Depressive symptoms linked to amyloid accumulation, suggesting ties to preclinical AD

Key takeaways:

• Depressive symptoms may be an early feature of preclinical Alzheimer’s disease.
• Associations between increasing depressive symptoms and amyloid accumulation persisted independent of cognitive changes.

Increasing depressive symptoms among cognitively unimpaired older adults appeared significantly associated with early amyloid accumulation in brain regions involved in emotional control, according to a study published in JAMA Network Open.

These associations occurred independently of cognitive changes and suggest affective symptoms should be monitored in this population when screening for Alzheimer’s disease, according to the researchers.

“Prior work from our group found that baseline cortical amyloid levels moderated the association between increasing depressive symptoms and worsening cognition in cognitively unimpaired older adults,” Catherine E. Munro, PhD, of the department of neurology at Brigham and Women’s Hospital, and colleagues wrote.

“However, more work is needed to better understand trajectories of depressive symptoms in cognitively unimpaired older adults and early amyloid accumulation in the context of cognitive decline,” they added.

Munro and colleagues conducted a cohort study to determine whether increasing depressive symptoms were associated with amyloid accumulation in key brain regions related to emotional control, including the medial orbitofrontal cortex (mOFC), isthmus cingulate cortex (IC) and middle frontal cortex (MFC).

The analysis included 154 adults aged 60 years and older (mean age, 72.6 years; 61% women; 84.4% white) in the Harvard Aging Brain Study, who were cognitively unimpaired and had mild or no depressive symptoms at baseline and who were followed for a mean 8.6 years.

The researchers annually assessed depressive symptoms using the 30-item Geriatric Depression Scale (GDS) and objective cognitive performance using the Preclinical Alzheimer Cognitive Composite-5 (PACC).

Additionally, participants underwent cortical amyloid positron emission tomography imaging at baseline and every following 2 to 3 years to identify amyloid accumulation, measured via Pittsburgh compound B (PiB).

Munro and colleagues found that greater GDS scores over time were associated with increasing PiB slopes in the mOFC (B = 11.07; 95% CI, 5.26-16.87), IC (B = 12.83; 95% CI, 5.68-19.98) and MFC (B = 9.22; 95% CI, 2.25-16.2).

They also found that this association persisted even after adjusting for cognitive changes measured by the PACC slopes (mOFC: B = 10.84; 95% CI, 5.22-16.46; IC: B = 11.86; 95% CI, 4.88-18.85; MFC: B = 7.81; 95% CI, 0.95-14.66).

“These findings suggest that increasing depressive symptoms in older adults may be associated with increasing regional Alzheimer disease pathology, which has implications for recognizing individuals in preclinical Alzheimer disease stages who may be candidates for disease-modifying treatments and for considering depression treatment to prevent dementia,” the researchers wrote.

They acknowledged several study limitations, including the relatively small sample size, which was primarily composed of highly educated, non-Hispanic white individuals.

“Thus, it will be critical in future work to examine associations in larger and more diverse samples, particularly as racially and ethnically minoritized individuals are at greater risk of developing dementia,” the researchers wrote.