{"title":"Alzheimer's Polygenic Risk and Clinical Severity Manifest in Greater Cognitive Intra-Individual Variability.","authors":"Chin Hong Tan","doi":"10.1017/S1355617725101252","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Cognitive intra-individual variability (IIV) is a neuropsychological marker reflecting divergent performance across cognitive domains. In this brief communication, we examined whether clinical severity, apolipoprotein E (<i>APOE</i>) ε4 carriers, and higher polygenic risk were associated with higher cognitive IIV, and whether higher polygenic risk and cognitive IIV synergistically influence clinical severity.</p><p><strong>Method: </strong>This large study involved up to 24,248 participants (mean age = 72) from the National Alzheimer's Coordinating Center (NACC) and multiple regression controlling for age, sex, and education was used to analyze the data.</p><p><strong>Results: </strong>We found that disease severity (B = 0.055, SE = 0.001, <i>P</i> < 0.001), <i>APOE</i> ε4 carriers (B = 0.02, SE = 0.003, <i>P</i> < 0.001), and higher polygenic risk (B = 0.02, SE = 0.004, <i>P</i> < 0.001) were associated with higher cognitive IIV. Polygenic risk and cognitive IIV also interacted to influence clinical severity, beyond <i>APOE</i> ε4 (B = 0.11, SE = 0.05, <i>P</i> = 0.02), such that individuals with high polygenic risk and cognitive IIV had the greatest clinical severity.</p><p><strong>Conclusions: </strong>Heightened polygenic risk and increased cross-domain cognitive variation are implicated in dementia and may impact clinical decline in tandem.</p>","PeriodicalId":49995,"journal":{"name":"Journal of the International Neuropsychological Society","volume":" ","pages":"1-5"},"PeriodicalIF":2.6000,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the International Neuropsychological Society","FirstCategoryId":"102","ListUrlMain":"https://doi.org/10.1017/S1355617725101252","RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Objective: Cognitive intra-individual variability (IIV) is a neuropsychological marker reflecting divergent performance across cognitive domains. In this brief communication, we examined whether clinical severity, apolipoprotein E (APOE) ε4 carriers, and higher polygenic risk were associated with higher cognitive IIV, and whether higher polygenic risk and cognitive IIV synergistically influence clinical severity.
Method: This large study involved up to 24,248 participants (mean age = 72) from the National Alzheimer's Coordinating Center (NACC) and multiple regression controlling for age, sex, and education was used to analyze the data.
Results: We found that disease severity (B = 0.055, SE = 0.001, P < 0.001), APOE ε4 carriers (B = 0.02, SE = 0.003, P < 0.001), and higher polygenic risk (B = 0.02, SE = 0.004, P < 0.001) were associated with higher cognitive IIV. Polygenic risk and cognitive IIV also interacted to influence clinical severity, beyond APOE ε4 (B = 0.11, SE = 0.05, P = 0.02), such that individuals with high polygenic risk and cognitive IIV had the greatest clinical severity.
Conclusions: Heightened polygenic risk and increased cross-domain cognitive variation are implicated in dementia and may impact clinical decline in tandem.
目的：认知个体内变异（IIV）是一种反映不同认知领域表现差异的神经心理学指标。在这篇简短的文章中，我们研究了临床严重程度、载脂蛋白E (APOE) ε4携带者和较高的多基因风险是否与较高的认知IIV相关，以及较高的多基因风险和认知IIV是否协同影响临床严重程度。方法：这项大型研究涉及来自国家阿尔茨海默病协调中心（NACC）的24248名参与者（平均年龄= 72岁），采用控制年龄、性别和教育程度的多元回归分析数据。结果：疾病严重程度（B = 0.055, SE = 0.001, P < 0.001）、APOE ε4携带者（B = 0.02, SE = 0.003, P < 0.001）、多基因风险高（B = 0.02, SE = 0.004, P < 0.001）与认知IIV升高相关。除APOE ε4外，多基因风险和认知IIV还相互作用影响临床严重程度（B = 0.11, SE = 0.05, P = 0.02），多基因风险和认知IIV高的个体临床严重程度最大。结论：增加的多基因风险和增加的跨领域认知变异与痴呆有关，并可能连带影响临床衰退。
期刊介绍：
The Journal of the International Neuropsychological Society is the official journal of the International Neuropsychological Society, an organization of over 4,500 international members from a variety of disciplines. The Journal of the International Neuropsychological Society welcomes original, creative, high quality research papers covering all areas of neuropsychology. The focus of articles may be primarily experimental, applied, or clinical. Contributions will broadly reflect the interest of all areas of neuropsychology, including but not limited to: development of cognitive processes, brain-behavior relationships, adult and pediatric neuropsychology, neurobehavioral syndromes (such as aphasia or apraxia), and the interfaces of neuropsychology with related areas such as behavioral neurology, neuropsychiatry, genetics, and cognitive neuroscience. Papers that utilize behavioral, neuroimaging, and electrophysiological measures are appropriate.
To assure maximum flexibility and to promote diverse mechanisms of scholarly communication, the following formats are available in addition to a Regular Research Article: Brief Communication is a shorter research article; Rapid Communication is intended for "fast breaking" new work that does not yet justify a full length article and is placed on a fast review track; Case Report is a theoretically important and unique case study; Critical Review and Short Review are thoughtful considerations of topics of importance to neuropsychology and include meta-analyses; Dialogue provides a forum for publishing two distinct positions on controversial issues in a point-counterpoint format; Special Issue and Special Section consist of several articles linked thematically; Letter to the Editor responds to recent articles published in the Journal of the International Neuropsychological Society; and Book Review, which is considered but is no longer solicited.
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