Women exposed to famine in early gestation have increased mortality up to age 76 years.

BACKGROUND: We have previously shown that exposure to famine in early gestation was associated with poorer adult health and, in women, with reduced survival up to age 64. OBJECTIVES: Here, we explore the association between prenatal famine exposure and mortality up to age 76 for men and women separately. METHODS: We studied adult mortality (>18 years) in men (n = 989) and women (n = 1002) born as term singletons around the time of the 1944-1945 Dutch famine. We compared overall and cause-specific mortality among men and women exposed to famine in late, mid, or early gestation to that among unexposed persons (born before or conceived after the famine) using Cox regression. RESULTS: In total, 500 persons (25.1%) had died after age 18. Women exposed to famine in early gestation had higher overall (HR 1.49, 95% CI 1.00, 2.23), cancer (HR 2.17, 95% CI 1.32,3.58) and cardiovascular mortality (HR 2.33, 95% CI 0.91, 5.95) compared to unexposed women. Mortality rates among men were not different between exposure groups. CONCLUSION: This study showed that women, but not men, exposed to famine in early gestation had increased overall, cardiovascular and cancer mortality up to age 76. Although prenatal famine exposure affects adult health of both men and women, it seems to only lead to increased mortality among women.

Prenatal exposure to undernutrition is associated with a specific lipid profile predicting future brain aging.

Prenatal adversity affects cognitive and brain aging. Both lipid and leptin concentrations may be involved. We investigated if prenatal undernutrition is associated with a specific blood lipid profile and/or leptin concentrations, and if these relate to cognitive function and brain aging. 801 plasma samples of members of the Dutch famine birth cohort were assessed for lipidomics and leptin at age 58. Cognitive performance was measured with a Stroop task at 58, and MRI-based BrainAGE was derived in a subsample at 68. Out of 259 lipid signals, a signature of five identified individuals who were undernourished prenatally. These five lipids were not associated with cognitive performance, but three were predictive of BrainAGE. Leptin was not associated with prenatal famine exposure, Stroop performance, or BrainAGE. In conclusion, prenatal undernutrition was associated with an altered lipid profile predictive of BrainAGE 10 years later, demonstrating the potential of lipid profiles as early biomarkers for accelerated brain aging.

Associations Between Early-Pregnancy Vitamin D Status and Postpartum Depressive and Anxiety Symptoms.

OBJECTIVE: Maternal postpartum depressive and anxiety symptoms are risk factors for subsequent maternal and child mental health problems. Little is known about the potential role of antepartum vitamin D and C-reactive protein (CRP) in the etiology of maternal postpartum affective symptoms. We investigated associations between antepartum vitamin D status and postpartum depressive and anxiety symptoms and whether antepartum CRP mediated these associations. METHODS: In 2483 participants of the Amsterdam Born Children and their Development prospective cohort, maternal serum vitamin D and CRP were measured at a median of 13 weeks' gestation. Vitamin D status was defined as deficient (≤29.9 nM), insufficient (30-49.9 nM), sufficient (50-79.9 nM), or normal (≥80 nM). Maternal depressive symptoms (Center for Epidemiologic Studies-Depression) and anxiety (State-Trait Anxiety Inventory) were assessed 3 months postpartum. RESULTS: After adjustments for confounders, vitamin D deficiency was only associated with increased postpartum anxiety symptoms ( B = 0.17, 95% confidence interval [CI] = 0.03-0.30, p = .017) compared to normal vitamin D levels (≥80 nM). In women not taking vitamin D supplementation ( n = 2303), vitamin D deficiency was associated with increased postpartum depressive and anxiety symptoms ( B = 0.14, 95% CI = 0.03-0.28, p = .045; and B = 0.17, 95% CI = 0.03-0.32, p = .015). Antepartum CRP did not mediate these links. CONCLUSIONS: We found some evidence that antepartum vitamin D deficiency was associated with increased postpartum affective symptoms, especially in women not taking vitamin D supplementation. Clinical trials should determine whether vitamin D supplementation can reduce the risk for postpartum affective disorders.

Prenatal Exposure to the 1944-45 Dutch Famine and Risk for Dementia up to Age 75: An Analysis of Primary Care Data.

BACKGROUND: A poor prenatal environment adversely affects brain development. Studies investigating long-term consequences of prenatal exposure to the 1944-45 Dutch famine have shown that those exposed to famine in early gestation had poorer selective attention, smaller brain volumes, poorer brain perfusion, older appearing brains, and increased reporting of cognitive problems, all indicative of increased dementia risk. OBJECTIVE: In the current population-based study, we investigated whether dementia incidence up to age 75 was higher among individuals who had been prenatally exposed to famine. METHODS: We included men (n=6,714) and women (n=7,051) from the Nivel Primary Care Database who had been born in seven cities affected by the Dutch famine. We used Cox regression to compare dementia incidence among individuals exposed to famine during late (1,231), mid (1,083), or early gestation (601) with those unexposed (born before or conceived after the famine). RESULTS: We did not observe differences in dementia incidence for those exposed to famine in mid or early gestation compared to those unexposed. Men and women exposed to famine in late gestation had significantly lower dementia rates compared to unexposed individuals (HR 0.52 (95%CI 0.30-0.89)). Sex-specific analyses showed a lower dementia rate in women exposed to famine in late gestation (HR 0.39 (95%CI 0.17-0.86)) but not in men (HR 0.68 (95%CI 0.33-1.41)). CONCLUSION: Although prenatal exposure to the Dutch famine has previously been associated with measures of accelerated brain aging, the present population-based study did not show increased dementia incidence up to age 75 in those exposed to famine during gestation.

Aging, sex, metabolic and life experience factors: Contributions to neuro-inflammaging in Alzheimer's disease research.

Alzheimer's disease (AD) is prevalent around the world, yet our understanding of the disease is still very limited. Recent work suggests that the cornerstone of AD may include the inflammation that accompanies it. Failure of a normal pro-inflammatory immune response to resolve may lead to persistent central inflammation that contributes to unsuccessful clearance of amyloid-beta plaques as they form, neuronal death, and ultimately cognitive decline. Individual metabolic, and dietary (lipid) profiles can differentially regulate this inflammatory process with aging, obesity, poor diet, early life stress and other inflammatory factors contributing to a greater risk of developing AD. Here, we integrate evidence for the interface between these factors, and how they contribute to a pro-inflammatory brain milieu. In particular, we discuss the importance of appropriate polyunsaturated fatty acids (PUFA) in the diet for the metabolism of specialised pro-resolving mediators (SPMs); raising the possibility for dietary strategies to improve AD outlook.

Maternal stress is associated with higher protein-bound amino acid concentrations in human milk.

Background: Maternal stress in the postpartum period affects not only the mother but also her newborn child, who is at increased risk of developing metabolic and mental disorders later in life. The mechanisms by which stress is transmitted to the infant are not yet fully understood. Human milk (HM) is a potential candidate as maternal stress affects various components of HM, e.g., fat and immunoglobulin concentrations. To date, it is unknown whether maternal stress also affects the amino acids (AAs) in HM, even though this nutrient is of extreme importance to child health and development. This study aimed to investigate whether and how maternal stress is associated with the AA composition of HM. Methods: In this observational cohort study (Amsterdam, The Netherlands), lactating women were recruited in two study groups: a high-stress (HS) group; women whose child was hospitalized (n = 24), and a control (CTL) group; women who gave birth to a healthy child (n = 73). HM was collected three times a day, on postpartum days 10, 17, and 24. Perceived psychological stress was measured using validated questionnaires, while biological stress measures were based on hair, saliva, and HM cortisol concentrations. HM protein-bound and free AAs were analyzed by liquid chromatography and compared between groups. Results: Maternal perceived stress scores were higher in the HS group (p < 0.01). The concentrations of protein-bound AAs in HM were higher in the HS group compared to the CTL group (p = 0.028) and were positively associated with HM cortisol concentrations (p = 0.024). The concentrations of free AAs did not differ between study groups and were unrelated to cortisol concentrations. Conclusion: Findings from this prospective cohort study suggest that maternal stress in the postpartum period is associated with an altered human milk amino acid composition, which could play a role in the transmission of maternal stress effects to her child. The physiological implications of these stress-induced changes for infant development await future research.

Effects of prenatal exposure to the 1944-45 Dutch famine and glucocorticoid receptor polymorphisms on later life PTSD susceptibility.

Background: Exposure to adversity in utero is thought to increase susceptibility to develop posttraumatic stress disorder (PTSD) following later life trauma, due to neurobiological programming effects during critical developmental periods. It remains unknown whether effects of prenatal adversity on PTSD susceptibility are modulated by genetic variations in neurobiological pathways implicated in PTSD susceptibility.Objective: We investigated whether genetic variation in the glucocorticoid receptor (GR) modulated effects of prenatal famine exposure on late adulthood PTSD symptom severity after trauma exposure in childhood and mid-to-late adulthood.Method: We included N = 439 term-born singleton adults (mean age: 72 years, 54.2% women) from the Dutch Famine Birth Cohort, born around the time of the Dutch Famine of 1944/1945, divided into exposure and control groups based on timing of the famine during gestation. Participants filled out self-report questionnaires on childhood (Childhood Trauma Questionnaire) and mid-to-late adulthood (Life Events Checklist for DSM-5) trauma, and current PTSD symptom severity (PTSD Checklist for DSM-5). GR haplotypes were determined from four functional GR single nucleotide polymorphisms (ER22/23EK, N363S, BclI and exon 9ß) in previously collected DNA. Linear regression analyses were performed to investigate associations of GR haplotype and prenatal famine exposure in conjunction with later life trauma on PTSD symptom severity.Results: We observed a significant three-way interaction between the GR Bcll haplotype, famine exposure during early gestation, and adulthood trauma exposure on PTSD symptom severity in late adulthood. Only participants exposed to famine during early gestation without the GR Bcll haplotype showed a significantly stronger positive association between adulthood trauma and PTSD symptom severity than non-exposed participants, indicating increased PTSD susceptibility.Conclusions: Our results illustrate the importance of integrated approaches considering genetics and environmental contexts throughout various life periods, including the rarely investigated prenatal environment, to elucidate how PTSD susceptibility evolves throughout life.HIGHLIGHTS Adversity during pregnancy is thought to increase offspring's PTSD risk following later life trauma, but exact neurobiological mechanisms underlying this process remain unknown.We found that effects of prenatal famine exposure on PTSD symptom severity were influenced by genetic variation in the glucocorticoid receptor, which signals effects of the stress hormone cortisol.Integrated approaches considering genetics and environmental contexts throughout both early and later life are important to understand how PTSD risk evolves throughout life.

Do prenatal factors shape the risk for dementia?: A systematic review of the epidemiological evidence for the prenatal origins of dementia.

PURPOSE: Prenatal factors such as maternal stress, infection and nutrition affect fetal brain development and may also influence later risk for dementia. The purpose of this systematic review was to provide an overview of all studies which investigated the association between prenatal factors and later risk for dementia. METHODS: We systematically searched MEDLINE and Embase for original human studies reporting on associations between prenatal factors and dementia from inception to 23 November 2022. Prenatal factors could be any factor assessed during pregnancy, at birth or postnatally, provided they were indicative of a prenatal exposure. Risk of bias was assessed using the Newcastle Ottawa Scale. We followed PRISMA guidelines for reporting. RESULTS: A total of 68 studies met eligibility criteria (including millions of individuals), assessing maternal age (N = 30), paternal age (N = 22), birth order (N = 15), season of birth (N = 16), place of birth (N = 13), prenatal influenza pandemic (N = 1) or Chinese famine exposure (N = 1), birth characteristics (N = 3) and prenatal hormone exposure (N = 4). We observed consistent results for birth in a generally less optimal environment (e.g. high infant mortality area) being associated with higher dementia risk. Lower and higher birth weight and prenatal famine exposure were associated with higher dementia risk. The studies on season of birth, digit ratio, prenatal influenza pandemic exposure, parental age and birth order showed inconsistent results and were hampered by relatively high risk of bias. CONCLUSION: Our findings suggest that some prenatal factors, especially those related to a suboptimal prenatal environment, are associated with an increased dementia risk. As these associations may be confounded by factors such as parental socioeconomic status, more research is needed to examine the potential causal role of the prenatal environment in dementia.

Exposure to the Dutch Famine in Early Gestation and Cognitive Function and Decline in Older Age.

People exposed to the 1944-1945 Dutch famine in early gestation performed worse on a selective attention task at age 58 and reported more cognitive problems at age 72. We here hypothesized that undernutrition in early gestation is associated with poorer cognitive functioning in older age and a higher rate of cognitive decline. We tested this hypothesis in the Dutch famine birth cohort in men and women combined and separately. We assessed cognitive function using a Stroop-like, trail-making and 15-word task (at ages 68 and 74) and the Montreal cognitive assessment as well as self-perceived cognitive problems (at age 74) in 73 men (n = 34) and women (n = 39). We compared cognitive function and decline (change in cognitive function between age 68 and 74) between those exposed in early gestation and those not exposed (born before or conceived after the famine). Although in both men and women cognitive function declined from age 68 to 74, cognitive task scores and the rate of decline did not differ between those exposed or unexposed to famine. At age 74, men exposed to famine in early gestation more often reported cognitive problems, although this was not statistically different from unexposed men (OR 3.1 [95%CI 0.7 to 13.0]). We did not find evidence of increased cognitive decline after prenatal undernutrition. Selective participation and mortality may have hampered our ability to detect potential true effects. The self-perceived cognitive problems among men who had been exposed to famine in early gestation might be an indication of future dementia risk.

The gut microbiota and depressive symptoms across ethnic groups.

The gut microbiome is thought to play a role in depressive disorders, which makes it an attractive target for interventions. Both the microbiome and depressive symptom levels vary substantially across ethnic groups. Thus, any intervention for depression targeting the microbiome requires understanding of microbiome-depression associations across ethnicities. Analysing data from the HELIUS cohort, we characterize the gut microbiota and its associations with depressive symptoms in 6 ethnic groups (Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Turkish, Moroccan; N = 3211), living in the same urban area. Diversity of the gut microbiota, both within (α-diversity) and between individuals (ß-diversity), predicts depressive symptom levels, taking into account demographic, behavioural, and medical differences. These associations do not differ between ethnic groups. Further, ß-diversity explains 29%-18% of the ethnic differences in depressive symptoms. Bacterial genera associated with depressive symptoms belong to mulitple families, prominently including the families Christensenellaceae, Lachnospiraceae, and Ruminococcaceae. In summary, the results show that the gut microbiota are linked to depressive symptom levels and that this association generalizes across ethnic groups. Moreover, the results suggest that ethnic differences in the gut microbiota may partly explain parallel disparities in depression.

Associations Between Child Maltreatment, Inflammation, and Comorbid Metabolic Syndrome to Depressed Mood in a Multiethnic Urban Population: The HELIUS Study.

Background: Child maltreatment is a common negative experience and has potential long-lasting adverse consequences for mental and physical health, including increased risk for major depressive disorder (MDD) and metabolic syndrome. In addition, child maltreatment may increase the risk for comorbid physical health conditions to psychiatric conditions, with inflammation as an important mediator linking child maltreatment to poor adult health. However, it remains unresolved whether experiencing child maltreatment increases the risk for the development of comorbid metabolic syndrome to MDD. Therefore, we investigated whether child maltreatment increased the risk for comorbid metabolic syndrome to depressed mood. Subsequently, we examined whether C-reactive protein (CRP), as an inflammatory marker, mediated this association. In addition, we investigated whether effects differed between men and women. Methods: Associations were examined within cross-sectional data from the multiethnic HELIUS study (N = 21,617). Adult residents of Amsterdam, Netherlands, self-reported on child maltreatment (distinct and total number of types experienced before the age of 16 years) as well as current depressed mood (PHQ-9 score ≥ 10), and underwent physical examination to assess metabolic syndrome. The CRP levels were assessed in N = 5,998 participants. Logistic and linear regressions were applied for binary and continuous outcomes, respectively. All analyses were adjusted for relevant demographic, socioeconomic, and lifestyle characteristics, including ethnicity. Results: A higher number of maltreatment types as well as distinct types of emotional neglect, emotional abuse, and sexual abuse were significantly associated with a higher risk for current depressed mood. Child maltreatment was not significantly associated with the risk for metabolic syndrome in the whole cohort, nor within individuals with depressed mood. As child maltreatment was not significantly associated with the CRP levels, subsequent mediation analyses were not performed. No significant moderating effects by sex were observed. Conclusion: In this multiethnic urban cohort, child maltreatment was associated with a higher risk for depressed mood. Contrary to our expectations, child maltreatment was not significantly associated with an increased risk for metabolic syndrome, neither in the whole cohort nor as a comorbid condition in individuals with depressed mood. As the data were cross-sectional and came from a non-clinical adult population, longitudinal perspectives in relation to various stages of the investigated conditions were needed with more comprehensive assessments of inflammatory markers.

Are Brain and Cognitive Reserve Shaped by Early Life Circumstances?

When growing older, many people are faced with cognitive deterioration, which may even amount to a form of dementia at some point in time. Although neuropathological signs of dementia disorders can often be demonstrated in brains of patients, the degree to which clinical symptoms are present does mostly not accurately reflect the amount of neuropathology that is present. Sometimes existent pathology even goes without any obvious clinical presentation. An explanation for this phenomenon may be found in the concept of reserve capacity. Reserve capacity refers to the ability of the brain to effectively buffer changes that are associated with normal aging processes and to cope with pathological damage. A larger reserve capacity has been suggested to increase resilience against age-associated cognitive deterioration and dementia disorders. Traditionally, a division has been made between brain reserve, which is based on morphological characteristics of the brain, and cognitive reserve, which is based on functional characteristics of the brain. The present review discusses the premises that brain and cognitive reserve capacity are shaped by prenatal and early postnatal factors. Evidence is accumulating that circumstances during the first 1,000 days of life are of the utmost importance for the lifelong health of an individual. Cognitive deterioration and dementia disorders may also have their origin in early life and a potentially important pathway by which the early environment affects the risk for neurodegenerative diseases is by developmental programming of the reserve capacity of the brain. The basic idea behind developmental programming of brain and cognitive reserve is explained and an overview of studies that support this idea is presented. The review is concluded by a discussion of potential mechanisms, synthesis of the evidence and relevance and future directions in the field of developmental origins of reserve capacity.

Prenatal exposure to the Dutch famine is associated with more self-perceived cognitive problems at 72 years of age.

BACKGROUND: Undernutrition during critical periods of neurodevelopment can hinder the developing brain with lasting negative consequences for brain size, structure and function. In this study, we describe self-perceived cognitive problems of men and women who were born around the time of the Dutch famine of 1944-45. METHODS: We compared self-perceived cognitive problems between men and women who had been exposed to the 1944-45 Dutch famine in late, mid or early gestation and those who were born before or conceived after the famine (and had thus not been exposed prenatally). We included 595 participants aged 71-74 years. RESULTS: Women who had been exposed to famine in late gestation more often reported cognitive problems compared to those who had not been exposed (OR 2.2 [95% CI 1.1-4.4]), whereas for men, this was the case for those exposed in early gestation (OR 2.3 [0.9-5.5]). Furthermore, men and women exposed in early gestation more often reported consulting a healthcare practitioner for cognitive problems in the past 12 months (OR 3.2 [1.3-8.1]). Especially men exposed in early gestation reported having consulted a healthcare practitioner more often than unexposed men (OR 4.4 [1.2-16.0]). CONCLUSIONS: These findings suggest that prenatal undernutrition does not only have lasting effects on brain size, but also on its function, with more self-perceived cognitive problems at older age, which also require more medical attention. Also, the effects of undernutrition depend on sex and its timing during gestation.

Cardiovascular reactions to acute psychological stress and academic achievement.

Cardiovascular reactions to acute psychological stress have been associated with cognitive function. However, previous work has assessed cardiovascular reactions and cognitive function in the laboratory at the same time. The present study examined the association between cardiovascular reactions to acute psychological stress in the laboratory and academic performance in final year high school students. Heart rate, blood pressure, stroke volume, and cardiac output reactions to an acute psychological stress task were measured in 131 participants during their final year of high school. Performance on high school A-levels were obtained the following year. Higher heart rate and cardiac output reactivity were associated with better A-level performance. These associations were still statistically significant after adjusting for a wide range of potentially confounding variables. The present results are consistent with a body of literature suggesting that higher heart rate reactions to acute psychological stress are associated with better cognitive performance across a variety of domains.

Sex-dependence and comorbidities of the early-life adversity induced mental and metabolic disease risks: Where are we at?

Early-life adversity (ELA) is a major risk factor for developing later-life mental and metabolic disorders. However, if and to what extent ELA contributes to the comorbidity and sex-dependent prevalence/presentation of these disorders remains unclear. We here comprehensively review and integrate human and rodent ELA (pre- and postnatal) studies examining mental or metabolic health in both sexes and discuss the role of the placenta and maternal milk, key in transferring maternal effects to the offspring. We conclude that ELA impacts mental and metabolic health with sex-specific presentations that depend on timing of exposure, and that human and rodent studies largely converge in their findings. ELA is more often reported to impact cognitive and externalizing domains in males, internalizing behaviors in both sexes and concerning the metabolic dimension, adiposity in females and insulin sensitivity in males. Thus, ELA seems to be involved in the origin of the comorbidity and sex-specific prevalence/presentation of some of the most common disorders in our society. Therefore, ELA-induced disease states deserve specific preventive and intervention strategies.

Sex-specific effects of prenatal undernutrition on resting-state functional connectivity in the human brain at age 68.

Prenatal nutrition may significantly impact brain aging. Results from the Dutch Famine Birth Cohort indicated that prenatal undernutrition is negatively associated with cognition, brain volumes, perfusion and structural brain aging in late life, predominantly in men. This study investigates the association between prenatal undernutrition and late-life functional brain network connectivity. In an exploratory resting-state functional magnetic resonance imaging study of 112 participants from the Dutch Famine Birth Cohort, we investigated whether the within- and between-network functional connectivity of the default mode network, salience network and central executive network differ at age 68 in men (N = 49) and women (N = 63) either exposed or unexposed to undernutrition in early gestation. Additionally, we explored sex-specific effects. Compared to unexposed participants, exposed participants revealed multiple clusters of different functional connectivity within and between the three networks studied. Sex-specific analyses suggested a pattern of network desegregation fitting with brain aging in men and a more diffuse pattern of group differences in women. This study demonstrates that associations between prenatal undernutrition and brain network functional connectivity extend late into life.

Lessons learned from 25 Years of Research into Long term Consequences of Prenatal Exposure to the Dutch famine 1944-45: The Dutch famine Birth Cohort.

This paper describes the findings of a historical cohort study of men and women born around the time of the Dutch famine 1944-45. It provided the first direct evidence in humans of the lasting consequences of prenatal undernutrition. The effects of undernutrition depended on its timing during gestation, and the organs and tissues undergoing periods of rapid development at that time. Early gestation appeared to be particularly critical, with the effects of undernutrition being most apparent, even without reductions in size at birth. Undernutrition during gestation affected the structure and function of organs and tissues, altered behaviour and increased risks of chronic degenerative diseases. This demonstrates the fundamental importance of maternal nutrition during gestation as the building blocks for future health.

Early life predictors of late life cerebral small vessel disease in four prospective cohort studies.

Development of cerebral small vessel disease, a major cause of stroke and dementia, may be influenced by early life factors. It is unclear whether these relationships are independent of each other, of adult socio-economic status or of vascular risk factor exposures. We examined associations between factors from birth (ponderal index, birth weight), childhood (IQ, education, socio-economic status), adult small vessel disease, and brain volumes, using data from four prospective cohort studies: STratifying Resilience And Depression Longitudinally (STRADL) (n = 1080; mean age = 59 years); the Dutch Famine Birth Cohort (n = 118; mean age = 68 years); the Lothian Birth Cohort 1936 (LBC1936; n = 617; mean age = 73 years), and the Simpson's cohort (n = 110; mean age = 78 years). We analysed each small vessel disease feature individually and summed to give a total small vessel disease score (range 1-4) in each cohort separately, then in meta-analysis, adjusted for vascular risk factors and adult socio-economic status. Higher birth weight was associated with fewer lacunes [odds ratio (OR) per 100 g = 0.93, 95% confidence interval (CI) = 0.88 to 0.99], fewer infarcts (OR = 0.94, 95% CI = 0.89 to 0.99), and fewer perivascular spaces (OR = 0.95, 95% CI = 0.91 to 0.99). Higher childhood IQ was associated with lower white matter hyperintensity burden (OR per IQ point = 0.99, 95% CI 0.98 to 0.998), fewer infarcts (OR = 0.98, 95% CI = 0.97 to 0.998), fewer lacunes (OR = 0.98, 95% CI = 0.97 to 0.999), and lower total small vessel disease burden (OR = 0.98, 95% CI = 0.96 to 0.999). Low education was associated with more microbleeds (OR = 1.90, 95% CI = 1.33 to 2.72) and lower total brain volume (mean difference = -178.86 cm3, 95% CI = -325.07 to -32.66). Low childhood socio-economic status was associated with fewer lacunes (OR = 0.62, 95% CI = 0.40 to 0.95). Early life factors are associated with worse small vessel disease in later life, independent of each other, vascular risk factors and adult socio-economic status. Risk for small vessel disease may originate in early life and provide a mechanistic link between early life factors and risk of stroke and dementia. Policies investing in early child development may improve lifelong brain health and contribute to the prevention of dementia and stroke in older age.