Pacific Health Research and Education Institute, Honolulu, HI, USA.
Department of Neurology, UC Irvine, Irvine, CA, USA.
J Alzheimers Dis. 2023;95(1):307-316. doi: 10.3233/JAD-230331.
Decedents with late-life dementia are often found at autopsy to have vascular pathology, cortical Lewy bodies, hippocampal sclerosis, and/or TDP-43 encephalopathy alone or with concurrent Alzheimer's disease (AD) lesions. Nonetheless, it is commonly believed that AD neuropathologic changes (NC) are the dominant or exclusive drivers of late-life dementia.
Assess associations of end-of-life cognitive impairment with any one or any combination of five distinct NC. Assess impairment prevalence among subjects having natural resistance to each type of NC.
Brains from 1,040 autopsied participants of the Honolulu-Asia Study, the Nun Study, and the 90 + Study were examined for NC of AD, Lewy body dementia, microvascular brain injury, hippocampal sclerosis, and limbic predominate TDP-43 encephalopathy. Associations with impairment were assessed for each NC and for NC polymorbidity (variable combinations of 2-5 concurrent NC).
Among 387 autopsied decedents with severe cognitive impairment, 20.4% had only AD lesions (ADNC), 25.3% had ADNC plus 1 other NC, 11.1% had ADNC plus 2 or more other NC, 28.7% had no ADNC but 1-4 other NC, and 14.5% had no/negligible NC. Combinations of any two, three, or four NC were highly frequent among the impaired. Natural resistance to ADNC or any other single NC had a modest impact on overall cohort impairment levels.
Polymorbidity involving 1-5 types of concurrent NC is a dominant neuropathologic feature of AD and related dementias. This represents a daunting challenge to future prevention and could explain failures of prior preventive intervention trials and of efforts to identify risk factors.
在尸检中，患有晚期痴呆的死者通常被发现存在血管病理学、皮质路易体、海马硬化和/或 TDP-43 脑病，单独或伴有同时发生的阿尔茨海默病（AD）病变。尽管如此，人们普遍认为 AD 神经病理学变化（NC）是导致晚期痴呆的主要或唯一驱动因素。
评估临终时认知障碍与任何一种或五种不同 NC 的任何组合之间的关联。评估对每种 NC 具有天然抵抗力的受试者的损伤发生率。
对来自檀香山-亚洲研究、修女研究和 90+研究的 1040 名尸检参与者的大脑进行检查，以评估 AD、路易体痴呆、微血管脑损伤、海马硬化和边缘优势 TDP-43 脑病的 NC。评估每种 NC 以及 NC 多态性（2-5 种同时存在的 NC 的变量组合）与损伤的关联。
在 387 名患有严重认知障碍的尸检死者中，20.4%仅有 AD 病变（ADNC），25.3%有 ADNC 加 1 种其他 NC，11.1%有 ADNC 加 2 种或更多其他 NC，28.7%没有 ADNC 但有 1-4 种其他 NC，14.5%没有/可忽略不计的 NC。受损者中任何两种、三种或四种 NC 的组合非常常见。对 ADNC 或任何其他单一 NC 的天然抵抗力对整个队列的损伤水平有一定影响。
涉及 1-5 种同时存在的 NC 的多态性是 AD 和相关痴呆的主要神经病理学特征。这对未来的预防构成了巨大挑战，也可以解释先前预防干预试验和识别风险因素的努力的失败。
