关键词: 稳态负荷评分; 新型冠状病毒感染; 脑小血管病; 脑微出血; 腔隙; 队列研究

Abstract: Objective  To explore the association between baseline allostatic load score (ALS) and imaging progression of cerebral small vessel disease (CSVD) in individuals with coronavirus disease 2019 (COVID‑19).
Methods  This study was conducted based on the polyvascular evaluation for cognitive impairment and vascular events (PRECISE) cohort, with community residents in Lishui, Zhejiang as research participants. Baseline assessment of the cohort was conducted from May 2017 to September 2019, with centralized follow‑up every two years, and a special survey on COVID-19 was completed between May and June 2024. Participants with a history of COVID‑19 who completed the second follow‑up [median follow-up duration of 4.7 (4.4-4.8) years] and underwent cranial MRI were enrolled in the present study. ALS was calculated from ten baseline clinical indicators: systolic and diastolic blood pressure, resting pulse, BMI, waist-to-hip ratio, TC, HDL-C, glycated hemoglobin, serum albumin, and high‑sensitivity C‑reactive protein. According to the total ALS score, participants were classified into low‑ALS (0-1 points), moderate‑ALS (2-3 points), and high‑ALS (≥4 points) groups. CSVD imaging markers were assessed based on cranial MRI, including lacunes, cerebral microbleeds, enlarged perivascular spaces (EPVS), and white matter hyperintensities. By comparing cranial MRI findings at baseline and follow-up, progression was determined for each individual CSVD imaging marker, for overall CSVD imaging progression (defined as progression of any of the above markers), and for total CSVD burden progression according to the Wardlaw criteria and the modified Rothwell criteria. Associations between ALS groups and CSVD progression were estimated using generalized linear models.
Results  A total of 1663 participants were included in this study, including 555 in the low‑ALS group, 697 in the moderate‑ALS group, and 411 in the high‑ALS group. After adjustment for covariates, compared with the low‑ALS group, the high‑ALS group had a 90% higher risk of incident lacunes (RR 1.90, 95%CI 1.24-2.90, P=0.003). Each 1‑point increment in ALS was associated with an 18% higher risk of incident lacunes (RR 1.18, 95%CI 1.09-1.29, P<0.001). In terms of EPVS grading progression, each 1‑point increase in ALS was associated with a 5% higher risk of EPVS grading progression in the basal ganglia (RR 1.05, 95%CI 1.01-1.10, P=0.030). Compared with the low-ALS group, both the moderate‑ALS group (RR 1.14, 95%CI 1.03-1.25, P=0.010) and the high‑ALS group (RR 1.13, 95%CI 1.01-1.26, P=0.028) showed a higher risk of overall CSVD imaging progression. Each 1‑point increase in ALS was associated with a 3% higher risk (RR 1.03, 95%CI 1.01-1.05, P=0.007). According to the Wardlaw criteria, both the moderate‑ALS group (RR 1.18, 95%CI 1.04-1.35, P=0.012) and the high‑ALS group (RR 1.22, 95%CI 1.05-1.40, P=0.008) also exhibited a higher risk of total CSVD burden progression than the low-ALS group. Each 1‑point ALS increment was associated with a 4% higher risk (RR 1.04, 95%CI 1.01-1.07, P=0.007).
Conclusions  Among individuals with COVID‑19, higher ALS levels were associated with increased risks of imaging progression and total burden progression of CSVD, primarily manifested as an increased risk of incident lacunes. These findings suggest that long‑term physiological stress may contribute to COVID‑19-related cerebral microvascular injury.

Key words: Allostatic load score; Coronavirus disease 2019; Cerebral small vessel disease; Cerebral microbleed; Lacune; Cohort study