Leading determinants of incident dementia among individuals with and without the apolipoprotein E ε4 genotype: a retrospective cohort study
Abstract Background Little is known regarding the leading risk factors for dementia/Alzheimer’s disease (AD) in individuals with and without APOE4. The identification of key risk factors for dementia/Alzheimer’s disease (AD) in individuals with and without the APOE4 gene is of significant importance...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-02-01
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| Series: | BMC Neurology |
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| Online Access: | https://doi.org/10.1186/s12883-024-03557-8 |
| _version_ | 1797274229753774080 |
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| author | Siting Ye Eddy Roccati Wei Wang Zhuoting Zhu Katerina Kiburg Yu Huang Xueli Zhang Xiayin Zhang Jiahao Liu Shulin Tang Yijun Hu Zongyuan Ge Honghua Yu Mingguang He Xianwen Shang |
| author_facet | Siting Ye Eddy Roccati Wei Wang Zhuoting Zhu Katerina Kiburg Yu Huang Xueli Zhang Xiayin Zhang Jiahao Liu Shulin Tang Yijun Hu Zongyuan Ge Honghua Yu Mingguang He Xianwen Shang |
| author_sort | Siting Ye |
| collection | DOAJ |
| description | Abstract Background Little is known regarding the leading risk factors for dementia/Alzheimer’s disease (AD) in individuals with and without APOE4. The identification of key risk factors for dementia/Alzheimer’s disease (AD) in individuals with and without the APOE4 gene is of significant importance in global health. Methods Our analysis included 110,354 APOE4 carriers and 220,708 age- and sex-matched controls aged 40–73 years at baseline (between 2006–2010) from UK Biobank. Incident dementia was ascertained using hospital inpatient, or death records until January 2021. Individuals of non-European ancestry were excluded. Furthermore, individuals without medical record linkage were excluded from the analysis. Moderation analysis was tested for 134 individual factors. Results During a median follow-up of 11.9 years, 4,764 cases of incident all-cause dementia and 2065 incident AD cases were documented. Hazard ratios (95% CIs) for all-cause dementia and AD associated with APOE4 were 2.70(2.55–2.85) and 3.72(3.40–4.07), respectively. In APOE4 carriers, the leading risk factors for all-cause dementia included low self-rated overall health, low household income, high multimorbidity risk score, long-term illness, high neutrophil percentage, and high nitrogen dioxide air pollution. In non-APOE4 carriers, the leading risk factors included high multimorbidity risk score, low overall self-rated health, low household income, long-term illness, high microalbumin in urine, high neutrophil count, and low greenspace percentage. Population attributable risk for these individual risk factors combined was 65.1%, and 85.8% in APOE4 and non-APOE4 carriers, respectively. For 20 risk factors including multimorbidity risk score, unhealthy lifestyle habits, and particulate matter air pollutants, their associations with incident dementia were stronger in non-APOE4 carriers. For only 2 risk factors (mother’s history of dementia, low C-reactive protein), their associations with incident all-cause dementia were stronger in APOE4 carriers. Conclusions Our findings provide evidence for personalized preventative approaches to dementia/AD in APOE4 and non-APOE4 carriers. A mother’s history of dementia and low levels of C-reactive protein were more important risk factors of dementia in APOE4 carriers whereas leading risk factors including unhealthy lifestyle habits, multimorbidity risk score, inflammation and immune-related markers were more predictive of dementia in non-APOE4 carriers. |
| first_indexed | 2024-03-07T14:55:24Z |
| format | Article |
| id | doaj.art-50c7bb1bfb874c28956750dc36ae0e9e |
| institution | Directory Open Access Journal |
| issn | 1471-2377 |
| language | English |
| last_indexed | 2024-03-07T14:55:24Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Neurology |
| spelling | doaj.art-50c7bb1bfb874c28956750dc36ae0e9e2024-03-05T19:28:14ZengBMCBMC Neurology1471-23772024-02-0124111310.1186/s12883-024-03557-8Leading determinants of incident dementia among individuals with and without the apolipoprotein E ε4 genotype: a retrospective cohort studySiting Ye0Eddy Roccati1Wei Wang2Zhuoting Zhu3Katerina Kiburg4Yu Huang5Xueli Zhang6Xiayin Zhang7Jiahao Liu8Shulin Tang9Yijun Hu10Zongyuan Ge11Honghua Yu12Mingguang He13Xianwen Shang14The Second Clinical College of Guangzhou University of Chinese MedicineWicking Dementia Research and Education Centre, University of TasmaniaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen UniversityGuangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical UniversityCentre for Eye Research AustraliaGuangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical UniversityGuangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical UniversityGuangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical UniversityCentre for Eye Research AustraliaGuangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical UniversityGuangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical UniversityMonash e-Research Center, Faculty of Engineering, Airdoc Research, Nvidia AI Technology Research Center, Monash UniversityGuangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical UniversityGuangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical UniversityGuangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical UniversityAbstract Background Little is known regarding the leading risk factors for dementia/Alzheimer’s disease (AD) in individuals with and without APOE4. The identification of key risk factors for dementia/Alzheimer’s disease (AD) in individuals with and without the APOE4 gene is of significant importance in global health. Methods Our analysis included 110,354 APOE4 carriers and 220,708 age- and sex-matched controls aged 40–73 years at baseline (between 2006–2010) from UK Biobank. Incident dementia was ascertained using hospital inpatient, or death records until January 2021. Individuals of non-European ancestry were excluded. Furthermore, individuals without medical record linkage were excluded from the analysis. Moderation analysis was tested for 134 individual factors. Results During a median follow-up of 11.9 years, 4,764 cases of incident all-cause dementia and 2065 incident AD cases were documented. Hazard ratios (95% CIs) for all-cause dementia and AD associated with APOE4 were 2.70(2.55–2.85) and 3.72(3.40–4.07), respectively. In APOE4 carriers, the leading risk factors for all-cause dementia included low self-rated overall health, low household income, high multimorbidity risk score, long-term illness, high neutrophil percentage, and high nitrogen dioxide air pollution. In non-APOE4 carriers, the leading risk factors included high multimorbidity risk score, low overall self-rated health, low household income, long-term illness, high microalbumin in urine, high neutrophil count, and low greenspace percentage. Population attributable risk for these individual risk factors combined was 65.1%, and 85.8% in APOE4 and non-APOE4 carriers, respectively. For 20 risk factors including multimorbidity risk score, unhealthy lifestyle habits, and particulate matter air pollutants, their associations with incident dementia were stronger in non-APOE4 carriers. For only 2 risk factors (mother’s history of dementia, low C-reactive protein), their associations with incident all-cause dementia were stronger in APOE4 carriers. Conclusions Our findings provide evidence for personalized preventative approaches to dementia/AD in APOE4 and non-APOE4 carriers. A mother’s history of dementia and low levels of C-reactive protein were more important risk factors of dementia in APOE4 carriers whereas leading risk factors including unhealthy lifestyle habits, multimorbidity risk score, inflammation and immune-related markers were more predictive of dementia in non-APOE4 carriers.https://doi.org/10.1186/s12883-024-03557-8DementiaAlzheimer diseaseApolipoproteins ELife styleMultimorbidity risk scoreBiomarker |
| spellingShingle | Siting Ye Eddy Roccati Wei Wang Zhuoting Zhu Katerina Kiburg Yu Huang Xueli Zhang Xiayin Zhang Jiahao Liu Shulin Tang Yijun Hu Zongyuan Ge Honghua Yu Mingguang He Xianwen Shang Leading determinants of incident dementia among individuals with and without the apolipoprotein E ε4 genotype: a retrospective cohort study BMC Neurology Dementia Alzheimer disease Apolipoproteins E Life style Multimorbidity risk score Biomarker |
| title | Leading determinants of incident dementia among individuals with and without the apolipoprotein E ε4 genotype: a retrospective cohort study |
| title_full | Leading determinants of incident dementia among individuals with and without the apolipoprotein E ε4 genotype: a retrospective cohort study |
| title_fullStr | Leading determinants of incident dementia among individuals with and without the apolipoprotein E ε4 genotype: a retrospective cohort study |
| title_full_unstemmed | Leading determinants of incident dementia among individuals with and without the apolipoprotein E ε4 genotype: a retrospective cohort study |
| title_short | Leading determinants of incident dementia among individuals with and without the apolipoprotein E ε4 genotype: a retrospective cohort study |
| title_sort | leading determinants of incident dementia among individuals with and without the apolipoprotein e ε4 genotype a retrospective cohort study |
| topic | Dementia Alzheimer disease Apolipoproteins E Life style Multimorbidity risk score Biomarker |
| url | https://doi.org/10.1186/s12883-024-03557-8 |
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