Development of cerebral small vessel disease, a major cause of stroke and dementia, may be influenced by early life factors. It is unclear whether these relationships are independent of each other, of adult socio-economic status or of vascular risk factor exposures. We examined associations between factors from birth (ponderal index, birth weight), childhood (IQ, education, socio-economic status), adult small vessel disease, and brain volumes, using data from four prospective cohort studies: STratifying Resilience And Depression Longitudinally (STRADL) (n = 1080; mean age = 59 years); the Dutch Famine Birth Cohort (n = 118; mean age = 68 years); the Lothian Birth Cohort 1936 (LBC1936; n = 617; mean age = 73 years), and the Simpson’s cohort (n = 110; mean age = 78 years). We analysed each small vessel disease feature individually and summed to give a total small vessel disease score (range 1–4) in each cohort separately, then in meta-analysis, adjusted for vascular risk factors and adult socio-economic status. Higher birth weight was associated with fewer lacunes [odds ratio (OR) per 100 g = 0.93, 95% confidence interval (CI) = 0.88 to 0.99], fewer infarcts (OR = 0.94, 95% CI = 0.89 to 0.99), and fewer perivascular spaces (OR = 0.95, 95% CI = 0.91 to 0.99). Higher childhood IQ was associated with lower white matter hyperintensity burden (OR per IQ point = 0.99, 95% CI 0.98 to 0.998), fewer infarcts (OR = 0.98, 95% CI = 0.97 to 0.998), fewer lacunes (OR = 0.98, 95% CI = 0.97 to 0.999), and lower total small vessel disease burden (OR = 0.98, 95% CI = 0.96 to 0.999). Low education was associated with more microbleeds (OR = 1.90, 95% CI = 1.33 to 2.72) and lower total brain volume (mean difference = −178.86 cm3, 95% CI = −325.07 to −32.66). Low childhood socio-economic status was associated with fewer lacunes (OR = 0.62, 95% CI = 0.40 to 0.95). Early life factors are associated with worse small vessel disease in later life, independent of each other, vascular risk factors and adult socio-economic status. Risk for small vessel disease may originate in early life and provide a mechanistic link between early life factors and risk of stroke and dementia. Policies investing in early child development may improve lifelong brain health and contribute to the prevention of dementia and stroke in older age.

中文翻译：

---

四项前瞻性队列研究中晚年脑小血管疾病的早期生命预测因子


脑小血管疾病是中风和痴呆的主要原因，其发展可能受到早期生活因素的影响。目前尚不清楚这些关系是否彼此独立、与成人社会经济状况或血管危险因素暴露无关。我们使用来自四项前瞻性队列研究的数据，研究了出生（体重指数、出生体重）、童年（智商、教育、社会经济地位）、成人小血管疾病和脑容量等因素之间的关联：纵向分层弹性和抑郁（ STRADL)（n = 1080；平均年龄 = 59 岁）；荷兰饥荒出生队列（n = 118；平均年龄 = 68 岁）； 1936 年洛锡安出生队列（LBC1936；n = 617；平均年龄 = 73 岁）和辛普森队列（n = 110；平均年龄 = 78 岁）。我们单独分析了每个小血管疾病的特征，并分别求和得出每个队列的小血管疾病总评分（范围 1-4），然后在荟萃分析中根据血管危险因素和成人社会经济状况进行调整。较高的出生体重与较少的腔隙[每 100 克比值比 (OR) = 0.93，95% 置信区间 (CI) = 0.88 至 0.99]、较少的梗塞（OR = 0.94，95% CI = 0.89 至 0.99）以及较少的梗塞相关。血管周围空间更少（OR = 0.95，95% CI = 0.91 至 0.99）。较高的儿童智商与较低的白质高信号负担（每智商点的 OR = 0.99，95% CI = 0.98 至 0.998）、较少的梗塞（OR = 0.98，95% CI = 0.97 至 0.998）、较少的腔隙（OR = 0.98， 95% CI = 0.97 至 0.999），并且总小血管疾病负担较低（OR = 0.98，95% CI = 0.96 至 0.999）。受教育程度低与微出血较多（OR = 1.90，95% CI = 1.33 至 2.72）和脑总体积较低（平均差 = −178.86 cm3，95% CI = −325.07 至 −32.66）相关。 儿童社会经济地位较低与缺陷较少相关（OR = 0.62，95% CI = 0.40 至 0.95）。早期生活因素与晚年更严重的小血管疾病相关，彼此独立、血管危险因素和成人社会经济状况。小血管疾病的风险可能起源于生命早期，并在生命早期因素与中风和痴呆风险之间提供了机制联系。投资于儿童早期发展的政策可能会改善终生大脑健康，并有助于预防老年痴呆症和中风。