Supplementary Material for: Antiphospholipid Antibodies: Cognitive and Motor Decline, Neuroimaging and Neuropathology

Background: Few data are available on associations of antiphospholipid (aPL) antibodies with cognitive and motor decline in aging, and cerebrovascular disease on in vivo neuroimaging and postmortem neuropathology. Methods: This longitudinal, clinical-pathologic study (aPL antibodies, brain infarcts, and cognitive and motor decline in aging), was derived from 2 ongoing community-based cohort studies. A panel of 3 aPL antibodies was assayed in serum from 956 older individuals (mean age = 81.1 years; 72% women). Serum was also tested in a subset for markers of inflammation (C-reactive protein [CRP]) and blood-brain barrier breakdown (matrix metalloproteinases, MMPs). Annual clinical evaluations documented cognitive (17 neuropsychological tests) and motor function including parkinsonism. Cerebrovascular disease data were derived from in vivo neuroimaging and postmortem neuropathologic evaluations (699 individuals). We examined associations of aPL with cognitive and motor decline, other serum markers, neuroimaging, and neuropathology. Results: Of 956 individuals, 197 (20.6%) had aPL positivity, defined as positivity on any of the assays, at the time of first measurement. During a mean follow-up of 6.6 years (SD 4), overall aPL positivity was not associated with change in global cognition (estimate = –0.005, SE 0.011; p = 0.622) or parkinsonian signs (estimate = –0.003, SE 0.017; p = 0.860). aPL were not associated with serum CRP or MMPs (both p > 0.268). aPL were not associated with in vivo brain magnetic resonance imaging white matter hyperintensities or infarcts (both p > 0.376). Among those autopsied, aPL were not associated with pathologically confirmed brain infarcts, or cerebral atherosclerosis or arteriolosclerosis (all p≥ 0.447). Conclusions: In older individuals followed longitudinally, aPL do not relate to cognitive or motor decline, inflammation, or cerebrovascular disease on in vivo neuroimaging or postmortem neuropathology.

背景：目前关于衰老过程中抗磷脂（antiphospholipid, aPL）抗体与认知、运动功能衰退的关联，以及其与活体神经影像、死后神经病理学层面脑血管疾病的关联相关数据仍较为匮乏。方法：本项纵向临床病理研究（聚焦衰老过程中的抗磷脂抗体、脑梗死及认知、运动功能衰退）源自两项正在进行的社区队列研究。研究对956名老年个体（平均年龄81.1岁，女性占比72%）的血清样本开展了3种抗磷脂抗体的检测。同时，研究还对部分亚组的血清样本进行了炎症标志物C反应蛋白（C-reactive protein, CRP）及血脑屏障破坏标志物基质金属蛋白酶（matrix metalloproteinases, MMPs）的检测。年度临床评估涵盖了17项神经心理学测试的认知功能评估，以及包括帕金森综合征在内的运动功能评估。脑血管疾病相关数据来源于699名受试者的活体神经影像及死后神经病理学评估。本研究旨在分析抗磷脂抗体与认知、运动功能衰退，其他血清标志物，神经影像及神经病理学结果之间的关联。结果：在956名受试者中，首次检测时共有197人（20.6%）呈现抗磷脂抗体阳性，阳性判定标准为任意一项检测结果呈阳性。在平均6.6年的随访期间（标准差为4），整体抗磷脂抗体阳性与整体认知变化（estimate = –0.005, SE 0.011; p = 0.622）或帕金森综合征体征变化（estimate = –0.003, SE 0.017; p = 0.860）均无显著关联。抗磷脂抗体与血清CRP及MMPs水平均无显著关联（二者p值均>0.268）。抗磷脂抗体与活体脑部磁共振成像显示的脑白质高信号及脑梗死均无显著关联（二者p值均>0.376）。在接受尸检的受试者中，抗磷脂抗体与病理学确认的脑梗死、脑动脉粥样硬化或小动脉硬化均无显著关联（所有p值均≥0.447）。结论：在长期随访的老年人群中，抗磷脂抗体与认知或运动功能衰退、炎症反应，以及活体神经影像或死后神经病理学层面的脑血管疾病均无关联。