Perlman George, Cogo-Moreira Hugo, Wu Che-Yuan, Herrmann Nathan, Swardfager Walter
Hurvitz Brain Sciences Program, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto M4N 3M5, Canada; Department of Pharmacology & Toxicology, University of Toronto, 1 King's College Circle, Toronto M5S 1A8, Canada; Sleep and Cardiopulmonary Program, University Health Network - Toronto Rehabilitation Institute, 347 Rumsey Road, Toronto M4G 2V6, Canada.
Department of Education, ICT and Learning, Østfold University College, P.O.Box 700, NO-1757, Halden, Norway.
Psychoneuroendocrinology. 2022 Dec;146:105922. doi: 10.1016/j.psyneuen.2022.105922. Epub 2022 Sep 12.
Allostatic load (AL) indicates the cumulative impact of stress on homeostatic mechanisms. Depression and AL have been associated with cognitive deficits, but it is unclear if they do so independently.
Using data from middle-aged participants in the observational longitudinal Midlife in the United States (MIDUS) study (n = 704, 57.5 % female, 63.8 ± 10.6 years old in 2014), we assessed whether the effect of prior depression (Composite International Diagnostic Interview Short-Form in 1995) on cognitive decline between 2004 and 2013 (composite Z-scores derived from the Brief Test of Adult Cognition by Telephone and the Stop & Go Switch Task) was moderated by AL Z-scores in 2004 (calculated from biomarkers in blood, urine, and electrocardiography).
A significant depression × AL interaction predicted a decline in a composite cognitive score (β = -0.066, SE=0.029, p = 0.024) and executive function (β = -0.068, SE=0.025, p = 0.007). Depression predicted a decline in composite cognition among those with AL Z-scores above - 0.055. AL subdomains of inflammation and lipid metabolism showed evidence of moderation.
Middle-aged adults with depression who had higher allostatic load were at greater risk of cognitive decline. Future studies should evaluate whether the interaction predicts incident dementia, and whether interventions targeting depression or elevated AL in people who have both can attenuate cognitive decline.
应激负荷（AL）表明压力对体内平衡机制的累积影响。抑郁与应激负荷均与认知缺陷有关，但它们是否独立导致认知缺陷尚不清楚。
利用美国中年纵向观察研究（MIDUS）中参与者的数据（n = 704，女性占57.5%，2014年时年龄为63.8±10.6岁），我们评估了既往抑郁（1995年采用复合国际诊断访谈简表）对2004年至2013年期间认知衰退（通过电话成人认知简短测试和停止与继续切换任务得出的复合Z分数）的影响是否受到2004年AL Z分数（根据血液、尿液和心电图中的生物标志物计算得出）的调节。
抑郁与AL的显著交互作用预示着复合认知得分（β = -0.066，SE = 0.029，p = 0.024）和执行功能（β = -0.068，SE = 0.025，p = 0.007）会下降。抑郁预示着AL Z分数高于 -0.055的人群中复合认知能力会下降。炎症和脂质代谢的AL子域显示出调节作用的证据。
应激负荷较高的中年抑郁症患者认知衰退风险更大。未来的研究应评估这种交互作用是否能预测痴呆症的发生，以及针对同时患有抑郁症和应激负荷升高的人群进行的抑郁或应激负荷升高干预是否能减轻认知衰退。
