Associations of Vascular Risk Factors, APOE and TOMM40 Polymorphisms With Cognitive Function in Dementia-Free Chinese Older Adults: A Community-Based Study

Objective: The associations of vascular risk factors (VRFs), apolipoprotein E (APOE), and translocase of outer mitochondrial membrane 40 (TOMM40) with cognitive function have been investigated mostly in western societies. In the present study, we sought to examine the associations of VRFs [i.e., current smoking, current drinking, physical inactivity, obesity, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), diabetes, and hypertension] and variants located in APOE (ε2/3/4) and TOMM40 (rs2075650) with global cognitive function in Chinese older adults, with a focus on their potential interactions.Methods: This is a cross-sectional study that included 422 permanent residents (mean age 69.2 years, 54.3% female) living in Beijing, who were free of dementia. Data were collected through interviews, clinical examinations, and laboratory tests. The two genetic polymorphisms were genotyped, and participants were dichotomized as carriers vs. non-carriers of APOE ε4 or TOMM40 G. Global cognitive function was assessed with the Mini-Mental State Examination (MMSE). Data were analyzed with multivariable linear regression models.Results: Physical inactivity and diabetes were independently associated with a lower MMSE score (all p < 0.05). When four putative VRFs (i.e., current smoking, physical inactivity, high LDL-C, and diabetes) were aggregated, an increasing number of having these factors was associated with a decreasing MMSE score in a dose–response manner (p = 0.001). TOMM40 polymorphisms, independent of the APOE ε4 allele, interacted with aggregated VRFs to influence cognitive performance, such that having one or more of these VRFs was particularly detrimental to the cognition of TOMM40 carriers. Further analyses revealed interactions of the TOMM40 polymorphism with (i) physical inactivity and (ii) diabetes, such that having either physical inactivity or diabetes in combination with carrying a TOMM40 G allele, compared to having neither, was significantly associated with a markedly lower MMSE score (all p < 0.05).Conclusion: This study provides some evidence supporting the association of vascular risk factors with poor cognitive performance among dementia-free Chinese older adults and further revealed their interactions with the TOMM40 polymorphism. The results underscore the vulnerability of global cognitive function to VRFs, which could be reinforced by carrying the TOMM40 rs2075650 G allele. These findings have potential implications for developing tailored intervention programs to maintain cognitive function.

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Associations of vascular risk factors, APOE ɛ4 allele, and TOMM40 G allele with cognitive function in Chinese older adults: a community-based study

10.21203/rs.3.rs-21163/v1 ◽

2020 ◽

Author(s):

Wenjun Gui ◽

Chengxuan Qiu ◽

Juan Li

Keyword(s):

Risk Factors ◽

Cognitive Function ◽

Physical Inactivity ◽

Mmse Score ◽

Vascular Risk ◽

Chinese Older Adults ◽

Apoe Ε4 ◽

Global Cognitive Function ◽

Ε4 Allele ◽

E4 Allele

Abstract Background : The associations of vascular risk factors (VRFs) , apolipoprotein E (APOE) ɛ4 allele, and translocase of outer mitochondrial membrane 40 (TOMM40) G allele with cognitive function have been investigated mostly in western societies. In the present study, we sought to examine the associations of VRFs, APOE ε4 allele, and TMM40 G allele (rs2075650) with global cognitive function among Chinese older adults, with a focus on potential interactions between VRFs and the susceptibility genes. Methods : This is a cross-sectional study that included 422 participants (mean age 69.2 years, 54.3% female) in the China Longitudinal Ageing Study , who were free of dementia. Data were collected through interviews, clinical examinations, and laboratory tests. The clustering of multiple VRFs was scored by counting the number of VRFs potentially related to cognitive function. Global cognitive function was assessed with the Mini-Mental State Examination (MMSE). Data were analyzed with multiple general linear regression models. Results : Physical inactivity and diabetes were independently associated with performance lower MMSE score ( p <0.05). Moreover, physical inactivity interacted with APOE ε4 and TOMM40 G allele (rs2075650), and diabetes interacted with TOM40 G allele to affect cognitive function, such that having physical inactivity in combination with either APOE ε4 allele or TOMM40 G allele, or having diabetes and TOMM40 G allele, compared to having neither, was significantly associated with markedly lower MMSE scores ( p <0.05). Finally, when four modifiable VRFs (i.e., current smoking, physical inactivity, high LDL-C, and diabetes) were aggregated, an increasing number of having these factors was associated with a decreasing MMSE score in a dose-response manner ( p for trend<0.05). Conclusion : Some VRFs (e.g., physical inactivity and diabetes), when concurrently occurring with APOE ε4 or TOMM40 G allele, are associated with substantially poor performance in global cognitive function among the Chinese elderly .

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P2-461: ASSOCIATIONS OF VASCULAR RISK FACTORS AND SUSCEPTIBILITY GENES WITH COGNITIVE FUNCTION IN CHINESE OLDER ADULTS: A COMMUNITY-BASED STUDY

Alzheimer s & Dementia ◽

10.1016/j.jalz.2019.06.2868 ◽

2019 ◽

Vol 15 ◽

pp. P793-P793

Author(s):

Juan Li ◽

Wenjun Gui ◽

Chengxuan Qiu

Keyword(s):

Risk Factors ◽

Older Adults ◽

Cognitive Function ◽

Susceptibility Genes ◽

Vascular Risk Factors ◽

Vascular Risk ◽

Community Based ◽

Chinese Older Adults

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Associations between vascular risk factors and subsequent Alzheimer’s disease in older adults

Alzheimer s Research & Therapy ◽

10.1186/s13195-020-00690-7 ◽

2020 ◽

Vol 12 (1) ◽

Author(s):

Hyewon Lee ◽

Kiwon Kim ◽

Yeong Chan Lee ◽

Soyeon Kim ◽

Hong-Hee Won ◽

...

Keyword(s):

Risk Factors ◽

Alzheimer’S Disease ◽

Blood Pressure ◽

Older Adults ◽

Alzheimer's Disease ◽

Clinical Guidelines ◽

Density Lipoprotein ◽

Vascular Risk Factors ◽

Lipoprotein Cholesterol ◽

Vascular Risk

Abstract Background The clinical guidelines related to the primary prevention of Alzheimer’s disease (AD) have focused on the management of vascular risk factors. However, the link between vascular risk factors and AD in older adults remains unclear. This study aimed to determine the association between vascular risk factors and subsequent AD in 178,586 older adults (age ≥ 65 years). Methods Participants were recruited from 2009 through 2010 and followed up for 6 years. We assessed various vascular risk factors (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], triglycerides [TG], fasting glucose [FG], systolic blood pressure [SBP], diastolic blood pressure [DBP], pulse pressure [PP], and body mass index [BMI]) and their association with AD incidence, categorizing each vascular factor using current clinical guidelines. Results AD was observed in 6.0% of participants at follow-up. All lipid profiles (TC, LDL-C, HDL-C and TG) were positively associated with the risk of AD. SBP and PP were in negative associations with AD, and DBP was positively associated with AD. BMI exhibited a negative association with AD incidence. We found no significant association between FG and AD risk. The sex difference was observed to have effects on vascular risk factors. Conclusions In this study, we comprehensively investigated the association between eight vascular risk factors and the risk of incident AD. Our findings suggest that multiple vascular risk factors are related to the development of AD in older adults. These results can help inform future guidelines for reducing AD risk.

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Associations between vascular risk factors and subsequent Alzheimer’s disease in older adults

10.21203/rs.3.rs-22762/v1 ◽

2020 ◽

Author(s):

Hyewon Lee ◽

Kiwon Kim ◽

Yeong Chan Lee ◽

Soyeon Kim ◽

Hong-Hee Won ◽

...

Keyword(s):

Risk Factors ◽

Alzheimer’S Disease ◽

Blood Pressure ◽

Older Adults ◽

Alzheimer's Disease ◽

Clinical Guidelines ◽

Density Lipoprotein ◽

Vascular Risk Factors ◽

Lipoprotein Cholesterol ◽

Vascular Risk

Abstract Background: The clinical guidelines related to the primary prevention of Alzheimer’s disease (AD) have focused on the management of vascular risk factors. However, the link between vascular risk factors and AD in older adults remains unclear. This study aimed to determine the association between vascular risk factors and subsequent AD in 178,586 older adults (age: ≥65 years).Methods: Participants were recruited from 2009 through 2010 and followed up for 6 years. We assessed various vascular risk factors (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], triglycerides [TG], fasting glucose [FG], systolic blood pressure [SBP], diastolic blood pressure [DBP], pulse pressure [PP] and body mass index [BMI]) and their association with AD incidence, categorizing each vascular factor using current clinical guidelines.Results: AD was observed in 6.0% of participants at follow-up. All lipid profiles (TC, LDL-C, HDL-C, TG) were positively associated with the risk of AD. SBP and PP were in negative associations with AD, and DBP was positively associated with AD. BMI exhibited a negative association with AD incidence. We found no significant association between FG and AD risk. The sex difference was observed to have effects on vascular risk factors.Conclusions: In this study, we comprehensively investigated the association between eight vascular risk factors and the risk of incident AD. Our findings suggest that multiple vascular risk factors are related to the development of AD in older adults. These results can help inform future guidelines for reducing AD risk.

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Associations between vascular risk factors and subsequent Alzheimer’s disease in older adults

10.21203/rs.3.rs-22762/v2 ◽

2020 ◽

Author(s):

Hyewon Lee ◽

Kiwon Kim ◽

Yeong Chan Lee ◽

Soyeon Kim ◽

Hong-Hee Won ◽

...

Keyword(s):

Risk Factors ◽

Alzheimer’S Disease ◽

Blood Pressure ◽

Older Adults ◽

Alzheimer's Disease ◽

Clinical Guidelines ◽

Density Lipoprotein ◽

Vascular Risk Factors ◽

Lipoprotein Cholesterol ◽

Vascular Risk

Abstract Background: The clinical guidelines related to the primary prevention of Alzheimer’s disease (AD) have focused on the management of vascular risk factors. However, the link between vascular risk factors and AD in older adults remains unclear. This study aimed to determine the association between vascular risk factors and subsequent AD in 178,586 older adults (age: ≥65 years). Methods: Participants were recruited from 2009 through 2010 and followed up for 6 years. We assessed various vascular risk factors (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], triglycerides [TG], fasting glucose [FG], systolic blood pressure [SBP], diastolic blood pressure [DBP], pulse pressure [PP] and body mass index [BMI]) and their association with AD incidence, categorizing each vascular factor using current clinical guidelines. Results: AD was observed in 6.0% of participants at follow-up. All lipid profiles (TC, LDL-C, HDL-C, TG) were positively associated with the risk of AD. SBP and PP were in negative associations with AD, and DBP was positively associated with AD. BMI exhibited a negative association with AD incidence. We found no significant association between FG and AD risk. The sex difference was observed to have effects on vascular risk factors.Conclusions: In this study, we comprehensively investigated the association between eight vascular risk factors and the risk of incident AD. Our findings suggest that multiple vascular risk factors are related to the development of AD in older adults. These results can help inform future guidelines for reducing AD risk.

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