Amyloid pathologies modulate the associations of minimal depressive symptoms with cognitive impairments in older adults without dementia,Biological Psychiatry

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Amyloid pathologies modulate the associations of minimal depressive symptoms with cognitive impairments in older adults without dementia
Biological Psychiatry ( IF 9.6 ) Pub Date : 2020-07-01 , DOI: 10.1016/j.biopsych.2020.07.004
Wei Xu ₁ , Wei Feng ₂ , Xue-Ning Shen ₃ , Yan-Lin Bi ₄ , Ya-Hui Ma ₁ , Jie-Qiong Li ₅ , Qiang Dong ₃ , Lan Tan ₁ , , Jin-Tai Yu ₃

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BACKGROUND The relationship between depression and Alzheimer's disease (AD) is complex and still not well understood. We aimed to examine the roles of the AD core pathologies in modulating the associations of minimal depressive symptoms (MDSs) with cognitive impairments. METHODS A total of 721 participants who had measures of cognition, depressive symptoms, and cerebrospinal fluid AD biomarkers were included from the CABLE (Chinese Alzheimer's Biomarker and LifestylE) study. Causal mediation analyses with 10,000 bootstrapped iterations were conducted to explore the mediation effects of AD pathologies on cognition. The ADNI (Alzheimer's Disease Neuroimaging Initiative) was used 1) to replicate the mediation effects and 2) to examine the longitudinal relationships of MDSs with amyloid pathology and incident AD risk. RESULTS In CABLE, MDSs were associated with poorer global cognition (p = .006) and higher amyloid burden as indicated by cerebrospinal fluid amyloid markers (p < .0001). The influence of MDSs on cognition was partially mediated by amyloid pathology (a maximum of 85%). The mediation effects were replicated in 725 elderly persons without dementia (age, mean ± SD = 73.5 ± 6.9 years; 301 female subjects [42%]) in ADNI, such that the mediation percentage varied from 10% to 30% for general cognition, memory, and executive functions. Longitudinal analyses revealed a bidirectional relationship between MDSs and amyloid pathology (p = .01). MDSs were associated with 83% increased risk of developing AD dementia (hazard ratio = 1.83, p < .01). CONCLUSIONS Overall, amyloid pathology might partially mediate and magnify the influences of MDSs on cognitive impairments and AD risk.

更新日期：2020-07-01

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