Sugary beverage intake and genetic risk of dementia in relation to incident dementia and brain structure: evidence from the UK Biobank

Abstract Importance: Sugary beverage intake was associated with higher risk of dementia, but the specific amounts and types related to it and its interactions with genetic predisposition to dementia remained poorly understood.Objective: To investigate the relation of sugary beverage intake and genetic preposition to the long-term risk of dementia and brain structure.Design, Setting, and Participants: We leveraged data of 187,994 UK Biobank participants without dementia at baseline and followed them until March 2021.Exposures: Intake of sugary beverages (SBs, one unit=250 ml), including sugar-sweetened beverages (SSB), artificially-sweetened beverages (ASB), and natural sweet juices (NSJ), was assessed using repeated web-based 24-h dietary recall from 2009 to 2012. A polygenic risk score (PRS) was calculated to capture each participant’s load of common genetic variants related to the risk of dementia.Main Outcomes and Measures: Incident dementia was identified through hospital admissions and death registries. Brain magnetic resonance imaging was conducted in a subgroup of 12,566 participants in 2014.Results: During a total of 1,790,996 person-years of follow up, 1,351 incident dementia cases were identified. Higher intake of SSB and ASB (>2 units/d v. none) was independently associated with a substantially increased risk of dementia (p-trend=0.013 for SSB, and <0.001 for ASB). The corresponding multivariable-adjusted hazard ratio [HR] and 95% confidence intervals [CI] were 1.47 (1.13~1.92), and 1.41 (1.00~1.99), respectively. The significant association of ASB was observed among ASB consumptions regardless of the intake level. In contrast, moderate intake of NSJ (0~1 unit/d v. none) was related to a decreased risk of dementia (HR=0.80, 0.71~0.90) and a larger volume of brain grey matter (beta=0.03, 0.01~0.06) and a lower volume of white matter hyperintensities (beta=-0.08, -0.13~-0.02). Moreover, the genetic risks were significantly magnified by higher intake of SSB and ASB, and was instead attenuated by moderate intake of NSJ (P-interaction<0.002).Conclusions and Relevance: Higher intake of SSB and ASB was associated with higher risk of dementia, especially among individuals at high genetic risk for dementia. Inversely, moderate NSJ intake was associated with a reduced risk of dementia, possibly through the beneficial role maintaining brain grey matter volume and reducing white matter hyperintensities.

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Sugary beverage intake and genetic risk in relation to brain structure and incident dementia: evidence from the UK Biobank

10.21203/rs.3.rs-882320/v2 ◽

2021 ◽

Author(s):

Hui Chen ◽

Jie Chen ◽

Yaying Cao ◽

Yuhao Sun ◽

Liyan Huang ◽

...

Keyword(s):

Brain Structure ◽

Genetic Risk ◽

Medical Records ◽

Uk Biobank ◽

Sweetened Beverages ◽

Dementia Risk ◽

Incident Dementia ◽

Genetic Risks ◽

The Uk ◽

Artificially Sweetened Beverages

Abstract IntroductionThis study investigated the relation of sugary beverage (SB) intake to brain structure and dementia risk.MethodsAmong 187,994 UK Biobank participants, intake of SBs (one unit=250 mL) and specific subtypes was assessed using repeated 24-hr dietary recalls. Multivariable-adjusted hazard rations (HR) was estimated for incident dementia identified through medical records and death registries.ResultsDuring 1,790,996 person-years, 1,351 dementia cases were identified. Higher intake (>2 units/d v. none) of sugar-sweetened beverages (SSB) (HR=1.47, 95%CI: 1.13~1.92) and artificially-sweetened beverages (ASB) (HR=1.41, 1.00~1.99) was associated with an elevated dementia risk. Conversely, moderate intake of natural sweet juices (NSJ) (>0 and <=1 unit/d v. none) was related to a decreased risk (HR=0.80, 0.71~0.90). The associations were consistent with related brain structural markers and modified by genetic risks (P-interaction<0.002).DiscussionThese findings underscored that SSB and ASB could be risk factors of dementia, while moderate NSJ intake could potentially reduce dementia risk.

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White matter hyperintensities in young individuals with bipolar disorder or at high genetic risk

Journal of Affective Disorders ◽

10.1016/j.jad.2018.10.368 ◽

2019 ◽

Vol 245 ◽

pp. 228-236 ◽

Cited By ~ 5

Author(s):

Riya Wadhwa ◽

Wei Wen ◽

Andrew Frankland ◽

Vivian Leung ◽

Carina Sinbandhit ◽

...

Keyword(s):

Bipolar Disorder ◽

White Matter ◽

Genetic Risk ◽

White Matter Hyperintensities ◽

High Genetic Risk

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Associations of cigarette smoking with gray and white matter in the UK Biobank

10.31234/osf.io/wyvnm ◽

2019 ◽

Author(s):

Joshua Gray ◽

Matthew Thompson ◽

Chelsie Benca-Bachman ◽

Max Michael Owens ◽

Mikela Murphy ◽

...

Keyword(s):

White Matter ◽

Cigarette Smoking ◽

Gray Matter ◽

Brain Structure ◽

Mean Diffusivity ◽

Medial Lemniscus ◽

Uk Biobank ◽

Matter Volume ◽

Increased Risk ◽

The Uk

Chronic cigarette smoking is associated with increased risk for myriad health consequences including cognitive decline and dementia, but research on the link between smoking and brain structure is nascent. We assessed the relationship of cigarette smoking (ever smoked, cigarettes per day, and duration) with gray and white matter using the UK Biobank cohort (gray matter N = 19,615; white matter N = 17,760), adjusting for numerous demographic and health confounders. Ever smoked and duration were associated with smaller total gray matter volume. Ever smoked was associated with reduced volume of the right VIIIa cerebellum, as well as elevated white matter hyperintensity volumes. Smoking duration was associated with reduced total white matter volume. With regard to specific tracts, ever smoked was associated with reduced fractional anisotropy in the left cingulate gyrus part of the cingulum, left posterior thalamic radiation, and bilateral superior thalamic radiation and increased mean diffusivity in the middle cerebellar peduncle, right medial lemniscus, bilateral posterior thalamic radiation, and bilateral superior thalamic radiation. Overall, we found significant associations of cigarette exposure with global measures of gray and white matter. Furthermore, we found select associations of ever smoked, but not cigarettes per day or duration, with specific gray and white matter regions. These findings inform our understanding of the connections between smoking and variation in brain structure and clarify potential mechanisms of risk for common neurological sequelae.

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Sex-Specific Associations of Testosterone and Genetic Factors With Health Span

Frontiers in Endocrinology ◽

10.3389/fendo.2021.773464 ◽

2021 ◽

Vol 12 ◽

Author(s):

Xiaoyu Zhao ◽

Shuang Liang ◽

Nanxi Wang ◽

Tongtong Hong ◽

Muhammed Lamin Sambou ◽

...

Keyword(s):

Genetic Risk ◽

Genetic Factors ◽

Cox Regression ◽

Polygenic Risk Score ◽

Health Span ◽

Baseline Serum ◽

Negatively Associated ◽

Testosterone Levels ◽

Common Genetic Variants ◽

Increased Risk

BackgroundPrevious studies have suggested associations between testosterone, genetic factors, and a series of complex diseases, but the associations with the lifespan phenotype, such as health span, remain unclear.MethodsIn this prospective cohort study, we analyzed 145,481 men and 147,733 women aged 38–73 years old from UK Biobank (UKB) to investigate the sex-specific associations of total testosterone (TT), free testosterone (FT), or polygenic risk score (PRS) with health span termination (HST) risk. At baseline, serum testosterone levels were measured. HST was defined by eight events strongly associated with longevity. PRS, an efficient tool combining the effect of common genetic variants to discriminate genetic risk of complex phenotypes, was constructed by 12 single-nucleotide polymorphisms related to health span from UKB (P ≤ 5.0 × 10−8). We used multivariable Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsWith a median follow-up time of 7.70 years, 26,748 (18.39%) men and 18,963 (12.84%) women had HST. TT was negatively associated with HST in men [HR per standard deviation (SD) increment of log-TT: 0.92, 95% CI: 0.88–0.97]. Inversely, both TT (HR per SD increment of log-TT: 1.05, 95% CI: 1.02–1.08) and FT (HR per SD increment of log-FT: 1.08, 95% CI: 1.05–1.11) presented an increased risk of HST in women. PRS was positively associated with HST risk (quintile 5 versus quintile 1, men, HR: 1.19, 95% CI: 1.15–1.24; women, HR: 1.21, 95% CI: 1.16–1.27). Moreover, men with high TT and low genetic risk showed the lowest HST risk (HR: 0.80, 95% CI: 0.73–0.88), whereas HST risk for women with both high TT and genetic risk increased obviously (HR: 1.32, 95% CI: 1.19–1.46). Similar joint effects were observed for FT in both genders.ConclusionsWe observed sex-specific associations that testosterone was negatively associated with HST risk in men and positively associated with HST risk in women. Genetic factors increased the HST risk, suggesting that participants with both high genetic risk and abnormal testosterone levels (high level in women or low level in men) should be the target for early intervention. Although our findings highlight the associations between testosterone and health span, further mechanistic studies and prospective trials are warranted to explore the causation behind.

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Associations of the Lifestyle for Brain Health Index With Structural Brain Changes and Cognition: Results From the Maastricht Study

Neurology ◽

10.1212/wnl.0000000000012572 ◽

2021 ◽

pp. 10.1212/WNL.0000000000012572

Author(s):

Irene S Heger ◽

Kay Deckers ◽

Miranda T Schram ◽

Coen DA Stehouwer ◽

Pieter C Dagnelie ◽

...

Keyword(s):

Cognitive Impairment ◽

Information Processing ◽

Executive Function ◽

White Matter ◽

Processing Speed ◽

Grey Matter ◽

White Matter Hyperintensities ◽

Information Processing Speed ◽

Brain Health ◽

Dementia Risk

Background and Objectives:Observational research has shown that a substantial proportion of all dementia cases worldwide is attributable to modifiable risk factors. Dementia risk scores might be useful to identify high-risk individuals and monitor treatment adherence. The objective of this study was to investigate whether a dementia risk score, the LIfestyle for BRAin health (LIBRA) index, is associated with MRI markers and cognitive functioning/impairment in the general population.Methods:Cross-sectional data was used from the observational population-based cohort of The Maastricht Study.. The weighted compound score of LIBRA (including twelve dementia risk and protective factors, e.g. hypertension, physical inactivity) was calculated, with higher scores indicating higher dementia risk. Standardized volumes of white matter, grey matter, CSF (as proxy for general brain atrophy), white matter hyperintensities, and presence of cerebral small vessel disease were derived from 3T MRI. Cognitive functioning was tested in three domains: memory, information processing speed, and executive function and attention. Values ≤1.5 SD below the average were defined as cognitive impairment. Multiple regression analyses and structural equation modelling were used, adjusted for age, sex, education, intracranial volume and type-2 diabetes.Results:Participants (n=4,164; mean age 59y; 49.7% men) with higher LIBRA scores (mean=1.19, range=-2.7 to +9.2), denoting higher dementia risk, had higher volumes of white matter hyperintensities (β=0.051, p=.002), and lower scores on information processing speed (β=-0.067, p=.001) and executive function and attention (β=-0.065, p=.004). Only in men, associations between LIBRA and volumes of grey matter (β=-0.093, p<.001), CSF (β=0.104, p<.001) and memory (β=-0.054, p=.026) were found. White matter hyperintensities and CSF volume partly mediated the association between LIBRA and cognition.Discussion:Higher health- and lifestyle-based dementia risk is associated with markers of general brain atrophy, cerebrovascular pathology and worse cognition, suggesting that LIBRA meaningfully summarizes individual lifestyle-related brain health. Improving LIBRA factors on an individual level might improve population brain health. Sex differences in lifestyle-related pathology and cognition need to be further explored.Classification of Evidence:This study provides Class II evidence that higher LIBRA scores are significantly associated with lower scores on some cognitive domains and a higher risk of cognitive impairment.

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

10.1101/327205 ◽

2018 ◽

Cited By ~ 1

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.

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White Matter Hyperintensities Are Associated with Grey Matter Atrophy and Cognitive Decline in Alzheimer's Disease and Frontotemporal Dementia

Neurobiology of Aging ◽

10.1016/j.neurobiolaging.2021.11.007 ◽

2021 ◽

Author(s):

Mahsa Dadar ◽

Ana Laura Manera ◽

Simon Ducharme ◽

D. Louis Collins

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

White Matter ◽

Cognitive Decline ◽

Frontotemporal Dementia ◽

Grey Matter ◽

White Matter Hyperintensities ◽

Grey Matter Atrophy

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The Relationship Between Isolated Hypertension with Brain Volumes in UK Biobank

10.31234/osf.io/jqn5y ◽

2021 ◽

Author(s):

Danielle Newby ◽

Laura Winchester ◽

William Sproviero ◽

Marco Fernandes ◽

Upamanyu Ghose ◽

...

Keyword(s):

White Matter ◽

Grey Matter ◽

Brain Mri ◽

Uk Biobank ◽

Brain Health ◽

Brain Volumes ◽

Dementia Risk ◽

Diastolic Hypertension ◽

The Impact ◽

The Relationship

Hypertension is a well-established risk factor for cognitive impairment, brain atrophy, and dementia. However, the relationship of other types of hypertension, such as, isolated hypertension on brain health and its comparison to systolic-diastolic hypertension (where systolic and diastolic measures are high), is still relatively unknown. Due to its increased prevalence, it is important to investigate the impact of isolated hypertension to help understand its potential impact on cognitive decline and future dementia risk. In this study, we compared a variety of global brain measures between participants with isolated hypertension to those with normal blood pressure or systolic-diastolic hypertension using the largest cohort of healthy individuals. Using the UK Biobank cohort, we carried out a cross-sectional study using 29775 participants [mean age 63 years, 53% female] with BP measurements and brain MRI data. We used linear regression models adjusted for multiple confounders to compare a variety of global, sub cortical and white matter brain measures. We compared participants with either isolated systolic or diastolic hypertension with normotensives and then with participants with systolic-diastolic hypertension. The results showed that participants with isolated systolic or diastolic hypertension taking BP medications had smaller grey matter but larger white matter microstructures and macrostructures compared to normotensives. However, isolated hypertensives had larger total grey matter and smaller white matter traits when comparing these regions with participants with systolic-diastolic hypertension.These results provide support to investigate possible preventative strategies that target isolated hypertension as well as systolic-diastolic hypertension to maintain brain health and/or reduce dementia risk earlier in life particularly in white matter regions.

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