Transcript שקופית 1 - World Events Forum

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
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.
Chaim Sheba Medical Center
Largest in Middle East
1,200 Acute and 800 Chronic Beds
750,000 Outpatient Visits
80,000 Admissions
150,000 ER Visits
35,000 Operations
9,000 Deliveries
2,000 Nurses
850 Doctors
30 pharmacists and technicians
Budget: $300 Million
Department of Geriatric
Medicine-A
Homocysteine Metabolism Pathway
Mizrahi E.H. at el, IMAJ 2002;4:187-190
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)
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
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
and 155 controls (DSM – IV)
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
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)
Table 1. Characteristics of AD patients and Controls in Wadi Ara - Israel
Variables
Cases
Controls
P
(n=75)
(n=155)
Demographic
Year of birth, mean(SD)
1915 (7)
1927 (7)
*< 0.001
Gender, n (%) females
46 (61.3)
80 (51.6)
**0.17
Current smokers, n (%)
30 (41.0)
74 (48.4)
**0.27
Plasma Homocysteine,mmol/L20.6 (8.7)
16.4 (6.5)
***<0.03
Plasma Folate, nmol/L
4.3 (3.2)
4.8 (2.6)
*0.160
Vitamin B12, pmol/L
322.9 (136.0) 350.5 (175.3)
Clinical, mean (SD)
*0.470
*Student's T-test
** Chi-square test
***after adjusting for year of birth, gender and smoke status
Figure - 1
Results(Continue)
Plasma B12
and
plasma folate levels
did not differ significantly between
AD patients
and
Controls (Table-1, Figure-2, Figure-3)
Table 1. Characteristics of AD patients and Controls in Wadi Ara - Israel
Variables
Cases
Controls
P
(n=75)
(n=155)
Demographic
Year of birth, mean(SD)
1915 (7)
1927 (7)
*< 0.001
Gender, n (%) females
46 (61.3)
80 (51.6)
**0.17
Current smokers, n (%)
30 (41.0)
74 (48.4)
**0.27
Plasma Homocysteine,mmol/L 20.6 (8.7)
16.4 (6.5)
***<0.03
Plasma Folate, nmol/L
4.8 (2.6)
*0.160
Clinical, mean (SD)
4.3 (3.2)
Vitamin B12, pmol/L
322.9 (136.0) 350.5 (175.3) *0.470
*Student's T-test
** Chi-square test
***after adjusting for year of birth, gender and smoke status
Figure - 2
Figure - 3
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)
Table 2.
Odds Ratios (and 95% CI) for AD by Total Homocysteine,
Vitamin B12 and Folic Acid Levels.
Tertiles
1
Adjusted for YOB*
and Gender
Homocysteine (mmol/L)
I <= 13.06
II 13.07-17.36
III > 17.36
1.0 2.2 (0.8 - 6.5)
2.6 (0.9 - 7.7)
Vitamin B12 (pmol/L)
I >259.95
II 203.70-259.95
III <= 203.69
1.0 0.7 (0.3 - 1.9)
1.3 (0.5 - 3.4)
Folic Acid (nmol/L)
I >11.40
II7.87-11.40
III <= 7.86
1.0 1.4 (0.5 - 3.8)
1.6 (0.6 - 4.2)
1 Tertiles based on the distribution of controls.
Conclusions
1. Plasma tHcy levels among AD patients
were higher significantly
than in Controls
Conclusions
2. Although plasma B12 and folate levels
were lower
among AD patients than controls,
these differences were not statistically significant
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
Conclusions
4. High levels of plasma Homocysteine
may suggest the need for
folate and vitamin 12 supplementation
in this population
Thank you for your
attention