scholarly journals Frailty, lifestyle, genetics and dementia risk

2021 ◽  
pp. jnnp-2021-327396
Author(s):  
David D Ward ◽  
Janice M Ranson ◽  
Lindsay M K Wallace ◽  
David J Llewellyn ◽  
Kenneth Rockwood
Keyword(s):  
Genetic Risk ◽  
Healthy Lifestyle ◽  
Frailty Index ◽  
Risk Scores ◽  
Prevention Strategies ◽  
Lifestyle Behaviours ◽  
High Genetic Risk ◽  
Dementia Risk ◽  
Incident Dementia ◽  
Dementia Prevention

ObjectiveTo optimise dementia prevention strategies, we must understand the complex relationships between lifestyle behaviours, frailty and genetics.MethodsWe explored relationships between frailty index, healthy lifestyle and polygenic risk scores (all assessed at study entry) and incident all-cause dementia as recorded on hospital admission records and death register data.ResultsThe analytical sample had a mean age of 64.1 years at baseline (SD=2.9) and 53% were women. Incident dementia was detected in 1762 participants (median follow-up time=8.0 years). High frailty was associated with increased dementia risk independently of genetic risk (HR 3.68, 95% CI 3.11 to 4.35). Frailty mediated 44% of the relationship between healthy lifestyle behaviours and dementia risk (indirect effect HR 0.95, 95% CI 0.95 to 0.96). Participants at high genetic risk and with high frailty had 5.8 times greater risk of incident dementia compared with those at low genetic risk and with low frailty (HR 5.81, 95% CI 4.01 to 8.42). Higher genetic risk was most influential in those with low frailty (HR 1.31, 95% CI 1.22 to 1.40) but not influential in those with high frailty (HR 1.09, 95% CI 0.92 to 1.28).ConclusionFrailty is strongly associated with dementia risk and affects the risk attributable to genetic factors. Frailty should be considered an important modifiable risk factor for dementia and a target for dementia prevention strategies, even among people at high genetic risk.

Genetic Risk Scores and Dementia Risk Across Different Ethnic Groups in UK Biobank

2021 ◽  
Author(s):  
Naaheed Mukadam ◽  
Olga Giannakopoulou ◽  
Nick Bass ◽  
Karoline Kuchenbaecker ◽  
Andrew McQuillin
Keyword(s):  
Ethnic Groups ◽  
Genetic Risk ◽  
Risk Scores ◽  
Uk Biobank ◽  
Genetic Risk Scores ◽  
Dementia Risk

scholarly journals 1389Do associations between a healthy lifestyle and incidence of cancer differ by genetic risk?

2021 ◽  
Vol 50 (Supplement_1) ◽  
Author(s):  
Stephanie Byrne ◽  
Terry Boyle ◽  
Beben Benyamin ◽  
Sang Hong Lee ◽  
Muktar Ahmed ◽  
...  
Keyword(s):  
Cancer Risk ◽  
Cancer Incidence ◽  
Genetic Risk ◽  
Cox Regression ◽  
Healthy Lifestyle ◽  
Lymphocytic Leukemia ◽  
European Ancestry ◽  
Risk Scores ◽  
Increased Risk ◽  
Cancer Types

Abstract Background It is unknown whether relationships between lifestyle and cancer differ by genetic risk. We investigated this for 13 cancer types using prospective data from the UK Biobank. Methods In 2006-2010, participants aged 37-73 years completed an assessment and provided biological samples. Those of European ancestry with no history of malignant cancer were included in our analysis (n = 196,485). For each individual, a healthy lifestyle index (HLI) was calculated based on recommendations, and polygenic risk scores (PRSs) were computed for 13 cancer types. Relationships with cancer incidence were assessed by cox regression, adjusting for age, sex, assessment centre, birth location, and measures of socioeconomic status. Interactions between the HLI and PRSs were explored. Results For all cancer outcomes, a high genetic risk was associated with an increased cancer risk, or there was a trend in that direction. Those in the top PRS tertile had a greater than 2-fold increased risk of colorectal cancer (HR[95%CI]=2.18[1.90,2.49]), pancreatic cancer (2.39[1.71,3.32]) and lymphocytic leukemia (2.45[1.67,3.59]). An unhealthy lifestyle was associated with a higher cancer risk for 8 cancer types, with strong relationships observed for lung (3.41[2.76,4.20]), pancreatic (2.06[1.47,2.91]), bladder (1.95[1.43,2.66]) and kidney cancers (1.90[1.43,2.54]). No interactions between HLI and PRSs were detected (all interaction p-values>0.10). Conclusions Associations between lifestyle and cancer incidence did not differ by genetic risk. Key messages A healthy lifestyle can reduce the risk of several cancers, even in those who are genetically predisposed to develop cancer.

scholarly journals Multiomic blood correlates of genetic risk identify presymptomatic disease alterations

2020 ◽  
Vol 117 (35) ◽  
pp. 21813-21820
Author(s):  
Michael Wainberg ◽  
Andrew T. Magis ◽  
John C. Earls ◽  
Jennifer C. Lovejoy ◽  
Nasa Sinnott-Armstrong ◽  
...  
Keyword(s):  
Biological Networks ◽  
Genetic Risk ◽  
Complex Traits ◽  
Clinical Laboratory ◽  
Clinical Symptoms ◽  
Association Studies ◽  
Risk Scores ◽  
Genome Wide Association Studies ◽  
High Genetic Risk ◽  
Genetic And Environmental Factors

Transitions from health to disease are characterized by dysregulation of biological networks under the influence of genetic and environmental factors, often over the course of years to decades before clinical symptoms appear. Understanding these dynamics has important implications for preventive medicine. However, progress has been hindered both by the difficulty of identifying individuals who will eventually go on to develop a particular disease and by the inaccessibility of most disease-relevant tissues in living individuals. Here we developed an alternative approach using polygenic risk scores (PRSs) based on genome-wide association studies (GWAS) for 54 diseases and complex traits coupled with multiomic profiling and found that these PRSs were associated with 766 detectable alterations in proteomic, metabolomic, and standard clinical laboratory measurements (clinical labs) from blood plasma across several thousand mostly healthy individuals. We recapitulated a variety of known relationships (e.g., glutamatergic neurotransmission and inflammation with depression, IL-33 with asthma) and found associations directly suggesting therapeutic strategies (e.g., Ω-6 supplementation and IL-13 inhibition for amyotrophic lateral sclerosis) and influences on longevity (leukemia inhibitory factor, ceramides). Analytes altered in high-genetic-risk individuals showed concordant changes in disease cases, supporting the notion that PRS-associated analytes represent presymptomatic disease alterations. Our results provide insights into the molecular pathophysiology of a range of traits and suggest avenues for the prevention of health-to-disease transitions.

scholarly journals Childhood socioeconomic status moderates genetic predisposition for peak smoking

2018 ◽  
Author(s):  
Laura Bierut ◽  
Pietro Biroli ◽  
Titus J. Galama ◽  
Kevin Thom
Keyword(s):  
At Risk ◽  
Socioeconomic Status ◽  
Genetic Predisposition ◽  
Genetic Variants ◽  
Genetic Risk ◽  
Risk Scores ◽  
Low Ses ◽  
High Genetic Risk ◽  
Childhood Socioeconomic Status ◽  
The U.S

AbstractSmoking is the leading cause of preventable disease and death in the U.S., and it is strongly influenced both by genetic predisposition and childhood socioeconomic status (SES). Using genetic variants exhibiting credible and robust associations with smoking, we construct polygenic risk scores (PGS) and evaluate whether childhood SES mediates genetic risk in determining peak-cigarette consumption in adulthood. We find a substantial protective effect of childhood SES for those genetically at risk of smoking: adult smokers who grew up in high-SES households tend to smoke roughly the same amount of cigarettesper day at peak (∼ 23 for low and ∼ 25 for high genetic risk individuals, or about 8%more), while individuals from low-SES backgrounds tend to smoke substantially more ifgenetically at risk (∼ 25 for low and ∼ 32 for high genetic risk individuals, or about 28% more).

scholarly journals Dementia Risk Scores and Their Role in the Implementation of Risk Reduction Guidelines

2022 ◽  
Vol 12 ◽  
Author(s):  
Kaarin J. Anstey ◽  
Lidan Zheng ◽  
Ruth Peters ◽  
Scherazad Kootar ◽  
Mariagnese Barbera ◽  
...  
Keyword(s):  
Risk Reduction ◽  
World Health Organisation ◽  
World Health ◽  
Risk Scores ◽  
Policy And Practice ◽  
Targeted Interventions ◽  
Dementia Risk ◽  
Dementia Prevention ◽  
Wide Range ◽  
Evidence Based Guidelines

Dementia prevention is a global health priority. In 2019, the World Health Organisation published its first evidence-based guidelines on dementia risk reduction. We are now at the stage where we need effective tools and resources to assess dementia risk and implement these guidelines into policy and practice. In this paper we review dementia risk scores as a means to facilitate this process. Specifically, we (a) discuss the rationale for dementia risk assessment, (b) outline some conceptual and methodological issues to consider when reviewing risk scores, (c) evaluate some dementia risk scores that are currently in use, and (d) provide some comments about future directions. A dementia risk score is a weighted composite of risk factors that reflects the likelihood of an individual developing dementia. In general, dementia risks scores have a wide range of implementations and benefits including providing early identification of individuals at high risk, improving risk perception for patients and physicians, and helping health professionals recommend targeted interventions to improve lifestyle habits to decrease dementia risk. A number of risk scores for dementia have been published, and some are widely used in research and clinical trials e.g., CAIDE, ANU-ADRI, and LIBRA. However, there are some methodological concerns and limitations associated with the use of these risk scores and more research is needed to increase their effectiveness and applicability. Overall, we conclude that, while further refinement of risk scores is underway, there is adequate evidence to use these assessments to implement guidelines on dementia risk reduction.

Exercise and dementia prevention

2020 ◽  
Vol 20 (3) ◽  
pp. 234-240 ◽  
Author(s):  
Jane Alty ◽  
Maree Farrow ◽  
Katherine Lawler
Keyword(s):  
Risk Factors ◽  
Physical Inactivity ◽  
Lifestyle Changes ◽  
Current Evidence ◽  
Prevention Strategies ◽  
Neuroprotective Drugs ◽  
Age Related ◽  
Dementia Risk ◽  
Dementia Prevention ◽  
Age Related Cognitive Decline

Ageing, genetic, medical and lifestyle factors contribute to the risk of Alzheimer’s disease and other dementias. Around a third of dementia cases are attributable to modifiable risk factors such as physical inactivity, smoking and hypertension. With the rising prevalence and lack of neuroprotective drugs, there is renewed focus on dementia prevention strategies across the lifespan. Neurologists encounter many people with risk factors for dementia and are frequently asked whether lifestyle changes may help. Exercise has emerged as a key intervention for influencing cognition positively, including reducing the risk of age-related cognitive decline and dementia. This article focuses on the current evidence for physical inactivity as a modifiable dementia risk factor and aims to support neurologists when discussing risk reduction.

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