Nutritional factors and cognitive function in chinese older adults

NUTRITIONAL FACTORS AND COGNITIVE FUNCTION IN CHINESE OLDER ADULTS FENG LEI (BACHELOR OF MEDICINE) A THESIS SUBMITTED FOR THE DEGREE OF DOCTOR OF PHILOSOPHY DEPARTMENT OF PSYCHOLOGICAL MEDICINE NATIONAL UNIVERSITY OF SINGAPORE December, 2008 ACKNOWLEDGEMENT I am most grateful to Associate Professor Ng Tze Pin. As a knowledgeable and dedicated supervisor, he guided me through this exciting but hard journey of research and study. It is impossible for me to complete this PhD thesis without his expertise, encouragements, and concrete helps. I would like to express my sincere gratitude to my Co-Supervisor Prof. Kua Ee Heok, for his wise counsel and full supports. I benefited a lot from him, especially on geriatric psychiatry and Structured clinical psychiatric interview. I wish to give cordial thanks to all the team members of the Singapore Longitudinal Ageing Study (SLAS, NUS), the staffs in the Department of Psychological Medicine (PCM, NUS), the lecturers in the School Graduate Programme of Yoog Loo Lin School of Medicine (SOM, NUS), and the lecturers in the Centre for English Language Communication (CELC, NUS), for all your helps, supports, and instructions in the past four and half years. I would express my special thanks to Ms.Hin-Hiang Susan, for her heartening words, encouragements, and helps, especially during my low tide time. Finally, I would thanks to National University of Singapore, for awarding me the Research Scholarship, and thus make all those research works possible. I wish I will be able to contribute more to Singapore as well as the science world when I continue my academic life in this small but promising country. I CONTENTS ACKNOWLEDGEMENT ABSTRACT I V LIST OF TABLES VII LIST OF FIGURES VIII LIST OF ABBRIVIATIONS IX LIST OF APPENDICES XI 1. INTRODUCTION 1.1 Fast ageing population and its impact 1.2 Cognitive function and Cognitive decline in elderly population 1.3 Nutrition as potential modifiable cognitive risk/protective factor 1.4 Objectives of the current study 2. LITERATURE REVIEW 2.1 Nutritional status and Cognitive function 2.1.1 Diet and cognitive function 2.1.2 Albumin and cognitive function 2.1.3 Hemoglobin and cognitive function 2.1.4 Body mass index and cognitive function 2.2 Homocysteine, folate, vitamin B-12 and Cognitive function 17 2.2.1 Case-control studies 2.2.2 Cross-sectional studies 2.2.3 Cohort studies II 2.2.4 Clinical trials 2.3 Nutrition and cognitive function: the role of Apolipoprotein E Genotype 23 3. METHODS 3.1 Participants 25 3.2 Questionnaire interview and clinical measurements 29 3.2.1 Demographic data and substances use 3.2.2 Medical conditions and medication 3.2.3 Physical functional status 3.2.4 Global cognitive status 3.2.5 Other questionnaire data 3.2.6 Clinical measurements 3.3 Laboratory measurements 33 3.4 Neuropsychological assessment 34 3.5 Statistical analysis 36 3.5.1 Study I 3.5.2 Study II 3.5.3 Study III 3.5.4 Study IV 4. RESULTS 4.1 Study I 42 4.2 Study II 48 4.3 Study III 53 III 4.4 Study IV 60 5. DISCUSSION 5.1 Study I 64 5.2 Study II 67 5.3 Study III 72 5.4 Study IV 75 6. SUMMARY AND CONCLUSION 80 7. REFERENCES 85 8. LIST OF PUBLICATIONS 93 9. LIST OF CONFERENCE PRESENTATIONS 94 10. APPENDICES 95 IV ABSTRACT Background: Nutritional factors as modifiable cognitive protective/risk factors have been examined in recent years, published findings are inconsistent and/or insufficient. Few data are available for Asian population. Objective: To investigate aspects of the relationship between selected nutritional factors (albumin, hemoglobin, low body mass index, homocysteine, folate, and vitamin B-12), and cognitive performance, cognitive decline, and possible effect modification by Apolipoprotein E (APOE) genotype among Chinese older adults aged 55 and above. Methods: Population based study with both cross-sectional and longitudinal study designs. A group of Chinese older adults (N=2611) were assessed at baseline and were reassessed one to two years later. Cognitive performance was measured by Mini-Mental State Examination both at baseline and follow-up. Weight, height, serum albumin, hemoglobin, serum folate, serum vitamin B-12, plasma total homocysteine, and APOE genotype were measured at baseline. Data collected on confounding variables included cigarette smoking, alcohol consumption, cardiometabloic risk factors, activity of daily living, and depression. A comprehensive neuropsychological test battery was administered on a random subsample (N=841) at baseline. Study I investigated the relationships between body mass index, albumin, hemoglobin and cognitive performance. Study II investigated the effect of serum albumin on cognitive performance and cognitive decline and the effect modification by APOE genotype. Study III investigated the independent effects of folate, vitamin B-12, and homocysteine on specific cognitive functions. Study IV investigated the role of APOE ε4 as a genetic predisposing factor modulating the effect of vitamin B-12 on cognitive performance. V Results: Study I found that low hemoglobin in the bottom quintile (OR, 1.56; 95%CI, 1.00-2.47) and low BMI-with-chronic comorbidity (OR, 1.73; 95%CI, 1.02-2.95) were independently associated with poor cognitive performance (MMSE ≤ 23). Study II showed that decreasing levels of albumin were associated with an increased risk of cognitive impairment (P for trend=0.002), and with cognitive decline (P for trend=0.001). APOE- ε4 modified the association (P for interaction=0.049). Study III showed that homocysteine (log transformed) was inversely associated with performance on Block Design (β = -0.319, P=0.006) and Symbol Digit Modality Test written version (β= 0.129, P=0.031). Folate (log transformed) was significantly associated with Rey Auditory Verbal Learning Test delayed recall (β= 0.139, P=0.010), verbal learning (β= 0.112, P=0.038), percentage of forgetting (β= -0.139, P=0.013) and Categorical Verbal Fluency (β = 0.104, P=0.042). Study IV found that low vitamin B-12 was associated with poorer performance on several cognitive measures in APOE ε4 allele carriers but not in nonAPOE ε4 carriers. The interaction between low vitamin B-12 and APOE ε4 was significant for MMSE (P=0.007), Digit Span backward (P=0.006), and RAVLT immediate recall (P=0.02). Conclusions: Poor nutritional status was associated with poor cognitive performance. Low albumin was independently associated with cognitive decline, and its association was more pronounced in carriers of the APOE-ε4 allele. Folate and homocysteine was independently related with different cognitive domains. Vitamin B-12 was associated with cognitive performance in the presence of APOE ε4. VI LIST OF TABLES Study I Page 1. Prevalence of Risk factors for Cognitive Impairment by Quintiles of Haemoglobin and Albumin and Low BMI-with-chronic comorbidity 43 2. Multiple logistic regression model parameters: albumin, hemoglobin, low BMI, chronic comorbidity and low BMI * chronic comorbidity interaction. 44 3. Odds Ratios (95% CI) of Association of Quintiles of Haemoglobin and Albumin and low BMI-and-Chronic Illness with Cognitive Impairment 46 4. MMSE scores by Albumin, Hemoglobin, BMI and MICS categories in subset of participants with MMSE ≥24 (N=2252) 47 Study II 5. Baseline descriptive characteristics of participants by albumin categories 50 6. Cross-sectional and longitudinal analyses of association of serum albumin level (in tertiles) with cognitive function 51 7. Longitudinal association of serum albumin level (in tertiles) with cognitive decline in participants with MMSE≥24 at baseline 52 Study III 8. Demographic and laboratory test characteristics of study participants 54 9. Cognitive performance of study participants 55 10. Associations between natural log transformed homocysteine, folate, vitamin B-12 and cognitive test scores (model I) 57 11. Associations between natural log transformed homocysteine and cognitive test scores, adjusted for confounding in multivariable models 58 VII 12. Associations between natural log transformed folate and cognitive test scores, adjusted for confounding in multivariable models 59 Study IV 13. Baseline characteristics of the study sample 61 14. Natural log-transformed vitamin B-12, APOE ε4, and cognitive performance 62 15. Low vitamin B-12, APOE ε4 status, and cognitive performance 63 LIST OF FIGURES Figure1. 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Tea consumption and cognitive impairment and decline in older Chinese adults. Am J Clin Nutr. 2008 Jul; 88 (1): 224-231. 4. Ng TP, Niti M, Feng L, Kua EH, Yap KB. Albumin, APOE- ε4 and Cognitive Decline in Community-Dwelling Chinese Older Adults. J Am Geriatr Soc. 2008 Nov 19. [Epub ahead of print] 5. Ng TP, Feng L, Niti M, Kua EH, Yap KB. Folate, Vitamin B-12, Homocysteine and Depressive Symptoms in a Population Sample of Chinese Older Adults. J Am Geriatr Soc. [Accepted for publication] 6. Ng TP, Feng L, Gwee X, Kua EH. Cognitive functioning associated with tea consumption in cognitively well functioning Chinese older adults in the Singapore Longitudinal Ageing Study Cohort. [Submitted] 7. Feng L, Li J, Yap KB, Kua EH, Ng TP. Vitamin B-12, Apolipoprotein E genotype and cognitive performance in community-living older adults: evidence of gene-micronutrient interaction [Submitted] 8. Gao Q, Ng TP, Feng L, Niti M, Kua EH. Omega-3 polyunsaturated fatty acid supplements and cognitive decline: Singapore Longitudinal Aging Studies [drafted] 93 LIST OF CONFERENCE PRESENTATIONS 1. Homocysteine, Folate, Vitamin B-12 and Cognitive Performance in Older Chinese Adults. Podium Session. Society for Geriatric Medicine 8th Scientific Meeting. September 16 -17, 2006. Tan Tock Seng Hospital, Singapore. 2. Vitamin B-12 APOE genotype and Cognitive Performance. Poster Session. Alzheimer's Association Prevention of Dementia conference. June 9-12, 2007. Washington DC, USA 3. Tea Consumption and Cognitive Impairment and Decline. Poster session. 11th International Conference on Alzheimer’s disease. July 26-31, 2008. Chicago, USA. 94 Appendix SLAS Mini-Mental State Examination 95 96 97 98 99 100 [...]... important to find modifiable risk and protective factors for cognitive impairment and decline, in order to prevent cognitive impairment, slow cognitive decline, and delay the onset of dementia This thesis focused on aspects of the relationship between cognitive function, cognitive decline and selected nutritional factors in community-living Chinese older adults, namely albumin, hemoglobin, body mass index,... strategies to maintain and promote cognitive health of the elderly population On the other hand, even small increments in delaying in dementia onset and progression can significantly reduce the global burden of the disease.(2) Therefore, a better understanding of cognitive function and cognitive decline in the elderly population is clearly needed 1.2 Cognitive function and cognitive decline in elderly population... the link between homocysteine, folate, vitamin B-12 and the risk of dementia and cognitive impairment in older adults The thiol-containing amino acid homocysteine links the methionine cycle with the folate cycle and is a sensitive marker for folate and vitamin B-12 deficiency (42, 43) In the methionine cycle, folate 17 and vitamin B-12 are important cofactors for the remethylation of homocysteine to... serum albumin and global cognitive decline (measured by MMSE) and its effect modification by APOE-ε4 among community-living older adults Study III: To examine the independent associations between homocysteine, folate, vitamin B-12 and cognitive performance (measured by MMSE and neuropsychological tests) in community-dwelling elderly Chinese with generally well cognitive (Mini-Mental State Examination... the understanding of the roles of nutritional factors on cognitive functioning in older adults It could provide the evidence 5 and rationale for the design of future clinical trials and the establishment of a prevention and intervention framework for cognitive impairment Furthermore, the introduction of APOE genotype in this study could expand our knowledge of gene-environmental interaction in the development... score equal or above 24) and physical functioning (fully independent on Activities of Daily Living) Study IV: To examine the role of APOE ε4 as a genetic predisposing factor modulating the effect of vitamin B-12 on cognitive function (measured by MMSE and neuropsychological tests) in “cognitively normal” community-dwelling elderly Chinese (no cognitive impairment and cognitive decline) Hopefully, this... mobility, and agerelated physiological and social changes (41), establishing the relationship between cognitive and nutritional status using nutritional markers such as BMI thus has practical significance Body mass index, albumin, and hemoglobin could be examined together to reveal the possible independent effects 2.2 Homocysteine, folate, vitamin B-12 and cognitive function Recent research has investigated... selected nutritional factors: albumin, hemoglobin, low body mass index, folate, homocysteine and vitamin B-12 and potential effect modification by APOE genotype Among these factors, albumin, hemoglobin and 4 body mass index are conventionally considered as clinical markers of general nutritional status while the two B-vitamins are closely associated with homocysteine in one-carbon metabolism Accordingly,... not included in order to preserve integrity and coherence of the thesis as a whole 7 CHAPTER 2 LITERATURE REVIEW The literature review focuses on clinical and epidemiological studies that are related to this thesis 2.1 Nutritional status and cognitive function In the past, both overall dietary intake and conventional clinical markers of nutritional status (albumin, hemoglobin and body mass index) have... important factors (e.g defective dentition, gastrointestinal maldigestion and malabsorption, food-drug interactions) have not been taken into account For that reason, biochemical or anthropometric markers have been utilized to represent nutritional status in other studies As such, literatures on albumin, hemoglobin and body mass index are reviewed in the following sections 2.1.2 Albumin and cognitive function . 2.1 Nutritional status and Cognitive function 8 2.1.1 Diet and cognitive function 2.1.2 Albumin and cognitive function 2.1.3 Hemoglobin and cognitive function 2.1.4 Body mass index and cognitive. between cognitive function, cognitive decline and selected nutritional factors in community-living Chinese older adults, namely albumin, hemoglobin, body mass index, homocysteine, folate, and vitamin. investigate aspects of the relationship between selected nutritional factors (albumin, hemoglobin, low body mass index, homocysteine, folate, and vitamin B-12), and cognitive performance, cognitive