Eliyahu H. Mizrahi, M.D . Head of Geriatric Department A The Chaim Sheba Medical Center

1. Plasma Homocysteine, Vitamin B12 and Folate Levels in Alzheimer’s Disease and Healthy Aged Controls in Arabs Residing in Israel Eliyahu H. Mizrahi, M.D. Head of Geriatric Department A The Chaim Sheba Medical Center Affiliated to the Tel-Aviv University Sackler School of Medicine, Israel

2. Collaborators Jacobsen D.W., Ph.D Laboratory for Homocysteine Research, Department of Cell Biology, Lerner Research Institute, the Cleveland Clinic Foundation, U.S.A. Debanne S.M., PhD Department of Epidemiology and Biostatistics,School of Medicine Case Western Reserve University, U.S.A. Petot G.J., M.S Department of Nutrition,School of Medicine Case Western Reserve University, U.S.A. Traore F., M.S; A.J. Lerner A.J., M.D. Laboratory of Neurogeriatrics, Department of Neurology School of Medicine, Case Western Reserve University Bowirrat A.,M.D.,Ph.D.,Boston University,School of Medicine Korczyn A.D., M.D.,MSc,Tel-Aviv University, Israel. Friedland R.P., M.D Laboratory of Neurogeriatrics, Department of Neurology School of Medicine, Case Western Reserve University, U.S.A.

3. Chaim Sheba Medical Center • Largest in Middle East • 1,200 Acute and 800 Chronic Beds • 750,000 Outpatient Visits • 80,000 Admissions • 150,000ER Visits • 35,000 Operations • 9,000 Deliveries • 2,000 Nurses • 850 Doctors • 30 pharmacists and technicians • Budget: $300 Million

4. Department of Geriatric Medicine-A

5. Homocysteine Metabolism Pathway Mizrahi E.H. at el, IMAJ 2002;4:187-190

6. Background High levels of plasma tHcy is believed to damage vessels in the heart and brain and are an independent risk factor for: • Cardio - and Cerebrovascular disease (Jacobsen, Clinical Chemistry, 1998; Herrmann et al, Atherosclerosis, 2003) • All cause mortality (Kark et al, Annals of Internal Medicine, 1999) • Possible Alzheimer's disease -? (Clarke et al, Arch. Neurol., 1998)

7. Objective • Because an inverse relationship has been reported between tHcy levels and plasma B12 and folate levels in AD, we measured plasma total Homocysteine levels, vitamin B12 and folate in: • AD patients • Healthy controls

8. Study design • Subjects • In Wadi Ara, Israel: • Three Arab villages • (Umm-El-Fahm; Ara-AR’ara and Kafar-Qara) • Door to door survey-Dr. Bowirrat • 75 Dementia Alzheimer type patients • and155 controls(DSM – IV)

9. Study design(cont) Methods • Plasma tHcy was determined using a commercial fluorescence polarization immunoassay • B12 and folate were determined by using a commercial radioisotope dilution assay (ICN) • Data was analyzed using Natural- Log and potential confounders evaluated with Logistic- Regression

10. Results • 1.Plasma homocysteine levels were significantly • higher in AD patients than controls in • Wadi - Ara. • 2. This difference remain significant after • adjusting for: • year of birth • gender • smoking status • (p=0.03)(Table-1, Figure-1)

12. Figure - 1

13. Results(Continue) • Plasma B12 • and • plasma folate levels • did not differ significantly between • AD patients • and • Controls(Table-1, Figure-2, Figure-3)

15. Figure - 2

16. Figure - 3

17. Results(Continue) • 1. Subjects in the: • highest tHcy tertile • or in the • lowest B12 and folate tertile • did not have greater risk to develop AD after • adjustment for year of birth and gender(Table-2) • 2. Subjects in the lower folate tertile • had statistically significant trend to • acquire AD (p<0.01)(Table-2)

19. Conclusions • 1.Plasma tHcy levels amongAD patients • were higher significantly • than in Controls

20. Conclusions • Although plasma B12 and folate levels • were lower • among AD patients than controls, • these differences were not statistically significant

21. Conclusions 3. No significant association was found between: plasma Homocysteine Vitamin - B12 Folate level among controls or AD patients in Arabs residing in Wadi Ara

22. Conclusions 4. High levels of plasma Homocysteine may suggest the need for folate and vitamin 12 supplementation in this population

23. Thank you for your attention