Department of Neurology, University of California, Irvine, CA, USA.
Department of Neurobiology and Behavior, University of California, Irvine, CA, USA.
J Alzheimers Dis. 2023;93(2):561-575. doi: 10.3233/JAD-221062.
Some oldest-old individuals can maintain superior cognition despite advanced age. Little is known about the neuropathological changes in the brains of oldest-old superior cognitive performers.
Our objective was to examine the associations between Alzheimer's disease (AD) and non-AD neuropathologic features in relation to superior cognitive performance in oldest-old individuals.
We analyzed brain autopsy data from 102 participants with normal cognition from The 90+ Study. Superior global cognitive performers (SGCP) were defined as having Mini-Mental State Examination (MMSE) score ≥28 in the last visit 12 to 2 months before death. To examine the associations between individual and multiple comorbid neuropathologic features with SGCP status we used multiple logistic regression models adjusting for age, sex, and education.
Alzheimer's disease neuropathological change (ADNC) and low levels of vascular pathologic change were not associated with superior cognition. In contrast, participants with limbic (OR = 8.37; 95% CI: 1.48-47.44) and neocortical (OR = 10.80;95% CI: 1.03-113.82) Lewy body disease (LBD), or with hippocampal sclerosis (HS) (OR = 5.28; 95% CI: 1.10-25.47) were more likely to be non-SGCP. High total burden of multiple comorbid neuropathologic features was associated with a lower likelihood of being SGCP.
Oldest-old superior cognitive performers were resilient to ADNC and low levels of vascular pathologic change and were resistant to non-AD neurodegenerative changes and multiple comorbid neuropathologic features. Understanding the factors underlying the ability of superior cognitive performers to resist these changes might provide useful insights on maintenance of superior cognition despite advanced age.
一些非常高龄的个体尽管年龄较大，但仍能保持优越的认知能力。对于非常高龄的认知能力超群者的大脑神经病理学变化知之甚少。
我们的目的是研究阿尔茨海默病（AD）与非 AD 神经病理学特征与非常高龄个体认知能力超群之间的关系。
我们分析了来自 90+ 研究的 102 名认知正常的参与者的脑尸检数据。将总体认知表现优异者（SGCP）定义为在死亡前 12 至 2 个月的最后一次就诊时，Mini-Mental State Examination（MMSE）评分≥28。为了研究个体和多种共病神经病理学特征与 SGCP 状态之间的关系，我们使用了多元逻辑回归模型，调整了年龄、性别和教育因素。
AD 神经病理学改变（ADNC）和低水平的血管病理学改变与优越认知无关。相反，具有边缘（OR=8.37；95%CI：1.48-47.44）和新皮质（OR=10.80；95%CI：1.03-113.82）路易体病（LBD）或具有海马硬化（HS）（OR=5.28；95%CI：1.10-25.47）的参与者更不可能是非 SGCP。多种共病神经病理学特征的总负担较高与成为 SGCP 的可能性较低相关。
非常高龄的认知能力超群者对 ADNC 和低水平的血管病理学改变具有弹性，对非 AD 神经退行性变化和多种共病神经病理学特征具有抵抗力。了解认知能力超群者抵抗这些变化的能力背后的因素可能为理解尽管年龄较大仍能保持优越认知提供有用的见解。
