Supplementary Material for: Associations of Peripheral Neuropathy Defined by Monofilament Insensitivity with Mild Cognitive Impairment and Dementia in Older Adults

Introduction: The aim of this study was to assess the association of peripheral neuropathy (PN) as defined by monofilament insensitivity with mild cognitive impairment (MCI) and dementia in older adults with and without diabetes. Methods: We conducted a cross-sectional analysis of 3,362 Black and White participants in the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS) who underwent monofilament testing at visit 6 (2016–2017, age 71–94 years). Participants’ cognitive status was classified by an adjudication committee as cognitively normal, MCI, or dementia after completing a comprehensive battery of neurocognitive assessments. We used logistic regression to evaluate the association of PN with MCI or dementia overall and stratified by diabetes status after adjusting for traditional dementia risk factors. We also compared age-adjusted brain MRI measures among a subset (N = 1,095) of participants with versus without PN. Results: Overall, the prevalence of MCI (21.9% vs. 16.7%) and dementia (7.8% vs. 3.9%) were higher among participants with versus without PN (both p < 0.05). After adjustment, PN was positively associated with MCI or dementia in the overall study population (OR 1.45, 95% CI 1.23, 1.73). Results were similar by diabetes status (diabetes: OR 1.38, 95% CI 1.03–1.87; no diabetes: OR 1.48, 95% CI 1.20–1.83; p-for-interaction = 0.46). Age-adjusted total and lobar brain volumes were significantly lower in participants with versus without PN (both, p < 0.05). Discussion/Conclusions: PN as defined by monofilament insensitivity was associated with cognitive status independent of vascular risk factors and regardless of diabetes status. Our findings support a connection between PN and cognitive impairment, even in the absence of diabetes.

引言：本研究旨在评估以单丝触觉缺失定义的周围神经病（peripheral neuropathy, PN）在伴或不伴糖尿病的老年人群中，与轻度认知障碍（mild cognitive impairment, MCI）及痴呆的关联。

方法：我们对动脉粥样硬化风险社区神经认知研究（Atherosclerosis Risk in Communities Neurocognitive Study, ARIC-NCS）的3362名黑人和白人参与者开展横断面分析，所有参与者均在第6次随访（2016至2017年，年龄71至94岁）时接受了单丝触觉检测。参与者经全套综合神经认知评估后，由裁决委员会将其认知状态划分为认知正常、轻度认知障碍或痴呆。我们采用logistic回归分析，评估总体人群中周围神经病与轻度认知障碍或痴呆的关联，并按糖尿病状态进行分层校正分析，校正因素涵盖传统痴呆危险因素。此外，我们在1095名亚组参与者中，对比了伴与不伴周围神经病者的年龄校正后脑磁共振成像（magnetic resonance imaging, MRI）指标。

结果：总体而言，合并周围神经病的参与者其轻度认知障碍患病率（21.9% vs. 16.7%）及痴呆患病率（7.8% vs. 3.9%）均显著高于无周围神经病的参与者（两组比较均p<0.05）。校正混杂因素后，总体研究人群中周围神经病与轻度认知障碍或痴呆呈正相关（优势比（odds ratio, OR）=1.45，95%置信区间（confidence interval, CI）：1.23~1.73）。按糖尿病状态分层的分析结果与之相似（糖尿病组：OR=1.38，95%CI：1.03~1.87；无糖尿病组：OR=1.48，95%CI：1.20~1.83；交互作用检验p=0.46）。年龄校正后的全脑及脑叶体积在合并周围神经病的参与者中显著低于无周围神经病者（两组比较均p<0.05）。

讨论与结论：以单丝触觉缺失定义的周围神经病与认知状态的关联独立于血管危险因素，且不受糖尿病状态的影响。本研究结果支持周围神经病与认知损害之间存在关联，即便在无糖尿病的人群中亦是如此。