scholarly journals Is glycaemia associated with poorer brain health and risk of dementia? Cross sectional and follow-up analysis of the UK Biobank

2020 ◽  
Author(s):  
Victoria Garfield ◽  
Aliki-Eleni Farmaki ◽  
Sophie V. Eastwood ◽  
Rohini Mathur ◽  
Christopher T. Rentsch ◽  
...  
Keyword(s):  
Cognitive Function ◽  
White Matter ◽  
Cognitive Decline ◽  
Visual Memory ◽  
White Matter Hyperintensities ◽  
Undiagnosed Diabetes ◽  
Uk Biobank ◽  
Brain Health ◽  
Cross Sectional ◽  
The Uk

ABSTRACTObjectiveTo understand the relationship across the glycaemic spectrum with incident dementia, brain structure, and cognitive decline.Research Design and Methods: UK Biobank participants, aged 40-69 at recruitment. HbA1c and diabetes diagnosis define baseline glycaemic categories. Outcomes included incident vascular dementia (VD), Alzheimer’s dementia (AD), hippocampal volume (HV), white matter hyperintensity (WMH) volume, cognitive function and decline. All results are in reference to normoglycaemic individuals (HbA1c 35-<42 mmol/mol).Results210433 (47%), 15246 (3%), 3280 (0.7%), 20793 (5%) individuals had low HbA1c, pre-diabetes, undiagnosed diabetes, and known diabetes, respectively. Pre- and known diabetes markedly increased incident VD, (hazard ratios (HR) 1.51, 95%CI=1.01;2.25 and 1.96, 95%CI=1.49;2.58, respectively), less so AD (1.18, 0.92;1.52 and 1.13 0.95,1.33), adjusting for demographic and socioeconomic variables. For VD, multivariate adjustment, driven by antihypertensives, attenuated associations, HR 1.27, 0.84;1.91 and 1.45,1.07;1.97. Pre- and known diabetes conferred elevated risks of cognitive decline (odds ratio OR 1.53, 1.02;2.29 and 1.49, 1.02;2.18, respectively). People with pre-diabetes, undiagnosed and known diabetes had higher WMH volumes (4%, 30%, 3%, respectively), and lower HV (34.51 mm3, 11.73 mm3 and 61.13 mm3 respectively). People with low-normal HbA1c (<35 mmol/mol) had 5% lower WMH volume and 13.6 mm3 greater HV than normoglycaemic individuals.ConclusionsPre and known diabetes increase VD risks, less so AD. Excess VD risks were largely accounted for by treated hypertension. Hyperglycaemic states were associated with adverse, whereas low normal HbA1c was associated with favourable brain structure compared to normoglycaemic individuals. Our findings have implications for cardiovascular medication in hyperglycaemia for brain health.Type-2 diabetes and, more generally, hyperglycaemic states, have been associated with poorer cognitive function (such as learning and memory)(1), increased risk of dementia(2) and alterations in key brain structures, particularly the hippocampus(3). In contrast, recent evidence from a randomised crossover trial also suggests that, in people with diabetes, even modest hypoglycaemia has a detrimental effect on cognitive function(4). Thus, it is also important to explore how low levels of glycated haemoglobin (HbA1c) relate to these outcomes. A previous paper explored the cross sectional association between baseline diabetes and two cognition measures in the UK Biobank (reaction time and visual memory)(5). The authors found that diabetes was associated with poorer scores on the reaction time test, but paradoxically, better scores on the visual memory test. They did not explore other outcomes or lesser glycaemic states.Memory loss is the most conclusively reported adverse effect of hyperglycaemia on cognitive function(6). Hippocampal atrophy is a crucial feature of age-related memory loss and the hippocampus is particularly vulnerable to the neurotoxic consequences of diabetes(7). Evidence relating diabetes to the presence and progression of white matter hyperintensities is equivocal(8), but some research suggests that those with diabetes have greater volumes of white matter hyperintensities(9,10). Although there have been numerous studies in this area, the role of glycaemia in brain health across the entire glycaemic spectrum remains unclear, in particular no studies have investigated how lesser hyperglycaemic states relate to these outcomes, as most studies have focused on diagnosed diabetes only.Thus, the aim of this study was to investigate the associations between five glycaemic states across the entire spectrum (low HbA1c, normoglycaemia, pre-diabetes, undiagnosed diabetes and known diabetes) and Alzheimer’s dementia (AD) risk, vascular dementia (VD) risk, baseline cognitive function and cognitive decline, hippocampal volume, and white matter hyperintensities volume in the UK Biobank. We hypothesised that there would be a U-shaped association between glycaemia and our outcomes of interest, such that those with lower and higher HbA1c would have worse outcomes than those with normal glycaemic levels.

Arterial Stiffness Is Associated with White Matter Disruption and Cognitive Impairment: A Community-Based Cohort Study

2021 ◽  
Vol 80 (2) ◽  
pp. 567-576
Author(s):  
Fei Han ◽  
Fei-Fei Zhai ◽  
Ming-Li Li ◽  
Li-Xin Zhou ◽  
Jun Ni ◽  
...  
Keyword(s):  
Cognitive Function ◽  
White Matter ◽  
Arterial Stiffness ◽  
Cognitive Decline ◽  
Sex Education ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
White Matter Injury ◽  
White Matter Integrity ◽  
Cross Sectional

Background: Mechanisms through which arterial stiffness impacts cognitive function are crucial for devising better strategies to prevent cognitive decline. Objective: To examine the associations of arterial stiffness with white matter integrity and cognition in community dwellings, and to investigate whether white matter injury was the intermediate of the associations between arterial stiffness and cognition. Methods: This study was a cross-sectional analysis on 952 subjects (aged 55.5±9.1 years) who underwent diffusion tensor imaging and measurement of brachial-ankle pulse wave velocity (baPWV). Both linear regression and tract-based spatial statistics were used to investigate the association between baPWV and white matter integrity. The association between baPWV and global cognitive function, measured as the mini-mental state examination (MMSE) was evaluated. Mediation analysis was performed to assess the influence of white matter integrity on the association of baPWV with MMSE. Results: Increased baPWV was significantly associated with lower mean global fractional anisotropy (β= –0.118, p < 0.001), higher mean diffusivity (β= 0.161, p < 0.001), axial diffusivity (β= 0.160, p < 0.001), and radial diffusivity (β= 0.147, p < 0.001) after adjustment of age, sex, and hypertension, which were measures having a direct effect on arterial stiffness and white matter integrity. After adjustment of age, sex, education, apolipoprotein E ɛ4, cardiovascular risk factors, and brain atrophy, we found an association of increased baPWV with worse performance on MMSE (β= –0.093, p = 0.011). White matter disruption partially mediated the effect of baPWV on MMSE. Conclusion: Arterial stiffness is associated with white matter disruption and cognitive decline. Reduced white matter integrity partially explained the effect of arterial stiffness on cognition.

An Exploratory Study of Pathways from White Matter Hyperintensities to Cognitive Impairment through Depressive Symptoms Using Structural Equation Modeling: A Cross Sectional Study in Patients with Dementia

2020 ◽  
Vol 26 (7) ◽  
pp. 679-689
Author(s):  
Chang Hyun Lee ◽  
Do Hoon Kim
Keyword(s):  
Cognitive Impairment ◽  
Structural Equation Modeling ◽  
Depressive Symptoms ◽  
Cognitive Function ◽  
White Matter ◽  
Structural Equation ◽  
White Matter Hyperintensities ◽  
Mediating Effect ◽  
Equation Modeling ◽  
Cross Sectional

AbstractObjective:The aim of this study was to model the relationships among white matter hyperintensities (WMHs), depressive symptoms, and cognitive function and to examine the mediating effect of depressive symptoms on the relationship between WMHs and cognitive impairment.Methods:We performed structural equation modeling using cross-sectional data from 1158 patients from the Clinical Research for Dementia of South Korea (CREDOS) registry who were diagnosed with mild-to-moderate dementia. Periventricular white matter hyperintensities (PWMHs) and deep white matter hyperintensities (DWMHs) were obtained separately on the protocol of magnetic resonance imaging (MRI). Depression and cognitive function were assessed using the Korean Form of the Geriatric Depression Scale (KGDS) and the Seoul Neuropsychological Screening Battery (SNSB), respectively.Results:The model that best reflected the relationships among the variables was the model in which DWMHs affected cognitive function directly and indirectly through the depressive symptoms; on the other hand, PWMHs only directly affected cognitive function.Conclusions:This study presents the mediation model including the developmental pathway from DWMHs to cognitive impairment through depressive symptoms and suggests that the two types of WMHs may affect cognitive impairment through different pathways.

scholarly journals Social engagement after stroke – is it relevant to cognitive function? A cross-sectional analysis of UK Biobank data

2019 ◽  
Vol 1 ◽  
pp. 3
Author(s):  
Bogna A. Drozdowska ◽  
Carlos A. Celis-Morales ◽  
Donald M. Lyall ◽  
Terence J. Quinn
Keyword(s):  
Cognitive Function ◽  
Prospective Memory ◽  
Social Engagement ◽  
Visual Memory ◽  
Reaction Times ◽  
Stroke Survivors ◽  
Uk Biobank ◽  
Cross Sectional ◽  
Numerical Reasoning ◽  
Health Lifestyle

Background: Findings from studies in older adult populations suggest that measures of social engagement may be associated with health outcomes, including cognitive function. Plausibly the magnitude and direction of this association may differ in stroke.  The disabling nature of stroke increases the likelihood of social isolation and stroke survivors are at high risk of cognitive decline. We assessed the association between social engagement and cognitive function in a sample of stroke survivors. Methods: We included available data from stroke survivors in the UK Biobank (N=8776; age range: 40-72; 57.4% male). In a series of regression models, we assessed cross-sectional associations between proxies of social engagement (frequency of family/friend visits, satisfaction with relationships, loneliness, opportunities to confide in someone, participation in social activities) and performance on domain specific cognitive tasks: reaction time, verbal-numerical reasoning, visual memory and prospective memory. We adjusted for demographics, health-, lifestyle-, and stroke-related factors. Accounting for multiple testing, we set our significance threshold at p<0.003. Results: After adjusting for covariates, we found independent associations between faster reaction times and monthly family visits as compared to no visit (standardised beta=-0.32, 95% CI: -0.51 to -0.13, p=0.001, N=4,930); slower reaction times and religious group participation (standardised beta=0.25, 95% CI 0.13 to 0.38, p<0.001, N=4,938); and poorer performance on both verbal-numerical reasoning and prospective memory tasks with loneliness (standardised beta=-0.19, 95% CI: -0.29 to -0.08, p<0.001, N=2,074; odds ratio=0.66, 95% CI: 0.52 to 0.84, p=0.001, N=2,188; respectively). In models where all proxies of social engagement were combined, no associations remained significant. Conclusions: We found limited task-specific associations between cognitive performance and proxies of social engagement, with only loneliness related to two tasks. Further studies are necessary to confirm and improve our understanding of these relationships and investigate the potential to target psychosocial factors to support cognitive function in stroke survivors.

scholarly journals Modelling the distribution of white matter hyperintensities due to ageing on MRI images using Bayesian inference

2018 ◽  
Author(s):  
Vaanathi Sundaresan ◽  
Ludovica Griffanti ◽  
Petya Kindalova ◽  
Fidel Alfaro-Almagro ◽  
Giovanna Zamboni ◽  
...  
Keyword(s):  
White Matter ◽  
Vascular Disease ◽  
White Matter Hyperintensities ◽  
Age Groups ◽  
Clinical Importance ◽  
Population Level ◽  
Distribution Model ◽  
Ageing Population ◽  
Uk Biobank ◽  
The Uk

AbstractWhite matter hyperintensities (WMH), also known as white matter lesions, are localised white matter areas that appear hyperintense on MRI scans. WMH commonly occur in the ageing population, and are often associated with several factors such as cognitive disorders, cardiovascular risk factors, cerebrovascular and neurodegenerative diseases. Despite the fact that some links between lesion location and parametric factors such as age have already been established, the relationship between voxel-wise spatial distribution of lesions and these factors is not yet well understood. Hence, it would be of clinical importance to model the distribution of lesions at the population-level and quantitatively analyse the effect of various factors on the lesion distribution model.In this work we compare various methods, including our proposed method, to generate voxel-wise distributions of WMH within a population with respect to various factors. Our proposed Bayesian spline method models the spatio-temporal distribution of WMH with respect to a parametric factor of interest, in this case age, within a population. Our probabilistic model takes as input the lesion segmentation binary maps of subjects belonging to various age groups and provides a population-level parametric lesion probability map as output. We used a spline representation to ensure a degree of smoothness in space and the dimension associated with the parameter, and formulated our model using a Bayesian framework.We tested our algorithm output on simulated data and compared our results with those obtained using various existing methods with different levels of algorithmic and computational complexity. We then compared the better performing methods on a real dataset, consisting of 1000 subjects of the UK Biobank, divided in two groups based on hypertension diagnosis. Finally, we applied our method on a clinical dataset of patients with vascular disease.On simulated dataset, the results from our algorithm showed a mean square error (MSE) value of 7.27 × 10−5, which was lower than the MSE value reported in the literature, with the advantage of being robust and computationally efficient. In the UK Biobank data, we found that the lesion probabilities are higher for the hypertension group compared to the non-hypertension group and further verified this finding using a statistical t-test. Finally, when applying our method on patients with vascular disease, we observed that the overall probability of lesions is significantly higher in later age groups, which is in line with the current literature.

scholarly journals Consumption of Red Meat Is Negatively Associated with Cognitive Function: A Cross-Sectional Analysis of UK Biobank

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1510-1510
Author(s):  
Huifeng Zhang ◽  
Janet Cade ◽  
Laura Hadie
Keyword(s):  
Cognitive Function ◽  
Prospective Memory ◽  
Red Meat ◽  
Uk Biobank ◽  
Cross Sectional ◽  
Meat Intake ◽  
Visual Spatial ◽  
Additional Portion ◽  
The Uk ◽  
Sectional Analysis

Abstract Objectives In the largest study of its type, we tested for associations between red meat consumption and cognitive function using data from half a million participants enrolled into the UK Biobank cohort study. Methods Baseline data was obtained from the UK Biobank cohort, comprising half a million participants aged 37–73 years recruited between 2006 and 2010. The intake of red meat (frequency per week) was obtained using a self-reported food frequency questionnaire. Cognitive tests included the reaction-time (RT) test (reaction ability, N = 496, 695), fluid intelligence (FI) (reasoning ability, N = 165,467), the numeric memory test (short-term memory, N = 50,364), the pairs-matching (PM) test (visual-spatial memory, N = 482,650) and the prospective memory test (N = 171,509). Logistic and linear regression modelling was conducted with adjustment for potential confounders including age at recruitment, sex, ethnicity, Townsend deprivation index, smoking, alcohol, education, body mass index, physical activity level, sleeping hours, stroke history, and family history of dementia. Results Each additional portion per week of red-meat intake was associated with slower reaction time by 0.26 milliseconds (95% CI: 0.02, 0.50), lower FI score by 0.01 points (−0.02, −0.00), reduced numeric memory by 0.02 digits (−0.03, −0.01), and increased odds of incorrect prospective memory by 1% (0%, 2%). In men these associations were larger regarding the RT test (β = 0.54, [0.21, 0.87]), FI score (β = −0.02, [−0.03, −0.01]), and prospective memory (OR = 1.03, [1.01, 1.04]), while in women these were not significant. In terms of the PM test, a single additional portion of red-meat intake was associated with reduced incorrect matches by 0.004 pairs (−0.003, −0.006), both in men (β = −0.003, [−0.001, −0.005]) and women (β = −0.006, [−0.004, −0.008]). Conclusions In this cross-sectional analysis of the adult UK population, higher intake of red meat was associated with poorer cognitive function including reaction and reasoning ability, short-term and prospective memory especially among men; but not visual-spatial memory which showed a weak protective effect of red meat. Funding Sources The joint scholarship of University of Leeds and China Scholarship Council.

scholarly journals Ethnic differences in prevalence of actionable HbA1c levels in UK Biobank: implications for screening

2021 ◽  
Vol 9 (1) ◽  
pp. e002176
Author(s):  
Jana J Anderson ◽  
Paul Welsh ◽  
Frederick K Ho ◽  
Lyn D Ferguson ◽  
Claire E Welsh ◽  
...  
Keyword(s):  
General Population ◽  
South Asian ◽  
Cross Sectional Study ◽  
Undiagnosed Diabetes ◽  
Uk Biobank ◽  
Cross Sectional ◽  
Treatment Of Diabetes ◽  
The Uk ◽  
Design And Methods ◽  
Crude Prevalence

IntroductionEarly detection and treatment of diabetes as well as its prevention help lessen longer-term complications. We determined the prevalence of pre-diabetes and undiagnosed diabetes in the UK Biobank and standardized the results to the UK general population.Research design and methodsThis cross-sectional study analyzed baseline UK Biobank data on plasma glycated hemoglobin (HbA1c) to compare the prevalence of pre-diabetes and undiagnosed diabetes mellitus in white, South Asian, black, and Chinese participants. The overall and ethnic-specific results were standardized to the UK general population aged 40–70 years of age.ResultsWithin the UK Biobank, the overall crude prevalence was 3.6% for pre-diabetes, 0.8% for undiagnosed diabetes, and 4.4% for either. Following standardization to the UK general population, the results were similar at 3.8%, 0.8%, and 4.7%, respectively. Crude prevalence was much higher in South Asian (11.0% pre-diabetes; 3.6% undiagnosed diabetes; 14.6% either) or black (13.8% pre-diabetes; 3.0% undiagnosed diabetes; 16.8% either) participants. Only six middle-aged or old-aged South Asian individuals or seven black would need to be tested to identify an HbA1c result that merits action.ConclusionsSingle-stage population screening for pre-diabetes or undiagnosed diabetes in middle-old or old-aged South Asian and black individuals using HbA1c could be efficient and should be considered.

scholarly journals Coagulation factor VIII, white matter hyperintensities and cognitive function: Results from the Cardiovascular Health Study

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242062
Author(s):  
Jessica L. Rohmann ◽  
W. T. Longstreth ◽  
Mary Cushman ◽  
Annette L. Fitzpatrick ◽  
Susan R. Heckbert ◽  
...  
Keyword(s):  
Cognitive Function ◽  
White Matter ◽  
White Matter Hyperintensities ◽  
Cardiovascular Health ◽  
Coagulation Factor ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
Digit Symbol Substitution Test ◽  
Cross Sectional ◽  
Over Time

Objective To investigate the relationship between high FVIII clotting activity (FVIII:C), MRI-defined white matter hyperintensities (WMH) and cognitive function over time. Methods Data from the population-based Cardiovascular Health Study (n = 5,888, aged ≥65) were used. FVIII:C was measured in blood samples taken at baseline. WMH burden was assessed on two cranial MRI scans taken roughly 5 years apart. Cognitive function was assessed annually using the Modified Mini-Mental State Examination (3MSE) and Digit Symbol Substitution Test (DSST). We used ordinal logistic regression models adjusted for demographic and cardiovascular factors in cross-sectional and longitudinal WMH analyses, and adjusted linear regression and linear mixed models in the analyses of cognitive function. Results After adjustment for confounding, higher levels of FVIII:C were not strongly associated with the burden of WMH on the initial MRI scan (OR>p75 = 1.20, 95% CI 0.99–1.45; N = 2,735) nor with WMH burden worsening over time (OR>p75 = 1.18, 95% CI 0.87–1.59; N = 1,527). High FVIII:C showed no strong association with cognitive scores cross-sectionally (3MSE>p75 β = -0.06, 95%CI -0.45 to 0.32, N = 4,005; DSST>p75 β = -0.69, 95%CI -1.52 to 0.13, N = 3,954) or over time (3MSE>p75 β = -0.07,95% CI -0.58 to 0.44, N = 2,764; DSST>p75 β = -0.22, 95% CI -0.97 to 0.53, N = 2,306) after confounding adjustment. Interpretation The results from this cohort study of older adult participants indicate no strong relationships between higher FVIII:C levels and WMH burden or cognitive function in cross-sectional and longitudinal analyses.

scholarly journals Midlife blood pressure is associated with the severity of white matter hyperintensities: analysis of the UK Biobank cohort study

2020 ◽  
Author(s):  
Karolina Agnieszka Wartolowska ◽  
Alastair John Stewart Webb
Keyword(s):  
Blood Pressure ◽  
White Matter ◽  
White Matter Hyperintensities ◽  
Linear Models ◽  
Population Attributable Fraction ◽  
Relative Role ◽  
Uk Biobank ◽  
Assessment Centre ◽  
The Uk

Abstract Aims White matter hyperintensities (WMH) progress with age and hypertension, but the key period of exposure to elevated blood pressure (BP), and the relative role of systolic BP (SBP) vs. diastolic BP (DBP), remains unclear. This study aims to determine the relationship between WMH and concurrent vs. past BP.  Methods and results  UK Biobank is a prospective community-based cohort of 40–69-year olds from 22 centres, with magnetic resonance imaging in a subgroup of over 40 000 people at 4–12 years after baseline assessment. Standardized associations between WMH load (WMH volume normalized by total white matter volume and logit-transformed) and concurrent vs. past BP were determined using linear models, adjusted for age, sex, cardiovascular risk factors, BP source, assessment centre, and time since baseline. Associations adjusted for regression dilution bias were determined between median WMH and usual SBP or DBP, stratified by age and baseline BP. In 37 041 eligible participants with WMH data and BP measures, WMH were more strongly associated with concurrent SBP [DBP: β = 0.064, 95% confidence interval (CI) 0.050–0.078; SBP: β = 0.076, 95% CI 0.062–0.090], but the strongest association was for past DBP (DBP: β = 0.087, 95% CI 0.064–0.109; SBP: β = 0.045, 95% CI 0.022–0.069), particularly under the age of 50 (DBP: β = 0.103, 95% CI 0.055–0.152; SBP: β = 0.012, 95% CI −0.044 to 0.069). Due to the higher prevalence of elevated SBP, median WMH increased 1.126 (95% CI 1.107–1.146) per 10 mmHg usual SBP and 1.106 (95% CI 1.090–1.122) per 5 mmHg usual DBP, whilst the population attributable fraction of WMH in the top decile was greater for elevated SBP (19.1% for concurrent SBP; 24.4% for past SBP). Any increase in BP, even below 140 for SBP and below 90 mmHg for DBP, and especially if requiring antihypertensive medication, was associated with increased WMH. Conclusions WMH were strongly associated with concurrent and past elevated BP with the population burden of severe WMH greatest for SBP. However, before the age of 50, DBP was more strongly associated with WMH. Long-term prevention of WMH may require control of even mildly elevated midlife DBP.

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