Shaping the risk for late-life neurodegenerative disease: A systematic review on prenatal risk factors for Alzheimer’s disease-related volumetric brain biomarkers

• Published in: Neuroscience and biobehavioral reviews Vol. 146; p. 105019
• Main Authors: Boots, A., Wiegersma, A.M., Vali, Y., van den Hof, M., Langendam, M.W., Limpens, J., Backhouse, E.V., Shenkin, S.D., Wardlaw, J.M., Roseboom, T.J., de Rooij, S.R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.03.2023
• Subjects: Alzheimer Disease - psychology; Alzheimer’s disease; Biomarkers; Brain - pathology; Brain reserve; Child; Developmental programming; Female; Humans; Magnetic Resonance Imaging; MRI; Neurodegenerative Diseases; Placenta - pathology; Pregnancy; Prenatal Exposure Delayed Effects; Risk Factors; Systematic review; Brain reserve; Developmental programming; Systematic review; Alzheimer’s disease; MRI
• ISSN: 0149-7634; 1873-7528
• DOI: 10.1016/j.neubiorev.2022.105019

Environmental exposures including toxins and nutrition may hamper the developing brain in utero, limiting the brain’s reserve capacity and increasing the risk for Alzheimer’s disease (AD). The purpose of this systematic review is to summarize all currently available evidence for the association between prenatal exposures and AD-related volumetric brain biomarkers. We systematically searched MEDLINE and Embase for studies in humans reporting on associations between prenatal exposure(s) and AD-related volumetric brain biomarkers, including whole brain volume (WBV), hippocampal volume (HV) and/or temporal lobe volume (TLV) measured with structural magnetic resonance imaging (PROSPERO; CRD42020169317). Risk of bias was assessed using the Newcastle Ottawa Scale. We identified 79 eligible studies (search date: August 30th, 2020; Ntotal=24,784; median age 10.7 years) reporting on WBV (N = 38), HV (N = 63) and/or TLV (N = 5) in exposure categories alcohol (N = 30), smoking (N = 7), illicit drugs (N = 14), mental health problems (N = 7), diet (N = 8), disease, treatment and physiology (N = 10), infections (N = 6) and environmental exposures (N = 3). Overall risk of bias was low. Prenatal exposure to alcohol, opioids, cocaine, nutrient shortage, placental dysfunction and maternal anemia was associated with smaller brain volumes. We conclude that the prenatal environment is important in shaping the risk for late-life neurodegenerative disease. •Prenatal factors may increase the risk for Alzheimer’s disease by limiting brain development and brain reserve capacity.•We identified 79 eligible studies reporting on whole brain volume, hippocampal volume and/or temporal lobe volume.•Prenatal alcohol, opioids, cocaine, nutrient shortage, placental dysfunction and anemia were related to smaller volumes.•We found evidence for smaller volumes in Alzheimer’s disease-related brain regions after adverse prenatal exposures.•The prenatal environment is critical in shaping the risk for late-life neurodegenerative disease.