of Depression Symptoms With Cognition and Cortical Amyloid Among Community-Dwelling Older Adults,” was published online in JAMA Psychiatry.

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