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Genetic predisposition, modifiable-risk-factor profile and long-term dementia risk in the general population

The exact etiology of dementia is still unclear, but both genetic and lifestyle factors are thought to be key drivers of this complex disease. The recognition of familial patterns of dementia has led to the discovery of genetic factors that have a role in the pathogenesis of dementia, including the... Full description

Journal Title: Nature medicine 2019, Vol.25 (9), p.1364-+
Main Author: Licher, Silvan
Other Authors: Ahmad, Shahzad , Comic, Hata , Voortman, Trudy , Leening, Maarten , Ikram, Arfan , Ikram, Kamran
Format: Electronic Article Electronic Article
Language: English
Subjects:
Publisher: United States: Nature Publishing Group
ID: ISSN: 1078-8956
Link: https://www.ncbi.nlm.nih.gov/pubmed/31451782
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recordid: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6739225
title: Genetic predisposition, modifiable-risk-factor profile and long-term dementia risk in the general population
format: Article
creator:
  • Licher, Silvan
  • Ahmad, Shahzad
  • Comic, Hata
  • Voortman, Trudy
  • Leening, Maarten
  • Ikram, Arfan
  • Ikram, Kamran
subjects:
  • Aged
  • Aged, 80 and over
  • Apolipoprotein E
  • Apolipoproteins E - genetics
  • Article
  • Clinical Trials as Topic
  • Cognitive ability
  • Cognitive Dysfunction - epidemiology
  • Cognitive Dysfunction - genetics
  • Cognitive Dysfunction - pathology
  • Dementia
  • Dementia - epidemiology
  • Dementia - genetics
  • Dementia - pathology
  • Dementia disorders
  • Etiology
  • Female
  • Genetic factors
  • Genetic Predisposition to Disease
  • Genotype
  • Genotypes
  • Health risk assessment
  • Humans
  • Life Style
  • Male
  • Middle Aged
  • Pathogenesis
  • Population studies
  • Risk analysis
  • Risk assessment
  • Risk Factors
ispartof: Nature medicine, 2019, Vol.25 (9), p.1364-+
description: The exact etiology of dementia is still unclear, but both genetic and lifestyle factors are thought to be key drivers of this complex disease. The recognition of familial patterns of dementia has led to the discovery of genetic factors that have a role in the pathogenesis of dementia, including the apolipoprotein E (APOE) genotype and a large and still-growing number of genetic variants . Beyond genetic architecture, several modifiable risk factors have been implicated in the development of dementia . Prevention trials of measures to halt or delay cognitive decline are increasingly recruiting older individuals who are genetically predisposed to dementia. However, it remains unclear whether targeted health and lifestyle interventions can attenuate or even offset increased genetic risk. Here, we leverage long-term data on both genetic and modifiable risk factors from 6,352 individuals aged 55 years and older in the population-based Rotterdam Study. In this study, we demonstrate that, in individuals at low and intermediate genetic risk, favorable modifiable-risk profiles are related to a lower risk of dementia compared to unfavorable profiles. In contrast, these protective associations were not found in those at high genetic risk.
language: eng
source:
identifier: ISSN: 1078-8956
fulltext: no_fulltext
issn:
  • 1078-8956
  • 1546-170X
url: Link


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descriptionThe exact etiology of dementia is still unclear, but both genetic and lifestyle factors are thought to be key drivers of this complex disease. The recognition of familial patterns of dementia has led to the discovery of genetic factors that have a role in the pathogenesis of dementia, including the apolipoprotein E (APOE) genotype and a large and still-growing number of genetic variants . Beyond genetic architecture, several modifiable risk factors have been implicated in the development of dementia . Prevention trials of measures to halt or delay cognitive decline are increasingly recruiting older individuals who are genetically predisposed to dementia. However, it remains unclear whether targeted health and lifestyle interventions can attenuate or even offset increased genetic risk. Here, we leverage long-term data on both genetic and modifiable risk factors from 6,352 individuals aged 55 years and older in the population-based Rotterdam Study. In this study, we demonstrate that, in individuals at low and intermediate genetic risk, favorable modifiable-risk profiles are related to a lower risk of dementia compared to unfavorable profiles. In contrast, these protective associations were not found in those at high genetic risk.
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subjectAged ; Aged, 80 and over ; Apolipoprotein E ; Apolipoproteins E - genetics ; Article ; Clinical Trials as Topic ; Cognitive ability ; Cognitive Dysfunction - epidemiology ; Cognitive Dysfunction - genetics ; Cognitive Dysfunction - pathology ; Dementia ; Dementia - epidemiology ; Dementia - genetics ; Dementia - pathology ; Dementia disorders ; Etiology ; Female ; Genetic factors ; Genetic Predisposition to Disease ; Genotype ; Genotypes ; Health risk assessment ; Humans ; Life Style ; Male ; Middle Aged ; Pathogenesis ; Population studies ; Risk analysis ; Risk assessment ; Risk Factors
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abstractThe exact etiology of dementia is still unclear, but both genetic and lifestyle factors are thought to be key drivers of this complex disease. The recognition of familial patterns of dementia has led to the discovery of genetic factors that have a role in the pathogenesis of dementia, including the apolipoprotein E (APOE) genotype and a large and still-growing number of genetic variants . Beyond genetic architecture, several modifiable risk factors have been implicated in the development of dementia . Prevention trials of measures to halt or delay cognitive decline are increasingly recruiting older individuals who are genetically predisposed to dementia. However, it remains unclear whether targeted health and lifestyle interventions can attenuate or even offset increased genetic risk. Here, we leverage long-term data on both genetic and modifiable risk factors from 6,352 individuals aged 55 years and older in the population-based Rotterdam Study. In this study, we demonstrate that, in individuals at low and intermediate genetic risk, favorable modifiable-risk profiles are related to a lower risk of dementia compared to unfavorable profiles. In contrast, these protective associations were not found in those at high genetic risk.
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