Depressive Symptoms Linked to Increased Cortical Amyloid Burden

Increasing depressive symptoms are associated with higher cortical amyloid levels in brain regions related to emotional control and mood, as well as decreased cognitive performance. These study findings were published in JAMA Network Open.

Depression has been linked to pathophysiological changes among both patients with Alzheimer disease (AD) and cognitively unimpaired patients. However, little is known about the temporal concurrence of amyloid burden and mood among individuals with low cortical amyloid levels at baseline.

To this aim, researchers conducted a longitudinal study using data from the Harvard Aging Brain Study to analyze the relationship between depressive symptoms over time and early regional amyloid accumulation in key regions of interest and its effect on objective cognitive performance. Regions of interest included the medial and lateral orbitofrontal cortices, middle frontal and superior frontal gyri, anterior cingulate cortex, isthmus and posterior cingulate cortices, and amygdala.

Participants were 60 years of age and older and at baseline had no cognitive impairment, mild depressive symptoms at most, and low global cortical amyloid burden. All participants with a history of head trauma, unstable or severe mental illness, or recent substance abuse were excluded. Participants underwent extensive cognitive testing annually and multimodal neuroimaging, including Pittsburgh compound B (PiB)-positron emission tomography (PET) amyloid imaging, every 2 to 3 years. The researchers used the Geriatric Depression Scale (GDS) to measure depressive symptoms.

A total of 154 participants were included in the analysis. The participants had a mean (SD) age of 72.6 (6.4) years, 61% were women, and 84.4% were White. The mean (SD) follow-up duration was 8.6 (2.2) years, GDS score was 3.3 (SD, 2.9), and PiB distribution volume ratio was 0.8 (0.03) at baseline.

The investigators observed a significant relationship between increasing PiB slope and increasing GDS score in the medial orbitofrontal cortex (β=11.07; 95% CI, 5.26-16.87; t=3.74; SE, 2.96; P=.004), isthmus cingulate cortex (β=12.83; 95% CI, 5.68-19.98; t=3.51; SE, 3.65; P=.004), and middle frontal cortex (β=9.22; 95% CI, 2.25-16.20; t=2.59; SE = 3.56; P=.03).

When adjusting for the slope of Preclinical Alzheimer Cognitive Composite-5 scores, a higher PiB slope was still significantly associated with increasing GDS scores in the medial orbitofrontal cortex (β=10.84; 95% CI, 5.22-16.46; t=3.78; SE, 2.87; P=.008), isthmus cingulate cortex (β=11.86; 95% CI, 4.88-18.85; t=3.33; SE, 3.56; P=.008), and middle frontal cortex (β=7.81; 95% CI, 0.95-14.66; t=2.23; SE, 3.50; P=.04).

“Our results support the idea that underlying AD pathology (eg, structural, inflammation, or excitotoxic damage from amyloid accumulation) could contribute to emerging depressive symptoms as a feature of early AD progression, in the preclinical disease stage, before objective cognitive impairment (ie, MCI, dementia),” the researchers concluded.

Study limitations include the relatively small sample size and the lack of diversity within the study population. Additionally, the researchers did not evaluate the effect of cerebrovascular disease on the variables examined.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

This article originally appeared on Psychiatry Advisor