Percy Maire E, Lukiw Walter J
Department of Physiology, University of Toronto, Toronto, Canada.
Department of Obstetrics & Gynaecology, Toronto, Canada.
Int J Dev Disabil. 2020;66(1):22-35. doi: 10.1080/20473869.2017.1301023. Epub 2017 Apr 9.
Certain heart conditions and diseases are common in Down syndrome (DS; trisomy 21), but their role in early onset dementia that is prevalent in older adults with DS has not been evaluated. To address this knowledge gap, we conducted a study of risk factors for low neurocognitive/behavioral scores obtained with a published dementia test battery (DTB). Participants were adults with DS living in New York ( = 29; average age 46 years). We asked three questions. 1. Does having any type of heart disease affect the association between DTB scores and chronological age? 2. Does thyroid status affect the association between heart disease and DTB scores? 3. Are the E4 or E2 alleles of apolipoprotein E (APOE) associated with DTB scores or with heart disease?
The study was retrospective, pilot, and exploratory. It involved analysis of information in a database previously established for the study of aging in DS. Participants had moderate intellectual disability on average. Information for each person included: gender, age, a single DTB score obtained by combining results from individual subscales of the DTB, the presence or absence of heart disease, thyroid status (treated hypothyroidism or normal), and APOE genotype. Trends were visualized by inspection of graphs and contingency tables. Statistical methods used to evaluate associations included Pearson correlation analysis, Fisher's exact tests (2-tailed), and odds ratio analysis. values were interpreted at the 95% confidence level without Bonferroni correction. values >.05<.1 were considered trends.
The negative correlation between DTB scores and age was significant in those with heart disease but not in those without. Heart disease was significantly associated with DTB scores >1 SD below the sample mean; there was a strong association between heart disease and low DTB scores in those with treated hypothyroidism but not in those with normal thyroid status. The APOE genotype was weakly associated with heart disease (E4, predisposing; E2, protective) in males.
On the basis of the potentially important findings from the present study, large prospective studies are warranted to confirm and extend the observations. In these, particular heart conditions or diseases and other medical comorbidities in individuals should be documented.
某些心脏疾病在唐氏综合征（DS；21三体综合征）中很常见，但它们在DS老年患者中普遍存在的早发性痴呆中的作用尚未得到评估。为了填补这一知识空白，我们对一项已发表的痴呆测试组合（DTB）得出的低神经认知/行为评分的危险因素进行了研究。参与者是居住在纽约的成年DS患者（n = 29；平均年龄46岁）。我们提出了三个问题。1. 患有任何类型的心脏病是否会影响DTB评分与实际年龄之间的关联？2. 甲状腺状态是否会影响心脏病与DTB评分之间的关联？3. 载脂蛋白E（APOE）的E4或E2等位基因是否与DTB评分或心脏病相关？
该研究是回顾性、试点性和探索性的。它涉及对先前为DS衰老研究建立的数据库中的信息进行分析。参与者平均有中度智力残疾。每个人的信息包括：性别、年龄、通过合并DTB各个子量表的结果获得的单个DTB评分、是否患有心脏病、甲状腺状态（治疗过的甲状腺功能减退或正常）以及APOE基因型。通过检查图表和列联表来直观呈现趋势。用于评估关联的统计方法包括Pearson相关分析、Fisher精确检验（双侧）和比值比分析。P值在95%置信水平下解释，不进行Bonferroni校正。P值>.05<.1被视为趋势。
心脏病患者中DTB评分与年龄之间的负相关显著，而无心脏病患者中则不显著。心脏病与低于样本均值1个标准差的DTB评分显著相关；在治疗过甲状腺功能减退的患者中，心脏病与低DTB评分之间存在强关联，而甲状腺状态正常的患者中则不存在。APOE基因型在男性中与心脏病存在弱关联（E4，易患；E2，有保护作用）。
基于本研究潜在的重要发现，有必要进行大型前瞻性研究以证实并扩展这些观察结果。在这些研究中，应记录个体的特定心脏疾病或病症以及其他合并症。
