From the Departments of Psychiatry and Behavioral Sciences (W.D.B., K.Y.), Epidemiology (W.D.B., K.Y.), Biostatistics (W.D.B., K.Y.), and Neurology (K.Y.), University of California San Francisco, San Francisco; Department of Neurology (N.M.R.), Geisel School of Medicine, Dartmouth, Hannover, NH; Department of Epidemiology (E.S.S.), University of Pittsburgh, PA; and San Francisco VA Medical Center (K.Y.), CA.
Neurology. 2022 May 3;98(18):e1837-e1845. doi: 10.1212/WNL.0000000000200185. Epub 2022 Mar 9.
Peripheral nerve impairments and dementia are common among older adults and share risk factors. However, few studies have examined whether peripheral nerve function and dementia are associated. We evaluated whether lower extremity peripheral nerve impairments were associated with higher incidence of dementia and whether associations differed by comorbidity subgroups (diabetes, low vitamin B, and ε4 allele carriers).
We studied Black and White Health, Aging, and Body Composition Study participants 70 to 79 years of age and without dementia at enrollment. Lower extremity sensory and motor peripheral nerve function was measured at year 4 (the analytic baseline of this study). Sensory nerve impairments were measured with monofilament (1.4 g, 10 g) and vibration threshold of the toe. Monofilament insensitivity was defined as unable to detect monofilament (3 of 4 touches), and vibration detection impairment was defined as >130 μm. Fibular motor impairments were defined as <1 mV compound motor action potential (CMAP) amplitude and slow nerve conduction velocity <40 m/s. Incident dementia over the following 11 years was determined from medical records, cognitive scores, and medications. Cox proportional hazard models adjusted for demographics and health conditions assessed associations of nerve impairments with incident dementia.
Among 2,174 participants (52% women, 35% Black), 45% could not detect monofilament 1.4 g, 9% could not detect monofilament 10 g, 6% could not feel vibration, 10% had low CMAP amplitude, and 24% had slow conduction velocity. Monofilament 10 g (hazard ratio [HR] 1.35, 95% CI 0.99-1.84) and vibration detection insensitivity (HR 1.73, 95% CI 1.24-2.40) were associated/borderline associated with a higher risk of dementia after covariate adjustment. Estimates were elevated but not significant for monofilament 1.4 g, CMAP amplitude, and conduction velocity ( > 0.05). Increasing number of peripheral nerve impairments was associated with higher risk of dementia in a graded fashion; for ≥3 impairments, the HR was 2.37 (95% CI 1.29-4.38). In subgroup analyses, effect estimates were generally higher among those with diabetes, low vitamin B, and ε4 allele except for vibration detection.
Peripheral nerve impairments, especially sensory, were associated with a higher risk of dementia even after adjustment for age and other health factors. These associations may represent a shared susceptibility to nervous system degeneration.
周围神经损伤和痴呆在老年人中很常见，且具有共同的危险因素。然而，很少有研究探讨周围神经功能与痴呆之间是否存在关联。我们评估了下肢周围神经损伤是否与更高的痴呆发病率相关，以及这些关联是否因合并症亚组（糖尿病、低维生素 B 和 ε4 等位基因携带者）而有所不同。
我们研究了年龄在 70 至 79 岁且入组时无痴呆的黑人和白人健康、衰老和身体成分研究参与者。在第 4 年（本研究的分析基线）测量下肢感觉和运动周围神经功能。使用单丝（1.4 g、10 g）和脚趾振动阈值测量感觉神经损伤。单丝感觉丧失定义为无法检测到单丝（4 次触摸中有 3 次），振动检测受损定义为 >130 μm。腓总运动损伤定义为 <1 mV 复合运动动作电位（CMAP）幅度和慢神经传导速度 <40 m/s。在接下来的 11 年中，通过医疗记录、认知评分和药物确定痴呆的发病情况。Cox 比例风险模型调整了人口统计学和健康状况，以评估神经损伤与新发痴呆之间的关联。
在 2174 名参与者中（52%为女性，35%为黑人），45%的人无法检测到 1.4 g 的单丝，9%的人无法检测到 10 g 的单丝，6%的人无法感觉到振动，10%的人 CMAP 幅度较低，24%的人传导速度较慢。调整协变量后，单丝 10 g（风险比[HR]1.35，95%置信区间[CI]0.99-1.84）和振动检测感觉丧失（HR 1.73，95% CI 1.24-2.40）与痴呆风险升高相关/边缘相关。对于单丝 1.4 g、CMAP 幅度和传导速度，估计值升高但不显著（>0.05）。周围神经损伤的数量越多，痴呆的风险就越高，呈梯度上升；对于≥3 种损伤，HR 为 2.37（95% CI 1.29-4.38）。在亚组分析中，除了振动检测外，在糖尿病、低维生素 B 和 ε4 等位基因携带者中，效应估计值通常更高。
即使在调整年龄和其他健康因素后，周围神经损伤，尤其是感觉神经损伤，与痴呆风险增加相关。这些关联可能代表对神经系统退化的共同易感性。
