Neuropathologic Correlates of Cognition in a Population-Based Sample
Neuropathologic Correlates of Cognition in a Population-Based Sample
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DOI：
10.3233/jad-130281
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发表时间：
2013-01-01
影响因子：
4
通讯作者：
Montine, Thomas J.
中科院分区：
文献类型：
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作者：
Cholerton, Brenna;Larson, Eric B.;Montine, Thomas J.
许多认知正常的老年人都有阿尔茨海默病(AD)、血管脑损伤(VBI)或路易体病(LBD)的潜在神经病理变化，这些疾病增加了患痴呆症的风险。目前的研究集中在社区老年人样本中多种神经病理指标与特定认知领域表现之间的关联。在438名接受尸检的成人思维人群脑老化研究参与者中，363名受试者在最后一次研究访问时接受了认知测试，并被纳入其中。研究人员测量了死亡前在认知能力筛查工具上的表现与神经病理终点之间的相关性，包括AD神经病理变化、LBD、脑淀粉样血管病变和VBI测量。神经原纤维缠结的Braak分期、较低的脑重量和通过大脑皮质微血管病变(MUVBI)测量的VBI解释了与整体认知测试表现相关的很大比例的差异(R-2=0.31p<；0.0001)，无论是在整个样本中还是当分析限于非痴呆受试者时(R-2=0.23p<；0.0001)。特定的认知领域与神经病理损害类型存在差异：记忆和执行功能与AD病理改变和皮质MU VBI相关，执行功能与皮质下MU VBI相关，视觉空间构建与LBD相关。因此，在这个队列中，LBD和MU VBI的神经病理损害与认知能力较差有关，而不是AD的神经病理改变。这些发现强调，认知障碍是一种复杂的汇聚性特征，对老年人的临床研究和医疗管理具有重要意义。
Many cognitively normal older adults have underlying neuropathologic changes of Alzheimer's disease (AD), vascular brain injury (VBI), or Lewy body disease (LBD), which confer an increased risk of dementia. The current study focused on the association between multiple neuropathologic indices and performance on specific cognitive domains in a community sample of older adults. Of 438 participants in the Adult Changes in Thought population-based study of brain aging who were autopsied, 363 subjects had cognitive testing at their final study visit and were included. Associations were measured between performance on the Cognitive Abilities Screening Instrument prior to death and neuropathologic endpoints, including AD neuropathologic changes, LBD, cerebral amyloid angiopathy, and measures of VBI. Braak stage for neurofibrillary tangles, lower brain weight, and VBI as measured by cerebral cortical microvascular lesions (mu VBI) explained a significant proportion of the variance associated with global cognitive test performance (R-2 = 0.31, p < 0.0001) both in the entire sample and when analysis was restricted to non-demented subjects (R-2 = 0.23, p < 0.0001). Specific cognitive domains were differentially related to neuropathologic lesion type: memory and executive function with AD pathologic changes and cortical mu VBI, executive function with subcortical mu VBI, and visuospatial construction with LBD. Thus, neuropathologic lesions of LBD and mu VBI are associated with poorer cognitive performance over and above AD neuropathologic changes in subjects without dementia in this cohort. These findings underscore that cognitive impairment is a complex convergent trait that has important implications for clinical investigation and medical management of older adults.