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October 01, 2020
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Amyloid beta not linked to depression among older adults

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Depression among older adults did not appear associated with amyloid beta deposits, according to study results published in Biological Psychiatry.

“Evidence for increased [amyloid beta] pathology in [late-life depression] has been equivocal, with some studies showing no association of depression history or current depression with increased [amyloid beta],” R. Scott Mackin, PhD, of the department of psychiatry at University of California, San Francisco, and colleagues wrote. “In addition, many of the published studies showing elevated [amyloid beta] in [late-life depression] have been limited by small sample sizes. Only two studies evaluated APOE genotype in group comparisons, which is salient given the known association of APOE with [Alzheimer’s disease] risk.”

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Moreover, most prior studies contained incomplete depression and treatment histories, which is of note since some studies demonstrated a potential association between selective serotonin reuptake inhibitor treatment and reduced amyloid beta pathology.

In the current study, Mackin and colleagues aimed to determine whether late-life depression was linked to increased amyloid beta accumulation, as well as to evaluate the association between amyloid beta deposition and memory performance and depression history characteristics, such as SSRI use. They analyzed data of 119 adults aged 60 to 89 years with a current diagnosis of major depression and 119 adults aged 65 to 91 years without depression or cognitive impairment. The participants were matched on age, sex and APOE genotype. All participants were enrolled in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) Depression Project study

Results showed 33% of participants with late-life depression met amyloid beta criteria for mild cognitive impairment according to ADNI criteria. Those in the late-life depression group exhibited less global amyloid beta accumulation vs. those without depression. A total of 19.3% of those in the late-life depression and 31.1% in the group without depression had significant amyloid deposits. Global amyloid beta was not linked to lifetime depressive episodes, lifetime length of depression, length of lifetime SSRI use or lifetime length of untreated depression among those with late-life depression; however, it was associated with worse memory performance. The investigators observed similar results in secondary analyses that restricted comparisons to cognitively unimpaired participants with late-life depression, as well as when the late-life depression group was compared with a group without depression that included participants with mild cognitive impairment.

“Although we did not evaluate longitudinal outcomes in this study, our results suggest that increased cortical amyloid burden is not a primary causal factor in reported increased risk for dementia associated with major depression in older adults,” Mackin and colleagues wrote. “This conclusion is strengthened by a lack of association between depression characteristics and history of treatment with amyloid burden. In contrast, our findings that depression was strongly linked to memory dysfunction, independent of amyloid, suggests that [late-life depression] may accelerate progression to dementia by contributing to cognitive and functional burden among individuals with concurrent [mild cognitive impairment] or incipient neurodegenerative disease."