Depressive Symptoms and Amyloid Pathology.

Area of Science:

• Neuroscience
• Gerontology
• Psychiatry

Background:

• Depressive symptoms are linked to cognitive decline in older adults, but underlying mechanisms remain unclear.
• Understanding the relationship between depression and amyloid pathology is crucial for diagnosis and treatment.

Purpose of the Study:

• To investigate the association between depressive symptoms and amyloid pathology in older individuals without dementia.
• To examine if this association is influenced by age, sex, education, or APOE genotype.

Main Methods:

• Cross-sectional analysis of pooled data from 49 studies (Amyloid Biomarker Study).
• Included 9746 individuals with normal cognition (NC) and 3023 with mild cognitive impairment (MCI).
• Assessed amyloid pathology via cerebrospinal fluid (CSF) Aβ1-42 or PET scans; depressive symptoms via validated scales, diagnosis, or self-report.

Main Results:

• In NC individuals, depressive symptoms were not associated with amyloid pathology (OR, 1.13; P=.29).
• In MCI individuals, depressive symptoms were associated with a lower likelihood of amyloid pathology (OR, 0.73; P=.001).
• In NC individuals, depressive symptoms were linked to higher amyloid pathology in APOE ε4 non-carriers only (mean difference, 5.0%; P=.02).

Conclusions:

• Depressive symptoms are not consistently associated with increased amyloid pathology in normal cognition and are linked to decreased amyloid pathology in MCI.
• Age, sex, and education did not influence these associations.
• Non-amyloid mechanisms may frequently underlie depressive symptoms in older adults.