Late-life brain volume: a life-course approach. The AGES-Reykjavik study

Abstract

Background The “fetal-origins-of-adult-disease” hypothesis proposes that an unfavorable intrauterine environment, estimated from small birth size, may induce permanent changes in fetal organs, including the brain. These changes in combination with effects of (cardiovascular) exposures during adult life may condition the later risk of brain atrophy. We investigated the combined effect of small birth size and mid-life cardiovascular risk on late-life brain volumes. Methods and Findings Archived birth records of weight and height were abstracted for 1348 participants of the AGES-Reykjavik (2002-2006) population-based cohort, who participated jn the original cohort of the Reykjavik Study (RS; baseline 1967). Mid-life cardiovascular risk factors (CVRF) were collected in the RS. As a part of the late-life AGES-Reykjavik exam a brain MRI was acquired and from it, volumes of total brain (TB), gray matter, white matter, and white matter lesions were estimated. Adjusting for intracranial volume, demographics, and education showed small birth size (low Ponderal Index (PI)) and increased mid-life cardiovascular risk had an additive effect on having smaller late-life brain volumes. Compared with the reference group (high PI/absence of mid-life CVRF), participants with lower PI/presence of mid-life CVRF (BMI>25kg/m2, hypertension, diabetes, ‘ever smokers’) had smaller TB volume later in life; B (95%CI) were -10.9mL (-21.0; -0.9), -10.9mL (-20.4; -1.4), -20.9mL (-46.9; 5.2), and -10.8mL (-19.3; -2.2) respectively. Conclusions These results suggest that exposure to an unfavorable intrauterine environment contributes to the trajectory towards smaller brain volume, adding to the atrophy that may be associated with mid-life cardiovascular risk.

Birth weight is associated with brain tissue volumes seven decades later, but not with age-associated changes to brain structure

“…In this study we have used a relatively small sample due to the availability of detailed birth data. However, our findings with regards to the positive associations between birth weight and brain tissue volumes in later life and regional cortical surface area are consistent with other studies in both adolescents and adults in late life (13)(14)(15) We have provided additional analysis of the impact of birth weight on more detailed measures of white matter microstructure and integrity, as well as demonstrating that the regional effects observed in cortical surface area persist into older age and are likely due to the early impact of birth weight on head growth and maximal head size. Within the LBC1936 participants we compared age 11 IQ (as an indicator of potential early life differences) of those with and without birth weight and MRI data, and found no significant difference between the two groups.…”

“…Birth weight also demonstrates a relationship with brain volume (β ~ 0.17), and with a regional patterning of positive associations across the cortical surface area in a cohort of young adults and adolescents -the authors of this study suggested that the regional effects of birth weight on cortical surface area may be due to head size or body size, but this was not explicitly tested (13). Importantly, the association between birth weight and brain tissue volumes and intracranial volume is evident in later life (14,15). However, the distinct contributions of anthropometric variables such as height, weight and head size remain unclear.…”

Higher Blood Pressure is Associated with Greater White Matter Lesions and Brain Atrophy: A Systematic Review with Meta-Analysis

“…Fifty-two studies ( n = 343,794, weighted mean age (MWA) = 58.7 years, women = 53.2%) met the inclusion criteria presented in Supplementary Information; Table S2 . They included 33 cross-sectional [ 5 , 6 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ] and 26 longitudinal studies [ 5 , 28 , 39 , 41 , 45 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 ] with follow-up ranging from ~2 [ 39 , ...…”

“…Fifty-two studies reported on the peripheral BP measurement and one study additionally reported on non-invasive CPP measurement [ 60 ]. Typically, studies reported BP as a continuous measure (87.7%), but a small proportion (12.3%) reported a categorical measure (normotension vs. hypertension) [ 23 , 25 , 28 , 32 , 38 , 46 , 54 , 69 ] Several methods were used to assess BP including occasional BP (78.8%), 24-h ambulatory BP monitoring (ABP, 11.5%) [ 21 , 39 , 56 , 61 , 66 , 67 ], BP variability over different visits (9.6%) [ 26 , 57 , 62 , 63 ], BP during exercise (2%) [ 58 ], BP reactivity in response to stress (2%) [ 34 ], and inter-arm differences in SBP (2%) [ 27 ].…”

HIV disease and diabetes interact to affect brain white matter hyperintensities and cognition

“…A longer duration of DM was also significantly associated with lower brain volumes; those individuals whose diabetes was diagnosed in midlife had poorer brain structural integrity relative to those who were diagnosed later in life [37] . The AGES-Reykjavik Study found that individuals with midlife cardiovascular risk factors, including diabetes, had smaller total brain volumes in late life than those without such risk factors [38] . Although there was a trend in this direction among the HIV-infected men in the current study, the small number of diabetics overall (n = 82) rendered that analysis underpowered.…”