Table_1.docx

Background: Although increased cognitive activity (CA), both current and past, is known to be associated with a decreased occurrence of Alzheimer’s disease (AD) dementia in older adults, the exact neural mechanisms underlying the association between CA during different stages of life and human dementia remain unclear. Therefore, we investigated whether CA during different life stages is associated with cerebral amyloid-beta (Aβ) pathology and AD-related neurodegeneration in non-demented older adults.Methods: Cross-sectional analyses of data collected between April 2014 and March 2016 from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE), an ongoing prospective cohort. In total, 321 community-dwelling, non-demented older adults were involved in this study. Cerebral Aβ deposition and Aβ positivity were measured using 11C-Pittsburgh compound B (PiB)-positron emission tomography (PET). AD-signature region cerebral glucose metabolism (AD-CMglu) and AD-signature region neurodegeneration (AD-ND) positivity were measured using 18F-fluorodeoxyglucose (FDG)-PET. In addition, CA in early, mid, and late life was systematically evaluated using a structured questionnaire.Results: Of the 321 participants, 254 were cognitively normal (CN) and 67 had mild cognitive impairment (MCI). The mean age of participants was 69.6 years old [standard deviation (SD) = 8.0]. Higher early-life CA (CAearly) was associated with significantly increased AD-CMglu (B = 0.035, SE = 0.013, P = 0.009) and a decreasing trend of AD-ND positivity (OR = 0.65, 95% CI 0.43–0.98, P = 0.04) but was not associated with Aβ deposition or positivity. We observed no association between midlife CA (CAmid) and any AD-related brain changes. Late-life CA (CAlate) showed an association with both global Aβ deposition and AD-CMglu, although it was not statistically significant. Sensitivity analyses controlling for current depression or conducted only for CN individuals revealed similar results.Conclusion: Our results suggest that CA in early life may be protective against late-life AD-related neurodegeneration, independently of cerebral Aβ pathology.

背景：尽管已知认知活动（CA）的增加，无论是当前还是过去的，均与老年人群中阿尔茨海默病（AD）痴呆的发病率降低相关联，但不同生命阶段认知活动与人类痴呆之间所涉及的精确神经机制尚不明确。因此，本研究旨在探究不同生命阶段的认知活动是否与未患痴呆的老年人群中的脑淀粉样蛋白-β（Aβ）病理和AD相关神经退行性变相关。方法：对2014年4月至2016年3月期间收集的韩国脑老化研究（KBASE）数据进行了横断面分析，KBASE是一项正在进行的纵向队列研究。本研究共纳入了321名居住在社区的、未患痴呆的老年成年人。使用11C-Pittsburgh化合物B（PiB）正电子发射断层扫描（PET）测量脑淀粉样蛋白-β沉积和Aβ阳性。使用18F-氟代脱氧葡萄糖（FDG）PET测量AD特征区域脑葡萄糖代谢（AD-CMglu）和AD特征区域神经退行性变（AD-ND）阳性。此外，通过结构化问卷系统性地评估了早、中、晚三个生命阶段的认知活动。结果：在321名参与者中，254人认知正常（CN），67人存在轻度认知障碍（MCI）。参与者的平均年龄为69.6岁[标准差（SD）= 8.0]。早期生命阶段的认知活动（CAearly）与显著增加的AD-CMglu（B = 0.035，SE = 0.013，P = 0.009）和AD-ND阳性率的下降趋势（OR = 0.65，95% CI 0.43–0.98，P = 0.04）相关联，但与Aβ沉积或阳性无关。我们未观察到中年阶段认知活动（CAmid）与任何AD相关脑部变化之间的关联。晚期生命阶段的认知活动（CAlate）与全局Aβ沉积和AD-CMglu相关，尽管这种关联不具有统计学意义。通过控制当前抑郁或仅针对CN个体进行的敏感性分析揭示了相似的结果。结论：我们的研究结果提示，早期生命阶段的认知活动可能对晚年AD相关神经退行性变具有保护作用，且这种作用独立于脑淀粉样蛋白-β病理。