02 Oct 21. Featured Paper

Early life predictors of late life cerebral small vessel disease in four prospective cohort studies

Link to paper on Brain

Authors

Ellen V Backhouse, Susan D Shenkin, Andrew M McIntosh, Mark E Bastin, Heather C Whalley, Maria Valdez Hernandez, Susana Muñoz Maniega, Mathew A Harris, Aleks Stolicyn, Archie Campbell, Douglas Steele, Gordon D Waiter, Anca-Larisa Sandu, Jennifer M J Waymont, Alison D Murray, Simon R Cox, Susanne R de Rooij, Tessa J Roseboom, Joanna M Wardlaw

Abstract

Development of cerebral small vessel disease, a major cause of stroke & dementia, may be influenced by early life factors.

It is unclear whether these relationships are independent of each other, of adult socioeconomic status or of vascular risk factor exposures.

We examined associations between factors from birth (ponderal index, birth weight), childhood (IQ, education, socioeconomic status), adult small vessel disease, & 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), & the Simpson’s cohort (n = 110; mean age = 78 years).

We analysed each small vessel disease feature individually & 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 & adult socioeconomic status.

Higher birth weight was associated with fewer lacunes (OR per 100 g, 0.93 95%CI = 0.88–0.99), fewer infarcts (OR = 0.94 95%CI = 0.89–0.99), & fewer perivascular spaces (OR = 0.95 95%CI = 0.91–0.99).

Higher childhood IQ was associated with lower white matter hyperintensity burden (OR per IQ point = 0.99 95%CI 0.98–0.998), fewer infarcts (OR = 0.98, 95%CI = 0.97–0.998), fewer lacunes (OR = 0.98, 95%CI = 0.97–0.999), & lower total small vessel disease burden (OR = 0.98, 95%CI = 0.96–0.999).

Low education was associated with more microbleeds (OR = 1.90 95%CI = 1.33–2.72) & lower total brain volume (MD=-178.86 cm3, 95%CI=-325.07- -32.66). Low childhood socioeconomic status was associated with fewer lacunes (OR = 0.62, 95%CI = 0.40–0.95).

Early life factors are associated with worse small vessel disease in later life, independent of each other, vascular risk factors & adult socioeconomic status.

Risk for small vessel disease may originate in early life & provide a mechanistic link between early life factors & risk of stroke & dementia.

Policies investing in early child development may contribute to improve lifelong brain health to prevent dementia & stroke in older age.

Keywords

• Cerebral small vessel disease
• Childhood
• Education
• Epidemiology
• MR