scholarly journals Polygenic risk score for Alzheimer’s disease and trajectories of cardiometabolic risk factors in children

2019 ◽  
Author(s):  
Roxanna S Korologou-Linden ◽  
Linda O’Keeffe ◽  
Laura D Howe ◽  
George Davey Smith ◽  
Hannah Jones ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Genetic Variants ◽  
Cardiometabolic Risk ◽  
Cardiometabolic Risk Factors ◽  
Childhood And Adolescence ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Cardiometabolic Factors

AbstractINTRODUCTIONCardiometabolic factors are implicated in the aetiology of Alzheimer’s disease and may lie on the pathways linking genetic variants to Alzheimer’s disease across the life course. We examined whether polygenic risk scores (PRS) were associated with cardiometabolic health indicators through childhood and adolescence.METHODSIn 7,977 participants from the Avon Longitudinal Study of Parents and Children, we tested whether a PRS for Alzheimer’s disease was associated with trajectories of cardiometabolic risk factors. We examined trajectories for height 1-18 years; lean and fat mass 9-18 years; systolic and diastolic blood pressure 7-18 years; glucose and C-reactive protein 9-18 years; insulin 10-18 years; high and low-density lipoproteins and triglycerides birth-18 years. We also examined birthweight, interleukin-6 (IL-6) at age 9 years and physical activity at ages 11, 12, and 15 years.RESULTSNo consistent associations were observed between the PRS excluding genetic variants in the apolipoprotein E (ApoE) gene region and cardiometabolic factors trajectories across childhood and adolescence.CONCLUSIONWe did not detect evidence to suggest that the PRS for Alzheimer’s disease acts through childhood and adolescent cardiometabolic risk factors. Further studies should examine whether these associations emerge later in adulthood when variation in cardiometabolic risk factors is likely to be greater.

scholarly journals Polygenic risk score for Alzheimer’s disease and trajectories of cardiometabolic risk factors in children

2019 ◽  
Vol 4 ◽  
pp. 125 ◽  
Author(s):  
Roxanna Korologou-Linden ◽  
Linda O'Keeffe ◽  
Laura D. Howe ◽  
George Davey-Smith ◽  
Hannah J. Jones ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Genetic Variants ◽  
Cardiometabolic Risk ◽  
Cardiometabolic Risk Factors ◽  
Childhood And Adolescence ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Cardiometabolic Factors

Introduction: Cardiometabolic factors are implicated in the aetiology of Alzheimer’s disease and may lie on the pathways linking genetic variants to Alzheimer’s disease across the life course. We examined whether polygenic risk scores (PRS) were associated with cardiometabolic health indicators through childhood and adolescence. Methods: In 7,977 participants from the Avon Longitudinal Study of Parents and Children, we tested whether a PRS for Alzheimer’s disease was associated with trajectories of cardiometabolic risk factors. We examined trajectories for height at 1-18 years; lean and fat mass at 9-18 years; systolic and diastolic blood pressure at 7-18 years; glucose and C-reactive protein at 9-18 years; insulin at 10-18 years; and high and low-density lipoproteins and triglycerides birth at 18 years. We also examined birthweight and interleukin-6 (IL-6) at age 9 years and physical activity at ages 11, 12, and 15 years. Results: No consistent associations were observed between the PRS excluding genetic variants in the apolipoprotein E gene region and cardiometabolic factors trajectories across childhood and adolescence. Conclusions: We did not detect evidence to suggest that the PRS for Alzheimer’s disease acts through childhood and adolescent cardiometabolic risk factors. Further studies should examine whether these associations emerge later in adulthood when variation in cardiometabolic risk factors is likely to be greater.

scholarly journals Cardiometabolic risk factors predict executive function scores in high-risk individuals

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 651-651
Author(s):  
Joshua Gills ◽  
Megan Jones ◽  
Anthony Campitelli ◽  
Sally Paulson ◽  
Erica Madero ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Blood Pressure ◽  
Alzheimer's Disease ◽  
Executive Function ◽  
High Risk ◽  
Cardiometabolic Risk ◽  
Density Lipoprotein ◽  
Cardiometabolic Risk Factors ◽  
Walking Test

Abstract Alzheimer’s disease (AD) is expected to triple by 2050, affecting 16 million Americans. As a result, it is essential to combat this alarming increase in cognitive impairment through early detection. Cardiometabolic risk factors have shown to be associated with higher risk of AD. The purpose of this study was to determine if cardiometabolic risk factors could predict executive function scores in a high-risk population. Fifty (60.9±8.8 years) high-risk adults (classified by the Australian National University Alzheimer’s Disease Risk Index) were enrolled in this study. Participants completed a 6-minute walking test, venous blood draw, blood pressure measurement, and the digit coding symbol test (DCS). Results were examined through a multiple linear regression with DCS as the dependent variable and age, sex, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), glucose, 6-minute walking test, systolic blood pressure (SBP), and diastolic blood pressure (DBP) as predictor variables. The model explained 42% of the variance of DCS (p = .04) with SBP (45%; p = .003) as a significant predictor. LDL (p = .087) and DBP (p = .123) accounted for 24% and 22% of the variance for this model, respectively. These results suggest cardiometabolic risk factors predict executive function values in high-risk individuals. Higher SBP was significantly associated with lower DCS scores indicating SBP as a valuable tool for practitioners when evaluating cognitive decline. Further research should expand sample size and track values longitudinally to substantiate these claims.

scholarly journals Genetic risk for Alzheimer's disease influences neuropathology via multiple biological pathways

2020 ◽  
Author(s):  
Eilis Hannon ◽  
Gemma L Shireby ◽  
Keeley Brookes ◽  
Johannes Attems ◽  
Rebecca Sims ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Genetic Variants ◽  
Genetic Risk ◽  
Cognitive Assessment ◽  
Apoe Genotype ◽  
Amyloid Plaques ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Β Amyloid

Alzheimer's disease is a highly heritable, common neurodegenerative disease characterised neuropathologically by the accumulation of β-amyloid plaques and tau-containing neurofibrillary tangles. In addition to the well-established risk associated with the APOE locus, there has been considerable success in identifying additional genetic variants associated with Alzheimer's disease. Major challenges in understanding how genetic risk influences the development of Alzheimer's disease are clinical and neuropathological heterogeneity, and the high level of accompanying comorbidities. We report a multimodal analysis integrating longitudinal clinical and cognitive assessment with neuropathological data collected as part of the Brains for Dementia Research (BDR) study to understand how genetic risk factors for Alzheimer's disease influence the development of neuropathology and clinical performance. 693 donors in the BDR cohort with genetic data, semi-quantitative neuropathology measurements, cognitive assessments and established diagnostic criteria were included in this study. We tested the association of APOE genotype and Alzheimer's disease polygenic risk score - a quantitative measure of genetic burden - with survival, four common neuropathological features in Alzheimer's disease brains (neurofibrillary tangles, β-amyloid plaques, Lewy bodies and TDP-43 proteinopathy), clinical status (clinical dementia rating) and cognitive performance (Mini-Mental State Exam, Montreal Cognitive Assessment). The APOE ϵ4 allele was significantly associated with younger age of death in the BDR cohort. Our analyses of neuropathology highlighted two independent pathways from APOE ϵ4, one where β-amyloid accumulation mediates the development of tauopathy, and a second characterized by direct effects on tauopathy independent of β-amyloidosis. Although we also detected association between APOE ϵ4 and dementia status and cognitive performance, these were all mediated by tauopathy, highlighting that they are a consequence of the neuropathological changes. Analyses of polygenic risk score identified associations with tauopathy and β-amyloidosis, which appeared to have both shared and unique contributions, suggesting that different genetic variants associated with Alzheimer's disease affect different features of neuropathology to different degrees. Taken together, our results provide insight into how genetic risk for Alzheimer's disease influences both the clinical and pathological features of dementia, increasing our understanding about the interplay between APOE genotype and other genetic risk factors.

P4-240: Using polygenic risk score to predict Alzheimer's disease

2015 ◽  
Vol 11 (7S_Part_19) ◽  
pp. P872-P872 ◽  
Author(s):  
Valentina Escott-Price ◽  
Rebecca Sims ◽  
Denise Harold ◽  
Maria Vronskaya ◽  
Peter Holmans ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Score ◽  
Polygenic Risk Score ◽  
Polygenic Risk
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