From the Departments of Neurology and Medicine, Albert Einstein College of Medicine, Bronx, NY.
Neurology. 2019 Mar 26;92(13):e1427-e1434. doi: 10.1212/WNL.0000000000007141. Epub 2019 Feb 8.
To examine polygenic inheritance of motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by the presence of subjective cognitive complaints and slow gait.
We analyzed 4,915 individuals, age 65 years and above, with European ancestry (mean age 75.0 ± 6.8 years, 56.6% women) in the Health and Retirement Study. Polygenic scores (PGS) were calculated as weighted sums of the effect of single nucleotide polymorphisms, with effect sizes derived from genome-wide association studies. The association between PGSs of 9 phenotypes (general cognition, body mass index [BMI], mean arterial pressure, education, Alzheimer disease [AD], neuroticism, well-being, waist circumference, and depressive symptoms) and MCR as well as its key components (cognitive complaints and slow gait) were examined by logistic regression, adjusting for age, sex, education, and genetic ancestry, and reported as odds ratios (ORs) with 95% confidence intervals (CIs).
There were 260 prevalent MCR cases, 529 with slow gait, and 1,928 with subjective cognitive complaints. Higher PGSs for BMI (OR 1.22, 95% CI 1.07-1.39) and waist circumference (OR 1.23, 95% CI 1.07-1.40) were associated with MCR, and PGS of AD showed a suggestive association (OR 1.16, 95% CI 1.02-1.32). Higher PGS for neuroticism (OR 1.10, 95% CI 1.03-1.18) was associated with cognitive complaints, whereas higher well-being PGS (OR 0.92, 95% CI 0.87-0.98) was protective. PGS for BMI (OR 1.16, 95% CI 1.06-1.28), waist circumference (OR 1.19, 95% CI 1.08-1.31), and AD (OR 1.13, 95% CI 1.03-1.24) was associated with slow gait.
Obesity-related genetic traits increase risk of MCR syndrome; further investigation is required to identify potential therapeutic targets.
研究运动认知风险综合征（MCR）的多基因遗传，MCR 是一种前驱痴呆综合征，其特征为存在主观认知主诉和步态缓慢。
我们分析了来自健康与退休研究（Health and Retirement Study）的 4915 名年龄在 65 岁及以上、具有欧洲血统的个体（平均年龄 75.0±6.8 岁，56.6%为女性）。多基因评分（PGS）是通过单核苷酸多态性的加权和计算得出的，其效应大小来自全基因组关联研究。通过逻辑回归分析了 9 种表型（一般认知、体重指数[BMI]、平均动脉压、教育、阿尔茨海默病[AD]、神经质、幸福感、腰围和抑郁症状）的 PGS 与 MCR 及其关键成分（认知主诉和步态缓慢）之间的关联，调整了年龄、性别、教育和遗传背景，并以比值比（OR）及其 95%置信区间（CI）报告。
有 260 例现患 MCR 病例，529 例有步态缓慢，1928 例有主观认知主诉。较高的 BMI（OR 1.22，95%CI 1.07-1.39）和腰围（OR 1.23，95%CI 1.07-1.40）PGS 与 MCR 相关，AD 的 PGS 呈提示性关联（OR 1.16，95%CI 1.02-1.32）。较高的神经质 PGS（OR 1.10，95%CI 1.03-1.18）与认知主诉相关，而较高的幸福感 PGS（OR 0.92，95%CI 0.87-0.98）具有保护作用。BMI（OR 1.16，95%CI 1.06-1.28）、腰围（OR 1.19，95%CI 1.08-1.31）和 AD（OR 1.13，95%CI 1.03-1.24）PGS 与步态缓慢相关。
肥胖相关的遗传特征增加了 MCR 综合征的风险；需要进一步研究以确定潜在的治疗靶点。
