Longitudinal changes in late-life brain health after prenatal exposure to the Dutch famine

The consequences of harmful prenatal exposures for brain health may last a lifetime. Previous studies showed smaller adult brain volumes and altered perfusion at age 68 after prenatal famine exposure, particularly in men. To investigate whether the previously observed effects reflect persistent developmental effects or accelerated brain aging, we here studied longitudinal changes in brain volumes, white matter integrity, white matter hyperintensities and perfusion between ages 68 and 74 in individuals exposed and unexposed to famine in early gestation.

Brain MRI scans were obtained at age 68 (n = 118; 41 exposed to famine in early gestation) and 74 (n = 81; 25 exposed) in participants of the Dutch famine birth cohort (total n = 129, longitudinal n = 70; 23 exposed). We assessed longitudinal change in brain volumes (T1w), white matter hyperintensities (FLAIR), white matter integrity (DTI) and cerebral blood flow (ASL) between those exposed in early gestation and those unexposed (born before or conceived after the famine).

In longitudinal models, aging-related changes were observed between ages 68 and 74. We observed significantly smaller brain volumes in exposed compared to unexposed men, and alterations in cerebral blood flow in both exposed men and women compared to unexposed individuals. We observed no group differences in rate of brain health changes over time.

Our results support prenatal famine exposure affecting brain structure and perfusion across the lifespan. The absence of group differences in rate of change over time supports a hypothesis of persistent developmental effects rather than accelerated brain aging after prenatal famine exposure.