Early life risk factors for cerebrovascular disease and depressive symptoms in later life

Abstract

Cerebrovascular disease (CVD) can result in cerebral small vessel disease (cSVD) and structural brain changes such as decreased cortical volume, brain atrophy and cerebral infarcts which are major causes of stroke and dementia. CVD is also associated with increased depression and depressive symptoms in later life. Midlife vascular disease and adult socioeconomic status (SES) are well established risk factors but less is known about the effect of factors from earlier in life on CVD and depressive symptoms in later life. A series of systematic reviews of current literature examining early life factors and stroke, cSVD and depression following stroke are presented at the beginning of this thesis. These reviews found that childhood IQ, education and childhood SES were associated with stroke and cSVD in later life. The reviews also found that education level was associated with depression following stroke. However few of the studies adjusted for vascular risk factors and adult SES. Therefore this thesis aimed to investigate associations between birth and childhood factors and cerebrovascular disease and depressive symptoms, after adjustment for vascular risk factors and adult SES, in four community dwelling cohorts: the Stratifying Resilience & Depression Longitudinally (STRADL) cohort (n=280, 45% male, mean age= 62.1 (SD=4.1) years), the Dutch Famine Birth cohort (n= 151, 44% male, mean age 67.6 (SD=0.9) years), the Lothian Birth Cohort 1936 (LBC 1936, n= 865, 50% male, mean age 72.7 (SD=0.7) years), and the Simpson cohort (n=130, 31% male, mean age 78.5, (SD=1.5) years). This Thesis first examined associations between (i) cSVD burden (ii) total and regional brain volumes and (iii) self-reported symptoms of depression and anxiety measured using the Hospital Anxiety and Depression Scale. All analyses were adjusted for age, sex, hypertension, smoking behaviour, adult SES and cognition. Neither cSVD nor brain volumes were associated with symptoms of anxiety. Higher white matter hyperintensity volumes, having one or more cerebral infarct and increased cerebral atrophy were associated with increased depressive symptoms independent of vascular risk factors and adult SES. Secondly, this thesis examined associations between birth and childhood factors and cSVD burden and total and regional brain volumes. Each cohort was analysed individually and then all available data meta-analysed. All analyses were adjusted for age, sex, hypertension, smoking behaviour, adult SES and other early life factors. Meta-analysis found that increasing birth weight was associated with decreased risk of lacunes across all cohorts. Placental weight, which was only available for the Simpson cohort, was associated with decreased risk total cSVD, WMH severity and volume and cerebral infarcts. In the LBC 1936 and Simpson cohort increasing childhood and premorbid IQ and more years of education were associated with fewer cortical infarcts. The association between premorbid and childhood IQ and infarcts was independent of education level. Across three cohorts low education level was associated with more microbleeds. These findings suggest that factors other than traditional vascular risk factors may contribute to cSVD and structural brain changes in later life. Thirdly, this thesis examined associations between birth and childhood factors and self-reported symptoms of depression and anxiety measured using the Hospital Anxiety and Depression Scale (HADS) and the Quick Inventory of Depressive Symptoms (QIDS-16). All analyses were adjusted for age, sex, hypertension, smoking behaviour, adult SES and cognition In the Dutch Famine Birth Cohort people born before the famine had lower scores of depression and anxiety on the HADS compared to those exposed to famine in early gestation and those conceived after the famine. In the LBC 1936 increasing ponderal index was associated with lower depressive symptoms, increasing childhood and premorbid IQ were associated with lower symptoms of anxiety and depression. Lower educational attainment and some indicators of childhood SES were associated with higher symptoms of depression and anxiety. Overall results suggest that early life factors, particularly childhood IQ, may contribute to structural brain changes and symptoms of depression and anxiety in later life, independent of vascular risk factors and other early life factors. Efforts to understand factors which may contribute to late life health, from the earliest stages of life, are important and may be used to inform changes in social policy. The effect sizes and potential impact of these findings suggest that larger sample sizes with more vascular disease and more depression are needed to robustly test these associations.