Utilizing apolipoprotein E genotypes and associated comorbidities for the assessment of the risk for dementia

Hsin Tung; Ching-Heng Lin; Yi-Ming Chen; Wei-Ju Lee; Li-Sheng Chien; Ting-Hsuan Sun; Cai-Sian Liao; Yung-Yang Lin; Tzu-Hung Hsiao

doi:10.3389/fnagi.2022.927656

Utilizing apolipoprotein E genotypes and associated comorbidities for the assessment of the risk for dementia

Front Aging Neurosci. 2022 Dec 12:14:927656. doi: 10.3389/fnagi.2022.927656. eCollection 2022.

Authors

Hsin Tung^{1

2

3

4}, Ching-Heng Lin^{5

6

7

8}, Yi-Ming Chen^{2

5

9}, Wei-Ju Lee^{2

4

10

11

12}, Li-Sheng Chien⁵, Ting-Hsuan Sun⁵, Cai-Sian Liao⁵, Yung-Yang Lin^{1

13

14}, Tzu-Hung Hsiao^{5

15

16

17}

Affiliations

¹ Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
² Department of Post-Baccalaureate Medicine, National Chung Hsing University, Taichung, Taiwan.
³ Center of Faculty Development, Taichung Veterans General Hospital, Taichung, Taiwan.
⁴ Neurological Institute, Taichung Veterans General Hospital, Taichung, Taiwan.
⁵ Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
⁶ Department of Public Health, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan.
⁷ Institute of Public Health and Community Medicine Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.
⁸ Department of Industrial Engineering and Enterprise Information, Tunghai University, Taichung, Taiwan.
⁹ Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
¹⁰ Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
¹¹ Dementia Center, Taichung Veterans General Hospital, Taichung, Taiwan.
¹² Center for Geriatrics and Gerontology, Taichung Veterans General Hospital, Taichung, Taiwan.
¹³ Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei, Taiwan.
¹⁴ Department of Critical Care Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
¹⁵ Institute of Genomics and Bioinformatics, National Chung Hsing University, Taichung, Taiwan.
¹⁶ Research Center for Biomedical Science and Engineering, National Tsing Hua University, Hsinchu, Taiwan.
¹⁷ Department of Public Health, Fu Jen Catholic University, New Taipei City, Taiwan.

Abstract

Introduction: Dementia is associated with many comorbidities while being related to Apolipoprotein E (ApoE) polymorphism. However, it is unclear how these clinical illnesses and genetic factors modify the dementia risk.

Methods: We enrolled 600 dementia cases and 6000 matched non-dementia controls, with identified ApoE genotype (ε4/ε4, ε4/ε3, and ε3/ε3). Eight comorbidities were selected by medical records, and counted if occurring within 3 years of enrollment.

Results: The dementia group had a higher ratio of carrying ε4 allele and prevalence of comorbidities than the non-dementia group. Homozygous ε4 carriers presented the broken line of dementia risk with the peak age at 65-75 years and odds ratio (OR) up to 6.6. The risk only emerged after 65 years of age in ε3/ε4 subjects with OR around 1.6-2.4 when aged > 75 years. Cerebrovascular accident (CVA) is the commonest comorbidity (14.6%). CVA, sleep disorder, and functional gastrointestinal disorders remained as significant risk comorbidities for dementia throughout all age groups (OR = 1.7-5.0). When functional gastrointestinal disorder and ε4 allele both occurred, the dementia risk exceeded the summation of individual risks (OR = 3.7 and 1.9 individually, OR = 6.0 for the combination). Comorbidities could also be predictors of dementia.

Conclusion: Combining the genetic and clinical information, we detected cognitive decline and optimize interventions early when the patients present a specific illness in a particular age and carry a specific ApoE allele. Of comorbidities, functional gastrointestinal disorder is the strongest predicting factor for dementia in ε4 allele carriers.

Keywords: apolipoprotein E (ApoE); cerebrovascular accident (CVA); comorbidity; dementia; functional gastrointestinal disorder.