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Omega-3 fatty acids, cognitive impairment and Alzheimer's disease

Part of: Bespoke shallow archive Weizmann

Published online by Cambridge University Press:  21 July 2010

MA Phillips
MA Phillips*
Affiliation:
Department of Experimental Psychology, University of Bristol, UK
*
Address for correspondence: Dr Michelle Phillips, Department of Experimental Psychology, University of Bristol, Bristol, UK. Email: [email protected]
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Summary

The continued imbalance of fatty acids in western diets has led to concerns about the effect this may be having on physical and mental wellbeing. Diets rich in omega-3 fatty acids, mainly docosahexaenoic acid (DHA) and eicosahexanoic acid (EPA), are argued to help with cardiovascular health as well as cognition. The mechanisms by which this happens are complex and not well understood. However, results from research in this area speculate that individuals with cognitive difficulties may benefit from increasing their omega-3 fatty acid intake, especially if they already show depleted levels of omega-3 fatty acids. This review examines mechanistic reasons behind why low intake of omega-3 fatty acids may affect physical and cognitive health, as well as evidence suggesting diets high in omega-3 fatty acids fend off cognitive disorders. It will also discuss the small body of evidence indicating that omega-3 fatty acids are depleted in those with already manifest cognitive disorders and the possibility that elevating omega-3 fatty acid status in such individuals may benefit their cognition.

Keywords

omega-3 fatty acidscognitive impairmentAlzheimer's diseasebrain functionelderly
Type
Neuropsychiatry of old age
Information
Reviews in Clinical Gerontology , Volume 20 , Issue 3 , August 2010 , pp. 219 - 238
Copyright
Copyright © Cambridge University Press 2010

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References

1Simopoulos, AP. Essential fatty acids in health and chronic disease. Am J Clin Nutr 1999; 70: S560–69.CrossRefGoogle ScholarPubMed
2Young, G, Conquer, J. Omega-3 fatty acids and neuropsychiatric disorders. Reprod Nutr Dev 2005; 45: 1–28.CrossRefGoogle ScholarPubMed
3Lunn, J, Theobald, HE. The health effects of dietary unsaturated fatty acids. Br Nutr Found Nutrition Bull 2006; 31: 178–224.CrossRefGoogle Scholar
4Morris, MC, Sacks, F, Rosner, B. Does fish oil lower blood pressure – a meta-analysis of controlled trials. Circulation 1993; 88: 523–33.CrossRefGoogle ScholarPubMed
5Bao, DQ, Mori, TA, Burke, V, Puddey, IB, Beilin, LJ. Effects of dietary fish and weight reduction on ambulatory blood pressure in overweight hypertensives. Hypertension 1998; 32: 710–17.CrossRefGoogle ScholarPubMed
6Leaf, A, Kang, JX, Xiao, YF, Billman, GE. Clinical prevention of sudden cardiac death by n-3 polyunsaturated fatty acids and mechanism of prevention of arrhythmias by n-3 fish oils. Circulation 2003; 107: 2646–52.CrossRefGoogle ScholarPubMed
7Gillum, RF, Mussolino, ME, Madans, JH. The relationship between fish consumption and stroke incidence: the NHANES I Epidemiologic Follow-up Study (National Health and Nutrition Examination Survey). Arch Intern Med 1996; 156: 537–42.CrossRefGoogle ScholarPubMed
8Iso, H, Rexrode, KM, Stampfer, MJ, Manson, JE, Colditz, GA, Speizer, F, Hennekens, CH, Willett, WC. Intake of fish and omega-3 fatty acids and risk of stroke in women. J Am Med Assoc 2001; 285: 304–12.CrossRefGoogle ScholarPubMed
9Virtanen, JK, Siscovick, DS, Longstreth, WT, Kuller, LH, Mozaffarian, D. Fish consumption and risk of subclinical brain abnormalities on MRI in older adults. Neurology 2008; 71: 439–46.CrossRefGoogle ScholarPubMed
10Hornstra, G. Influence of dietary fat type on arterial thrombosis tendency. J Nutr Health Aging 2001; 5: 160–66.Google ScholarPubMed
11Von Schacky, C, Harris, WS. Cardiovascular benefits of omega-3 fatty acids. Cardiovasc Res 2007; 73: 310–15.CrossRefGoogle ScholarPubMed
12Mensink, RP, Katan, MB. Effect of dietary fatty acids on serum lipids and lipoproteins. A meta-analysis of 27 trials. Arterioscler Thromb 1992; 12: 911–19.CrossRefGoogle ScholarPubMed
13Clarke, R, Frost, C, Collins, Appleby P, Peto, R. Dietary lipids and blood cholesterol: Quantitative meta-analysis of metabolic ward studies. BMJ 1997; 314: 112.CrossRefGoogle ScholarPubMed
14Howell, WH, McNamara, DJ, Tosca, MA, Smith, BT, Gaines, JA. Plasma lipid and lipoprotein responses to dietary fat and cholesterol: A meta-analysis. Am J Clin Nutr 1997; 65: 1747–64.CrossRefGoogle ScholarPubMed
15Simopoulos, AP. Evolutionary aspects of nutrition and health. Diet, exercise genetics and chronic disease. World Rev Nutr and Diet 1999; 84. Karger: Basel.Google Scholar
16Tanaka, K, Ishikawa, Y, Yokoyama, M, Origasa, H, Matsuzaki, M, Saito, Y, Matsuzawa, Y, Sasaki, J, Oikawa, S, Hishida, H, Itakura, H, Kita, T, Kitabatake, A, Nakaya, N, Sakata, T, Shimada, K, Shirato, K; JELIS Investigators, Japan. Reduction in the recurrence of stroke by eicosapentaenoic acid for hypercholesterolemic patients. Stroke 2008; 39: 2052–58.CrossRefGoogle ScholarPubMed
17Breteler, MM, Claus, JJ, Grobbee, DE, Hofman, A. Cardiovascular disease and distribution of cognitive function in elderly people: the Rotterdam study. BMJ 1994; 308: 1604–8.CrossRefGoogle ScholarPubMed
18Muller, M, Grobbee, DE, Aleman, A, Bots, M, van der Schouw, YT. Cardiovascular disease and cognitive performance in middle-aged and elderly men. Atherosclerosis 2007; 190: 143–49.CrossRefGoogle ScholarPubMed
19Lim, C, Alexander, MP, LaFleche, G, Schnyer, DM, Verfaellie, M. The neurological and cognitive sequelae of cardiac arrest. Neurology 2004; 63: 1774–78.CrossRefGoogle ScholarPubMed
20Verhaeghen, P, Borchelt, M, Smith, J. Relation between cardiovascular and metabolic disease and cognition in very old age: Cross-sectional and longitudinal findings from the Berlin aging study. Health Psychol 2003; 22: 559–69.CrossRefGoogle Scholar
21Murray, L. Cardiovascular disease: Effects upon cognition and communication. The ASHA Leader 2006; 11: 10–11, 22–23.CrossRefGoogle Scholar
22de la Torre, JC. Alzheimer's disease as a vascular disorder: nosological evidence. Stroke 2002; 33: 1152–62.CrossRefGoogle ScholarPubMed
23Hooijmans, CR, Kiliaan, AJ. Review: Fatty acids, lipid metabolism and Alzheimer pathology. Eur J Pharmacol 2008; 585: 176–96.CrossRefGoogle ScholarPubMed
24Skoog, I, Gustafson, D. Update on hypertension and Alzheimer's disease. Neurol Res 2006; 28: 605–11.CrossRefGoogle ScholarPubMed
25Scahill, RI, Schott, JM, Stevens, JM, Rossor, MN, Fox, NC. Mapping the evolution of regional atrophy in Alzheimer's disease: Unbiased analysis of fluid-registered serial MRI. Proc Natl Acad Sci USA 2002; 99: 4703–7.CrossRefGoogle ScholarPubMed
26Vandenberghe, R, Tournoy, J. Cognitive aging and Alzheimer's disease. Postgrad Med J 2005; 81: 343–52.CrossRefGoogle ScholarPubMed
27Henry-Feugeas, MC. MRI of the ‘Alzheimer syndrome’. J Neuroradiol 2007; 34: 220–7.CrossRefGoogle ScholarPubMed
28Tully, AM, Roche, HM, Doyle, R, Fallon, C, Bruce, I, Lawlor, B, Coakley, D, Gibney, MJ. Low serum cholesteryl ester-docosahexaenoic acid levels in Alzheimer's disease: a case-control study. Br J Nutr 2003; 89: 843–49.CrossRefGoogle ScholarPubMed
29He, K, Rimm, EB, Merchant, A, Rosner, BA, Stampfer, MJ, Willett, WC, Ascherio, A. Consumption and risk of stroke in men. J Am Med Assoc 2002; 288: 56–62.CrossRefGoogle ScholarPubMed
30Iso, H, Rexrode, KM, Stampfer, MJ, Manson, JE, Colditz, GA, Speizer, FE, Hennekens, CH, Willett, WC. Intake of fish and omega-3 fatty acids and risk of stroke in women. J Am Med Assoc 2001; 285: 304–12.CrossRefGoogle ScholarPubMed
31Merino, JG, Hachinski, V. Stroke-related dementia. Curr Atheroscler Rep 2002; 4: 285–90.CrossRefGoogle ScholarPubMed
32Din, JN, Newby, DE, Flapan, AD. Science medicine and the future: Omega-3 fatty acids and cardiovascular disease-fishing for natural treatment. BMJ 2004; 328: 30–35.CrossRefGoogle Scholar
33Akiyama, H, Barger, S, Barnum, S, Bradt, B, Bauer, J, Cole, GM, Cooper, NR, Eikelenboom, P, Emmerling, M, Fiebich, BL, Finch, CE, Frautschy, S, Griffin, WS, Hampel, H, Hull, M, Landreth, G, Lue, L, Mrak, R, Mackenzie, IR, McGeer, PL, O'Banion, MK, Pachter, J, Pasinetti, G, Plata-Salaman, C, Rogers, J, Rydel, R, Shen, Y, Streit, W, Strohmeyer, R, Tooyoma, I, Van Muiswinkel, FL, Veerhuis, R, Walker, D, Webster, S, Wegrzyniak, B, Wenk, G, Wyss-Coray, T. Inflammation and Alzheimer's disease. Neurobiol Aging 2000; 21: 383–421.CrossRefGoogle ScholarPubMed
34Bourre, JM. Effects of nutrients (in food) on the structure and function of the nervous system: Update on dietary requirements for brain. Part 2: Macronutrients. J Nutr Health Aging 2006; 10: 386–99.Google ScholarPubMed
35Van de Weyer, C. Food for thought. Diet and Mental Health: Health Matters 2006; issue 64; available at: http://www.sustainweb.org/pdf/HealthMatters.pdf (accessed 1 May, 2010).Google Scholar
36Logan, AC. Omega-3 fatty acids and major depression: A primer for the mental health professional. Lipids Health Dis 2004; 3: 24–31.CrossRefGoogle ScholarPubMed
37Catalan, J, Toru, M, Slotnick, B, Murthy, M, Greiner, RS, Salem, N. Cognitive deficits in docosahexaenoic acid-deficient rats. Behav Neurosci 2002; 116: 1022–31.CrossRefGoogle ScholarPubMed
38Salem, N, Niebylski, CD. The nervous system has an absolute molecular species requirement for proper function. Mol Membr Biol 1995; 12: 131–34.CrossRefGoogle ScholarPubMed
39Maclean, CH, Issa, AM, Newberry, SJ, Mojica, WA, Morton, SC, Garland, RH, Hilton, LG, Traina, SB, Shekelle, PG. Effects of omega-3 fatty acids on cognitive function with aging, dementia, and neurological diseases. Evid Rep Technol Assess 2005; 114: 3–88.Google Scholar
40Lauritzen, L, Hansen, HS, Jorgensen, MH, Michaelsen, KF. The essentiality of long chain n-3 fatty acids in relation to development and function of the brain and retina. Prog Lipid Res 2001; 40: 1–94.CrossRefGoogle ScholarPubMed
41Becker, CC, Kyle, D. The importance of DHA in optimal cognitive function in rodents. In Mostofsky, D, Yehuda, S, Salem, N (eds), Fatty Acids: Physiological and Behavioral Functions. USA: Human Press Inc., 2001; pp. 357–76.CrossRefGoogle Scholar
42Yehuda, S. Omega-6/omega-3 ratio and brain-related functions. In Simopoulos, AP, Cleland, LG (eds), Omega-6/Omega-3 Essential Fatty Acid Ratio: The Scientific Evidence, Basel, Karger. World Rev Nutrition Dietetics 2003; 92: 37–56.CrossRefGoogle Scholar
43Yehuda, S, Rabinovitz, S, Carasso, RL, Mostofsky, DI. The role of polyunsaturated fatty acids in restoring the ageing neuronal membrane. Neurobiol Aging 2002; 23: 843–53.CrossRefGoogle ScholarPubMed
44Yehuda, S, Rabinovitz, S, Mostofsky, DI. Essential fatty acids are mediators of brain biochemistry and cognitive functions. J Neurosci Res 1999; 56: 565–70.3.0.CO;2-H>CrossRefGoogle ScholarPubMed
45Jones, C, Arai, T, Rapoport, S. Evidence for the involvement of docosahexaenoic acid in cholinergic stimulated signal transduction at the synapse. Neurochem Res 1997; 22: 663–70.CrossRefGoogle ScholarPubMed
46Carrie, I, Clement, M, de Javel, D, Francis, H, Bourre, JM. Specific phospholipid fatty acid composition of brain regions in mice. Effects on n-3 polyunsaturated fatty acid deficiency and phospholipids supplementation. J Lipid Res 2000; 41: 465–72.CrossRefGoogle Scholar
47Carrie, I, Clement, M, de Javel, D, Francis, H, Bourre, JM. Phospholipid supplementation reverses behavioural and biochemical alterations induced by n-3 polyunsaturated fatty acid deficiency in mice. J Lipid Res 2000; 41: 473–80.CrossRefGoogle ScholarPubMed
48Hashimoto, M, Hossain, S, Shimada, T, Sugioka, K, Yamasaki, H, Fujii, Y, Ishibashi, Y, Oka, J, Shido, O. Docosahexaenoic acid provides protection from impairment of learning ability in Alzheimer's disease model rats. J Neurochem 2002; 81: 1084–91.CrossRefGoogle ScholarPubMed
49Hung, MC, Shibasaki, K, Yoshida, R, Sato, M, Imaizumi, K. Learning behaviour and cerebral protein kinase C, antioxidant status, lipid composition in senescence-accelerated mouse: influence of a phosphatidylcholine vitamin B12 diet. Br J Nutr 2001; 86: 163–71.CrossRefGoogle ScholarPubMed
50Moriguchi, T, Greiner, RS, Salem, N. Behavioral deficits associated with dietary induction of decreased brain docosahexaenoic acid concentration. J Neurochem 2000; 75: 2563–73.CrossRefGoogle ScholarPubMed
51Umezawa, M, Ohta, A, Tojo, H, Yagi, H, Hosokawa, M, Takeda, T. Dietary α-linolenate/linoleate balance influences learning and memory in the senescence-accelerated mouse (SAM). Brain Res 1995; 669: 225–33.CrossRefGoogle ScholarPubMed
52Ahmad, A, Murthy, M, Greiner, RS, Moriguchi, T, Salem, N. A decrease in cell size accompanies a loss of docosahexaenoate in the rat hippocampus. Nutr Neurosci 2002; 5: 103–13.CrossRefGoogle ScholarPubMed
53Ximenes da Silva, A, Lavialle, F, Gendrot, G, Guesnet, P, Alessandri, JM, Lavialle, M. Glucose transport and utilization are altered in the brain of rats deficient in n-3 polyunsaturated fatty acids. J Neurochem 2002; 81: 1328–37.CrossRefGoogle ScholarPubMed
54Nanjo, A, Kanazawa, A, Sato, K, Banno, F, Fujimoto, K. Depletion of dietary n-3 fatty acid affects the level of cyclic AMP in rat hippocampus. J Nutr Sci Vitaminol 1999; 45: 633–41.CrossRefGoogle ScholarPubMed
55Gazzah, N, Gharib, A, Croset, M, Bobillier, P, Lagarde, M, Sarda, N. Decrease of brain phospholipid synthesis in free-moving n-3 fatty acid deficient rats. J Neurochem 1995; 64: 908–18.CrossRefGoogle ScholarPubMed
56Murthy, M, Hamilton, J, Greiner, RS, Morigushi, T, Salem, N, Kim, HY. Differential effects of n-3 fatty acid deficiency on phospholipid molecular species composition in the rat hippocampus. J Lipid Res 2002; 43: 611–17.CrossRefGoogle ScholarPubMed
57De Vries, HE, Kuiper, J, De Boer, AG, Van Berkel, TJC, Breimer, DD. The blood–brain barrier in neuroinflammatory diseases. Pharmacol Rev 1997; 49: 143–55.Google ScholarPubMed
58Lim, WS, Gammack, JK, van Niekerk, JK, Dangour, AD. Omega-3 fatty acid for the prevention of dementia (Review). Cochrane Collaboration: John Wiley and Sons Ltd, 2006; pp. 1–14.Google Scholar
59Söderburg, M, Edlund, C, Kristensson, K, Dallner, G. Fatty acid composition of brain phospholipids in aging and in Alzheimer's disease. Lipids 1991; 26: 421–28.CrossRefGoogle Scholar
60Söderburg, M, Edlund, C, Kristensson, K, Alafuzoff, I, Dallner, G. Lipid composition in different regions of the brain in Alzheimer's disease/senile dementia of the Alzheimer's type. J Neurochem 1992; 59: 1646–53.CrossRefGoogle Scholar
61Nitsch, R, Pittas, A, Blustztajn, JK, Slock, BE, Growdon, J. Alterations of phospholipid metabolites in post-mortem brains from patients with Alzheimer's disease. Ann NY Acad Sci 1991; 640: 110–13.CrossRefGoogle Scholar
62Mulder, M, Ravid, R, Swaab, DF, de Kloet, ER, Haasdijk, ED, Julk, J, Van Der Boom, JJ, Havekes, LM. Reduced levels of cholesterol, phospholipids, and fatty acids in CSF of Alzheimer's disease patients are not related to Apo E4. Alzheimer Dis Assoc Disord 1998; 12: 198–203.CrossRefGoogle ScholarPubMed
63Morris, MC, Evans, DA, Bienias, JL, Tangney, CC, Bennett, DA, Aggarwal, N, Schneider, J, Wilson, RS. Dietary fats and the risk of incident Alzheimer's disease. Arch Neurol 2003; 60: 194–200.CrossRefGoogle Scholar
64Friedland, RP. Fish consumption and the risk of Alzheimer's disease. Arch Neurol 2003; 60: 923–24.CrossRefGoogle Scholar
65Lim, GP, Calon, F, Yang, F, Morihara, T, Ubeda, O, Ashe, KH et al. Omega-3 fatty acid enriched diet reduces amyloid in an Alzheimer's disease mouse model. Neurobiol Aging 2004; 25: S570.CrossRefGoogle Scholar
66Green, KN, Martinez-Coria, H, Khashwji, H, Hall, EB, Yurko-Mauro, KA, Ellis, L, LaFerla, FM. Dietary docosahexaenoic acid and docosapentaenoic acid ameliorate amyloid and tau pathology via a mechanism involving presenilin 1 levels. J Neurosci 2007; 27: 4385–95.CrossRefGoogle Scholar
67Calon, F, Lim, GP, Yang, F, Morihara, T, Teter, B, Ubeda, O, Rostaing, P, Triller, A, Salem, N Jr, Ashe, KH, Frautschy, SA, Cole, GM. Docosahexaenoic acid protects from dendritic pathology in an Alzheimer's disease mouse model. Neuron 2004; 43: 633–45.CrossRefGoogle Scholar
68Favreliere, S, Perault, MC, Huguet, F, De Javel, D, Bertrand, N, Piriou, A, Durand, G. DHA enriched phospholipid diets modulate age-related alterations in rat hippocampus. Neurobiol Aging 2003; 24: 233–43.CrossRefGoogle ScholarPubMed
69Minami, M, Kimura, S, Endo, T, Hamaue, N, Hirafuji, M, Togashi, H, Matsumoto, M, Yoshioka, M, Saito, H, Watanabe, S, Kobayashi, T, Okuyama, H. Dietary docosahexaenoic acid increases cerebral acetylcholine levels and improves passive avoidance in stroke-prone spontaneously hypertensive rats. Pharmacol Biochem Behav 1997; 58: 1123–29.CrossRefGoogle ScholarPubMed
70Gamoh, S, Hashimoto, M, Sugioka, K, Shahdat Hossain, M, Hata, N, Misawa, Y, Masumura, S. Chronic administration of docosahexaenoic acid improves reference memory-related learning ability in young rats. Neuroscience 1999; 93: 237–41.CrossRefGoogle ScholarPubMed
71Gamoh, S, Hashimoto, M, Hossain, S, Masumura, S. Chronic administration of docosahexaenoic acid improves the performance of radial arm maze task in aged rats. Clin Exp Pharmacol Physiol 2001; 28: 266–270.CrossRefGoogle ScholarPubMed
72Cole, GM, Lim, GP, Yang, F, Teter, B, Begum, A, Ma, Q, Harris-White, ME, Frautschy, SA. Prevention of Alzheimer's disease: Omega-3 fatty acid and phenolic anti-oxidant interventions. Neurobiol Aging 2005; 26S: S133–36.CrossRefGoogle Scholar
73Kris-Etherton, PM, Harris, WS, Appel, JL. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Arterioscler Thromb Vasc Biol 2003; 23: 20–30.Google ScholarPubMed
74Belluzzi, A, Boschi, S, Brignola, C, Munarini, A, Cariani, G, Miglio, F. Polyunsaturated fatty acids and inflammatory bowel disease. Am J Clin Nutr 2000; 71: 339–42s.CrossRefGoogle ScholarPubMed
75Geschwind, DH, Robidoux, J, Alarcon, M, Miller, BL, Wilhelmsen, KC, Cummings, JL, Nasreddine, ZS. Dementia and neurodevelopmental predisposition: Cognitive dysfunction in presymptomatic subjects precedes dementia by decades in frontotemporal dementia. Ann Neurol 2001; 50: 741–46.CrossRefGoogle ScholarPubMed
76Pradignac, A, Schlienger, JL, Velten, M, Mejean, L. Relationships between macronutrient intake, handicaps, and cognitive impairments in free living elderly people. Aging Clin Exp Res 1995; 7: 67–74.CrossRefGoogle ScholarPubMed
77Kalmijn, S, Feskens, EJM, Launer, LJ, Kromhout, D. Polyunsaturated fatty acids, antioxidants, and cognitive function in very old men. Am J Epidemiol 1997; 145: 33–41.CrossRefGoogle ScholarPubMed
78Ortega, RM, Requejo, AM, Andres, P, Lopez-Sobaler, AM, Quintas, ME, Redondo, MR, Navia, B, Rivas, T. Dietary intake and cognitive function in a group of elderly people. Am J Clin Nutr 1997; 66: 803–9.CrossRefGoogle Scholar
79Solfrizzi, V, Panza, F, Torres, F, Mastroianni, F, Del Parigi, A, Venezia, A, Capurso, A. High monounsaturated fatty acid intake protects against age-related cognitive decline. Neurology 1999; 52: 1563–69.CrossRefGoogle ScholarPubMed
80Engelhart, MJ, Geerling, MI, Ruitenberg, A, van Swieten, JC, Hofman, A, Witteman, JC, Breteler, MM. Diet and risk of dementia: Does fat matter? Neurology 2002; 59: 1915–21.CrossRefGoogle ScholarPubMed
81Capurso, A, Panza, F, Capurso, C, Colacicco, AM, D'Introno, A, Torres, F et al. Olive oil consumption and health. Ann Nutr Metab 2003; 47: 243–44.Google Scholar
82Kalmijn, S, van Boxtel, MPJ, Ocké, M, Verschuren, WMM, Kromhout, D, Launer, LJ. Dietary intake of fatty acids and fish in relation to cognitive performance at middle age. Neurology 2004; 62: 275–80.CrossRefGoogle ScholarPubMed
83Morris, MC, Evans, DA, Bienias, JL, Tangney, CC, Bennett, DA, Wilson, RS. Dietary fat intake and 6-year cognitive change in an older biracial community population. Neurology 2004; 62: 1573–79.CrossRefGoogle Scholar
84Solfrizzi, V, Colacicco, AM, D'Introno, A, Capurso, C, Torres, F, Rizzo, C, Capurso, A, Panza, F. Dietary intake of unsaturated fatty acids and age-related cognitive decline: a 85-year follow-up of the Italian Longitudinal Study on Aging. Neurobiol Aging 2006; 27: 1694–704.CrossRefGoogle Scholar
85Solfrizzi, V, Colacicco, AM, D'Introno, A, Capurso, C, Del Parigi, A, Capurso, SA, Argentieri, G, Capurso, A, Panza, F. Dietary polyunsaturated fatty acids intakes and rate of mild cognitive impairment. The Italian Longitudinal Study on Aging. Exp Gerontol 2006; 41: 619–27.CrossRefGoogle ScholarPubMed
86Nurk, E, Drevon, CA, Refsum, H, Solvoll, K, Vollset, SE, Nygård, O, Nygaard, HA, Engedal, K, Tell, GS, Smith, AD. Cognitive performance among the elderly and dietary fish intake: the Hordaland Health Study. Am J Clin Nutr 2007; 86: 1470–78.CrossRefGoogle ScholarPubMed
87Scarmeas, N, Luchsinger, JA, Mayeux, R, Stern, Y. Mediterranean diet and Alzhiemer's disease mortality. Neurology 2007; 69: 1084–93.CrossRefGoogle Scholar
88van Gelder, BM, Tijhuis, M, Kalmijn, S, Kromhout, D. Fish consumption, n-3 fatty acids, and subsequent 5-y cognitive decline in elderly men: the Zutphen Elderly Study. Am J Clin Nutr 2007; 85: 1142–47.CrossRefGoogle ScholarPubMed
89Eskelinen, MH, Ngandu, T, Helkala, EL, Tuomilehto, J, Nissinen, A, Soininen, H, Kivipelto, M. Fat intake at midlife and cognitive impairment later in life: a population-based CAIDE study. Int J Geriatr Psychiat 2008; 23: 741–47.CrossRefGoogle ScholarPubMed
90Dangour, AD, Allen, E, Elbourne, D, Fletcher, A, Richards, M, Uauy, R. Fish consumption and cognitive function among older people in the UK: baseline data from the OPAL study. J Nutr Health Aging 2009; 13: 198–202.CrossRefGoogle ScholarPubMed
91Bosman, GJCGM, Bartholomeus, IGP, De Man, AJM, Van Kalmthout, PJC, De Grip, WJ. Erythrocyte membrane characteristics indicate abnormal cellular aging in patients with Alzheimer's disease. Neurobiol Aging 1991; 12: 13–18.CrossRefGoogle ScholarPubMed
92Corrigan, FM, Van Rhijn, A, Horrobin, DF. Essential fatty acids in Alzheimer's disease. Ann NY Acad Sci 1991; 640: 250–50.CrossRefGoogle ScholarPubMed
93Kyle, DJ, Schaefer, E, Patton, G, Beiser, A. Low serum docosahexaenoic acid is a significant risk factor for Alzheimer's dementia. Lipids 1999; 34: S245.CrossRefGoogle ScholarPubMed
94Conquer, JA, Tierney, MC, Zecevic, J, Bettger, WJ, Fisher, RH. Fatty acid analysis of blood plasma of patients with Alzheimer's disease, other types of dementia, and cognitive impairment. Lipids 2000; 35: 1305–12.CrossRefGoogle ScholarPubMed
95Heude, B, Ducimitiere, P, Berr, C. Cognitive decline and fatty acid composition of erythrocyte membranes – The Eva study. Am J Clin Nutr 2003; 77: 803–8.CrossRefGoogle ScholarPubMed
96Laurin, D, Verreault, R, Lindsay, J, Dewailly, E, Holub, BJ. Omega-3 fatty acids and risk of cognitive impairment and dementia. J Alzheimer's Dis 2003; 5: 315–22.CrossRefGoogle ScholarPubMed
97Manzato, E, Roselli della Rovere, G, Zambon, S, Romanato, G, Corti, MC, Sartori, L, Baggio, G, Crepaldi, G. Cognitive functions are not affected by dietary fatty acids in elderly in the Pro.V.A. study population. Aging Clin Exp Res 2003; 15: 83–86.CrossRefGoogle Scholar
98Ruggiero, C, Cherubini, A, Andres-Lacueva, C, Martin, A, Lauretani, F, Di Iorio, A et al. Low plasma N-3 fatty acids and dementia in community dwelling elderly subjects: the invecchiare in chianti (inchianti) study. J Nutr Health Aging 2004; 8: 263.Google Scholar
99Schaefer, EJ, Bongard, V, Beiser, AS, Lamon-Fava, S, Robins, SJ, Au, R, Tucker, KL, Kyle, DJ, Wilson, PW, Wolf, PA. Plasma phosphatidylcholine docosahexaenoic acid content and risk of dementia and alzheimer disease: The Framingham Heart Study. Arch Neurol 2006; 63: 1545–50.CrossRefGoogle ScholarPubMed
100Samieri, C, Féart, C, Letenneur, L, Dartigues, JF, Pérès, K, Auriacombe, S, Peuchant, E, Delcourt, C, Barberger-Gateau, P. Low plasma eicosapentaenoic acid and depressive symptomatology are independent predictors of dementia risk. Am J Clin Nutr 2008; 88: 714–21.CrossRefGoogle ScholarPubMed
101van de Rest, O, Geleijnse, JM, Kok, FJ, van Staveren, WA, Dullemeijer, C, OldeRikkert, MGM, Beekman, ATF, de Groot, CPGM. Effect of fish oil on cognitive performance in older subjects. Neurology 2008; 71: 430–38.CrossRefGoogle ScholarPubMed
102Yurko-Mauro, K, McCarthy, D, Bailey-Hall, E, Nelson, EB, Blackwell, A et al. Results of the MIDAS trial: effects of docosahexaenoic acid on physiological and safety parameters in age-related cognitive decline. Alzheimers Dement 2009; 5: 84. Alzheimer's Association International Conference on Alzheimer's Disease.CrossRefGoogle Scholar
103Yehuda, S, Rabinovtz, S, Carasso, RL, Mostofsky, DI. Essential fatty acids preparation (Sr-3) improves Alzheimer's patients’ quality of life. Int J Neurosci 1996; 87: 141–49.CrossRefGoogle ScholarPubMed
104Terano, T, Fujishiro, S, Ban, T, Yamamoto, K, Tanaka, T, Noguchi, Y, Tamura, Y, Yazawa, K, Hirayama, T. Docosahexaenoic acid supplementation improves the moderately severe dementia from thrombotic cerebrovascular diseases. Lipids 1999; 34: S345–46.CrossRefGoogle ScholarPubMed
105Otsuka, M. Analysis of dietary factors in Alzheimer's disease: clinical use of nutritional intervention for prevention and treatment of dementia. Nippon Ronen Igakkai Zasshi 2000; 37: 970–73.CrossRefGoogle ScholarPubMed
106Suzuki, H, Morikawa, Y, Takahashi, H. Effect of DHA oil supplementation on intelligence and visual acuity in the elderly. World Rev Nutr Diet 2001; 88: 68–71.CrossRefGoogle ScholarPubMed
107Boston, PF, Bennett, A, Horrobin, DF, Bennett, CN. Ethyl-EPA in Alzheimer's disease – a pilot study. Prostaglandins Leukot Essent Fatty Acids 2004; 71: 341–46.CrossRefGoogle ScholarPubMed
108Freund-Levi, Y, Eriksdotter-Jönhagen, M, Cederholm, T, Basun, H, Faxén-Irving, G, Garlind, A, Vedin, I, Vessby, B, Wahlund, LO, Palmblad, J. Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer's disease: OmegAD study: a randomized double-blind trial. Arch Neurol 2006; 63: 1402–8.CrossRefGoogle ScholarPubMed
109Freund-Levi, Y, Basun, H, Cederholm, T, Faxén-Irving, G, Garlind, A, Grut, M, Vedin, I, Palmblad, J, Wahlund, LO, Eriksdotter-Jönhagen, M. Omega-3 supplementation in mild to moderate Alzheimer's disease: effects on neuropsychiatric symptoms. Int J Geriatr Psychiatry 2008; 23: 161–69.CrossRefGoogle ScholarPubMed
110Kontani, S, Sakaguchi, E, Warashina, S, Matsukawa, N, Ishikura, Y, Kiso, Y et al. Dietary supplementation of arachidonic and docosahexaenoic acids improves cognitive dysfunction. Neurosci Res 2006; 56: 159–64.CrossRefGoogle Scholar
111Chiu, CC, Su, KP, Cheng, TC, Lui, HC, Chang, CJ, Dewey, ME, Stewart, R, Huang, SY. The effects of omega-3 fatty acid monotherapy in Alzheimer's disease and mild cognitive impairment: a preliminary randomized double blind placebo controlled study. Prog Neuro-psychopharmacol Biol Psychiat 2008; 32: 1538–44.CrossRefGoogle ScholarPubMed
112Stern, Y. The concept of cognitive reserve: A catalyst for research. J Clin Exp Neuropsychol 2003; 25: 589–93.CrossRefGoogle ScholarPubMed
113Roe, CM, Xiong, C, Miller, PJ, Morris, JC. Education and Alzheimer's disease without dementia: Support for the cognitive reserve hypothesis. Neurology 2007; 68: 223–28.CrossRefGoogle ScholarPubMed