Late-life brain volume: a life-course approach. The AGES-Reykjavik study.
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. Archived birth records of weight and height were abstracted for 1348 participants of the age, gene/environment susceptibility-Reykjavik study (RS; 2002-2006) population-based cohort, who participated in the original cohort of the RS (baseline 1967). Mid-life cardiovascular risk factors (CVRF) were collected in the RS. As a part of the late-life age, gene/environment susceptibility-RS examination, a brain magnetic resonance imaging was acquired and from it, volumes of total brain, 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 (body mass index >25 kg/m(2), hypertension, diabetes, "ever smokers") had smaller total brain volume later in life; B (95% confidence interval) were -10.9 mL (-21.0 to -0.9), -10.9 mL (-20.4 to -1.4), -20.9 mL (-46.9 to 5.2), and -10.8 mL (-19.3 to -2.2), respectively. These results suggest that exposure to an unfavorable intrauterine environment contributes to the trajectory toward smaller brain volume, adding to the atrophy that may be associated with mid-life cardiovascular risk.
Intramural Research Program, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, MD, USA; Department of Internal Medicine, VU University Medical Center, the Netherlands.
Majon
M
Muller
The Icelandic Heart Association, Kopavogur, Iceland.
Sigurdur
S
Sigurdsson
The Icelandic Heart Association, Kopavogur, Iceland; Department of Neurology, Landspitali University Hospital, Reykjavik, Iceland; Department of Radiology, Landspitali University Hospital, Reykjavik, Iceland.
Olafur
O
Kjartansson
Unit for Nutrition Research, University of Iceland and Landspitali University Hospital, Reykjavik, Iceland.
Ingibjorg
I
Gunnarsdottir
Unit for Nutrition Research, University of Iceland and Landspitali University Hospital, Reykjavik, Iceland.
Inga
I
Thorsdottir
Intramural Research Program, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, MD, USA.
Tamara B
TB
Harris
Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands.
Mark
M
van Buchem
The Icelandic Heart Association, Kopavogur, Iceland.
Vilmundur
V
Gudnason
Intramural Research Program, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, MD, USA. Electronic address: launerl@nia.nih.gov.
Lenore J
LJ
Launer
D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D001284:Atrophy; D001724:Birth Weight; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology*; D002318:Cardiovascular Diseases; D015331:Cohort Studies; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D006801:Humans; D007055:Iceland; D008297:Male; D009929:Organ Size; D012307:Risk Factors; D012494:Sampling Studies
Birth size; Brain volume; Cardiovascular risk factors; Life-course