scholarly journals Midlife vascular risk factors and risk of incident dementia: Longitudinal cohort and Mendelian randomization analyses in the UK Biobank

2021 ◽  
Author(s):  
Rainer Malik ◽  
Marios K. Georgakis ◽  
Julia Neitzel ◽  
Kristiina Rannikmäe ◽  
Michael Ewers ◽  
...  
Keyword(s):  
Risk Factors ◽  
Mendelian Randomization ◽  
Vascular Risk Factors ◽  
Vascular Risk ◽  
Uk Biobank ◽  
Longitudinal Cohort ◽  
Incident Dementia ◽  
The Uk

Abstract 71: Sex and Genetic Predisposition Synergistically Influence Risk of Stroke and Myocardial Infarction in Middle-Aged Persons Without Risk Factors

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Guido J Falcone ◽  
Julian Acosta ◽  
Audrey C Leasure ◽  
Kevin N Vanent ◽  
Rommell B Noche ◽  
...  
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Genetic Predisposition ◽  
Genetic Risk ◽  
Vascular Risk Factors ◽  
Vascular Risk ◽  
Uk Biobank ◽  
Middle Aged ◽  
High Genetic Risk ◽  
The Uk

Background and Hypothesis: Driven by aging-related physiological changes, the incidence of stroke and myocardial infarction rises rapidly in persons aged >40 years. A significant proportion of these acute vascular events (AVE) take place in persons without vascular risk factors. We tested the hypothesis that sex and genetic predisposition synergistically increase the risk of AVE in middle-aged persons without vascular risk factors. Methods: We analyzed data from the UK Biobank, a prospective longitudinal study that enrolled persons aged 40 to 69 years. Our analysis was restricted to middle-aged participants, defined as those aged 40 to 60 years. Prevalent and incident cases of stroke (ischemic and hemorrhagic) and myocardial infarction were included. To quantify the genetic predisposition to sustain an AVE, we constructed a polygenic risk score using 68 independent (R 2 <0.1) genetic variants known to associate (p<5x10 -8 ) with AVE. Participants were classified as having low, intermediate or high genetic risk according to tertiles of the score. We used Cox models for association and interaction testing. Results: Of the 502,536 study participants enrolled in the UK Biobank, 303,295 (60%) did not have any vascular risk factors. During the follow-up period, there were 5,746 AVEs, including 1,954 strokes and 3,792 myocardial infarctions. The cumulative risk of AVE was 0.12% (n=352), 0.46% (n = 1,386) and 1.32% (n = 4,008) at ages 40, 50 and 60 years (test-for-trend p<0.001). The risk of AVE was 3 times greater in men than women (HR 3.30, 95%CI 3.08 - 3.53). Compared to persons with low genetic risk, those with intermediate and high genetic risk had a 22% (HR 1.22, 95%CI 1.13 - 1.32) and 52% (HR 1.52, 95%CI 1.41 - 1.65) increase in risk of AVE, respectively. There was significant synergy (interaction) between sex and genetic predisposition: compared to females with low genetic risk, males with high genetic risk had 4 times (HR 3.91, 95%CI 3.58 - 4.26) the risk of AVE (interaction analysis p<0.001). Conclusion: Genetic information constitutes a promising tool to risk stratify middle-aged persons without vascular risk factors. The synergistic effect of sex and genetic predisposition points to specific subgroups that could benefit from aggressive preventive interventions.

Association between carotid stenosis or lacunar infarction and incident dementia in patients with vascular risk factors

2014 ◽  
Vol 22 (1) ◽  
pp. 187-192 ◽  
Author(s):  
K. Kitagawa ◽  
K. Miwa ◽  
Y. Yagita ◽  
S. Okazaki ◽  
M. Sakaguchi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Carotid Stenosis ◽  
Vascular Risk Factors ◽  
Lacunar Infarction ◽  
Vascular Risk ◽  
Incident Dementia

scholarly journals Prevalence of dementia in African–Caribbean compared with UK-born White older people: two-stage cross-sectional study

2011 ◽  
Vol 199 (2) ◽  
pp. 119-125 ◽  
Author(s):  
Simon Adelman ◽  
Martin Blanchard ◽  
Greta Rait ◽  
Gerard Leavey ◽  
Gill Livingston
Keyword(s):  
Risk Factors ◽  
Older People ◽  
Vascular Risk Factors ◽  
Country Of Birth ◽  
Vascular Risk ◽  
Cross Sectional ◽  
Caribbean Country ◽  
African Caribbean ◽  
The Uk ◽  
Prevalence Of Dementia

BackgroundPreliminary studies in the UK, all using screening instruments of unknown cultural validity, indicate that there may be an increased prevalence of dementia in African–Caribbean people, possibly related to vascular risk factors and potentially amenable to preventative measures.AimsTo determine the prevalence of dementia in older people of African–Caribbean country of birth compared with their White UK-born counterparts.MethodA total of 218 people of African–Caribbean country of birth and 218 White UK-born people aged ⩾60 years were recruited from five general practices in North London. Those who screened positive for cognitive impairment using a culturally valid instrument were offered a standardised diagnostic interview. Two independent assessors diagnosed dementia according to standard operationalised criteria.ResultsAfrican–Caribbean participants were 2 years younger, and those with dementia nearly 8 years younger than their White counterparts. The prevalence of dementia was significantly higher in the African–Caribbean (9.6%) than the White group (6.9%) after adjustment for the confounders age and socioeconomic status (odds ratio (OR) = 3.1, 95%CI 1.3–7.3, P = 0.012).ConclusionsThere is an increased prevalence of dementia in older people of African–Caribbean country of birth in the UK and at younger ages than in the indigenous White population. These findings have implications for service provision and preventive interventions. Further research is needed to explore the role of vascular risk factors and social adversity in the excess of dementia in this population.

scholarly journals Stroke, vascular risk factors and depression

2001 ◽  
Vol 178 (1) ◽  
pp. 23-28 ◽  
Author(s):  
R. Stewart ◽  
M. Prince ◽  
M. Richards ◽  
C. Brayne ◽  
A. Mann
Keyword(s):  
Risk Factors ◽  
Geriatric Depression Scale ◽  
Depression Scale ◽  
Vascular Risk Factors ◽  
Vascular Risk ◽  
Geriatric Depression ◽  
Community Based ◽  
Blood Tests ◽  
Mediating Factor ◽  
The Uk

BackgroundStroke, hypertension and diabetes are common in older Caribbean-born populations in the UK who may be at risk of depression secondary to vascular disease.AimsWe examined the association between stroke, vascular risk factors and depression in a community-based Caribbean-born population aged 55–75 years.MethodVascular risk factors were identified by interview, examination and blood tests. Depression was categorised using the Geriatric Depression Scale. Disablement was assessed as a potential mediating factor.ResultsPhysical illness and disablement were strongly associated with depression, independent of disablement. Previous stroke was associated with depression, independent of disablement. No vascular risk factors were associated with depression.ConclusionsThe risk of depression associated with stroke was not explained by disablement. However, the hypothesis that vascular risk factors are important in the genesis of depression was not supported.

DO DEMOGRAPHIC AND VASCULAR RISK FACTORS PREDICT COGNITIVE CHANGE IN 11,070 UK BIOBANK PARTICIPANTS?

2017 ◽  
Vol 13 (7) ◽  
pp. P1556
Author(s):  
Chloe Fawns-Ritchie ◽  
Simon R. Cox ◽  
Marcus Richards ◽  
John Gallacher ◽  
John M. Starr ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cognitive Change ◽  
Vascular Risk Factors ◽  
Vascular Risk ◽  
Uk Biobank

scholarly journals Effect of n-3 polyunsaturated fatty acids on ischemic heart disease and cardiometabolic risk factors: a two-sample Mendelian randomization study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Bayi Xu ◽  
Zhixia Xu ◽  
Duanmin Xu ◽  
Xuerui Tan
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Blood Pressure ◽  
Fatty Acids ◽  
Cardiometabolic Risk ◽  
Mendelian Randomization ◽  
Meta Analysis ◽  
Cardiometabolic Risk Factors ◽  
Uk Biobank ◽  
The Uk

Abstract Background The cardioprotective ability of n-3 polyunsaturated fatty acids (PUFAs) is controversial. Most studies suggest a specific role for PUFAs in cardioprotection from ischemic heart disease (IHD). However, few studies have used genetic biomarkers of n-3 PUFAs to examine their potential relationships with IHD. This study aimed to use Mendelian randomization to evaluate whether genetically-predicted n-3 PUFAs affect IHD and cardiometabolic risk factors (CRFs). Methods Genetic variants strongly (p < 5 × 10–8) and independently (r2 > 0.1) associated with n-3 PUFAs were derived from the CHARGE Consortium (including 8,866 subjects of European ancestry) and were used as instrumental variables (IVs) for evaluating the effect of n-3 PUFAs, including α-linolenic acid (ALA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA). Data on the associations between the IVs and IHD, myocardial infarction, and CRFs (including diabetes, lipids, blood pressure, body mass index, and waist-to-hip ratio (WHR)) were obtained from the UK Biobank SOFT CAD GWAS with the CARDIoGRAMplusC4D 1000 Genomes-based GWAS (113,937 IHD cases and 339,115 controls), the Myocardial Infarction Genetics and CARDIoGRAM Exome consortia (42,335 MI cases and 78,240 controls), the DIAbetes Genetics Replication And Meta-analysis consortium (26,676 diabetes mellitus cases and 132,532 controls), the Global Lipids Genetics Consortium (n = 196,475), the International Consortium for Blood Pressure (n = 69,395), and the meta-analysis of GWAS for body fat distribution in the UK Biobank and Genetic Investigation of Anthropometric Traits (n = 694,649). Results Genetically-predicted higher ALA was associated with lower risk of IHD, type 2 diabetes (T2D), and lower serum lipids. The effect size per 0.05-unit increase (about 1 standard deviation) in plasma ALA level) was − 1.173 (95% confidence interval − 2.214 to − 0.133) for IHD. DPA and EPA had no association with IHD but were associated with a higher risk of T2D, higher levels of lipids or WHR. DHA had no association with IHD or CRFs. Conclusions Our study suggests a benefit of ALA for IHD and its main risk factors. DHA, DPA, and EPA had no association with IHD but were partly associated with increasing cardiometabolic risk factors.

Abstract 98: Midlife Vascular Risk Factors and Incident Dementia in the ARIC Cohort

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Rebecca F Gottesman ◽  
Marilyn Albert ◽  
Laura Coker ◽  
Josef Coresh ◽  
Sonia M Davis ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cognitive Status ◽  
Vascular Risk Factors ◽  
Vascular Risk ◽  
Atherosclerosis Risk In Communities ◽  
Black And White ◽  
Apoe Ε4 ◽  
Phone Calls ◽  
Incident Dementia ◽  
Increased Risk

Background: Vascular risk factors have been associated with risk of cognitive decline, with increasing evidence that midlife exposure to these risk factors may be most important in conferring late-life risk of cognitive impairment. We explored associations between vascular risk factors measured in midlife and the development of dementia over 25 years in the biracial Atherosclerosis Risk in Communities (ARIC) cohort. Methods: Participants in the ARIC study were recruited from four U.S. communities in 1987-1989, at ages 45-64, with four additional in-person visits, surveillance for hospitalizations, annual phone calls, and repeated cognitive evaluations over a 25-year period. In 2011-2013, ARIC participants were seen for the ARIC Neurocognitive Study (ARIC-NCS), and underwent a detailed neurocognitive battery and informant interviews. Through adjudicated review, dementia cases were defined. Additional dementia cases were identified through the telephone interview for cognitive status (TICS) or informant interview for those participants not attending ARIC-NCS; or by a prior dementia ICD-9 code during a hospitalization. Results: Of 15,744 participants in the cohort, 1516 cases of dementia were identified, of whom over one third were among black participants. Risk of dementia was highest in individuals of black race, with less than a high school education, older age, APOE ε4 carriage, and who, at ARIC baseline, had hypertension, diabetes, or were current smokers (table). APOE ε4 and smoking were each stronger risk factors for dementia in whites than in blacks. Discussion: Vascular risk factors measured in midlife are associated with increased risk of dementia in this biracial cohort, in black and white participants. The risk associated with diabetes nears the increased risk associated with having an APOE ε4 allele. Further studies are needed to evaluate the mechanism of and opportunities for prevention of the cognitive sequelae of these risk factors in midlife.

Increased Total Homocysteine Levels Predict the Risk of Incident Dementia Independent of Cerebral Small-Vessel Diseases and Vascular Risk Factors

2015 ◽  
Vol 49 (2) ◽  
pp. 503-513 ◽  
Author(s):  
Kaori Miwa ◽  
Makiko Tanaka ◽  
Shuhei Okazaki ◽  
Yoshiki Yagita ◽  
Manabu Sakaguchi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Vascular Risk Factors ◽  
Small Vessel ◽  
Vascular Risk ◽  
Incident Dementia ◽  
Total Homocysteine ◽  
Cerebral Small Vessel Diseases
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