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Absolute 10-year risk of dementia by age, sex and APOE genotype: a population-based cohort study.

ABSTRACT: BACKGROUND:Dementia is a major cause of disability, and risk-factor reduction may have the potential to delay or prevent the disease. Our aim was to determine the absolute 10-year risk of dementia, by age, sex and apolipoprotein E (APOE) genotype. METHODS:We obtained data from the Copenhagen General Population Study (from 2003 to 2014) and the Copenhagen City Heart Study (from 1991 to 1994 and 2001 to 2003). Participants underwent a questionnaire, physical examination and blood sampling at baseline. Diagnoses of dementia and cerebrovascular disease were obtained from the Danish National Patient Registry up to Nov. 10, 2014. RESULTS:Among 104 537 individuals, the absolute 10-year risk of Alzheimer disease in 3017 women and men who were carriers of the APOE ?44 genotype was, respectively, 7% and 6% at age 60-69 years, 16% and 12% at age 70-79 years, and 24% and 19% at age 80 years and older. Corresponding values for all dementia were 10% and 8%, 22% and 19%, and 38% and 33%, respectively. Adjusted hazard ratios (HRs) for all dementia increased by genotype, from genotype ?22 to ?32 to ?33 to ?42 to ?43 to ?44 (p for trend < 0.001). Compared with ?33 carriers, ?44 carriers were more likely to develop Alzheimer disease (adjusted HR 8.74, 95% confidence interval [CI] 7.08-10.79), vascular dementia (adjusted HR 2.87, 95% CI 1.54-5.33), unspecified dementia (adjusted HR 4.68, 95% CI 3.74-5.85) and all dementia (adjusted HR 5.77, 95% CI 4.89-6.81). INTERPRETATION:Age, sex and APOE genotype robustly identify high-risk groups for Alzheimer disease and all dementia. These groups can potentially be targeted for preventive interventions.

SUBMITTER: Rasmussen KL

PROVIDER: S-EPMC6148649 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Absolute 10-year risk of dementia by age, sex and <i>APOE</i> genotype: a population-based cohort study.

Rasmussen Katrine L KL Tybjærg-Hansen Anne A Nordestgaard Børge G BG Frikke-Schmidt Ruth R

CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne 20180901 35

<h4>Background</h4>Dementia is a major cause of disability, and risk-factor reduction may have the potential to delay or prevent the disease. Our aim was to determine the absolute 10-year risk of dementia, by age, sex and apolipoprotein E (<i>APOE</i>) genotype.<h4>Methods</h4>We obtained data from the Copenhagen General Population Study (from 2003 to 2014) and the Copenhagen City Heart Study (from 1991 to 1994 and 2001 to 2003). Participants underwent a questionnaire, physical examination and b ...[more]

PMID: 30181149

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Project description:ImportanceApolipoprotein E (APOE)*2 and APOE*4 are, respectively, the strongest protective and risk-increasing, common genetic variants for late-onset Alzheimer disease (AD), making APOE status highly relevant toward clinical trial design and AD research broadly. The associations of APOE genotypes with AD are modulated by age, sex, race and ethnicity, and ancestry, but these associations remain unclear, particularly among racial and ethnic groups understudied in the AD and genetics research fields.ObjectiveTo assess the stratified associations of APOE genotypes with AD risk across sex, age, race and ethnicity, and global population ancestry.Design, setting, participantsThis genetic association study included case-control, family-based, population-based, and longitudinal AD-related cohorts that recruited referred and volunteer participants. Data were analyzed between March 2022 and April 2023. Genetic data were available from high-density, single-nucleotide variant microarrays, exome microarrays, and whole-exome and whole-genome sequencing. Summary statistics were ascertained from published AD genetic studies.Main outcomes and measuresThe main outcomes were risk for AD (odds ratios [ORs]) and risk of conversion to AD (hazard ratios [HRs]), with 95% CIs. Risk for AD was evaluated through case-control logistic regression analyses. Risk of conversion to AD was evaluated through Cox proportional hazards regression survival analyses.ResultsAmong 68 756 unique individuals, analyses included 21 852 East Asian (demographic data not available), 5738 Hispanic (68.2% female; mean [SD] age, 75.4 [8.8] years), 7145 non-Hispanic Black (hereafter referred to as Black) (70.8% female; mean [SD] age, 78.4 [8.2] years), and 34 021 non-Hispanic White (hereafter referred to as White) (59.3% female; mean [SD] age, 77.0 [9.1] years) individuals. There was a general, stepwise pattern of ORs for APOE*4 genotypes and AD risk across race and ethnicity groups. Odds ratios for APOE*34 and AD risk attenuated following East Asian (OR, 4.54; 95% CI, 3.99-5.17),White (OR, 3.46; 95% CI, 3.27-3.65), Black (OR, 2.18; 95% CI, 1.90-2.49) and Hispanic (OR, 1.90; 95% CI, 1.65-2.18) individuals. Similarly, ORs for APOE*22+23 and AD risk attenuated following White (OR, 0.53, 95% CI, 0.48-0.58), Black (OR, 0.69, 95% CI, 0.57-0.84), and Hispanic (OR, 0.89; 95% CI, 0.72-1.10) individuals, with no association for Hispanic individuals. Deviating from the global pattern of ORs, APOE*22+23 was not associated with AD risk in East Asian individuals (OR, 0.97; 95% CI, 0.77-1.23). Global population ancestry could not explain why Hispanic individuals showed APOE associations with less pronounced AD risk compared with Black and White individuals. Within Black individuals, decreased global African ancestry or increased global European ancestry showed a pattern of APOE*4 dosage associated with increasing AD risk, but no such pattern was apparent for APOE*2 dosage with AD risk. The sex-by-age-specific interaction effect of APOE*34 among White individuals (higher risk in women) was reproduced but shifted to ages 60 to 70 years (OR, 1.48; 95% CI, 1.10-2.01) and was additionally replicated in a meta-analysis of Black individuals and Hispanic individuals (OR, 1.72; 95% CI, 1.01-2.94).Conclusion and relevanceThrough recent advances in AD-related genetic cohorts, this study provided the largest-to-date overview of the association of APOE with AD risk across age, sex, race and ethnicity, and population ancestry. These novel insights are critical to guide AD clinical trial design and research.

Project description:Background and Purpose- APOE-ε4 genotype is a risk factor for sporadic Alzheimer disease and reduced recovery from brain injury. Since data on APOE genotype and dementia associated with transient ischemic attack/stroke are sparse, we determined the associations in a longitudinal population-based cohort. Methods- All patients with transient ischemic attack or stroke (2002-2012) in a defined population of 92 728 OxVASC (Oxford Vascular Study) had follow-up to 5-years. Pre-event and incident postevent dementia were ascertained through direct patient assessment and follow-up, supplemented by review of hospital/primary care records. Associations between pre- and post-event dementia and APOE genotype (ε4/ε4-homozygous and ε4/ε3-heterozygous versus ε3/ε3) were examined using logistic regression and Cox regression models, respectively, adjusted for age, sex, education, cerebrovascular burden (stroke severity, prior stroke, white matter disease), diabetes mellitus, and dysphasia. Results- Among 1767 genotyped patients (mean/SD age, 73.0/13.0 years, 901 [51%] male, 602 [34%] transient ischemic attack), 1058 (59.9%) were APOE-ε3/ε3, 403 (22.8%) were ε4/ε3 and 30 (1.7%) were ε4-homozygous. Homozygosity was associated with both pre-event (adjusted odds ratio, 5.81 [95% CI, 1.93-17.48]; P=0.002) and postevent dementia (adjusted hazard ratio, 3.64 [95% CI, 1.90-7.00]; P<0.0001). Association with postevent dementia was maintained after further adjustment for baseline cognitive impairment (hazard ratio, 2.41 [95% CI, 1.19-4.89]; P=0.01). There were no associations overall between ε4/ε3 and pre-event dementia (adjusted odds ratio, 1.47 [95% CI, 0.88-2.45]; P=0.14) or postevent dementia (hazard ratio, 1.11 [95% CI, 0.84-1.48]; P=0.47). Conclusions- In patients with transient ischemic attack and stroke, APOE-ε4 homozygosity was associated with both pre- and post-event dementia. Associations were independent of cerebrovascular burden and may be mediated through increased neurodegenerative pathology or vulnerability to injury.

Dataset Information

Absolute 10-year risk of dementia by age, sex and APOE genotype: a population-based cohort study.

Publications

Absolute 10-year risk of dementia by age, sex and <i>APOE</i> genotype: a population-based cohort study.

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