Skip to main content
Log in

Nutrient patterns and brain biomarkers of Alzheimer’s disease in cognitively normal individuals

  • Published:
The journal of nutrition, health & aging

Abstract

Objectives

Epidemiological evidence linking diet, one of the most important modifiable lifestyle factors, and risk of Alzheimer’s disease (AD) is rapidly increasing. However, there is little or no evidence for a direct association between dietary nutrients and brain biomarkers of AD. This study identifies nutrient patterns associated with major brain AD biomarkers in a cohort of clinically and cognitively normal (NL) individuals at risk for AD.

Design

Cross-sectional study.

Setting

Manhattan (broader area).

Participants

Fifty-two NL individuals (age 54+12 y, 70% women, Clinical Dementia Rating=0, MMSE>27, neuropsychological test performance within norms by age and education) with complete dietary information and cross-sectional, 3D T1-weighted Magnetic Resonance Imaging (MRI; gray matter volumes, GMV, a marker of brain atrophy), 11CPittsburgh compound-B (PiB; a marker of fibrillar amyloid-β, Aβ) and 18F-fluorodeoxyglucose (FDG; a marker of glucose metabolism, METglc) Positron Emission Tomography (PET) scans were examined.

Measurements

Dietary intake of 35 nutrients associated with cognitive function and AD was assessed using the Harvard/Willet Food Frequency Questionnaire. Principal component analysis was used to generate nutrient patterns (NP) from the full nutrient panel. Statistical parametric mapping and voxel based morphometry were used to assess the associations of the identified NPs with AD biomarkers.

Results

None of the participants were diabetics, smokers, or met criteria for obesity. Five NPs were identified: NP1 was characterized by most B-vitamins and several minerals [VitB&Minerals]; NP2 by monounsaturated and polyunsaturated fats, including ω-3 and ω-6 PUFA, and vitamin E [VitE&PUFA]; NP3 by vitamin A, vitamin C, carotenoids and dietary fibers [Antioxidants&Fibers]; NP4 by vitamin B12, vitamin D and zinc [VitB12&D]; NP5 by saturated, trans-saturated fats, cholesterol and sodium [Fats]. Voxel-based analysis showed that NP4 scores [VitB12&D] were positively associated with METglc and GMV, and negatively associated with PiB retention in AD-vulnerable regions (p<0.001). In addition, both METglc and GMV were positively associated with NP2 scores [VitE&PUFA], and negatively associated with NP5 scores [Fats] (p<0.001), and METglc was positively associated with higher NP3 scores [Anti-oxidants&Fibers] (p<0.001). Adjusting for age, gender, ethnicity, education, caloric intake, BMI, alcohol consumption, family history and Apolipoprotein E (APOE) status did not attenuate these relationships. The identified ‘AD-protective’ nutrient combination was associated with higher intake of fresh fruit and vegetables, whole grains, fish and low-fat dairies, and lower intake of sweets, fried potatoes, high-fat dairies, processed meat and butter.

Conclusion

Specific dietary NPs are associated with brain biomarkers of AD in NL individuals, suggesting that dietary interventions may play a role in the prevention of AD by modulating AD-risk through its effects on Aβ and associated neuronal impairment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D’Agostino RB, Wilson PW, Wolf PA. Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N Engl J Med 2002;346, 476–483.

    Article  CAS  PubMed  Google Scholar 

  2. Schaefer 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, 1545–1550.

    Article  PubMed  Google Scholar 

  3. Scarmeas N, Stern Y, Tang MX, Mayeux R, Luchsinger JA. Mediterranean diet and risk for Alzheimer’s disease. Ann Neurol 2006;59, 912–921.

    Article  PubMed Central  PubMed  Google Scholar 

  4. Scarmeas N, Stern Y, Mayeux R, Manly JJ, Schupf N, Luchsinger JA. Mediterranean diet and mild cognitive impairment. Arch Neurol 2009;66, 216–225.

    PubMed Central  PubMed  Google Scholar 

  5. Rinaldi P, Polidori MC, Metastasio A, Mariani E, Mattioli P, Cherubini A, Catani M, Cecchetti R, Senin U, Mecocci P. Plasma antioxidants are similarly depleted in mild cognitive impairment and in Alzheimer’s disease. Neurobiol Aging 2003;24, 915–919.

    Article  CAS  PubMed  Google Scholar 

  6. Morris MC, Evans DA, Tangney CC, Bienias JL, Wilson RS. Fish consumption and cognitive decline with age in a large community study. Arch Neurol 2005;62, 1849–1853.

    Article  PubMed  Google Scholar 

  7. Morris MC, Evans DA, Bienias JL, Tangney CC, Bennett DA, Aggarwal N, Wilson RS, Scherr PA. Dietary intake of antioxidant nutrients and the risk of incident Alzheimer disease in a biracial community study. JAMA 2002;287, 3230–3237.

    Article  CAS  PubMed  Google Scholar 

  8. Cardoso BR, Cominetti C, Cozzolino SM. Importance and management of micronutrient deficiencies in patients with Alzheimer’s disease. Clin Interv Aging 2013;8, 531–542.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Gu Y, Luchsinger JA, Stern Y, Scarmeas N. Mediterranean diet, inflammatory and metabolic biomarkers, and risk of Alzheimer’s disease. J Alzheimers Dis 2010;22, 483–492.

    PubMed Central  CAS  PubMed  Google Scholar 

  10. Morris MC, Tangney CC. A potential design flaw of randomized trials of vitamin supplements. JAMA 2011;305, 1348–1349.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Jack CR, Knopman DS, Jagust WJ, Shaw LM, Aisen PS, Weiner MW, Petersen RC, Trojanowski JQ. Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade. Lancet Neurol 2010;9, 119–128.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Pottala JV, Yaffe K, Robinson JG, Espeland MA, Wallace R, Harris WS. Higher RBC EPA + DHA corresponds with larger total brain and hippocampal volumes: WHIMS-MRI Study. Neurology 2014;82, 435–442.

    Article  PubMed Central  PubMed  Google Scholar 

  13. Samieri C, Maillard P, Crivello F, Proust-Lima C, Peuchant E, Helmer C, Amieva H, Allard M, Dartigues JF, Cunnane SC, Mazoyer BM, Barberger-Gateau P. Plasma long-chain omega-3 fatty acids and atrophy of the medial temporal lobe. Neurology 2012;79, 642–650.

    Article  CAS  PubMed  Google Scholar 

  14. Tan ZS, Harris WS, Beiser AS, Au R, Himali JJ, Debette S, Pikula A, Decarli C, Wolf PA, Vasan RS, Robins SJ, Seshadri S. Red blood cell omega-3 fatty acid levels and markers of accelerated brain aging. Neurology 2012;78, 658–664.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Bowman GL, Silbert LC, Howieson D, Dodge HH, Traber MG, Frei B, Kaye JA, Shannon J, Quinn JF. Nutrient biomarker patterns, cognitive function, and MRI measures of brain aging. Neurology 2012;78, 241–249.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Gu Y, Nieves JW, Stern Y, Luchsinger JA, Scarmeas N. Food combination and Alzheimer disease risk: a protective diet. Arch Neurol 2010;67, 699–706.

    Article  PubMed Central  PubMed  Google Scholar 

  17. Gu Y, Scarmeas N. Dietary patterns in Alzheimer’s disease and cognitive aging. Curr Alzheimer Res 2011;8, 510–519.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Mosconi L, Brys M, Switalski R, Mistur R, Glodzik L, Pirraglia E, Tsui W, De Santi S, de Leon MJ. Maternal family history of Alzheimer’s disease predisposes to reduced brain glucose metabolism. Proc Natl Acad Sci U S A 2007;104, 19067–19072.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Mosconi L, Mistur R, Switalski R, Brys M, Glodzik L, Rich K, Pirraglia E, Tsui W, De Santi S, Leon MJ. Declining brain glucose metabolism in normal individuals with a maternal history of Alzheimer disease. Neurology 2009;72, 513–520.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Mosconi L, Rinne JO, Tsui WH, Berti V, Li Y, Wang H, Murray J, Scheinin N, Nagren K, Williams S, Glodzik L, De Santi S, Vallabhajosula S, de Leon MJ. Increased fibrillar amyloid-beta burden in normal individuals with a family history of late-onset Alzheimer’s. Proc Natl Acad Sci U S A 2010;107, 5949–5954.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. de Leon MJ, Convit A, Wolf OT, Tarshish CY, DeSanti S, Rusinek H, Tsui W, Kandil E, Scherer AJ, Roche A, Imossi A, Thorn E, Bobinski M, Caraos C, Lesbre P, Schlyer D, Poirier J, Reisberg B, Fowler J. Prediction of cognitive decline in normal elderly subjects with 2-[(18)F]fluoro-2-deoxy-D-glucose/poitron-emission tomography (FDG/PET). Proc Natl Acad Sci U S A 2001;98, 10966–10971.

    Article  PubMed Central  PubMed  Google Scholar 

  22. Willett WC, Sampson L, Stampfer MJ, Rosner B, Bain C, Witschi J, Hennekens CH, Speizer FE. Reproducibility and validity of a semiquantitative food frequency questionnaire. Am J Epidemiol 1985;122, 51–65.

    CAS  PubMed  Google Scholar 

  23. Smith W, Mitchell P, Reay EM, Webb K, Harvey PW. Validity and reproducibility of a self-administered food frequency questionnaire in older people. Aust N Z J Public Health 1998;22, 456–463.

    Article  CAS  PubMed  Google Scholar 

  24. Patel PS, Sharp SJ, Jansen E, Luben RN, Khaw KT, Wareham NJ, Forouhi NG. Fatty acids measured in plasma and erythrocyte-membrane phospholipids and derived by food-frequency questionnaire and the risk of new-onset type 2 diabetes: a pilot study in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohort. Am J Clin Nutr 2010;92, 1214–1222.

    Article  CAS  PubMed  Google Scholar 

  25. Pirouzpanah S, Taleban FA, Mehdipour P, Atri M, Hooshyareh-Rad A, Sabour S. The biomarker-based validity of a food frequency questionnaire to assess the intake status of folate, pyridoxine and cobalamin among Iranian primary breast cancer patients. Eur J Clin Nutr 2014;68, 316–323.

    Article  CAS  PubMed  Google Scholar 

  26. Feunekes GI, Van Staveren WA, De Vries JH, Burema J, Hautvast JG. Relative and biomarker-based validity of a food-frequency questionnaire estimating intake of fats and cholesterol. Am J Clin Nutr 1993;58, 489–496.

    CAS  PubMed  Google Scholar 

  27. Luchsinger JA, Tang MX, Miller J, Green R, Mayeux R. Relation of higher folate intake to lower risk of Alzheimer disease in the elderly. Arch Neurol 2007;64, 86–92.

    Article  PubMed  Google Scholar 

  28. Luchsinger JA, Tang MX, Siddiqui M, Shea S, Mayeux R. Alcohol intake and risk of dementia. J Am Geriatr Soc 2004;52, 540–546.

    Article  PubMed  Google Scholar 

  29. Cunnane SC, Plourde M, Pifferi F, Begin M, Feart C, Barberger-Gateau P. Fish, docosahexaenoic acid and Alzheimer’s disease. Prog Lipid Res 2009;48, 239–256.

    Article  CAS  PubMed  Google Scholar 

  30. Gu Y, Schupf N, Cosentino SA, Luchsinger JA, Scarmeas N. Nutrient intake and plasma beta-amyloid. Neurology 2012;78, 1832–1840.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Kalmijn S, Launer LJ, Ott A, Witteman JC, Hofman A, Breteler MM. Dietary fat intake and the risk of incident dementia in the Rotterdam Study. Ann Neurol 1997;42, 776–782.

    Article  CAS  PubMed  Google Scholar 

  32. Morris MC, Evans DA, Bienias JL, Tangney CC, Bennett DA, Aggarwal N, Schneider J, Wilson RS. Dietary fats and the risk of incident Alzheimer disease. Arch Neurol 2003;60, 194–200.

    Article  PubMed  Google Scholar 

  33. Morris MC, Evans DA, Bienias JL, Tangney CC, Bennett DA, Wilson RS, Aggarwal N, Schneider J. Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease. Arch Neurol 2003; 60, 940–946.

    Article  PubMed  Google Scholar 

  34. Morris MC, Evans DA, Bienias JL, Tangney CC, Wilson RS. Dietary fat intake and 6-year cognitive change in an older biracial community population. Neurology 2004;62, 1573–1579.

    Article  CAS  PubMed  Google Scholar 

  35. de Oliveira BF, Veloso CA, Nogueira-Machado JA, de Moraes EN, Santos RR, Cintra MT, Chaves MM. Ascorbic acid, alpha-tocopherol, and beta-carotene reduce oxidative stress and proinflammatory cytokines in mononuclear cells of Alzheimer’s disease patients. Nutr Neurosci, 2012.

    Google Scholar 

  36. Ford AH, Flicker L, Alfonso H, Thomas J, Clarnette R, Martins R, Almeida OP. Vitamins B(12), B(6), and folic acid for cognition in older men. Neurology 2010;75, 1540–1547.

    Article  CAS  PubMed  Google Scholar 

  37. Kesse-Guyot E, Andreeva VA, Ducros V, Jeandel C, Julia C, Hercberg S, Galan P. Carotenoid-rich dietary patterns during midlife and subsequent cognitive function. Br J Nutr, 2013;1–9.

    Google Scholar 

  38. Zandi PP, Anthony JC, Khachaturian AS, Stone SV, Gustafson D, Tschanz JT, Norton MC, Welsh-Bohmer KA, Breitner JC. Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: the Cache County Study. Arch Neurol 2004;61, 82–88.

    Article  PubMed  Google Scholar 

  39. Morris MC, Evans DA, Bienias JL, Tangney CC, Hebert LE, Scherr PA, Schneider JA. Dietary folate and vitamin B12 intake and cognitive decline among communitydwelling older persons. Arch Neurol 2005;62, 641–645.

    Article  PubMed  Google Scholar 

  40. Balion C, Griffith LE, Strifler L, Henderson M, Patterson C, Heckman G, Llewellyn DJ, Raina P. Vitamin D, cognition, and dementia: a systematic review and metaanalysis. Neurology 2012;79, 1397–1405.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Buell JS, Dawson-Hughes B, Scott TM, Weiner DE, Dallal GE, Qui WQ, Bergethon P, Rosenberg IH, Folstein MF, Patz S, Bhadelia RA, Tucker KL. 25-Hydroxyvitamin D, dementia, and cerebrovascular pathology in elders receiving home services. Neurology 2010;74, 18–26.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  42. Doraiswamy PM, Finefrock AE. Metals in our minds: therapeutic implications for neurodegenerative disorders. Lancet Neurol 2004;3, 431–434.

    Article  CAS  PubMed  Google Scholar 

  43. Kaczmarczyk MM, Miller MJ, Freund GG. The health benefits of dietary fiber: beyond the usual suspects of type 2 diabetes mellitus, cardiovascular disease and colon cancer. Metabolism 2012;61, 1058–1066.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. Berti V, Mosconi L, Glodzik L, Li Y, Murray J, De Santi S, Pupi A, Tsui W, De Leon MJ. Structural brain changes in normal individuals with a maternal history of Alzheimer’s. Neurobiol Aging, 2011.

    Google Scholar 

  45. Mosconi L, Rinne JO, Tsui W, Murray J, Li Y, Glodzik L, McHugh P, Williams S, Cummings M, Pirraglia E, Goldsmith SJ, Vallabhajosula S, Scheinin N, Viljanen T, Nagren K, de Leon MJ (20. Amyloid and metabolic PET imaging of cognitively normal adults with Alzheimer’s parents. Neurobiol Aging in press, 2012.

    Google Scholar 

  46. Joshi A, Koeppe RA, Fessler JA. Reducing between scanner differences in multicenter PET studies. Neuroimage 2009;46, 154–159.

    Article  PubMed Central  PubMed  Google Scholar 

  47. Ashburner J, Friston KJ. Voxel-based morphometry—the methods. Neuroimage 2000;11, 805–821.

    Article  CAS  PubMed  Google Scholar 

  48. Price JC, Klunk WE, Lopresti BJ, Lu X, Hoge JA, Ziolko SK, Holt DP, Meltzer CC, DeKosky ST, Mathis CA. Kinetic modeling of amyloid binding in humans using PET imaging and Pittsburgh Compound-B. J Cereb Blood Flow Metab 2005;25, 1528–1547.

    Article  CAS  PubMed  Google Scholar 

  49. Minoshima S, Frey KA, Foster NL, Kuhl DE. Preserved pontine glucose metabolism in Alzheimer disease: a reference region for functional brain image (PET) analysis. J Comput Assist Tomogr 1995;19, 541–547.

    Article  CAS  PubMed  Google Scholar 

  50. Ashburner J. A fast diffeomorphic image registration algorithm. Neuroimage 2007;38, 95–113.

    Article  PubMed  Google Scholar 

  51. Morris MC, Schneider JA, Tangney CC. Thoughts on B-vitamins and dementia. J Alzheimers Dis 2006;9, 429–433.

    PubMed Central  CAS  PubMed  Google Scholar 

  52. Bush AI, Pettingell WH, Multhaup G, Paradis M, Vonsattel JP, Gusella JF, Beyreuther K, Masters CL, Tanzi RE. Rapid induction of Alzheimer A beta amyloid formation by zinc. Science 1994;265, 1464–1467.

    Article  CAS  PubMed  Google Scholar 

  53. Douaud G, Refsum H, de Jager CA, Jacoby R, Nichols TE, Smith SM, Smith AD. Preventing Alzheimer’s disease-related gray matter atrophy by B-vitamin treatment. Proc Natl Acad Sci U S A 2013;110, 9523–9528.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  54. Takasaki J, Ono K, Yoshiike Y, Hirohata M, Ikeda T, Morinaga A, Takashima A, Yamada M. Vitamin A has anti-oligomerization effects on amyloid-beta in vitro. J Alzheimers Dis 2011;27, 271–280.

    CAS  PubMed  Google Scholar 

  55. Haass C, Selkoe DJ. Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer’s amyloid beta-peptide. Nat Rev Mol Cell Biol 2007;8, 101–112.

    Article  CAS  PubMed  Google Scholar 

  56. Gillette Guyonnet S, Abellan Van Kan G, Andrieu S, Barberger Gateau P, Berr C, Bonnefoy M, Dartigues JF, de Groot L, Ferry M, Galan P, Hercberg S, Jeandel C, Morris MC, Nourhashemi F, Payette H, Poulain JP, Portet F, Roussel AM, Ritz P, Rolland Y, Vellas B. IANA task force on nutrition and cognitive decline with aging. J Nutr Health Aging 2007;11, 132–152.

    CAS  PubMed  Google Scholar 

  57. Scarmeas N, Stern Y, Mayeux R, Luchsinger JA. Mediterranean diet, Alzheimer disease, and vascular mediation. Arch Neurol 2006;63, 1709–1717.

    Article  PubMed Central  PubMed  Google Scholar 

  58. Barberger-Gateau P, Raffaitin C, Letenneur L, Berr C, Tzourio C, Dartigues JF, Alperovitch A. Dietary patterns and risk of dementia: the Three-City cohort study. Neurology 2007;69, 1921–1930.

    Article  CAS  PubMed  Google Scholar 

  59. Feart C, Samieri C, Rondeau V, Amieva H, Portet F, Dartigues JF, Scarmeas N, Barberger-Gateau P. Adherence to a Mediterranean diet, cognitive decline, and risk of dementia. JAMA 2009;302, 638–648.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  60. Morris MC, Tangney CC, Bienias JL, Evans DA, Wilson RS. Validity and reproducibility of a food frequency questionnaire by cognition in an older biracial sample. Am J Epidemiol 2003;158, 1213–1217.

    Article  PubMed  Google Scholar 

  61. Bayer-Carter JL, Green PS, Montine TJ, VanFossen B, Baker LD, Watson GS, Bonner LM, Callaghan M, Leverenz JB, Walter BK, Tsai E, Plymate SR, Postupna N, Wilkinson CW, Zhang J, Lampe J, Kahn SE, Craft S. Diet intervention and cerebrospinal fluid biomarkers in amnestic mild cognitive impairment. Arch Neurol 2011;68, 743–752.

    Article  PubMed Central  PubMed  Google Scholar 

  62. Droogsma E, van Asselt DZ, Scholzel-Dorenbos CJ, van Steijn JH, van Walderveen PE, van der Hooft CS. Nutritional status of community-dwelling elderly with newly diagnosed Alzheimer’s disease: prevalence of malnutrition and the relation of various factors to nutritional status. J Nutr Health Aging 2013;17, 606–610.

    Article  CAS  PubMed  Google Scholar 

  63. Silva P, Kergoat MJ, Shatenstein B. Challenges in managing the diet of older adults with early-stage Alzheimer dementia: a caregiver perspective. J Nutr Health Aging 2013;17, 142–147.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lisa Mosconi.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Berti, V., Murray, J., Davies, M. et al. Nutrient patterns and brain biomarkers of Alzheimer’s disease in cognitively normal individuals. J Nutr Health Aging 19, 413–423 (2015). https://doi.org/10.1007/s12603-014-0534-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12603-014-0534-0

Key words

Navigation