From the Departments of Medicine (L.M.K.W., O.T., S.D., M.K.A., J.D.F., K.R.), Physiotherapy (O.T.), Community Health and Epidemiology (S.K.), and Psychiatry (J.D.F.), Dalhousie University, Halifax, Canada; and Rush Alzheimer's Disease Center (D.A.B., A.S.B.), Rush University Medical Center, Chicago, IL.
Neurology. 2020 Dec 15;95(24):e3269-e3279. doi: 10.1212/WNL.0000000000010944. Epub 2020 Sep 28.
To test the hypothesis that degree of frailty and neuropathologic burden independently contribute to global cognition and odds of dementia.
This was a secondary analysis of a prospective cohort study of older adults living in Illinois. Participants underwent an annual neuropsychological and clinical evaluation. We included 625 participants (mean age 89.7 ± 6.1 years; 67.5% female) who died and underwent autopsy. We quantified neuropathology using an index measure of 10 neuropathologic features: β-amyloid deposition, hippocampal sclerosis, Lewy bodies, tangle density, TDP-43, cerebral amyloid angiopathy, arteriolosclerosis, atherosclerosis, and gross and chronic cerebral infarcts. Clinical consensus determined dementia status, which we coded as no cognitive impairment, mild cognitive impairment, or dementia. A battery of 19 tests spanning multiple domains quantified global cognition. We operationalized frailty using a 41-item frailty index. We employed regression analyses to model relationships between neuropathology, frailty, and dementia.
Both frailty and a neuropathology index were independently associated with global cognition and dementia status. These results held after controlling for traditional pathologic measures in a sample of participants with Alzheimer clinical syndrome. Frailty improved the fit of the model for dementia status (χ[2] 72.64; < 0.0001) and explained an additional 11%-12% of the variance in the outcomes.
Dementia is a multiply determined condition, to which both general health, as captured by frailty, and neuropathology significantly contribute. This integrative view of dementia and health has implications for prevention and therapy; specifically, future research should evaluate frailty as a means of dementia risk reduction.
验证以下假设，即衰弱程度和神经病理负担独立影响整体认知和痴呆的发病几率。
这是对伊利诺伊州老年人群进行的前瞻性队列研究的二次分析。参与者每年接受神经心理学和临床评估。我们纳入了 625 名（平均年龄 89.7 ± 6.1 岁，67.5%为女性）死亡并接受尸检的参与者。我们使用 10 种神经病理特征的综合指标来量化神经病理学：β-淀粉样蛋白沉积、海马硬化、路易体、缠结密度、TDP-43、脑淀粉样血管病、小动脉硬化、动脉粥样硬化以及大而慢性脑梗死。临床共识确定了痴呆状态，我们将其编码为无认知障碍、轻度认知障碍或痴呆。一系列跨越多个领域的 19 项测试用于量化整体认知。我们使用 41 项衰弱指数来操作衰弱。我们采用回归分析来建立神经病理学、衰弱和痴呆之间的关系。
衰弱和神经病理学指数都与整体认知和痴呆状态独立相关。在控制了具有阿尔茨海默病临床综合征的参与者样本中的传统病理测量值后，这些结果仍然成立。衰弱改善了痴呆状态模型的拟合度（χ[2]72.64；<0.0001），并解释了结果中 11%-12%的额外变异。
痴呆是一种多因素决定的疾病，衰弱和神经病理学都会显著影响痴呆的发生。这种对痴呆和健康的综合观点对预防和治疗具有重要意义；具体而言，未来的研究应评估衰弱作为降低痴呆风险的一种手段。
