Department of Psychiatry, University of California, San Francisco, California; Center for Imaging of Neurodegenerative Diseases, Veterans Administration Medical Center, San Francisco, California.
Department of Psychiatry, University of California, San Francisco, California; Clinical Memory Research Unit, Faculty of Medicine, Lund University, Lund, Sweden.
Biol Psychiatry. 2021 Apr 15;89(8):757-765. doi: 10.1016/j.biopsych.2020.06.017. Epub 2020 Jul 2.
We evaluated the role of cortical amyloid deposition as a factor contributing to memory dysfunction and increased risk of dementia associated with late-life depression (LLD).
A total of 119 older adult participants with a current diagnosis of major depression (LLD) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) Depression Project study and 119 nondepressed (ND) cognitively unimpaired participants matched on age, sex, and APOE genotype were obtained from the ADNI database.
Thirty-three percent of LLD participants met ADNI criteria for mild cognitive impairment. Compared with ND individuals, the LLD group exhibited less global amyloid beta (Aβ) accumulation (p = .05). The proportion of amyloid positivity in the LLD group was 19.3% compared with 31.1% for the ND participants (p = .02). Among LLD participants, global Aβ was not associated with lifetime number of depressive episodes, lifetime length of depression, length of lifetime selective serotonin reuptake inhibitor use, or lifetime length of untreated depression (p > .21 for all). Global Aβ was associated with worse memory performance (p = .05). Similar results were found in secondary analyses restricting comparisons to the cognitively unimpaired LLD participants as well as when comparing the LLD group with an ND group that included participants with mild cognitive impairment.
Contrary to expectation, the LLD group showed less Aβ deposition than the ND group and Aβ deposition was not associated with depression history characteristics. Aβ was associated with memory, but this relationship did not differ between LLD and ND. Our results suggest that memory deficits and accelerated cognitive decline reported in previous studies of LLD are not due to greater cortical Aβ accumulation.
我们评估了皮质淀粉样蛋白沉积作为导致与晚年抑郁症(LLD)相关的记忆功能障碍和痴呆风险增加的因素的作用。
从阿尔茨海默病神经影像学倡议(ADNI)抑郁项目研究中获得了 119 名患有当前重度抑郁症(LLD)的老年参与者和 119 名年龄、性别和 APOE 基因型匹配的无抑郁(ND)认知正常参与者。
33%的 LLD 参与者符合 ADNI 轻度认知障碍标准。与 ND 个体相比,LLD 组表现出较少的整体淀粉样蛋白β(Aβ)积累(p=0.05)。LLD 组的淀粉样蛋白阳性比例为 19.3%,而 ND 参与者为 31.1%(p=0.02)。在 LLD 参与者中,全球 Aβ与终生抑郁发作次数、抑郁持续时间、选择性 5-羟色胺再摄取抑制剂使用时间和未治疗抑郁持续时间无关(p>0.21 所有)。全球 Aβ与记忆表现较差相关(p=0.05)。在对认知正常的 LLD 参与者进行二次分析以及将 LLD 组与包括轻度认知障碍参与者的 ND 组进行比较时,也发现了类似的结果。
与预期相反,LLD 组的 Aβ 沉积量低于 ND 组,且 Aβ 沉积量与抑郁史特征无关。Aβ与记忆有关,但 LLD 和 ND 之间的这种关系没有差异。我们的研究结果表明,之前 LLD 研究报告的记忆缺陷和认知加速下降不是由于皮质 Aβ 积累增加所致。