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Low serum cholesteryl ester-docosahexaenoic acid levels in Alzheimer's disease: a case–control study

Published online by Cambridge University Press:  01 August 2008

A. M. Tully
Affiliation:
Unit of Nutrition, Department of Clinical Medicine, Trinity Centre for Health Sciences and The Mercer's Institute for Research in Ageing, St James Hospital, Dublin 8, Republic of Ireland
H. M. Roche*
Affiliation:
Unit of Nutrition, Department of Clinical Medicine, Trinity Centre for Health Sciences and The Mercer's Institute for Research in Ageing, St James Hospital, Dublin 8, Republic of Ireland
R. Doyle
Affiliation:
The Mercer's Institute for Research in Ageing, St James Hospital, Dublin 8, Republic of Ireland
C. Fallon
Affiliation:
The Mercer's Institute for Research in Ageing, St James Hospital, Dublin 8, Republic of Ireland
I. Bruce
Affiliation:
The Mercer's Institute for Research in Ageing, St James Hospital, Dublin 8, Republic of Ireland
B. Lawlor
Affiliation:
The Mercer's Institute for Research in Ageing, St James Hospital, Dublin 8, Republic of Ireland
D. Coakley
Affiliation:
The Mercer's Institute for Research in Ageing, St James Hospital, Dublin 8, Republic of Ireland
M. J. Gibney
Affiliation:
Unit of Nutrition, Department of Clinical Medicine, Trinity Centre for Health Sciences and The Mercer's Institute for Research in Ageing, St James Hospital, Dublin 8, Republic of Ireland
*
*Corresponding Author: Dr Helen M. Roche, fax +353 1 454 2043, email hmroche@tcd.ie
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Abstract

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Low n-3 polyunsaturated fatty acid (PUFA) status may be associated with neuro-degenerative disorders, in particular Alzheimer's disease, which has been associated with poor dietary fish or n-3 PUFA intake, and low docosahexaenoic acid (DHA) status. The present case–control study used an established biomarker of n-3 PUFA intake (serum cholesteryl ester-fatty acid composition) to determine n-3 PUFA status in patients with Alzheimer's disease, who were free-living in the community. All cases fulfilled the National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association criteria for Alzheimer's disease. Detailed neuropsychological testing and neuroimaging established the diagnosis in all cases. The subjects (119 females and twenty-nine males) aged 76·5 (SD 6·6) YEARS HAD A CLINICAL DEMENTIA RATING (CDR) OF 1 (sd 0·62) and a mini mental state examination (MMSE) score of 19·5 (sd 4·8). The control subjects (thirty-six females and nine males) aged 70 (sd 6·0) years were not cognitively impaired (defined as MMSE score <24): they had a mean MMSE score of 28·9 (sd 1·1). Serum cholesteryl ester-eicosapentaenoic acid and DHA levels were significantly lower (P<0·05 and P<0·001 respectively) in all MMSE score quartiles of patients with Alzheimer's disease compared with control values. Serum cholesteryl ester-DHA levels were progressively reduced with severity of clinical dementia. DHA levels did not differ in patients with Alzheimer's disease across age quartiles: all were consistently lower than in control subjects. Step-wise multiple regression analysis showed that cholesteryl ester-DHA and total saturated fatty acid levels were the important determinants of MMSE score and CDR. It remains to be determined whether low DHA status in Alzheimer's disease is a casual factor in the pathogenesis and progression of Alzheimer's disease.

Type
Research Article
Copyright
Copyright © The Nutrition Society 2003

References

Albert, CM, Hennekens, CH, O'Donnell, CJ, Ajani, UA, Carey, VJ, Willett, WC, Ruskin, JN & Manson, JE (1998) Fish consumption and risk of sudden cardiac death. Journal of the American Medical Association 279, 2328.CrossRefGoogle ScholarPubMed
Babin, F, Abderrazik, M, Favier, F, Cristol, JP, Léger, CL, Papoz, L & Descomps, B (1999) Differences between polyunsaturated fatty acid status of non-institutionalized elderly women and younger controls: a bioconversion defect can be suspected. European Journal of Clinical Nutrition 53, 591596.CrossRefGoogle Scholar
Bang, HO, Dyerberg, J & Nielsen, AB (1971) Plasma lipid and lipoprotein pattern in Greenlandic west-coast Eskimos. Lancet 1, 11431145.CrossRefGoogle ScholarPubMed
Bechoua, S, Dubois, M, Nemoz, G, Chapuy, P, Vericel, E, Lagarde, M & Prigent, AF (1999) Very low dietary intake of n-3 fatty acids affects the immune function of healthy elderly people. Lipids 34, 143S.CrossRefGoogle ScholarPubMed
Billiar, TR, Bankey, PE, Svingen, BA, Curran, RD, West, MA, Holman, RT, Simmons, RL & Cerra, FB (1988) Fatty acid intake and Kupffer cell function: fish oil alters eicosanoid and monokine production to endotoxin stimulation. Surgery 104, 343349.Google ScholarPubMed
Blok, WL, Deslypere, JP, Demacker, PN, van der Ven-Jongekrijg, J, Hectors, MP, van der Meer, JW & Katan, MB (1997) Pro- and anti-inflammatory cytokines in healthy volunteers fed various doses of fish oil for 1 year. European Journal of Clinical Investigation 27, 10031008.CrossRefGoogle ScholarPubMed
Broe, GA, Henderson, AS, Creasey, H, McCusker, E, Korten, AE, Jorm, AF, Longley, W & Anthony, JC (1990) A case–control study of Alzheimer's disease in Australia. Neurology 40, 16981707.CrossRefGoogle ScholarPubMed
Burr, ML, Fehily, AM, Gilbert, JF, Rodgers, S, Holliday, RM, Sweetman, PM, Elwood, PC & Deadman, NM (1989) Effects of changes in fat, fish and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART). Lancet 2, 757761.CrossRefGoogle ScholarPubMed
Caughey, GE, Mantzioris, E, Gibson, RA, Cleland, LG & James, MJ (1996) The effect on human necrosis factor α and interleukin 1β production of diets enriched in n-3 fatty acids from vegetable oil or fish oil. American Journal of Clinical Nutrition 63, 116122.CrossRefGoogle ScholarPubMed
Compston, A (1994) Brain repair: an overview. Journal of Neurology 241, 1S4S.CrossRefGoogle Scholar
Cunningham, CJ, Sinnott, M, Denihan, A, Rowan, M, Walsh, JB, O'Moore, R, Coakley, D, Coen, RF, Lawlor, BA & O'Neill, DD (2001) Endogenous sex hormone levels in postmenopausal women with Alzheimer's disease. Journal of Clinical Endocrinology and Metabolism 86, 10991103.Google ScholarPubMed
Folch, J, Lees, M & Stanley, GHS (1957) A simple method for the isolation and purification of total lipides from animal tissues. Journal of Biological Chemistry 226, 497509.CrossRefGoogle ScholarPubMed
Folstein, MF, Folstein, SE & McHugh, PR (1975) Mini-Mental State: a practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research 12, 189198.CrossRefGoogle Scholar
Gibney, MJ & Bolton-Smith, C (1988) The effect of a dietary supplement of n-3 polyunsaturated fat on platelet lipid composition, platelet function and platelet plasma membrane fluidity in healthy volunteers. British Journal of Nutrition 60, 512.CrossRefGoogle ScholarPubMed
Glatz, JF, Soffers, AE & Katan, MB (1989) Fatty acid composition of serum cholesteryl esters and erythrocyte membranes as indicators of linoleic acid intake in man. American Journal of Clinical Nutrition 49, 269276.CrossRefGoogle ScholarPubMed
Hendrie, HC (1998) Epidemiology of dementia and Alzheimer's disease. American Journal of Geriatric Psychiatry 6, 3S18S.CrossRefGoogle ScholarPubMed
Hibbeln, JR (1998) Fish consumption and major depression. Lancet 351, 1213.CrossRefGoogle ScholarPubMed
Hofman, A, Ott, A, Breteler, MM, Bots, ML, Slooter, AJ, van Harskamp, F, van Duijn, CN, van Broeckhoven, C & Grobbee, DE (1997) Atherosclerosis, apolipoprotein E and the prevalence of dementia and Alzheimer's disease in the Rotterdam study. Lancet 349, 151154.CrossRefGoogle ScholarPubMed
Hughes, CP, Berg, L, Danziger, WL, Coben, LA & Martin, RL (1982) A new clinical scale for the staging of dementia. British Journal of Psychiatry 140, 566572.CrossRefGoogle ScholarPubMed
Jorm, AF, Korten, AE & Henderson, AS (1987) The prevalence of dementia: a quantitative integration of the literature. Acta Psychiatrica Scandinavica 76, 465479.CrossRefGoogle ScholarPubMed
Kalmijn, S, Feskens, EJM, Launer, LJ & Kromhout, D (1997a) Polyunsaturated fatty acids, antioxidants and cognitive function in very old men. American Journal of Epidemiology 145, 3341.CrossRefGoogle ScholarPubMed
Kalmijn, S, Launer, LJ, Ott, A, Witteman, JCM, Hofman, A & Breteler, MMB (1997b) Dietary fat intake and the risk of incident dementia in the Rotterdam study. Annals of Neurology 42, 776782.CrossRefGoogle ScholarPubMed
Kim, HY & Edsall, L (1999) The role of docosahexaenoic acid (22: 6 n-3) in neuronal signalling. Lipids 34, 249S.CrossRefGoogle Scholar
Kromhout, D, Bosschieter, EB & de Lezenne Coulander, C (1985) The inverse relation between fish consumption and 20-year mortality from coronary heart disease. New England Journal of Medicine 312, 12051209.CrossRefGoogle ScholarPubMed
Kyle, DJ, Schaefer, E, Patton, G & Beiser, A (1999) Low serum docosahexaenoic acid is a significant risk factor for Alzheimer's dementia. Lipids 34, 245S.CrossRefGoogle ScholarPubMed
Li, D, Mann, NJ & Sinclair, AJ (1999) Comparison of n-3 polyunsaturated fatty acids from vegetable oils, meat and fish in raising platelet eicosapentaenoic acid levels in humans. Lipids 34, 309S.CrossRefGoogle ScholarPubMed
McKhann, G, Drachman, D, Folstein, M, Katzman, R, Price, D & Stadlan, EM (1984) Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services and Human Services Task Force on Alzheimer's Disease. Neurology 34, 939945.CrossRefGoogle ScholarPubMed
Nakada, T, Kwee, IL & Ellis, WG (1990) Membrane fatty acid composition shows delta-6-desaturase abnormalities in Alzheimer's disease. Neuroreport 1, 153155.CrossRefGoogle ScholarPubMed
Neuringer, M & Connor, WE (1986) n-3 fatty acids in the brain and retina: evidence for their essentiality. Nutrition Reviews 44, 285294.CrossRefGoogle ScholarPubMed
Nikkari, T (1986) Serum fatty acids and coronary heart diesease in Finnish populations. Progress in Lipid Research 25, 437450.CrossRefGoogle Scholar
Nourhasémi, F, Gillette-Guyonnet, S, Andrieu, S, Ghisolfi, A, Ousset, PJ, Grandjean, H, Grand, A, Pous, J, Vellas, B & Albarede, JL (2000) Alzheimer disease: protective factors. American Journal of Clinical Nutrition 71, 643S649S.CrossRefGoogle Scholar
Peers, RJ (1990) Alzheimer's disease and omega-3 fatty acids: hypothesis. Medical Journal of Australia 153, 563564.CrossRefGoogle ScholarPubMed
Périchon, R, Bourre, JM, Kelly, JF & Roth, GS (1998) The role of peroxisomes in aging. Cellular and Molecular Life Sciences 54, 641652.CrossRefGoogle ScholarPubMed
Prasad, MR, Lovell, MA, Yatin, M, Dhillon, H & Markesbery, WR (1998) Regional membrane phospholipid alterations in Alzheimer's disease. Neurochemical Research 23, 8188.CrossRefGoogle ScholarPubMed
Reisberg, B, Ferris, SH, Anand, R, deLeon, MJ, Scheck, MJ & Crook, T (1985) Clinical assessment of cognitive decline in normal ageing and primary degenerative dementia: concordant ordinal measures. In Psychiatry 5, pp. 333338 [Pinchot, P, Berner, R, and Thau, K, editors]. New York: Plenum Press.Google Scholar
Simon, JA, Hodgkins, ML, Browner, WS, Neuhaus, JM, Bernert, JT Jr & Hulley, SB (1995) Serum fatty acids and the risk of coronary heart disease. American Journal of Epidemiology 142, 469476.CrossRefGoogle ScholarPubMed
Singh, RB, Niaz, MA, Sharma, JP, Kumar, R, Rastogi, V & Moshiri, M (1997) Randomized, double-blind, placebo-controlled trial of fish oil and mustard oil in patients with suspected acute myocardial infarction: the Indian experiment of infarct survival – 4. Cardiovascular Drugs and Therapy 11, 485491.CrossRefGoogle ScholarPubMed
Soderberg, M, Edlund, C, Kristensson, K & Dallner, G (1991) Fatty acid composition of brain phospholipids in aging and in Alzheimer's disease. Lipids 26, 421425.CrossRefGoogle ScholarPubMed
Stoll, AL, Severus, E, Freeman, MP, Rueter, S, Zboyan, HA, Diamond, E, Gress, KK & Marangell, LB (1999) Omega 3 fatty acids in bipolar disorder: a preliminary double-blind, placebo-controlled trial. Archives of General Psychiatry 56, 413416.CrossRefGoogle ScholarPubMed
Swanwick, GJ, Coen, RF, O'Mahony, D, Tully, M, Bruce, I, Buggy, F, Lawlor, BA, Walsh, JB & Coakley, D (1996) A memory clinic for the assessment of mild dementia. Irish Medical Journal 89, 104105.Google ScholarPubMed
Terano, T, Fujishiro, S, Ban, T, Yamamoto, K, Tanaka, T, Noguchi, Y, Tamura, Y, Yazawa, K & Hirayama, T (1999) Docosahexaenoic acid supplementation improves the moderately severe dementia from thrombotic cerebrovascular diseases. Lipids 34, 345S346S.CrossRefGoogle ScholarPubMed
Voss, A, Reinhart, M, Sankarappa, S & Sprecher, H (1991) The metabolism of 7,10,13,16,19-docosapentaenoic acid to 4,7,10,13,16,19-docosahexaenoic acid in rat liver is independent of a 4-desaturase. Journal of Biological Chemistry 266, 1999520000.CrossRefGoogle Scholar
World Health Organization (1992) ICD-10 Classification of Mental and Behavioural Disorders. Clinical Disorders and Diagnostic Guidelines. Geneva: WHO.Google Scholar
Yehuda, S, Rabinovitz, S, Carasso, RL & Mostofsky, DI (1996) Essential fatty acids preparation (SR-3) improves Alzheimer's patients quality of life. International Journal of Neuroscience 87, 141149.CrossRefGoogle ScholarPubMed