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

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.

Validity of recalled v. recorded birth weight: a systematic review and meta-analysis.

Low birth weight is associated with adverse health outcomes. If birth weight records are not available, studies may use recalled birth weight. It is unclear whether this is reliable. We performed a systematic review and meta-analysis of studies comparing recalled with recorded birth weights. We followed the Meta-Analyses of Observational Studies in Epidemiology (MOOSE) statement and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched MEDLINE, EMBASE and Cumulative Index to Nursing and Allied Health Literature (CINAHL) to May 2015. We included studies that reported recalled birth weight and recorded birth weight. We excluded studies investigating a clinical population. Two reviewers independently reviewed citations, extracted data, assessed risk of bias. Data were pooled in a random effects meta-analysis for correlation and mean difference. In total, 40 studies were eligible for qualitative synthesis (n=78,997 births from 78,196 parents). Agreement between recalled and recorded birth weight was high: pooled estimate of correlation in 23 samples from 19 studies (n=7406) was 0.90 [95% confidence interval (CI) 0.87-0.93]. The difference between recalled and recorded birth weight in 29 samples from 26 studies (n=29,293) was small [range -86-129 g; random effects estimate 1.4 g (95% CI -4.0-6.9 g)]. Studies were heterogeneous, with no evidence for an effect of time since birth, person reporting, recall bias, or birth order. In post-hoc subgroup analysis, recall was higher than recorded birth weight by 80 g (95% CI 57-103 g) in low and middle income countries. In conclusion, there is high agreement between recalled and recorded birth weight. If birth weight is recalled, it is suitable for use in epidemiological studies, at least in high income countries.

Maternity records in Edinburgh and Aberdeen in 1936: a comparison.

Historians have long used maternity records to understand the evolution of maternity services. More recently, epidemiologists have become interested in obstetric hospital records as a source of data (e.g. birth weight, social class), to study the influence of early life on future health and disease: life course epidemiology. Edinburgh and Aberdeen are unusual in holding detailed records from several maternity institutions. The records of 1936 are of particular interest because all children born in this year and at school in Scotland at age 11 sat a cognitive ability test, the Scottish Mental Survey 1947. This study aims to describe the maternity services in Edinburgh and Aberdeen in 1936, between the First and Second World Wars. Understanding the richness of data in birth records, the manner in which they were recorded, and the context of the institutions in their community is essential for interpreting life course epidemiology studies.

Development and initial testing of normal reference MR images for the brain at ages 65-70 and 75-80 years.

Interpretation of brain images from older patients requires knowledge of changes that occur with healthy ageing. We constructed and tested a reference template for older subjects. We used MR images from normal subjects aged 65-70 and 75-80 to generate average age-specific images. We ranked the T2-weighted images by worsening brain tissue loss to create a diagram of key centiles. Two neuroradiologists tested the template during routine reporting; eight radiologists read 99 MR examinations without and then with the template. Fifty-four subjects (65-70 years) and 25 subjects (75-80 years) formed the reference images. For the two neuroradiologists, the reference template reduced the abnormal scan reporting from 28/42 without to 3/42 with the template. Of 99 MR examinations assessed by eight radiologists, 39/58 scans (67%) reported as moderate or severe atrophy without the template were reported as normal with the template (p = 0.00011). Reference templates of the brain at older ages can "calibrate" radiology reporting. They could also be useful for research into ageing and related conditions. Larger numbers of examinations from more diverse populations and at different ages are required to increase the versatility of these templates.

Cognitive correlates of cerebral white matter lesions and water diffusion tensor parameters in community-dwelling older people.

BACKGROUND: The biological basis of cognitive ageing is unknown. One underlying process might be disruption of white matter tracts connecting cortical regions. White matter lesions (WML) seen on structural MRI may disrupt cortical connections, but diffusion tensor MRI (DT-MRI) parameters - mean diffusivity () and fractional anisotropy (FA) - may reflect more subtle changes in white matter integrity. Here the relationships between WML load, DT-MRI parameters and cognition in a large cohort of elderly subjects with a very narrow age range were investigated. METHODS: 105 community-dwelling volunteers underwent MRI and neuropsychological assessment. Seventy-two (68.6%) were female, and their mean age was 78.4 (SD 1.5) years. Scans were rated for WML load. and FA were measured from regions of interest in normal-appearing frontal and occipital white matter, and centrum semiovale. RESULTS: and FA differed significantly among the three brain regions studied (p << 0.01). increased with age (r = 0.22 to 0.35, p < 0.03), and was negatively correlated with FA (r = -0.20 to -0.51, p < 0.05) in all three regions. There was a trend towards increased WML load correlating with poorer cognitive function, and this was statistically significant for the Mini-Mental State Examination (rho = -0.23, p = 0.02). was generally negatively correlated with cognitive test score, and FA was positively correlated. This pattern was more consistent for than for FA, and particularly for verbal fluency (: r = -0.22 to -0.27, p < 0.03), which measures executive function. CONCLUSIONS: DT-MRI parameters, in particular , are sensitive to early ultrastructural changes underlying cognitive ageing. Executive function may be the cognitive domain most sensitive to age-related decline in white matter tract integrity.

Birth weight and cognitive function at age 11 years: the Scottish Mental Survey 1932.

AIMS: To examine the relation between birth weight and cognitive function at age 11 years, and to examine whether this relation is independent of social class. METHODS: Retrospective cohort study based on birth records from 1921 and cognitive function measured while at school at age 11 in 1932. Subjects were 985 live singletons born in the Edinburgh Royal Maternity and Simpson Memorial Hospital in 1921. Moray House Test scores from the Scottish Mental Survey 1932 were traced on 449 of these children. RESULTS: Mean score on Moray House Test increased from 30.6 at a birth weight of <2500 g to 44.7 at 4001-4500 g, after correcting for gestational age, maternal age, parity, social class, and legitimacy of birth. Multiple regression showed that 15.6% of the variance in Moray House Test score is contributed by a combination of social class (6.6%), birth weight (3.8%), child's exact age (2.4%), maternal parity (2.0%), and illegitimacy (1.5%). Structural equation modelling confirmed the independent contribution from each of these variables in predicting cognitive ability. A model in which birth weight acted as a mediator of social class had poor fit statistics. CONCLUSION: In this 1921 birth cohort, social class and birth weight have independent effects on cognitive function at age 11. Future research will relate these childhood data to health and cognition in old age.

Subclinical riboflavin deficiency is associated with outcome of seriously ill patients.

The biochemical status of 152 patients in the Intensive Therapy Unit (ITU) was examined in relation to their clinical outcome. Patients who died in ITU or within one week of discharge were found to have significantly poorer riboflavin status than those who survived, but the majority of these measurements were within the normal range. Normal ranges established on a healthy population may therefore not be appropriate in investigation of vitamin nutritional status in seriously ill patients. These results do however suggest that riboflavin status is a risk factor in critically ill patients, and that subclinical riboflavin depletion may affect outcome.