Size at birth, lifecourse factors, and cognitive function in late life: findings from the MYsore study of Natal effects on Ageing and Health (MYNAH) cohort in South India

Abstract

Objective: To examine if smaller size at birth, an indicator of growth restriction in utero, is associated with lower cognition in late life, and whether this may be mediated by impaired early life brain development and/or adverse cardiometabolic programming. Design: Longitudinal follow-up of a birth cohort. Setting: CSI Holdsworth Memorial Hospital (HMH), Mysore South India. Participants: 721 men and women (55–80 years) whose size at birth was recorded at HMH. Approximately 20 years earlier, a subset (n = 522) of them had assessments for cardiometabolic disorders in mid-life. Measurements: Standardized measurement of cognitive function, depression, sociodemographic, and lifestyle factors; blood tests and assessments for cardiometabolic disorders Results: Participants who were heavier at birth had higher composite cognitive scores (0.12 SD per SD birth weight [95% CI 0.05, 0.19] p = 0.001) in late life. Other lifecourse factors independently positively related to cognition were maternal educational level and participants’ own educational level, adult leg length, body mass index, and socioeconomic position, and negatively were diabetes in mid-life and current depression and stroke. The association of birth weight with cognition was independent cardiometabolic risk factors 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). Conclusions: The findings are consistent with positive effects of early life environmental factors (better fetal growth, education, and childhood socioeconomic status) on brain development resulting in greater long-term cognitive function. The results do not support a pathway linking poorer fetal development with reduced late life cognitive function through cardiometabolic programming.

The early life course-related traits with three psychiatric disorders: A two-sample Mendelian randomization study

“…Some studies have shown an association between LBW and a high risk of adult mental illness (57,58). Observational evidence has shown that smaller birth size and LBW are significantly associated with cognitive and motor impairment, which have lower composite cognitive scores (β = −0.12, 95% CI[−0.19, −0.05], p = 0.001) in later life compared to those with normal BW (59)(60)(61)(62). Other results also indicate that LBW newborns exhibit developmental alterations in gene expression involved in cell differentiation, neurogenesis, and neurodegeneration (63).…”

Highlighting the need for better care planning in young-onset dementia

“…Limited high-quality evidence from prospective longitudinal studies is available, but collective evidence is accruing about "critical windows" in early and adult life that differentially affect risk of neurodegenerative disease and a dose–response relationship for all-cause YOD depending on number and interaction with other exposures, across the life span (Cations et al , 2019). Recent commentary published in International Psychogeriatrics (Pini and Wennberg, 2022), for example, referenced a longitudinal follow-up of a birth cohort (Krishna et al ., 2022) which found that greater size at birth was associated with better cognitive function in later live, and this was partially mediated by childhood growth and environment. Of note, there was no evidence that midlife cardiometabolic factors mediated this association.…”

Identifying people at risk of dementia

“…For example, Krishna and colleagues reported that measures associated with early cognitive development, such as birth weight, maternal educational achievement, and adult leg length, were good predictors of cognitive performance in later life (Krishna et al, 2022), a finding that is consistent with the results of studies from other emerging economies (Scazufca et al, 2008). In addition, measures of early or mid-life adversity, such as limited educational attainment and low socioeconomic status (Krishna et al, 2022;Scazufca et al, 2010), have also been associated with declining cognitive function in later life. If these factors are causally related to cognitive impairment, population-based interventions targeting them could contribute to reducing the risk of dementia in the coming decades.…”