Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.
Translational Neuroscience, Mind Research Network, Albuquerque, NM, USA.
J Alzheimers Dis. 2021;80(3):1243-1256. doi: 10.3233/JAD-201187.
Alzheimer's disease neuropathologic change (ADNC) may contribute to dementia in patients with Lewy body disease (LBD) pathology.
To examine how co-occurring ADNC impacts domain specific cognitive impairments at each pathologic stage (brainstem, limbic, cerebral cortical) of LBD.
2,433 participants with antemortem longitudinal neuropsychological assessment and postmortem neuropathological assessment from the National Alzheimer's Coordinating Center's Uniform Data Set were characterized based on the evaluation of ADNC and LBD. Longitudinal mixed-models were used to derive measures of cumulative cognitive deficit for each cognitive domain at each pathologic stage of LBD (brainstem, limbic, and cerebral cortical).
111 participants with a pathologic diagnosis of LBD, 741 participants with combined LBD and ADNC, 1,357 participants with ADNC only, and 224 with no pathology (healthy controls) were included in the analyses. In the executive/visuospatial domain, combined LBD and ADNC showed worse deficits than LBD only when Lewy bodies were confined to the brainstem, but no difference when Lewy bodies extended to the limbic or cerebral cortical regions. The cerebral cortical LBD only group exhibited greater executive/visuospatial deficits than the ADNC only group. By contrast, the ADNC only group and the combined pathology group both demonstrated significantly greater cumulative memory deficits relative to Lewy body disease only, regardless of stage.
The impact of co-occurring ADNC on antemortem cumulative cognitive deficits varies not only by domain but also on the pathological stage of Lewy bodies. Our findings stress the cognitive impact of different patterns of neuropathological progression in Lewy body diseases.
阿尔茨海默病神经病理改变（ADNC）可能导致路易体病（LBD）患者的痴呆。
检查共存的 ADNC 如何影响 LBD 每个病理阶段（脑干、边缘系统、大脑皮质）的特定认知领域的认知障碍。
从国家阿尔茨海默病协调中心的统一数据集 2433 名有生前纵向神经心理学评估和死后神经病理学评估的参与者中，根据 ADNC 和 LBD 的评估对其进行特征描述。使用纵向混合模型，在 LBD 的每个病理阶段（脑干、边缘系统和大脑皮质）计算每个认知领域的累积认知缺陷的测量值。
在分析中纳入了 111 名病理诊断为 LBD 的参与者、741 名 LBD 合并 ADNC 的参与者、1357 名仅 ADNC 的参与者和 224 名无病理（健康对照）的参与者。在执行/视觉空间领域，当路易体仅局限于脑干时，合并的 LBD 和 ADNC 比仅 LBD 表现出更严重的缺陷，但当路易体延伸到边缘或大脑皮质区域时，两者没有差异。仅大脑皮质 LBD 组表现出比仅 ADNC 组更大的执行/视觉空间缺陷。相比之下，仅 ADNC 组和合并病理学组都表现出与仅 LBD 相比，无论阶段如何，都存在显著更大的累积记忆缺陷。
共存的 ADNC 对生前累积认知缺陷的影响不仅因域而异，而且因路易体的病理阶段而异。我们的研究结果强调了不同神经病理学进展模式在路易体病中的认知影响。
