Impact of APOE ε4 genotype on initial cognitive symptoms differs for Alzheimer's and Lewy body neuropathology.
Impact of APOE ε4 genotype on initial cognitive symptoms differs for Alzheimer's and Lewy body neuropathology.
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DOI：
10.1186/s13195-021-00771-1
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发表时间：
2021-01-23
期刊：
影响因子：
--
通讯作者：
Leverenz JB
中科院分区：
文献类型：
--
作者：
Pillai JA;Bena J;Bonner-Jackson A;Leverenz JB
APOE ε4携带状态会增加阿尔茨海默病病理中出现健忘的几率。目前尚不清楚APOE ε4载体状态如何影响路易体病理存在时特定初始认知症状的几率。本研究评估APOE ε4基因型对阿尔茨海默病病理（ADP）和lewy相关病理（LRP）患者初始认知症状的影响。一项回顾性队列研究纳入了2288名在国家阿尔茨海默病协调中心数据库中被神经病理学证实为ADP或LRP的参与者，这些参与者有初始认知症状记录，并且临床痴呆评分-全球（CDR-G）评分≤1（认知正常、MCI或早期痴呆）。考虑评估年龄、性别和教育程度的未调整和调整逻辑回归模型检验了APOE ε4基因型与ADP合并LRP组和ADP-LRP组的初始症状（记忆、执行、语言视觉空间）之间的关系。1303名受试者满足单独ADP的标准，90名受试者满足单独LRP的标准，895名受试者满足ADP和LRP共存（ADP-LRP）的标准。在所有三组中，年龄越小，出现非遗忘症状的几率越高。在调整后的模型中，APOE ε4携带者出现遗忘症状的几率为1.5 [95% CI, 1.7 ~ 2.14, p = 0.003]，出现语言症状的几率为0.67 [95% CI, 0.47 ~ 0.96, p = 0.03]，高于非携带者。ADP组和混合ADP- lrp组出现这两种症状的几率没有差异。在调整后的模型中，女性和高等教育程度增加了ADP组出现初始语言症状的几率。在未调整的模型中，携带APOE ε4的LRP患者出现视觉空间初始症状的几率更高（21.96）[95% CI, 4.02-110.62, p < 0.0001]，而出现执行/注意初始症状的几率没有差异。在LRP中，APOE ε4与遗忘症状的比值无统计学意义；而评价ADP组与LRP组遗忘症状优势比差异的交互效应也无统计学意义。APOE ε4携带者与非携带者相比，ADP和LRP患者出现特定初始认知症状的几率存在差异。ADP APOE ε4携带者出现初始遗忘症状的几率更高，LRP APOE ε4携带者出现视觉空间初始症状的几率更高。这支持了APOE ε4差异影响初始认知症状和潜在神经病理的假设。在线版本包含补充材料，可在10.1186/s13195-021-00771-1获得。
APOE ε4 carrier status is known to increase odds of amnestic presentations with Alzheimer’s pathology. It is unknown how APOE ε4 carrier status impacts odds of specific initial cognitive symptoms in the presence of Lewy body pathology. Here we evaluate the impact of APOE ε4 genotype on initial cognitive symptoms among those with Alzheimer’s disease pathology (ADP) and Lewy-related pathology (LRP). A retrospective cohort study of 2288 participants with neuropathology confirmed ADP or LRP in the National Alzheimer’s Coordinating Center database, who had initial cognitive symptoms documented and had a Clinical Dementia Rating-Global (CDR-G) score ≤ 1 (cognitively normal, MCI, or early dementia). Unadjusted and adjusted logistic regression models taking into account age at evaluation, sex, and education examined the relationship between APOE ε4 genotype and initial symptoms (memory, executive, language visuospatial) among ADP with LRP and ADP-LRP groups. One thousand three hundred three participants met criteria for ADP alone, 90 for LRP alone, and 895 for co-existing ADP and LRP (ADP-LRP). Younger age increased odds of non-amnestic symptoms across all three groups. In the adjusted model among ADP, APOE ε4 carriers had higher odds of amnestic initial symptoms 1.5 [95% CI, 1.7–2.14, p = 0.003] and lower odds of initial language symptoms 0.67 [95% CI, 0.47–0.96, p = 0.03] than non-carriers. The odds for these two symptoms were not different between ADP and mixed ADP-LRP groups. Female sex and higher education increased odds of initial language symptoms in the ADP group in the adjusted model. In the unadjusted model, APOE ε4 carriers with LRP had a higher odds of visuospatial initial symptoms 21.96 [95% CI, 4.02–110.62, p < 0.0001], while no difference was noted for initial executive/attention symptoms. Among LRP, the odds of APOE ε4 on amnestic symptom was not significant; however, the interaction effect evaluating the difference in odds ratios of amnestic symptom between ADP and LRP groups also did not reach statistical significance. The odds of specific initial cognitive symptoms differed between ADP and LRP among APOE ε4 carriers compared to non-carriers. The odds of initial amnestic symptom was higher among ADP APOE ε4 carriers and the odds of visuospatial initial symptom was higher with LRP APOE ε4 carriers. This supports the hypothesis that APOE ε4 differentially impacts initial cognitive symptoms together with underlying neuropathology. The online version contains supplementary material available at 10.1186/s13195-021-00771-1.
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影响因子：
6.4
作者：
Leverenz, James B.;Hamilton, Ronald;Montine, Thomas J.
通讯作者：
Montine, Thomas J.
DOI：
10.1017/s1355617709090638
发表时间：
2009-11
期刊：
Journal of the International Neuropsychological Society : JINS
影响因子：
--
作者：
Jak AJ;Urban S;McCauley A;Bangen KJ;Delano-Wood L;Corey-Bloom J;Bondi MW
通讯作者：
Bondi MW
影响因子：
12.7
作者：
Arold S;Sullivan P;Bilousova T;Teng E;Miller CA;Poon WW;Vinters HV;Cornwell LB;Saing T;Cole GM;Gylys KH
通讯作者：
Gylys KH
DOI：
10.1186/s13195-020-00710-6
发表时间：
2020-10-31
期刊：
Alzheimer's research & therapy
影响因子：
--
作者：
Baek MS;Cho H;Lee HS;Lee JH;Ryu YH;Lyoo CH
通讯作者：
Lyoo CH
影响因子：
7.1
作者：
Hesse, Raphael;Hurtado, Maica Llavero;Spires-Jones, Tara L.
通讯作者：
Spires-Jones, Tara L.