Background: The prevalence and incidence of dementia increase dramatically with age. Cognitive impairment is one major symptom of dementia. Older persons increase in our society, which means a big number of people with decreased cognitive function. So it is important to find out risk factors. The amino acid homocysteine may be a risk factor. Objective: The aim was to determine the independent association of homocysteine and cognitive performance in Thai elderly. Design: Concentrations of homocysteine were measured in fasting blood samples of 100 Thais aged 60 - 80 years. Global cognitive function was assessed by using with mini-Mental State Examination score (MMSE), and cognitive functions were assessed by a neuropsychological test battery. The relationship between homocysteine levels and neuropsychological test scores was assessed by multiple linear regression. Results: In the crude model, homocysteine was inversely associated with scores for learning slope test (B = ?0.048, p = 0.042) and verbal pair total test (B = ?0.124, p = 0.032). After adjusting for confounders, no association was found between homocysteine and cognitive impairment. Age (B = ?0.129, p = 0.007) was found to be a significant determinant of decreased learning slope score. Similarly, age (B = ?0.298, p = 0.009) and education (B = 0.267, p = 0.029) were found to be significant determinants of decreased verbal pair total score. Conclusions: In this study, it was found that no association between homocysteine and cognitive impairment in a population of institutionalized subjects. Age and education were more significantly associated with cognitive impairment scores than homocysteine.
The prevalence and incidence of dementia increase dramatically with age. It affects 8% of people age over 65 and more than 60,000 new cases each year in Canada. Alzheimer’s disease accounts more than 50% of dementia cases in Canada [
Studies investigate the relation between homocysteine and cognitive function scores, as shown in
Therefore, it is important to search for modifiable risk factors. The amino acid homocysteine may be such a risk factor [
Homocysteine is metabolized through 2 different pathways (
The 100 subjects in this study were recruited from the Baan Bangkae Social Welfare Development Center for Older Persons, Bangkok and the vicinity. The study was approved by the Medical Ethics Committee of Ramathibodi Hospital, Mahidol University, Bangkok, Thailand, and written informed consent was obtained from all participants. All resident who were aged 60 - 80 years were invited to participate. During a visit, trained interviewers administered a questionnaire covering, among other areas, sociodemographic background, medical history, and medication use. This was followed by 2 visits to the Baan Bangkae Social Welfare Development Center, where subjects underwent clinical examinations, including neuropsychologic testing.
Study | Study population | Study design | Cognitive assessment | Results | Comment |
---|---|---|---|---|---|
Budge et al., 2002 [ | 158 community dwelling people age 60 - 91 yr | Cross section of prospective cohort | CMCOG, MMSE, GDS | Higher tHcy levels associated with lower memory scores per umol/L (OR 1.15, 95% CI 1.10 - 1.27) | OR adjusted for age, sex, serum cystatin C level and systolic blood pressure |
Duthie et al., 2002 [ | 334 community dwelling people who had participated in Scottish Mental Survey of 1932 and 1947 | Cross section | MMSE,NART, RPM, AVLT, WAIS | tHcy levels negatively associated with scores on RPM, WAIS in older cohort with higher tHcy levels (mean 10.9 umol/l, 95% CI 10.1 - 11.5) | Results adjusted for childhood intelligence quotient |
Pins et al., 2002 [ | 1077 people aged 60 - 90 yr in Rotterdam Scan Study | Cross section of prospective cohort | Abbreviated Stroop tesatl Letter-Digit Substitution Task, Verbal fluency test, PPMST, Modified Rey’s test | Patients with tHcy > 14 umol/l had lower scores for global cognitive function (diference-0.20, 95%CI-0.30 - 0.11) | Results adjusted for age, sex, education level, depression, serum creatinine level |
Miller et al., 2003 [ | 1789 community dwelling people aged > 60 yr in Sacramento Area Latino Study on Aging | Cross section of prospective cohort | 3MSE, verbal and visual memory tests, object naming conceptualization and attention span tests | Inverse relation between tHcy levels and scores on 3MSE (p = 0.02), picture association (p = 0.05), verbal attention span (p = 0.04), and recognition tests (p = 0.001), | Multiple linear regression model included folate, cobalamin, age creatinine, sex, education and acculturation |
Ravaglia et al., 2003 [ | 650 community dwelling people aged 65 - 91 yr (mean 73 yr) with normal cognitive function in Conselice Study | Population based study | MMSE | Inverse relation between odds of tHcy level > 15 umol/l and MMSE scores | Results adjusted for age, income, education level, serum creatinine level, serum vitamin B index, active lifestyle, coffee and meat consumption |
Garcia et al., 2004 [ | 281 community dwelling people aged >65 yr | Cross section | Stroop, Mattis DRS, CVLT | Subjects with elevated tHcy levels (>13.9 umol/l) had lower stroop scores than those with normal tHcy levels in univariate analysis (p < 0.05) | Strongest association found between methylcitric acid and cognitive scores |
Dufouil et al., 2003 [ | 1241 people aged >60 yr in Epidemiology of Vascular Aging Study | prospective cohort; 4-yr follow-up | MMSE, Trail Making Test Part B, Digit Symbol Substitution Test from the WAIS, Finger Tapping Test | Odds of cognitive decline 2.8 (95% CI 1.2 - 6.2) in patients with tHcy level > 15 umol/l | OR adjusted for age, sex, education level, baseline cognition, BMI, alcohol consumption, smoking, hypertension, hypercholesterolemia, Glycemix status, history of vascular disease, and folate and B12 levels |
Kalmijn et al., 1999 [ | 702 community dwelling people aged > 55 yr in Rotterdam Study | prospective cohort; mean follow-up 2.7 yr | MMSE | No association between tHcy and cognitive impairment (highest v. lowest tertile, OR 0.91, 95% CI 0.52 - 1.58) | OR adjusted for age, education level, and baseline MMSE score |
Ravaglia et al., 2000 [ | 54 people aged > 65 yr in Conselice Study | Cross section of prospective cohort | MMSE, clock drawing test, prose memory test, Corsi block tapping task, Mental Deterioration Battery | No association between tHcy and cognitive test scores | Results adjusted for age, sex, education level, smoking status, alcohol or coffee consumption, and previous cardiovascular disease |
Box 1. Effects of elevated homocysteine levels in the brain
Venous blood sample after overnight fasting were drawn according to standard procedure. Plasma or serum was isolated and stored at −80˚C before analysis. Serum total homocysteine was measured at the clinical chemistry laboratory of the Ramathibodi Hospital, Mahidol University, Bangkok, using automated chemiluminescent enzyme immunoassay method (Diagnostic Products Corporation, Los Angeles, CA); the CV ranged from 4.1% to 10.2%.
Global cognitive function was assessed with the Thai language by using mini-Mental State Examination score (MMSE), and cognitive functions were assessed by a neuropsychological battery test for memory, executive function, attention, visual-spatial organization, information processing and motor speed.
Other measurements: The following variables were considered as possible confounders: age; sex; cigarette smoking (current, former, never); alcohol consumption, assessed with a semi quantitative food frequency questionnaire [
Multiple linear regression analysis was used to examine the relations between homocysteine levels and neuropsychological test scores with control for potential confounding variables to evaluate whether the relations were altered by these other variables. All tests were two-sided, and a p value of less than 0.05 was considered to be statistically significant. All data analyses were done with SPSS version 17.0 (SPSS Inc., Chicago, IL).
The characteristics of the study population are summarized in
In
High homocysteine levels have been associated with an increased risk of stroke and other cardiovascular events [
Variables | Value | % abnormal laboratory (only) |
---|---|---|
Age (y) | 72.8 ± 4.6 (61 - 80) | |
Education (y) | 6.3 (0 - 18) | |
Hypertension (%) | 54.6 | |
Diabetes mellitus (%) | 24.1 | |
Cardiovascular disease (%) | 15.1 | |
Homocysteine (µmol/L) | 14.2 | 34.0 |
Vitamin B 12 (pg/mL) | 612.1 | 4.26 |
Serum Folic (ng/ml) | 11.6 | 0.0 |
RBC folate (ng/ml) | 498.5 | 0.0 |
Cholesterol (mmol/L) | 5.54 | 60.0 |
LDL (mmol/L) | 3.49 | 50.0 |
HDL (mmol/L) | 1.36 | 23.40 |
Creatinine (µmol/L) | 70.8 | 4.3 (female) 12.0 (male) |
Test score | Median (95% CI ) | % abnormal (<1.5 SD) |
---|---|---|
MMSE | 27.0 (25.6 - 28.3) | 0.0 |
VP1 | 0.0 | 0.0 |
Learning slope | 2.09 (1.9 - 2.1) | 3.2 |
VP2 | 1.5 (1.43 - 1.57) | 13.8 |
VP total | 5.0 (4.75 - 5.25) | 22.3 |
Recognition | 23.0 (21.85 - 24.15) | 0.0 |
Retrieval | 21.0 (19.95 - 22.05) | 0.0 |
Retention | 66.7 (63.36 - 70.03) | 15.6 |
Digit forward | 8.0 (7.6 - 8.4) | 0.0 |
Digit backward | 4.0 (3.8 - 4.2) | 0.0 |
Block design | 9.0 (8.5 - 9.5) | 13.8 |
Trial Marking Test D-KEFS condition 5 | 52.6 (50.0 - 54.2) | 26.6 |
Digit symbol | 16.5 (15.6 - 17.4) | 38.3 |
C stimulus | 112.0 (106.4 - 117.6) | 34.4 |
C-W stimulus | 36.0 (34.2 - 37.8) | 73.1 |
Cognitive test | Homocysteine (b) | p-value |
---|---|---|
MMSE | −0.010 | 0.752 |
VP1 | −0.010 | 0.384 |
Learning slope | −0.048 (*) | 0.042 (*) |
VP2 | −0.021 | 0.273 |
VP total | −0.124 (*) | 0.032 (*) |
Recognition | 0.007 | 0.869 |
Retrieval | 0.032 | 0.373 |
Retention | 0.528 | 0.415 |
Digit forward | −0.007 | 0.798 |
Digit backward | 0.004 | 0.870 |
Block design | −0.063 | 0.436 |
Trial Marking Test D-KEFS condition 5 | 0.584 | 0.081 |
Digit symbol | −0.255 | 0.196 |
C stimulus | −0.069 | 0.586 |
C-W stimulus | −0.498 | 0.087 |
Verbal pair total: VP total, *significant p < 0.05.
Cognitive test | B | p-value |
---|---|---|
Homocysteine | −0.015 | 0.520 |
Vitamin B 12 | 0.000 | 0.824 |
RBC folate | −1.126 | 0.971 |
Serum folic | 0.005 | 0.876 |
Age | −0.129 | 0.007 (**) |
Education | 0.067 | 0.129 |
Cognitive test | B | p-value |
---|---|---|
Homocysteine | −0.080 | 0.252 |
Vitamin B 12 | 0.010 | 0.894 |
RBC folate | −0.006 | 0.716 |
Serum folic | 0.013 | 0.786 |
Age | −0.298 | 0.009 (**) |
Education | 0.267 | 0.029 (*) |
function and dementia [
Considerations arise when we try to explain our negative findings. We used only one global measure of cognitive function, the MMSE. However, the MMSE is a valid and reliable test [
In summary, although an association between homocysteine and cognitive impairment was biologically plausible, homocysteine did not seem to be a risk factor for cognitive impairment in this general population of the elderly. However, the possibility that homocysteine is truly not related to cognitive impairment cannot be discarded. Further researches such as a large number of participants and subjects in community are needed to find out for better quality of life in elderly population.
The authors gratefully acknowledge the coworkers at the research center of Ramathibodi Hospital, Mahidol University, Bangkok, Thailand and coworkers at Baan Bangkae Social Welfare Development Center for Older Persons, Bangkok and the vicinity. Finally, to the 100 subjects, whose were participated in this study.
Viroonudomphol, D., Kajanachumpol, S. and Prawettongsopon, C. (2016) Homocysteine and Cognitive Impairment in Thai Elderly. World Journal of Engineering and Technology, 4, 562-571. http://dx.doi.org/10.4236/wjet.2016.44054