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Title: Relationship between size at birth, socioeconomic position and cardiometabolic risk factors across the lifecourse with cognition and depression late in life
Author: Tiptur Nagaraj, Muralikrishna Krishna
ISNI:       0000 0004 8501 9121
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 2018
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Background: There is limited and inconsistent evidence, mainly from high income countries, indicating that growth restriction in utero may lead to lower cognition and a higher risk of depression in late life, either through impaired brain development or adverse metabolic programming. Methods: Between 2013-15, I examined associations of size at birth with cognition and depression among 721 men and women (55-80 yrs) whose size at birth had been recorded at Holdsworth Memorial Hospital, Mysore, South India. Approximately 20 yrs ago, a subset (n=522) of them had assessments for cardiometabolic disorders in midlife. In my study, cognitive function and depression were measured using a culturally adapted and validated 10/66 battery of cognitive tests and the Geriatric Mental State examination respectively. A reliable informant was interviewed for the evidence of cognitive decline and functional impairment of the participants. Other investigations included a structured assessment for sociodemographic and lifestyle factors; blood tests (for glucose tolerance, insulin resistance, diabetes, dyslipidemia, anaemia, B12 and folate deficiency, and hyperhomocysteinaemia), physical health assessments (for hypertension, coronary heart disease and stroke) and a genetic assay for Apoε lipoprotein. Results: Age was inversely and independently associated with cognition in late life, women had higher cognitive function than men. Those who were heavier at birth had higher composite cognitive score [0.12 SD per SD birth weight 95% CI (0.05, 0.19) p=0.001] in late life. Other lifecourse factors independently related to cognition were (positively) maternal educational level and participants' own educational level, adult leg length, body mass index (BMI) and socioeconomic position; and (negatively) diabetes in midlife and, current stroke and depression. The association of birth weight with cognition was independent of midlife and current cardiometabolic risk markers, was possibly mediated by attained educational level of the participants, and was attenuated after adjustment for all lifecourse factors [0.08 SD per SD birth weight (95% CI -0.01, 0.18) p=0.07)]. The greatest attenuation occurred after adjusting for indicators of the childhood environment (maternal education and adult leg length). Birth weight and markers of a better childhood environment were positively related to late life cognitive function, indicating the persistence of the effect of these exposures into late life. Findings from this study are consistent with the 'cognitive reserve', but not the 'fetal cardiometabolic programming' pathway of cognitive ageing. Those who were heavier at birth had lower rates of depression and this was of borderline significance [OR=0.82 per SD birth weight 95%CI (0.68, 1.00) p=0.09]. In a multiple regression model, factors independently associated with depression were (negatively) being married, current leg length, socioeconomic position, physical activity and haemoglobin, and (positively) Apoε4 genotype, stroke and current homocysteine level. After adjusting for lifecourse factors, birth weight was unrelated to depression. Conclusion: With the caveat that causality cannot be assumed from observational cohort data, better childhood environment, higher attained education and socioeconomic status, and better current nutritional status may be protective against late life depression. Further studies are required to elucidate the Developmental Origins of Health and Disease (DOHaD) mechanisms of brain ageing.
Supervisor: Fall, Caroline ; Kumaran, Kalyanaraman ; Osmond, Clive Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available