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Early life characteristics and late life burden of cerebral small vessel disease in the Lothian Birth Cohort 1936.

ABSTRACT: It is unknown whether relations between early-life factors and overall health in later life apply to burden of cerebral small vessel disease (cSVD), a major cause of stroke and dementia. We explored relations between early-life factors and cSVD in the Lothian Birth Cohort, a healthy aging cohort. Participants were recruited at age 70 (N = 1091); most had completed a test of cognitive ability at age 11 as part of the Scottish Mental Survey of 1947. Of those, 700 participants had brain MRI that could be rated for cSVD conducted at age 73. Presence of lacunes, white matter hyperintensities, microbleeds, and perivascular spaces were summed in a score of 0-4 representing all MRI cSVD features. We tested associations with early-life factors using multivariate logistic regression. Greater SVD score was significantly associated with lower age-11 IQ (OR higher SVD score per SD age-11 IQ = .78, 95%CI 0.65-.95, p=.01). The associations between SVD score and own job class (OR higher job class, .64 95%CI .43-.95, p=.03), age-11 deprivation index (OR per point deprivation score, 1.08, 95%CI 1.00-1.17, p=.04), and education (OR some qualifying education, .60 95%CI .37-.98, p=.04) trended towards significance (p<.05 for all) but did not meet thresholds for multiple testing. No early-life factor was significantly associated with any one individual score component. Early-life factors may contribute to age-73 burden of cSVD. These relations, and the potential for early social interventions to improve brain health, deserve further study.

SUBMITTER: Field TS

PROVIDER: S-EPMC5076451 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Early life characteristics and late life burden of cerebral small vessel disease in the Lothian Birth Cohort 1936.

Field Thalia S TS Doubal Fergus N FN Johnson Wendy W Backhouse Ellen E McHutchison Caroline C Cox Simon S Corley Janie J Pattie Alison A Gow Alan J AJ Shenkin Susan S Cvoro Vera V Morris Zoe Z Staals Julie J Bastin Mark M Deary Ian J IJ Wardlaw Joanna M JM

Aging 20160901 9

It is unknown whether relations between early-life factors and overall health in later life apply to burden of cerebral small vessel disease (cSVD), a major cause of stroke and dementia. We explored relations between early-life factors and cSVD in the Lothian Birth Cohort, a healthy aging cohort. Participants were recruited at age 70 (N = 1091); most had completed a test of cognitive ability at age 11 as part of the Scottish Mental Survey of 1947. Of those, 700 participants had brain MRI that co ...[more]

PMID: 27652981

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Project description:Abstract Introduction although neighbourhood may predict late-life cognitive function, studies mostly rely on measurements at a single time point, with few investigations applying a life-course approach. Furthermore, it is unclear whether the associations between neighbourhood and cognitive test scores relate to specific cognitive domains or general ability. This study explored how neighbourhood deprivation across eight decades contributed to late-life cognitive function. Methods data were drawn from the Lothian Birth Cohort 1936 (n = 1,091) with cognitive function measured through 10 tests at ages 70, 73, 76, 79 and 82. Participants’ residential history was gathered with ‘lifegrid’ questionnaires and linked to neighbourhood deprivation in childhood, young adulthood and mid-to-late adulthood. Associations were tested with latent growth curve models for levels and slopes of general (g) and domain-specific abilities (visuospatial ability, memory and processing speed), and life-course associations were explored with path analysis. Results higher mid-to-late adulthood neighbourhood deprivation was associated with lower age 70 levels (β = −0.113, 95% confidence intervals [CI]: −0.205, −0.021) and faster decline of g over 12 years (β = −0.160, 95%CI: −0.290, −0.031). Initially apparent findings with domain-specific cognitive functions (e.g. processing speed) were due to their shared variance with g. Path analyses suggested that childhood neighbourhood disadvantage is indirectly linked to late-life cognitive function through lower education and selective residential mobility. Conclusions to our knowledge, we provide the most comprehensive assessment of the life-course neighbourhood deprivation and cognitive ageing relationship. Living in advantaged areas in mid-to-late adulthood may directly contribute to better cognitive function and slower decline, whereas an advantaged childhood neighbourhood likely affects functioning through cognitive reserves.

Project description: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.

Project description:BackgroundDNA methylation outlier burden has been suggested as a potential marker of biological age. An outlier is typically defined as DNA methylation levels at any one CpG site that are three times beyond the inter-quartile range from the 25th or 75th percentiles compared to the rest of the population. DNA methylation outlier burden (the number of such outlier sites per individual) increases exponentially with age. However, these findings have been observed in small samples.ResultsHere, we showed an association between age and log10-transformed DNA methylation outlier burden in a large cross-sectional cohort, the Generation Scotland Family Health Study (N = 7010, β = 0.0091, p < 2 × 10-16), and in two longitudinal cohort studies, the Lothian Birth Cohorts of 1921 (N = 430, β = 0.033, p = 7.9 × 10-4) and 1936 (N = 898, β = 0.0079, p = 0.074). Significant confounders of both cross-sectional and longitudinal associations between outlier burden and age included white blood cell proportions, body mass index (BMI), smoking, and batch effects. In Generation Scotland, the increase in epigenetic outlier burden with age was not purely an artefact of an increase in DNA methylation level variability with age (epigenetic drift). Log10-transformed DNA methylation outlier burden in Generation Scotland was not related to self-reported, or family history of, age-related diseases, and it was not heritable (SNP-based heritability of 4.4%, p = 0.18). Finally, DNA methylation outlier burden was not significantly related to survival in either of the Lothian Birth Cohorts individually or in the meta-analysis after correction for multiple testing (HRmeta = 1.12; 95% CImeta = [1.02; 1.21]; pmeta = 0.021).ConclusionsThese findings suggest that, while it does not associate with ageing-related health outcomes, DNA methylation outlier burden does track chronological ageing and may also relate to survival. DNA methylation outlier burden may thus be useful as a marker of biological ageing.

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Early life characteristics and late life burden of cerebral small vessel disease in the Lothian Birth Cohort 1936.

Publications

Early life characteristics and late life burden of cerebral small vessel disease in the Lothian Birth Cohort 1936.

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