scholarly journals Is there association between APOE e4 genotype and structural brain ageing phenotypes, and does that association increase in older age in UK Biobank? (N = 8,395)

2017 ◽  
Author(s):  
Donald M. Lyall ◽  
Simon R. Cox ◽  
Laura M. Lyall ◽  
Carlos Celis-Morales ◽  
Breda Cullen ◽  
...  
Keyword(s):  
Social Deprivation ◽  
Mean Diffusivity ◽  
Brain Magnetic Resonance Imaging ◽  
Older Age ◽  
Smoking History ◽  
Future Research ◽  
Uk Biobank ◽  
Cognitive Ageing ◽  
Intermediate Phenotypes ◽  
Brain Ageing

AbstractApolipoprotein (APOE) e4 genotype is a purported risk factor for accelerated cognitive ageing and dementia, though its neurostructural substrates are unclear. The deleterious effects of this genotype on brain structure may increase in magnitude into older age. This study aimed to investigate in UK Biobank the association between APOE e4 allele presence vs. absence and brain imaging variables that have been associated with worse cognitive abilities; and whether this association varies by cross-sectional age. We used brain magnetic resonance imaging (MRI) and genetic data from a general-population cohort: the UK Biobank (N=8,395). We adjusted for the covariates of age in years, sex, Townsend social deprivation scores, smoking history and cardiometabolic diseases. There was a statistically significant association between APOE e4 genotype and increased (i.e. worse) white matter (WM) hyperintensity volumes (standardised beta = 0.088, 95 confidence intervals = 0.036 to 0.139, P = 0.001), a marker of poorer cerebrovascular health. There were no associations with left or right hippocampal, total grey matter (GM) or WM volumes, or WM tract integrity indexed by fractional anisotropy (FA) and mean diffusivity (MD). There were no statistically significant interactions with age. Future research in UK Biobank utilising intermediate phenotypes and longitudinal imaging hold significant promise for this area, particularly pertaining to APOE e4’s potential link with cerebrovascular contributions to cognitive ageing.

scholarly journals Association between APOE e4 and white matter hyperintensity volume, but not total brain volume or white matter integrity

2019 ◽  
Vol 14 (5) ◽  
pp. 1468-1476 ◽  
Author(s):  
Donald M. Lyall ◽  
Simon R. Cox ◽  
Laura M. Lyall ◽  
Carlos Celis-Morales ◽  
Breda Cullen ◽  
...  
Keyword(s):  
White Matter ◽  
Cognitive Aging ◽  
Social Deprivation ◽  
Mean Diffusivity ◽  
Brain Magnetic Resonance Imaging ◽  
Smoking History ◽  
White Matter Hyperintensity ◽  
Future Research ◽  
Uk Biobank ◽  
Intermediate Phenotypes

Abstract Apolipoprotein (APOE) e4 genotype is an accepted risk factor for accelerated cognitive aging and dementia, though its neurostructural substrates are unclear. The deleterious effects of this genotype on brain structure may increase in magnitude into older age. This study aimed to investigate in UK Biobank the association between APOE e4 allele presence vs. absence and brain imaging variables that have been associated with worse cognitive abilities; and whether this association varies by cross-sectional age. We used brain magnetic resonance imaging (MRI) and genetic data from a general-population cohort: the UK Biobank (N = 8395 after exclusions). We adjusted for the covariates of age in years, sex, Townsend social deprivation scores, smoking history and cardiometabolic diseases. There was a statistically significant association between APOE e4 genotype and increased (i.e. worse) white matter (WM) hyperintensity volumes (standardised beta = 0.088, 95% confidence intervals = 0.036 to 0.139, P = 0.001), a marker of poorer cerebrovascular health. There were no associations with left or right hippocampal, total grey matter (GM) or WM volumes, or WM tract integrity indexed by fractional anisotropy (FA) and mean diffusivity (MD). There were no statistically significant interactions with age. Future research in UK Biobank utilising intermediate phenotypes and longitudinal imaging hold significant promise for this area, particularly pertaining to APOE e4’s potential link with cerebrovascular contributions to cognitive aging.

scholarly journals Remote history of VTE is associated with severe COVID‐19 in middle and older age: UK Biobank cohort study

2021 ◽  
Author(s):  
Jana J Anderson ◽  
Frederick K Ho ◽  
Claire L Niedzwiedz ◽  
S. Vittal Katikireddi ◽  
Carlos Celis‐Morales ◽  
...  
Keyword(s):  
Cohort Study ◽  
Older Age ◽  
Uk Biobank ◽  
History Of

scholarly journals Age, Sex and Cerebral Microbleed Effects On White Matter Degradation After Traumatic Brain Injury

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 886-887
Author(s):  
Andrei Irimia ◽  
Ammar Dharani ◽  
Van Ngo ◽  
David Robles ◽  
Kenneth Rostowsky
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
Diffusion Tensor ◽  
Diffuse Axonal Injury ◽  
Principal Component ◽  
Older Age ◽  
Analysis Of Covariance ◽  
Future Research ◽  
Cerebral Microbleed

Abstract Mild traumatic brain injury (mTBI) affects white matter (WM) integrity and accelerates neurodegeneration. This study assesses the effects of age, sex, and cerebral microbleed (CMB) load as predictors of WM integrity in 70 subjects aged 18-77 imaged acutely and ~6 months after mTBI using diffusion tensor imaging (DTI). Two-tensor unscented Kalman tractography was used to segment and cluster 73 WM structures and to map changes in their mean fractional anisotropy (FA), a surrogate measure of WM integrity. Dimensionality reduction of mean FA feature vectors was implemented using principal component (PC) analysis, and two prominent PCs were used as responses in a multivariate analysis of covariance. Acutely and chronically, older age was significantly associated with lower FA (F2,65 = 8.7, p < .001, η2 = 0.2; F2,65 = 12.3, p < .001, η2 = 0.3, respectively), notably in the corpus callosum and in dorsolateral temporal structures, confirming older adults’ WM vulnerability to mTBI. Chronically, sex was associated with mean FA (F2,65 = 5.0, p = 0.01, η2 = 0.1), indicating males’ greater susceptibility to WM degradation. Acutely, a significant association was observed between CMB load and mean FA (F2,65 = 5.1, p = 0.009, η2 = 0.1), suggesting that CMBs reflect the acute severity of diffuse axonal injury. Together, these findings indicate that older age, male sex, and CMB load are risk factors for WM degeneration. Future research should examine how sex- and age-mediated WM degradation lead to cognitive decline and connectome degeneration after mTBI.

scholarly journals Epigenetic Age Acceleration and Hearing: Observations From the Baltimore Longitudinal Study of Aging

2021 ◽  
Vol 13 ◽  
Author(s):  
Pei-Lun Kuo ◽  
Ann Zenobia Moore ◽  
Frank R. Lin ◽  
Luigi Ferrucci
Keyword(s):  
Dna Methylation ◽  
Longitudinal Study ◽  
Smoking History ◽  
Future Research ◽  
Age Related ◽  
Epigenetic Age ◽  
Epigenetic Age Acceleration ◽  
Baltimore Longitudinal Study ◽  
Age Related Hearing Loss ◽  
The Relationship

Objectives: Age-related hearing loss (ARHL) is highly prevalent among older adults, but the potential mechanisms and predictive markers for ARHL are lacking. Epigenetic age acceleration has been shown to be predictive of many age-associated diseases and mortality. However, the association between epigenetic age acceleration and hearing remains unknown. Our study aims to investigate the relationship between epigenetic age acceleration and audiometric hearing in the Baltimore Longitudinal Study of Aging (BLSA).Methods: Participants with both DNA methylation and audiometric hearing measurements were included. The main independent variables are epigenetic age acceleration measures, including intrinsic epigenetic age acceleration—“IEAA,” Hannum age acceleration—“AgeAccelerationResidualHannum,” PhenoAge acceleration—“AgeAccelPheno,” GrimAge acceleration—“AgeAccelGrim,” and methylation-based pace of aging estimation—“DunedinPoAm.” The main dependent variable is speech-frequency pure tone average. Linear regression was used to assess the association between epigenetic age acceleration and hearing.Results: Among the 236 participants (52.5% female), after adjusting for age, sex, race, time difference between measurements, cardiovascular factors, and smoking history, the effect sizes were 0.11 995% CI: (–0.00, 0.23), p = 0.054] for Hannum’s clock, 0.08 [95% CI: (–0.03, 0.19), p = 0.143] for Horvath’s clock, 0.10 [95% CI: (–0.01, 0.21), p = 0.089] for PhenoAge, 0.20 [95% CI: (0.06, 0.33), p = 0.004] for GrimAge, and 0.21 [95% CI: (0.09, 0.33), p = 0.001] for DunedinPoAm.Discussion: The present study suggests that some epigenetic age acceleration measurements are associated with hearing. Future research is needed to study the potential subclinical cardiovascular causes of hearing and to investigate the longitudinal relationship between DNA methylation and hearing.

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

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.

Is hospitalization a risk factor for cognitive decline in older age adults?

2020 ◽  
pp. 1-18
Author(s):  
Lucia Chinnappa-Quinn ◽  
Steve Robert Makkar ◽  
Michael Bennett ◽  
Ben C. P. Lam ◽  
Jessica W. Lo ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Meta Analysis ◽  
Severity Of Illness ◽  
The Elderly ◽  
Preliminary Evidence ◽  
Older Age ◽  
Future Research ◽  
Cognitive Changes ◽  
Newcastle Ottawa Scale ◽  
Meta Analyses

ABSTRACT Objectives: Many studies document cognitive decline following specific types of acute illness hospitalizations (AIH) such as surgery, critical care, or those complicated by delirium. However, cognitive decline may be a complication following all types of AIH. This systematic review will summarize longitudinal observational studies documenting cognitive changes following AIH in the majority admitted population and conduct meta-analysis (MA) to assess the quantitative effect of AIH on post-hospitalization cognitive decline (PHCD). Methods: We followed Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Selection criteria were defined to identify studies of older age adults exposed to AIH with cognitive measures. 6566 titles were screened. 46 reports were reviewed qualitatively, of which seven contributed data to the MA. Risk of bias was assessed using the Newcastle–Ottawa Scale. Results: The qualitative review suggested increased cognitive decline following AIH, but several reports were particularly vulnerable to bias. Domain-specific outcomes following AIH included declines in memory and processing speed. Increasing age and the severity of illness were the most consistent risk factors for PHCD. PHCD was supported by MA of seven eligible studies with 41,453 participants (Cohen’s d = −0.25, 95% CI [−0.02, −0.49] I2 35%). Conclusions: There is preliminary evidence that AIH exposure accelerates or triggers cognitive decline in the elderly patient. PHCD reported in specific contexts could be subsets of a larger phenomenon and caused by overlapping mechanisms. Future research must clarify the trajectory, clinical significance, and etiology of PHCD: a priority in the face of an aging population with increasing rates of both cognitive impairment and hospitalization.

scholarly journals Association of Atrial Fibrillation With White Matter Disease

Stroke ◽  
2019 ◽  
Vol 50 (4) ◽  
pp. 989-991 ◽  
Author(s):  
Iris Yuefan Shao ◽  
Melinda C. Power ◽  
Thomas Mosley ◽  
Clifford Jack ◽  
Rebecca F. Gottesman ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
White Matter ◽  
Mean Diffusivity ◽  
Brain Magnetic Resonance Imaging ◽  
White Matter Disease ◽  
Linear Regression Models ◽  
Cross Sectional ◽  
Atherosclerosis Risk In Communities ◽  
Increased Risk ◽  
Microstructural Integrity

Background and Purpose— Evidence suggests that atrial fibrillation (AF) is associated with increased risk of cognitive decline and dementia, even in the absence of stroke. White matter disease (WMD) is a potential mechanism linking AF to cognitive impairment. In this study, we explored the association between prevalent AF and WMD. Methods— We performed a cross-sectional analysis of participants attending the ARIC-NCS (Atherosclerosis Risk in Communities–Neurocognitive Study) in 2011 to 2013 who underwent brain magnetic resonance imaging. AF was ascertained from study visit electrocardiograms or prior hospitalization codes. Extent of WMD was defined by measures of white matter (WM) microstructural integrity and WM hyperintensity volume. Multivariable linear regression models were used to assess the association between AF and WMD. Results— Among 1899 participants (mean age, 76 years; 28% black; 60% women), 133 (7%) had prevalent AF. After multivariable adjustment, differences between participants with and without AF were −0.001 (95% CI, −0.006 to 0.004) for global WM fractional anisotropy, 0.031×10 −4 mm 2 /s (95% CI, −0.075 to 0.137) for global WM mean diffusivity, and 0.08 mm 3 (95% CI, −0.14 to 0.30) for WM hyperintensity volume. Conclusions— The results suggest that there is no association between prevalent AF and WMD.

scholarly journals An exploratory non-randomized study of a 3-month electronic nicotine delivery system (ENDS) intervention with people accessing a homeless supported temporary accommodation service (STA) in Ireland

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Florian Scheibein ◽  
Kevin McGirr ◽  
Andy Morrison ◽  
Warren Roche ◽  
John Stephen Gary Wells
Keyword(s):  
Carbon Monoxide ◽  
Randomized Study ◽  
Physical Symptoms ◽  
Smoking History ◽  
Future Research ◽  
Small Scale ◽  
Positive Effects ◽  
Nicotine Delivery ◽  
Temporary Accommodation

Abstract Background Smoking is endemic amongst people accessing homeless services, and they are disproportionately affected by smoking-related diseases. This paper reports on the results of a 3-month small scale intervention which explored the efficacy, challenges and opportunities of using electronic nicotine delivery systems (ENDS) to support cessation of tobacco smoking with people accessing an Irish supported temporary accommodation (STA) homeless service. It considers the results of this intervention with reference to the balance of harms between the use of vaping to support smoking cessation and continued smoking. Methods Twenty-three participants were recruited. Demographic data, carbon monoxide (CO) measurements, homelessness status and smoking history were recorded. Participants were given an ENDS device and two 10-ml bottles containing e-liquid available in several flavours and at several strengths. Participants could pick up new bottles on a weekly basis. At weeks 1, 4, 8 and 12, the Fagerström Test and Mood and Physical Symptoms Scale (MPSS) were administered. Results Over 75% of the residents in the participating hostel were recruited (23/30). However, there was a substantial loss to follow-up (n = 14) as a result of data protection issues, the transient nature of the population of interest and non-compliance with the intervention. Self-reported reductions in cigarette consumption were found to be statistically significant (p < 0.001). However, reductions in carbon monoxide measurements were not statistically significant. Decreases in Fagerström Nicotine Dependence Test were statistically significant (p = 0.001), but decreases in MPSS “urge to smoke” and “strength of urges” composite scores were not. Reported side effects included coughing, runny nose, bleeding nose, slight sweating, dizziness, increased phlegm and a burning sensation at the back of the throat. Barriers to engagement were peer norms, vaping restrictions in accommodation and adverse life events. Positive effects reported included increased energy, less coughing, better breathing and financial benefits. An improvement in the domain “poor concentration” was also found to be statistically significant (p = 0.040). Conclusion ENDS-based interventions may be effective with this population. Future research should aim to improve follow-up, consider including behavioural components and monitor health effects in relation to ongoing concerns around risks and the balance of harms. Trial registration Registered retrospectively ISRCTN14767579

scholarly journals Recalibrating the risk of hamstring strain injury (HSI): A 2020 systematic review and meta-analysis of risk factors for index and recurrent hamstring strain injury in sport

2020 ◽  
Vol 54 (18) ◽  
pp. 1081-1088 ◽  
Author(s):  
Brady Green ◽  
Matthew N Bourne ◽  
Nicol van Dyk ◽  
Tania Pizzari
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Evidence Synthesis ◽  
Meta Analysis ◽  
Significant Risk ◽  
Older Age ◽  
Future Research ◽  
Hamstring Strain ◽  
Best Evidence Synthesis ◽  
History Of

ObjectiveTo systematically review risk factors for hamstring strain injury (HSI).DesignSystematic review update.Data sourcesDatabase searches: (1) inception to 2011 (original), and (2) 2011 to December 2018 (update). Citation tracking, manual reference and ahead of press searches.Eligibility criteria for selecting studiesStudies presenting prospective data evaluating factors associated with the risk of index and/or recurrent HSI.MethodSearch result screening and risk of bias assessment. A best evidence synthesis for each factor and meta-analysis, where possible, to determine the association with risk of HSI.ResultsThe 78 studies captured 8,319 total HSIs, including 967 recurrences, in 71,324 athletes. Older age (standardised mean difference=1.6, p=0.002), any history of HSI (risk ratio (RR)=2.7, p<0.001), a recent HSI (RR=4.8, p<0.001), previous anterior cruciate ligament (ACL) injury (RR=1.7, p=0.002) and previous calf strain injury (RR=1.5, p<0.001) were significant risk factors for HSI. From the best evidence synthesis, factors relating to sports performance and match play, running and hamstring strength were most consistently associated with HSI risk. The risk of recurrent HSI is best evaluated using clinical data and not the MRI characteristics of the index injury.Summary/conclusionOlder age and a history of HSI are the strongest risk factors for HSI. Future research may be directed towards exploring the interaction of risk factors and how these relationships fluctuate over time given the occurrence of index and recurrent HSI in sport is multifactorial.

Subclinical Late Cardiomyopathy After Doxorubicin Therapy for Lymphoma in Adults

2004 ◽  
Vol 22 (10) ◽  
pp. 1864-1871 ◽  
Author(s):  
O. Hequet ◽  
Q.H. Le ◽  
I. Moullet ◽  
E. Pauli ◽  
G. Salles ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cumulative Dose ◽  
Hodgkin’S Lymphoma ◽  
Clinical Signs ◽  
Left Ventricular ◽  
Older Age ◽  
Hodgkin's Lymphoma ◽  
Smoking History ◽  
High Dose ◽  
Male Sex

Purpose To assess the cardiac status of the long-term survivors and to estimate the incidence and the features of subclinical cardiotoxicity induced after conventional treatment with doxorubicin for non-Hodgkin's lymphoma or Hodgkin's lymphoma. Patients and Methods We analyzed a group of patients who previously received doxorubicin-based chemotherapy for lymphoma. Echocardiograms were performed at least 5 years after therapy with anthracyclines. Clinical cardiomyopathy was defined by the presence of clinical signs of congestive heart failure (CHF). Subclinical cardiomyopathy was defined by decrease of left ventricular fractional shortening (FS) without clinical signs of CHF. Cumulative dose of doxorubicin, male sex, older age, relapse, radiotherapy (mediastinal or total-body irradiation), autologous stem-cell transplantation, high-dose cyclophosphamide, and cardiovascular risk factors (hypertension, diabetes, hypercholesterolemia, familial history of cardiac disease, being overweight, and smoking history) were evaluated as potential risk factors for the development of cardiac dysfunction. Results Of 141 assessable patients (median age, 54 years; median cumulative dose of doxorubicin, 300 mg/m2), only one developed CHF. Criteria of subclinical cardiomyopathy were found in 39 patients. In multivariate analysis, factors that contributed to decreased FS were male sex (P < .01), older age (P < .01), higher cumulative dose of doxorubicin or association with another anthracycline (P = .04), radiotherapy (P = .04), and being overweight (P = .04). Conclusion Cardiac abnormalities can occur in patients treated with doxorubicin for lymphoma in the absence of CHF, even in patients who received moderate anthracycline doses. Male sex, older age, higher dose of doxorubicin, radiotherapy, and being overweight were risk factors for the development of cardiomyopathy.

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