Dataset Information

Incidental findings on brain imaging and blood tests: results from the first phase of Insight 46, a prospective observational substudy of the 1946 British birth cohort.

ABSTRACT: OBJECTIVE:To summarise the incidental findings detected on brain imaging and blood tests during the first wave of data collection for the Insight 46 study. DESIGN:Prospective observational sub-study of a birth cohort. SETTING:Single-day assessment at a research centre in London, UK. PARTICIPANTS:502 individuals were recruited from the MRC National Survey of Health and Development (NSHD), the 1946 British birth cohort, based on pre-specified eligibility criteria; mean age was 70.7 (SD: 0.7) and 49% were female. OUTCOME MEASURES:Data regarding the number and types of incidental findings were summarised as counts and percentages, and 95% confidence intervals were calculated. RESULTS:93.8% of participants completed a brain scan (n=471); 4.5% of scanned participants had a pre-defined reportable abnormality on brain MRI (n=21); suspected vascular malformations and suspected intracranial mass lesions were present in 1.9% (n=9) and 1.5% (n=7) respectively; suspected cerebral aneurysms were the single most common vascular abnormality, affecting 1.1% of participants (n=5), and suspected meningiomas were the most common intracranial lesion, affecting 0.6% of participants (n=3); 34.6% of participants had at least one abnormality on clinical blood tests (n=169), but few reached the prespecified threshold for urgent action (n=11). CONCLUSIONS:In older adults, aged 69-71 years, potentially serious brain MRI findings were detected in around 5% of participants, and clinical blood test abnormalities were present in around one third of participants. Knowledge of the expected prevalence of incidental findings in the general population at this age is useful in both research and clinical settings.

SUBMITTER: Keuss SE

PROVIDER: S-EPMC6678011 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Incidental findings on brain imaging and blood tests: results from the first phase of Insight 46, a prospective observational substudy of the 1946 British birth cohort.

Keuss Sarah E SE Parker Thomas D TD Lane Christopher A CA Hoskote Chandrashekar C Shah Sachit S Cash David M DM Keshavan Ashvini A Buchanan Sarah M SM Murray-Smith Heidi H Wong Andrew A James Sarah-Naomi SN Lu Kirsty K Collins Jessica J Beasley Daniel G DG Malone Ian B IB Thomas David L DL Barnes Anna A Richards Marcus M Fox Nick N Schott Jonathan M JM

BMJ open 20190731 7

<h4>Objective</h4>To summarise the incidental findings detected on brain imaging and blood tests during the first wave of data collection for the Insight 46 study.<h4>Design</h4>Prospective observational sub-study of a birth cohort.<h4>Setting</h4>Single-day assessment at a research centre in London, UK.<h4>Participants</h4>502 individuals were recruited from the MRC National Survey of Health and Development (NSHD), the 1946 British birth cohort, based on pre-specified eligibility criteria; mean ...[more]

PMID: 31371298

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Project description:BackgroundMidlife hypertension confers increased risk for cognitive impairment in late life. The sensitive period for risk exposure and extent that risk is mediated through amyloid or vascular-related mechanisms are poorly understood. We aimed to identify if, and when, blood pressure or change in blood pressure during adulthood were associated with late-life brain structure, pathology, and cognition.MethodsParticipants were from Insight 46, a neuroscience substudy of the ongoing longitudinal Medical Research Council National Survey of Health and Development, a birth cohort that initially comprised 5362 individuals born throughout mainland Britain in one week in 1946. Participants aged 69-71 years received T1 and FLAIR volumetric MRI, florbetapir amyloid-PET imaging, and cognitive assessment at University College London (London, UK); all participants were dementia-free. Blood pressure measurements had been collected at ages 36, 43, 53, 60-64, and 69 years. We also calculated blood pressure change variables between ages. Primary outcome measures were white matter hyperintensity volume (WMHV) quantified from multimodal MRI using an automated method, amyloid-β positivity or negativity using a standardised uptake value ratio approach, whole-brain and hippocampal volumes quantified from 3D-T1 MRI, and a composite cognitive score-the Preclinical Alzheimer Cognitive Composite (PACC). We investigated associations between blood pressure and blood pressure changes at and between 36, 43, 53, 60-64, and 69 years of age with WMHV using generalised linear models with a gamma distribution and log link function, amyloid-β status using logistic regression, whole-brain volume and hippocampal volumes using linear regression, and PACC score using linear regression, with adjustment for potential confounders.FindingsBetween May 28, 2015, and Jan 10, 2018, 502 individuals were assessed as part of Insight 46. 465 participants (238 [51%] men; mean age 70·7 years [SD 0·7]; 83 [18%] amyloid-β-positive) were included in imaging analyses. Higher systolic blood pressure (SBP) and diastolic blood pressure (DBP) at age 53 years and greater increases in SBP and DBP between 43 and 53 years were positively associated with WMHV at 69-71 years of age (increase in mean WMHV per 10 mm Hg greater SBP 7%, 95% CI 1-14, p=0·024; increase in mean WMHV per 10 mm Hg greater DBP 15%, 4-27, p=0·0057; increase in mean WMHV per one SD change in SBP 15%, 3-29, p=0·012; increase in mean WMHV per 1 SD change in DBP 15%, 3-30, p=0·017). Higher DBP at 43 years of age was associated with smaller whole-brain volume at 69-71 years of age (-6·9 mL per 10 mm Hg greater DBP, -11·9 to -1·9, p=0·0068), as were greater increases in DBP between 36 and 43 years of age (-6·5 mL per 1 SD change, -11·1 to -1·9, p=0·0054). Greater increases in SBP between 36 and 43 years of age were associated with smaller hippocampal volumes at 69-71 years of age (-0·03 mL per 1 SD change, -0·06 to -0·001, p=0·043). Neither absolute blood pressure nor change in blood pressure predicted amyloid-β status or PACC score at 69-71 years of age.InterpretationHigh and increasing blood pressure from early adulthood into midlife seems to be associated with increased WMHV and smaller brain volumes at 69-71 years of age. We found no evidence that blood pressure affected cognition or cerebral amyloid-β load at this age. Blood pressure monitoring and interventions might need to start around 40 years of age to maximise late-life brain health.FundingAlzheimer's Research UK, Medical Research Council, Dementias Platform UK, Wellcome Trust, Brain Research UK, Wolfson Foundation, Weston Brain Institute, Avid Radiopharmaceuticals.

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Project description:BackgroundFew studies have examined the impact of childhood obesity on later kidney disease, and consequently, our understanding is very limited.Study designLongitudinal population-based cohort.Setting & participantsThe Medical Research Council National Survey of Health and Development, a socially stratified sample of 5,362 singletons born in 1 week in March 1946 in England, Scotland, and Wales, of which 4,340 were analyzed.PredictorEarly-life overweight latent classes (never, prepubertal only, pubertal onset, or always), derived from repeated measurements of body mass index between ages 2 and 20 years.Outcomes & measurementsThe primary outcome was chronic kidney disease (CKD), defined as creatinine- or cystatin C-based estimated glomerular filtration rate (eGFRcr and eGFRcys, respectively) <60 mL/min/1.73 m² or urine albumin-creatinine ratio (UACR) ≥3.5 mg/mmol measured at age 60-64 years. Associations were explored through regression analysis, with adjustment for socioeconomic position, smoking, physical activity level, diabetes, hypertension, and overweight at ages 36 and 53 years.Results2.3% of study participants had eGFRcr <60 mL/min/1.73 m², 1.7% had eGFRcys <60 mL/min/1.73 m², and 2.9% had UACR ≥3.5 mg/mmol. Relative to being in the never-overweight latent class, being in the pubertal-onset- or always-overweight latent classes was associated with eGFRcys-defined CKD (OR, 2.04; 95% CI, 1.09-3.82). Associations with CKD defined by eGFRcr (OR, 1.27; 95% CI, 0.71-2.29) and UACR (OR, 1.33; 95% CI, 0.70-2.54) were less marked, but in the same direction. Adjustment for lifestyle and health factors had little impact on effect estimates.LimitationsA low prevalence of CKD resulted in low statistical power. No documentation of chronicity for outcomes. All-white study population restricts generalizability.ConclusionsBeing overweight in early life was found to be associated with eGFRcys-defined CKD in later life. The associations with CKD defined by eGFRcr and UACR were less marked, but in the same direction. Reducing or preventing overweight in the early years of life may significantly reduce the burden of CKD in the population.

Project description:BackgroundThe relationship between long-term exposure to whole body or central obesity and cognitive function, as well as its potential determinants, remain controversial. In this study, we assessed (1) the potential impact of 30 years exposure to different patterns of whole body and central adiposity on cognitive function at 60-64 years, (2) whether trajectories of central adiposity can provide additional information on later cognitive function compared to trajectories of whole body adiposity, and (3) the influence of vascular phenotypes on these associations.MethodsThe study included 1249 participants from the prospective cohort MRC National Survey of Health and Development. Body mass index (BMI), waist circumference (WC), and vascular (carotid intima-media thickness, carotid-femoral pulse wave velocity) and cognitive function (memory, processing speed, reaction time) data, at 60-64 years, were used to assess the associations between different patterns of adult WC or BMI (from 36 years of age) and late midlife cognitive performance, as well as the proportion of this association explained by cardiovascular phenotypes.ResultsLonger exposure to elevated WC was related to lower memory performance (p?<?0.001 for both) and longer choice reaction time (p?=?0.003). A faster gain of WC between 36 and 43 years of age was associated with the largest change in reaction time and memory test (P?<?0.05 for all). Similar associations were observed when patterns of WC were substituted with patterns of BMI, but when WC and BMI were included in the same model, only patterns of WC remained significantly associated with cognitive function. Participants who dropped one BMI category and maintained a lower BMI had similar memory performance to those of normal weight during the whole follow-up. Conversely, those who dropped and subsequently regained one BMI category had a memory function similar to those with 30 years exposure to elevated BMI. Adjustment for vascular phenotypes, levels of cardiovascular risk factors, physical activity, education, childhood cognition and socioeconomic position did not affect these associations.ConclusionsLonger exposure to elevated WC or BMI and faster WC or BMI gains between 36 and 43 years are related to lower cognitive function at 60-64 years. Patterns of WC in adulthood could provide additional information in predicting late midlife cognitive function than patterns of BMI. The acquisition of an adverse cardiovascular phenotype associated with adiposity is unlikely to account for these relationships.

Dataset Information

Incidental findings on brain imaging and blood tests: results from the first phase of Insight 46, a prospective observational substudy of the 1946 British birth cohort.

Publications

Incidental findings on brain imaging and blood tests: results from the first phase of Insight 46, a prospective observational substudy of the 1946 British birth cohort.

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