Person-specific contribution of neuropathologies to cognitive loss in old age.
Person-specific contribution of neuropathologies to cognitive loss in old age.
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DOI：
10.1002/ana.25123
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发表时间：
2018-01
影响因子：
11.2
通讯作者：
Bennett DA
中科院分区：
文献类型：
--
作者：
Boyle PA;Yu L;Wilson RS;Leurgans SE;Schneider JA;Bennett DA
混合神经病理是人群水平上痴呆的最常见原因，但不同的神经病理如何在个体水平上导致认知能力下降仍不清楚。我们量化了九种神经病理在个体水平上对认知丧失的贡献。参与者(n=1,079)来自2项关于衰老的纵向临床病理研究。所有人都完成了2+认知评估(最高=22)，死亡并接受了神经病理检查，以确定阿尔茨海默病(AD)、其他神经退行性疾病和血管病理。线性混合模型检验了神经病理与认知衰退的关系，并估计了每种神经病理在特定人水平上造成认知障碍的比例。神经病理无处不在，94%的参与者患有1+，78%的参与者患有2+，58%的参与者患有3+，35%的参与者患有4+。AD最常见(65%)，但很少单独发生(9%)。值得注意的是，观察到了230多种不同的神经病理组合，每种组合都出现在队列的6%。特定的神经病理对认知能力丧失的相对贡献因个体而异。虽然阿尔茨海默病平均占观察到的认知损失的50%左右，但在个人层面上的比例从22%到100%不等。路易小体和海马区硬化症也有很强的影响，但它们的影响在特定人的水平上也不同。年龄相关神经病理的共病和认知影响的异质性比目前所认识的要大得多，这表明迫切需要新的治疗方法来拥抱疾病的复杂性，以对抗老年认知能力的下降。
Mixed neuropathologies are the most common cause of dementia at the population level, but how different neuropathologies contribute to cognitive decline at the individual level remains unknown. We quantified the contribution of nine neuropathologies to cognitive loss at an individual level. Participants (n=1,079) came from 2 longitudinal clinical-pathologic studies of aging. All completed 2+ cognitive evaluations (maximum = 22), died and underwent neuropathologic examinations to identify Alzheimer's disease (AD), other neurodegenerative diseases, and vascular pathologies. Linear mixed models examined associations of neuropathologies with cognitive decline and estimated the proportion of cognitive loss accounted for by each neuropathology at a person-specific level. Neuropathology was ubiquitous, with 94% of participants having 1+, 78% having 2+, 58% having 3+, and 35% having 4+. AD was most frequent (65%) but rarely occurred in isolation (9%). Remarkably, more than 230 different neuropathologic combinations were observed, each of which occurred in <6% of the cohort. The relative contributions of specific neuropathologies to cognitive loss varied widely across individuals. Although AD accounted for an average of about 50% of the observed cognitive loss, the proportion accounted for at the individual level ranged widely from 22% to 100%. Lewy bodies and hippocampal sclerosis also had potent effects, but again their impacts varied at the person-specific level. There is much greater heterogeneity in the comorbidity and cognitive impact of age-related neuropathologies than currently appreciated, suggesting an urgent need for novel therapeutic approaches that embrace the complexity of disease to combat cognitive decline in old age.
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影响因子：
11.2
作者：
Bennett, David A.;Wilson, Robert S.;Boyle, Patricia A.;Buchman, Aron S.;Schneider, Julie A.
通讯作者：
Schneider, Julie A.
DOI：
10.1016/j.jalz.2016.11.003
发表时间：
2017-06
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
Dodge HH;Zhu J;Woltjer R;Nelson PT;Bennett DA;Cairns NJ;Fardo DW;Kaye JA;Lyons DE;Mattek N;Schneider JA;Silbert LC;Xiong C;Yu L;Schmitt FA;Kryscio RJ;Abner EL;SMART data consortium
通讯作者：
SMART data consortium
影响因子：
14.5
作者：
Nelson, Peter T.;Schmitt, Frederick A.;Kryscio, Richard J.
通讯作者：
Kryscio, Richard J.
影响因子：
11.2
作者：
Nag, Sukriti;Yu, Lei;Schneider, Julie A.
通讯作者：
Schneider, Julie A.
影响因子：
9.9
作者：
Wilson, Robert S.;Nag, Sukriti;Bennett, David A.
通讯作者：
Bennett, David A.