The Worldwide Challenge of the Dementias: A Role for B Vitamins and Homocysteine?

Food and Nutrition Bulletin - Tập 29 Số 2_suppl1 - Trang S143-S172 - 2008
A. David Smith1
1Oxford Project to Investigate Memory and Aging, University of Oxford, UK. [email protected]

Tóm tắt

Dementia has reached epidemic proportions, with an estimated 4.6 million new cases worldwide each year. With an aging world population, the prevalence of dementia will increase dramatically in the next few decades. Of the predicted 114 million who will have dementia in 2050, about three-quarters will live in less developed regions. Although strongly age-related, dementia is not an inevitable part of aging but is a true disease, caused by exposure to several genetic and nongenetic risk factors. Prevention will be possible when the nongenetic risk factors have been identified. Apart from age, more than 20 nongenetic risk factors have been postulated, but very few have been established by randomized intervention studies. Elevated blood concentrations of total homocysteine and low-normal concentrations of B vitamins (folate, vitamin B12, and vitamin B6) are candidate risk factors for both Alzheimer's disease and vascular dementia. Seventy-seven cross-sectional studies on more than 34,000 subjects and 33 prospective studies on more than 12,000 subjects have shown associations between cognitive deficit or dementia and homocysteine and/or B vitamins. Biologically plausible mechanisms have been proposed to account for these associations, including atrophy of the cerebral cortex, but a definite causal pathway has yet to be shown. Raised plasma total homocysteine is a strong prognostic marker of future cognitive decline, and is common in world populations. Low-normal concentrations of the B vitamins, the main determinant of homocysteine concentrations, are also common and occur in particularly vulnerable sections of the population, such as infants and elderly. Large-scale randomized trials of homocysteine-lowering vitamins are needed to see if a proportion of dementia in the world can be prevented.

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Tài liệu tham khảo

10.1001/archneur.57.3.418

WHO. Active Ageing. A Policy Framework 2002. Available at: http://whqlibdoc.who.int/hq/2002/WHO_NMH_NPH_02.8.pdf. Accessed 18 March 2008.

10.2165/00002512-199915050-00004

10.1056/NEJM199712043372306

10.1002/(SICI)1099-1166(200001)15:1<21::AID-GPS71>3.0.CO;2-5

10.1016/S0140-6736(03)12772-9

WHO. Point prevalence for selected causes by sex, age and WHO subregion 2002. Available at: http://www.who.int/healthinfo/statistics/gbdwhoregionprevalence2002.xls. Accessed 5 May 2008.

10.1097/00002093-200304000-00002

10.1001/archneur.60.8.1119

10.1002/gps.1355

10.1016/S0140-6736(05)67889-0

Wimo A, 1998, Health economics of dementia

10.1002/gps.499

10.1159/000090733

Rice DP, 2001, Am J Manag Care, 7, 809

Koppel R. Alzheimer's disease: The costs to U.S. businesses in 2002. Available at: http://www.alz.org/national/documents/report_alzcosttobusiness.pdf. Accessed 20 March 2008.

Lewin Group. Saving lives. Saving money: Dividends for Americans investing in Alzheimer research 2004. Available at: http://www.alz.org/national/documents/report_savinglivessavingmoney.pdf. Accessed 18 March 2008.

Khachaturian ZS, 2005, Alz Dem J Alz Assoc, 1, 2

10.1146/annurev.publhealth.23.100901.140525

10.1002/(SICI)1099-1166(199907)14:7<577::AID-GPS32>3.0.CO;2-M

10.1146/annurev.publhealth.25.101802.122951

10.1126/science.3299702

10.1016/S1474-4422(03)00305-3

10.1016/0140-6736(92)92177-H

Bowler JV, 2003, Vascular cognitive impairment: Preventable dementia, 10.1093/oso/9780192632678.001.0001

10.1001/jama.1997.03550160069041

10.1093/aje/kwi202

10.1016/S0197-4580(99)00110-4

10.1016/S0047-6374(01)00364-5

10.1016/S1474-4422(04)00683-0

10.1016/j.neurobiolaging.2004.03.016

10.1016/S0140-6736(02)11769-7

10.1016/S0140-6736(04)16405-2

10.1016/S0140-6736(05)67341-2

10.1373/clinchem.2003.021634

10.1001/jama.1993.03510220049033

Strachan RW, 1965, Q J Med, 34, 303

Strachan RW, 1967, Q J Med, 36, 189

10.1056/NEJM198806303182604

10.1002/(SICI)1099-1166(199610)11:10<851::AID-GPS452>3.0.CO;2-L

10.1093/ajcn/55.6.1237S

10.1016/0306-9877(92)90074-M

10.1016/0306-9877(92)90153-4

Regland B, 1990, Dementia, 1, 272

10.1111/j.1600-0447.1992.tb03285.x

10.1111/j.1365-2362.1994.tb01111.x

10.1111/j.1365-2362.1996.tb02129.x

10.1093/gerona/52A.2.M76

10.1002/(SICI)1099-1166(199804)13:4<235::AID-GPS761>3.0.CO;2-8

10.1001/archneur.55.11.1449

10.1212/WNL.58.10.1471

10.1159/000058327

10.1093/ajcn/71.2.614s

10.1093/geronb/56.6.P327

10.1002/gps.723

10.1093/ajcn/75.5.785

10.1016/S1474-4422(03)00438-1

10.1503/cmaj.1031586

10.1111/j.1365-277X.2004.00532.x

10.1055/s-2005-872406

10.1159/000017222

10.1212/WNL.56.9.1143

10.1176/appi.ajp.159.1.82

10.1161/01.STR.0000083050.44441.10

10.1159/000071006

10.1111/j.1749-6632.2000.tb06392.x

10.1093/ajcn/75.5.908

10.1016/j.pnpbp.2005.06.026

10.1111/j.1532-5415.2005.53153.x

10.1093/aje/kwi259

10.1212/01.WNL.0000129504.60409.88

10.1016/j.amjmed.2004.08.019

10.1515/CCLM.2005.192

10.1159/000051275

10.1056/NEJMoa011613

Teunissen CE, 2003, J Nutr Health Aging, 7, 153

10.1093/gerona/59.12.1323

10.1093/ajcn/82.3.636

10.1002/ana.20645

10.1001/jama.1983.03330450047024

10.1016/S0167-4943(97)00028-9

10.1161/CIRCULATIONAHA.105.580332

10.1093/ajcn/65.1.20

10.1016/j.jalz.2005.06.001

Glaso M, 2004, J Nutr Health Aging, 8, 407

10.1159/000069992

10.1212/WNL.56.9.1188

10.1002/ajh.2830340205

Carmel R, 2001, Homocysteine in health and disease, 289

10.1093/ajcn/59.5.1213S

10.1016/0002-9343(94)90149-X

10.1111/j.1365-2796.2004.01437.x

10.1136/jnnp.74.7.959

Clarke R, 2005, Haematologica Reports, 1, 3

Eussen S, 2002, J Nutr Health Aging, 6, 43

10.1002/ana.10440

10.1093/ajcn/82.4.866

10.1093/ajcn/82.3.627

10.1093/clinchem/42.10.1689

10.1001/archneur.62.4.641

10.1093/ajcn/85.1.193

10.1093/jn/136.1.189

10.1093/ajcn/82.6.1346

10.1093/ije/25.6.1107

10.1016/S0140-6736(04)16260-0

10.1093/qjmed/95.1.27

10.1093/ajcn/82.4.806

10.1016/0306-4522(95)90397-P

10.1001/archneur.57.6.808

10.1073/pnas.082107399

10.1073/pnas.2635903100

10.1016/S1474-4422(05)70286-6

10.1016/S0165-6147(00)01675-8

10.1093/ije/dyg070

10.1016/S0140-6736(05)70152-5

10.1093/ajcn/72.2.324

10.1002/(SICI)1096-8628(19970418)74:2<207::AID-AJMG20>3.0.CO;2-L

10.1038/sj.ejhg.5200651

10.1001/jama.1997.03540460039030

10.1016/S1474-4422(05)70141-1

10.1016/j.lfs.2005.02.014

10.1136/jnnp.2004.056119

10.1016/0378-4347(92)80362-T

10.1016/S0021-9258(17)35762-9

10.1046/j.1471-4159.2003.02297.x

10.1007/s007020170100

10.1016/S0166-2236(03)00032-8

10.1016/j.pnpbp.2005.06.025

10.1016/j.febslet.2006.04.088

10.1161/01.STR.0000153008.60517.ab

10.1016/S0140-6736(99)00309-8

10.1161/01.STR.32.5.1116

10.1002/ana.10111

10.1001/archneur.59.5.787

10.1001/archneur.61.9.1369

10.1161/01.STR.0000165923.02318.22

10.1007/s00415-005-0022-x

10.1073/pnas.94.11.5923

10.1016/j.atherosclerosis.2004.01.005

Kim WK, 1996, Neurosci Lett, 216, 117

10.1046/j.1471-4159.2001.00384.x

10.1046/j.1471-4159.2001.00178.x

10.1016/j.jns.2003.11.009

10.1002/jnr.20514

10.1007/s00702-003-0096-5

10.1016/j.mcn.2004.09.007

10.1016/S0014-5793(02)02702-3

Selhub J, 2002, J Nutr Health Aging, 6, 39

10.1016/S0014-5793(03)00277-1

10.1161/01.CIR.0000027586.64231.1B

10.1016/S0008-6363(03)00462-0

10.1179/016164104225016182

10.1212/WNL.58.9.1395

10.1016/S0969-9961(03)00070-6

10.1136/jnnp.69.4.565

10.1016/S0896-6273(04)00017-0

10.1523/JNEUROSCI.20-18-06920.2000

10.1523/JNEUROSCI.22-05-01752.2002

10.1093/jn/132.8.2444S

10.1182/blood.V94.3.959.415k20_959_967

10.1016/S0014-5793(03)01009-3

10.1093/ajcn/71.4.993

10.1097/00019442-200411000-00009

10.1093/ageing/31.6.440

10.1093/brain/awg006

10.1212/WNL.58.10.1539

10.1016/S0304-3940(02)01452-0

Seshadri S, Wolf PA, Beiser A, Au R, Wilson PWF, Selhub J, Jacques PF, Rosenberg IR, D'Agostino RB, DeCarli C. Elevated plasma homocysteine levels are associated with subclinical brain injury in healthy adults: Relation to silent cerebral infarcts, white matter hyperintensity and MRI brain volume in the Framingham offspring. AAN Abstracts 2003:(abstract S08.006).

10.1001/archneur.1965.00470050003001

10.1097/00001648-200107000-00005

10.1212/WNL.55.10.1428

Malouf R, Areosa-Sastre A. Vitamin B12 for cognition. Cochrane Database Syst Rev 2003:CD004326.

Malouf M, Grimley EJ, Areosa SA. Folic acid with or without vitamin B12 for cognition and dementia. Cochrane Database Syst Rev 2003:CD004514.

Malouf R, Evans JG. The effect of vitamin B6 on cognition. Cochrane Database Syst Rev 2003:CD004393.

10.1177/15648265080292S118

10.1093/ajcn/82.6.1320

10.1097/00019442-200303000-00016

Clinical Trials.gov. VITAL: Vitamins to slow Alzheimer's disease (Homocysteine study) 2003. Available at: http://clinicaltrials.gov/ct/gui/show/NCT00056225?order=1. Accessed 20 March 2008.

Clinical Trials.gov. Can oral vitamin B12 and folate supplementation preserve cognitive function of patients with early dementia? 2005. Available at: http://clinicaltrials.gov/ct/gui/show/NCT00164970?order=1. Accessed 20 March 2008.

International Standard Randomised Controlled Trial Number Register. VITACOG: Homocysteine and B vitamins in cognitive impairment 2005. Available at: http://www.controlled-trials.com/ISRCTN94410159. Accessed 20 March 2008.

10.1161/01.STR.0000127810.92616.78

10.1016/S1474-4422(05)70221-0

Manton KC, 2005, Adv Gerontol, 16, 30

10.1093/jn/135.9.2253

10.1161/CIRCULATIONAHA.105.570846

10.1177/15648265080292S107

10.1177/15648265080292S105

10.1146/annurev.nutr.24.012003.132440

10.1093/ajcn/74.2.233

10.1186/1471-2458-6-29

Hettiarachchi M, 2006, Asia Pac J Clin Nutr, 15, 56

10.1016/S0140-6736(99)03383-8

10.1093/jn/136.6.1731S

10.1016/S0140-6736(00)03589-3

WHO. Mental health global action programme 2002. Available at: http://www.who.int/mental_health/media/en/265.pdf. Accessed 18 March 2008.

WHO. Global strategy on diet, physical activity and health 2004. Available at: http://www.who.int/dietphysicalactivity/strategy/eb11344/strategy_english_web.pdf. Accessed 18 March 2008.

WHO. Preventing chronic diseases. A vital investment 2005. Available at: http://www.who.int/chp/chronic_disease_report/contents/en/index.html. Accessed 18 March 2008.

10.1016/S1474-4422(04)00800-2

10.1007/BF00308809

10.1212/01.wnl.0000172914.08967.dc

10.1001/archneur.62.10.1556

10.1016/S1474-4422(05)70248-9

10.1161/01.STR.0000143317.70478.b3

10.1212/01.WNL.0000150886.50187.30

10.1161/01.STR.28.2.316

10.1016/S1474-4422(05)70284-2

10.1136/bmj.38446.466238.E0

10.1016/S0197-4580(02)00156-2

10.1001/jama.289.11.1405

10.1111/j.1532-5415.2004.52159.x

10.1212/WNL.45.6.1161

10.1016/S1474-4422(04)00767-7

10.1016/S1474-4422(05)70198-8

10.7326/0003-4819-144-2-200601170-00004

10.7326/0003-4819-144-2-200601170-00011

10.1001/archneur.60.7.940

10.1212/01.wnl.0000183148.34197.2e

10.1212/01.wnl.0000176061.33817.90

10.1001/archneur.62.1.55

10.1093/aje/kwh018

10.1001/jama.287.24.3223

10.1001/jama.287.24.3230

10.1016/S1474-4422(04)00878-6

10.1159/000082884

10.1001/archneur.61.5.668

10.1002/ana.20721

10.1016/j.exger.2004.06.019

10.1212/WNL.62.2.188

10.1212/WNL.62.2.170

10.1016/S1474-4422(05)70022-3

10.1159/000078501

10.1046/j.1365-2265.2000.01146.x

10.1212/01.WNL.0000128134.84230.9F

10.1136/jnnp.74.7.857

10.1001/archneur.60.5.753

10.1002/ana.20405

10.1093/ageing/afj030

10.1016/S0167-4943(98)00004-1

10.1093/ageing/27.4.485

10.1159/000017092

10.1016/S0006-3223(98)00234-0

10.1093/oxfordjournals.aje.a010000

10.1212/01.WNL.0000032494.05619.93

10.1007/s007020070010

10.1080/07315724.2000.10718916

10.1016/S0047-6374(00)00221-9

Ravaglia G, 2000, J Nutr Health Aging, 4, 218

Ravaglia G, Forti P, Maioli F, Scali RC, Saccheitti L, Talerico T, Mantovani V, Bianchin M. Homocysteine and cognitive performance in healthy elderly subjects. Arch Gerontol Geriatr Suppl 2004:349–57.

10.1207/S15326942DN2003_1

10.1093/ajcn/73.5.927

10.1016/S0047-6374(01)00307-4

10.1159/000052822

10.1016/S0301-0511(01)00079-5

Tripathi M, 2001, Neurol India, 49, 284

10.1046/j.1532-5415.2002.50614.x

10.1161/01.STR.0000032550.90046.38

10.1016/S0197-4580(01)00327-X

10.1016/S0168-8227(01)00300-X

10.1016/S0006-291X(02)00422-9

10.1046/j.1532-5415.2002.50309.x

10.1097/00019442-200205000-00012

10.1093/ajcn/77.1.211

10.1093/gerona/58.4.M324

10.1093/ajcn/77.3.668

10.1016/S0006-3223(02)01451-8

10.1159/000070677

10.1046/j.1365-2796.2003.01154.x

10.1159/000072812

Storey SG, 2003, J Gerontol A Biol Sci Med Sci, 58, M1135, 10.1093/gerona/58.12.M1135

Mizrahi EH, 2003, J Nutr Health Aging, 7, 160

10.1093/ajcn/78.3.441

10.1016/S0197-4580(03)00007-1

10.1159/000068481

10.1002/gps.704

10.1002/gps.1092

10.1097/00001756-200404090-00025

10.1016/j.jns.2004.08.011

10.1212/01.WNL.0000129986.19019.5D

Quadri P, 2004, Am J Clin Nutr, 80, 114, 10.1093/ajcn/80.1.114

Gallucci M, Zanardo A, De Valentin L, Vianello A. Homocysteine in Alzheimer disease and vascular dementia. Arch Gerontol Geriatr Suppl 2004:195–200.

10.1515/CCLM.2004.208

10.1016/j.ejim.2004.05.008

10.1016/j.archger.2004.07.005

10.1016/j.neurobiolaging.2004.05.005

10.1016/j.archger.2004.07.001

10.1159/000085856

10.1016/j.cccn.2005.03.049

10.1016/j.neurobiolaging.2004.07.003

10.1080/03610730590948221

10.1212/01.wnl.0000183063.99107.5c

10.1097/00019442-200508000-00013

10.1300/J052v24n03_05

Manders M, Vasse E, de Groot LC, van Staveren WA, Bindels JG, Blom HJ, Hoefnagels WH. Homocysteine and cognitive function in institutionalised elderly. A cross-sectional analysis. Eur J Nutr 2005.

10.1515/CCLM.2005.191

10.1136/jnnp.2004.046219

Zhang YD, 2005, Chin Med Sci J, 20, 247

10.1093/ajcn/81.5.1155

10.1016/j.neulet.2005.03.073

10.1016/j.neurobiolaging.2005.01.001

10.1007/s00702-005-0333-1

10.1016/j.neurobiolaging.2005.01.003

10.1080/00365510310000420

10.1159/000087297

10.1016/S1474-4422(06)70355-6

10.1159/000089515

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Food and Nutrition Bulletin

Tập 29 Số 2_suppl1

S143-S172

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