From the Indianapolis – Ibadan Dementia Research Project. THE RELATIONSHIP BETWEEN HOMOCYSTEIN AND INCIDENT DEMENTIA IN ELDERLY AFRICAN AMERICANS AND ELDERLY NIGERIANS. From the Indianapolis – Ibadan Dementia Research Project. 27TH ADI INTERNATIONAL CONFERENCE, London , March 7-10,2012.

Introduction Current risk factors for dementia include, age, education, gait disorders, hypocampal atrophy, Apolipoprotein E allele and cardiovascular risk factors. Recently homocystein has been identified as a possible biomarker. Homocystein blood levels are influenced by folic acid and Vitamin B group. It has been suggested that there is no real relationship, rather older persons (including the demented) may have lower vitamin levels in blood.

Introduction 2 Cross-sectional studies fail to show relationship, but longitudinal studies show that high homocystein levels over time is related to incident dementia. Other studies show that treatment with folic acid and vitamin B lead to levels of homocystein and reduction in incident dementia, conversion of MCI to dementia and reduction of cognitive decline. Only one study from South Africa (Delport 2000) has reported relationship between homocystein and dementia in Africa.

Method This report is from the longitudinal study on risk factors for dementia and Alzheimer’s disease in the Indianapolis –Ibadan Dementia Project. This report includes data collected from the 2001, 2004, and 2007 waves of the study. Blood samples were collected in 2001 for measuring levels of homocysteine, folate and vitamin B12. The project consisted of a screening phase, with the Community Screening Interview for Dementia (CSI-D). It also had a clinical assessment phase. Scores on the CSI-D were classified into good, intermediate and poor performance for selecting subjects for clinical assessment.

Method 2 Diagnoses were made based on individual clinical examination with physical and neurological examination, modified CERAD neuropsychological battery, and structured informant interview for history, symptoms, and daily function. Multivariate logistic regression models were used to examine the association between homocysteine, folate, and vitamin B12 and incident dementia. To control for potential non-linear effects, quartile groups for homocysteine, folate, and vitamin B12 levels were used in the models.

Results 1 In Indianapolis, there were 72 subjects diagnosed with incident dementia during follow-up evaluations at 2004 or 2007, and 728 subjects who were determined to be cognitively normal at the 2007 evaluation. In Ibadan, there were 46 subjects with incident dementia and 560 subjects who remained normal at the end of 2007 evaluation. Higher baseline levels of homocystiene were associated with increased probability of incident dementia for both Indianapolis (p= 0.022) and Ibadan (p=0.027). For Indianapolis cohort, subjects in the third and fourth quartiles of homocysteine level had significantly higher risk of incident dementia comparing to subjects in the lowest quartile with odds ratios of 3.3 (95% CI: 1.5-7.3) and 2.6 ((95% CI: 1.2-6.0), respectively.

Results 2 For Ibadan, subjects in the highest quartile of homocysteine had significantly higher risk of incident dementia comparing to those in the lowest quartiles (OR=3.7, 95% CI: 1.4-10.0). Folate and vitamin B12, although associated with homocysteine levels, were not independently associated with incident dementia in the final models including homocysteine level as an independent variable. One of our expectations was that because of dietary differences, there may be differences in the mean serum levels of vitamins, and that probably leading to differences in the rates of dementia. However the information we have from our result is that higher levels of homocysteine in both populations is related to increased rate of dementia.

Table 1: Results of multiple logistic regression model with incident dementia as the outcome variable in the Indianapolis cohort. Variables Odd ratio 95% Confidence Interval P-value Female 1.419 0.791 2.545 0.240 Age at last evaluation 1.031 0.982 1.082 0.216 Year of education 0.857 0.783 0.938 0.001 Baseline BMI 0.940 0.895 0.987 0.013 APOE ε4 carriers 1.922 1.157 3.192 0.012 Homocysteine Quartiles 0.022 Quartile 4 2.646 1.164 6.012 0.020 Quartile 3 3.256 1.451 7.304 0.004 Quartile 2 1.705 0.712 4.083 0.231 Quartile 1 1.0 (ref) --

Table 2: Results of multiple logistic regression model with incident dementia as the outcome variable in the Ibadan cohort. Variables Odd ratio 95% Confidence Interval P-value Female 1.426 0.705 2.883 0.324 Age at last evaluation 1.087 1.033 1.144 0.001 Year of education 0.440 0.127 1.521 0.194 Baseline BMI 0.965 0.891 1.045 0.383 APOE ε4 carriers 1.772 0.938 3.348 0.078 Homocysteine Quartiles 0.027 Quartile 4 3.699 1.373 9.970 0.010 Quartile 3 1.651 0.563 4.839 0.361 Quartile 2 1.443 0.500 4.160 0.498 Quartile 1 1.0 (ref) --

Conclusion Higher baseline levels of homocysteine conferred risk for incident dementia and Alzheimer’s disease in the African Americans and the Yoruba Nigerians, populations living in very different environments. A number of studies in which patients were followed up over 2 to 5 years show results similar to ours. (Wald et al 2011, de Jager et al 2011) . Treatment with Folic acid and vitamin B affects the level of hymocysteine, therefore some prevention or delay could be achieved if older persons at risk of dementia are identified and adequately treated. However there is need for more research in this area.

Acknowledgement Supported by National Institute of Aging grant RO1 AG009956-15.

Collaborators Ibadan: Indianapolis: Olusegun Baiyewu. Kathleen Lane. Adesola Ogunniyi. Lisa Kamendulis. Oye Gureje. Fredrick Unverzagt. Sujan Gao. Valerie Smith-Gamble. Kathleen Hall. Hugh Hendrie.

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