8/8/2019 Dementia 222

1/4

International Psychogeriatrics, Vol. 13, No. 3, 2001, p. 259-2620 2001 International PsychogeriatricAssociation

G uest Ed itorialDietarv Antioxidants and Dementia

J

As the populations of the developedworld continue to age, the number ofpeople who develop Alzheimers dis-ease (AD) or other forms of dementia isset to rise. In the United States, for exam-ple, the prevalence of AD is projected toquadruple over the next 50years (Brook-meyer & Gray, 2000). The search for fac-tors that might help to prevent or treatthese conditions has therefore assumeda particular relevance.

One hypothesis that has attracted con-siderable interest in recent years sug-gests that oxidative stress plays animportant part in the pathogenesis ofAD, vascular dementia (VaD), and otherage-related degenerative conditions(Beckman& Ames, 1998; Christen, 2000).Around 2%-3% of the oxygen consumedby cells ends up as highly destructiveoxygen free radicals that can damage thecell nucleus, mitochondria1 DNA, mem-branes, and cytoplasmic proteins, andare thought to play a crucial role inatherogenesis (Witztum, 1994).The rateat which this damage accumulates de-pends on the balance between the gener-ation of toxic free radicals such assuperoxide and hydrogen peroxide andthe adequacy of the bodys antioxidantdefenses. The brain is particularly sus-ceptible to damage by free radicals be-cause its metabolism requires largequantities of oxygen and its membranes

are rich in polyunsaturated fatty acids,which are prone to lipid peroxidation(Markesbery &Carney, 1999).Recent re-search investigating oxidative stress inpatients with AD found that levels oftwo markers of lipid peroxidation (4-hydroxynonenal and the isoprostane,8,12,-iso-iPF2alpha-V1) were higher thanthose seen in controls and that the extentof lipid peroxidation in these patientscorrelated with measures of cognitive orfunctional impairment (McGra h e al.,2001; Pratico et al., 2000). Such findingsraise the possibility that increasing thebodys antioxidant defenses by dietarymeans might improve the symptoms ofdementia or prevent it from developing.

An article in this issue of the journal (seepp. 265-275) sets out to explore the rela-tion between dietary intake and antioxi-dant status in people with dementia. NajiTabet and colleagues studied 51 patientswith AD, VaD, or dementia with Lewybodies (DLB) and 30 controls and com-pared their dietary intake of vitamin D,vitamins B,, B,, and BI2,folate, niacin, ribo-flavin, biotin, pantothenate, copper, zinc,and selenium with blood levels of the en-dogenous antioxidants glutathione per-oxidase and superoxide dismutase, andtotal antioxidant capacity (TAC). Theyfound that patients with severe AD had alower intake of most of the vitamins andtrace elements than the control group, but

259

8/8/2019 Dementia 222

2/4

C. R . Gale60there were no differences in antioxidantstatus between any of the dementia groupsand the controls. The men and womenmaking up the control group in this studywere younger, on average, than those inthe dementia groups. Whether adjustingfor age would have made any difference tothese results is not clear. In some studieswhere an age-matched control group hasbeen used, there have been no differencesin vitamin or mineral intake between de-mented and nondemented subjects (Burnset al., 1989) nor has there been any differ-ence in TAC (Foy et al., 1999), though astudy that measured total radical-trappingantioxidant capacity did find that this wassignificantly reduced in demented patientscompared with the age-matched controls(De Leo et al., 1998). Among the subjectsstudied by Tabet and colleagues, therewas no evidence that TAC was linked todietary intake of the vitamins and miner-als measured in those with AD or DLB, butthere were significant positive associationsbetween TAC and intake of vitamin B,,vitamin BI2,zinc, and selenium in subjectswith VaD.

Most of the studies that have examinedwhether there is a link between antioxi-dant status and disorders in cognitivefunction have concentrated on intake orblood concentrations of the major antiox-idant vitamins, vitamin C, vitamin E, andbeta-carotene. The evidence from theseobservational studies provides some sup-port for the idea that higher antioxidantintakes might be protective, though it isnot consistent. In the Rotterdam study ofover 5,000 nondemented elderly people,for example, higher carotene intake wasassociated, in a cross-sectional analysis,with better performance on the Mini-Mental State Examination, but no rela-tion was found with intake of vitamins Cand E (Jama et al., 1996). A recent report

on a subset of this same cohort showedthat people with high blood concentra-tions of carotenoids had fewer white-matter lesions on magnetic resonanceimaging (den Heijer et al., 2001). In 4,800elderly participants in the NHANES I11survey, higher blood concentrations ofvitamin E were associated with bettermemory performance, but no significantrelations were found with concentrationsof vitamin C and beta-carotene (Perkinset al., 1999). n the Zutphen Elderly Study,no associations were found between in-take of any antioxidant and cognitivefunction (Kalmijn et al., 1997). All thesestudies controlled for potential confound-ing factors such as age, education, andvascular risk factors, but the fact that theywere cross-sectional makes it impossibleto be certain about the direction of anyrelation found between low intake orblood concentrations of antioxidant vita-mins and impaired cognition. Similar dif-ficulties arise when interpreting theresults of studies showing that dementedpatients have lower blood concentrationsof antioxidant vitamins than nondement-ed controls (Foy et al., 1999; Zaman et al.,1992).Such associations could result fromthe influence of the disease process itselfon dietary habits or antioxidant status,rather than reflecting any protective ef-fect of these vitamins. However, recentreports of studies where data on antioxi-dant status were collected prior to thedevelopment of cognitive impairmentprovide rather stronger evidence. After 6years of follow-up of the Rotterdam studycohort, people who at baseline had a high-er intake of vitamin E or vitamin C orwhose diet was richer in vegetables had asignificantly reduced incidence of AD orall forms of dementia (Engelhart et al.,2000). Suggestions that vitamin E or Cmight be protective have also come from

International Psychogeriatrics, 13(3),September 2001

8/8/2019 Dementia 222

3/4

Antioxidants and Dementiathe longitudinal Honolulu-Asia AgingStudy. Here, men who had reported tak-ing both vitamin E and vitamin C supple-ments were significantly less likely todevelop VaD during the follow-up peri-od (odds ratio 0.12,95%confidence inter-val 0.02-0.88), though risk of AD was notreduced (Masaki et al., 2000). Whetherthe reduction in risk seen in the mentaking supplements was due to the vita-mins themselves or merely a reflection ofthe distinctive characteristics of supple-ment users is not clear (Lyle et al., 1998).

As yet there are no data from random-ized controlled trials on the effect ofantioxidant vitamins in preventing de-mentia. There is some evidence from atrial of vitamin E and selegiline in pa-tients with AD that vitamin E may delaythe progression of the disease, as mea-sured by time to institutionalization, lossof ability to perform basic activities ofdaily life, or death, but it did not affectcognitive function (Sano et al., 1997).Until more data are available from ran-domized controlled trials, the uncertain-ties about the usefulness of antioxidantvitamins in the prevention or treatmentof dementia are unlikely to be resolved.

261Bums, A., Marsh, A., & Bender, D. A. (1989).

Dietary intake and clinical, anthropomet-ric andbiochemicalindices of malnutritionin elderly demented patients and non-demented subjects. Psychological Medicine,

Christen, Y. (2000). Oxidative stress andAlzheimer disease. American Journal ofClinical Nu trit ion , 72, 621s-629s.

De Leo, M. E., Borrello, S., Passantino, M.,Palazzotti, B., Mordente, A., et al. (1998).Oxidative stress and overexpression ofmanganese superoxide dismutase inpatients with Alzheimers disease. Neuro-science Letters, 250, 173-176.

den Heijer, T., Launer, L. J., de Groot, J. C., deLeeuw, F. E., Oudkerk, M., et al. (2001).Serum carotenoids and cerebral whitematter lesions: The Rotterdam scan study.Journal of the American Geriatrics Society, 49,

Engelhart, M. J.,Ruitenberg, A.,Sweieten, J. C.,Witteman, J. C. M., Hofman, A., et al.(2000). Dietary anti-oxidants and the riskof dementia. The Rotterdam Study (ab-stract).Neurobiology o Agzng, 22 (Suppl. l ) ,S203.

Foy,C. J.,Passmore,A. P.,Vahidassr,M.D.,Young,I. S., & Lawson, J. T. (1999). Plasma chain-breaking antioxidants n Alzheimers disease,vascular dementia and Parkinsons disease.Quartuly Journal@Medicine,92,3945.

Jama, W. J., Launer, L. J., Witteman, J. C. M.,den Breeijn, H., Breteler, M. M. B., et al.(1996). Dietary antioxidants and cognitivefunction in a population-based sample ofolder persons: The Rotterdam study.Ameri-can Journal o Epidemiology, 244,275-280.

Kalmijn, S. , Feskens, E. J. M., Launer, J. L., &Kromhout, D. (1997). Polyunsaturatedfatty acids, antioxidants and cognitivefunction in very old men. American Journalof Epidemiology, 145,33-41.

Lyle, B. J., Mares-Perlman, J. A., Klein, B. E.,Klein, R., & Greger, J. L. (1998). Supple-ment users differ from non-users indemographic, lifestyle, dietary and healthcharacteristics. Journal of Nutrition, 128,

29,383-391.

642-646.

2355-2362.

Catharine R.Gale , PhDMRC Environmental Epidemiology UnitSouthampton General Hospital

Southampton, UK

REFERENCESBeckman, K. B., & Ames, B. N. (1998). The free

radical theory of aging matures. Physi-ological Reviews, 78,547-581.Brookmeyer,R., &Gray, S. (2000).Methods for

projecting the incidence and prevalence ofchronic diseases in aging populations:Application to Alzheimers disease. Statis-tics in M edicine, 29, 1481-1493.

8/8/2019 Dementia 222

4/4

262 C. R. GaleMarkesbery, W. R., & Carney, J. M. (1999).

Oxidative alterations in Alzheimers dis-ease. Brain Pathology, 9, 133-146.Masaki, K. H., Losonczy, K. G., Izmirlian, G . ,

Foley, D. J., ROSS, G . W., et al. (2000).Association of vitamin E and C supple-ment use with cognitive function anddementia in elderly men. Neurology, 54,

McGrath, L. T., McGleenon, B. M., Brennan, S.,McColl, D., McIlroy, S., et al. (2001).Increased oxidative stress in Alzheimersdisease as assessed with 4-h ydroxynonenalbut not malondialdehyde. Quarterly Jour-nal of Medicine, 94,485-490.

Perkins, A. J., Hendrie, H. C., Callahan, C. M.,Gao, S., Unverszagt, F. W., et al. (1999).Association of antioxidants with memoryin a multiethnic elderly sample using theThird National Health and Nutrition Ex-amination Survey. American Journal ofEpidemiology, 150,37-44.

1265-1272.

Pratico, D., Clark, C. M., Lee, V. M.,Trojanowski, J. Q.,Rokach, J., et al. (2000).Increased 8,12,-iso-iPF2alpha-V1 inAlzheimers disease: Correlation of anoninvasive index of lipid peroxidationwith disease severity. Annals of Neurology,

Sano,M., Emesto, C., Thomas, R. G., Klauber,M. R., Schafer,K.,et al. (1997).Acontrolledtrial of selegiline, alpha-tocopherol, orboth as treatment for Alzheimers disease.The Alzheimers Disease CooperativeStudy. New England Journal of Medicine,

Witztum, J. L. (1994).The oxidationhypothesisof atherosclerosis. Lancet, 344,793-795.

Zaman, Z., Roche, S., Fielden, P., Frost, P. G.,Niriella, D. C., et al. (1992). Plasmaconcentrations of vitamin A and E andcarotenoids in Alzheimers disease. Ageand Ageing, 21, 91-94.

48,809-812.

336,1216-1222.

International Psychogeriatrics, 13(3),September2001