Current Nutrition Reports

, Volume 3, Issue 2, pp 110–129 | Cite as

Prevention of Late-life Cognitive Disorders: Diet-Related Factors, Dietary Patterns, and Frailty Models

  • Francesco Panza
  • Vincenzo Solfrizzi
  • Rosanna Tortelli
  • Francesco Resta
  • Carlo Sabbà
  • Giancarlo Logroscino
Neurological Disease and Cognitive Function (G Logroscino, Section Editor)


The need for preventing or postponing the onset of Alzheimer’s disease (AD) and delaying or slowing its progression is a direct consequence of the current symptomatic approach of existing drugs for the treatment of AD. Dietary factors may affect the risk of AD and dementia, with a substantial body of evidence suggesting that certain diets have been associated with a lower incidence of AD and late-life cognitive disorders. Among healthy diets, higher adherence to a Mediterranean-type diet and to the Dietary Approaches to Stop Hypertension diet was associated with decreased cognitive decline, although the Mediterranean diet (MeDi) combines several foods, micro-, and macronutrients already separately proposed as potential protective factors against dementia. Higher adherence to the MeDi was associated with a reduced risk of cognitive impairment, MCI, and AD, as well as the transition from MCI to AD, and decreased all-causes mortality in AD patients. Influencing some age-related conditions, such as frailty, may have an impact on the prevention of late-life cognitive decline. Frailty reflects a nonspecific state of vulnerability and a multisystem physiological change and it is a widely recognized risk factor for adverse health outcomes in older persons. At present, no operational definition has been established, although nutritional status, cognition, and mood have been proposed as markers of frailty. Physical frailty may be associated with late-life cognitive impairment/decline, incidence of AD, vascular dementia, non-AD dementias, and AD pathology in older persons with and without dementia, also suggesting the definition of cognitive frailty as a new clinical condition. The reviewed evidence supports the hypothesis that frailty could be important in the prevention of late-life cognitive disorders, and nutritional influences may be of major relevance. Nutritional interventions might be able to address the impaired nutrition and weight loss of frailty. There is a critical need for randomized, controlled trials investigating the role of nutrition on late-life cognitive disorders and frailty that might open new routes for the prevention and management of cognitive decline and AD, supplementing existing symptomatic approaches, also through the nutritional prevention of frailty.


Diet Alzheimer’s disease Dementia MCI Dietary patterns Frailty Nutrition Cognitive frailty 


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM. Forecasting the global burden of Alzheimer’s disease. Alzheimers Dement. 2007;3:186–91.PubMedGoogle Scholar
  2. 2.
    Solfrizzi V, Capurso C, D'Introno A, Colacicco AM, Santamato A, Ranieri M, et al. Lifestyle-related factors in predementia and dementia syndromes. Expert Rev Neurother. 2009;8:133–58.Google Scholar
  3. 3.
    Peters R. The prevention of dementia. Int J Geriatr Psychiatry. 2009;24:452–8.PubMedGoogle Scholar
  4. 4.
    de la Torre JC. Alzheimer’s disease is incurable but preventable. J Alzheimers Dis. 2010;20:861–70.PubMedGoogle Scholar
  5. 5.
    Solfrizzi V, Panza F, Frisardi V, Seripa D, Logroscino G, Imbimbo BP, et al. Diet and Alzheimer's disease risk factors or prevention: the current evidence. Expert Rev Neurother. 2011;11:677–708.PubMedGoogle Scholar
  6. 6.
    Panza F, Solfrizzi V, Logroscino G, Maggi S, Santamato A, Seripa D, et al. Current epidemiological approaches to the metabolic-cognitive syndrome. J Alzheimers Dis. 2012;30 Suppl 2:S31–75.PubMedGoogle Scholar
  7. 7.
    Richard E. Moll van Charante EP, van Gool WA. Vascular risk factors as treatment target to prevent cognitive decline. J Alzheimers Dis. 2012;32:733–40.PubMedGoogle Scholar
  8. 8.
    McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack Jr CR, Kawas CH, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging–Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7:263–9.PubMedCentralPubMedGoogle Scholar
  9. 9.
    Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, et al. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging–Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7:270–9.PubMedCentralPubMedGoogle Scholar
  10. 10.
    Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, et al. Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging–Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7:280–92.PubMedCentralPubMedGoogle Scholar
  11. 11.
    Bateman RJ, Xiong C, Benzinger TL, Fagan AM, Goate A, Fox NC, et al. Dominantly Inherited Alzheimer Network. Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. N Engl J Med. 2012;367:795–804.PubMedCentralPubMedGoogle Scholar
  12. 12.•
    Villemagne VL, Burnham S, Bourgeat P, Brown B, Ellis KA, Salvado O, et al. Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: a prospective cohort study. Lancet Neurol. 2013;12:357–67. This prospective cohort study, applying a multidisciplinary approach including β-amyloid (Aβ) and structural imaging, constructed a model of the natural history of Aβ deposition and the sequence of changes in brain structure and cognition leading to sporadic Alzheimer’s disease (AD). According to their estimates, Aβ deposition is a slow process that extends for more than two decades. PubMedGoogle Scholar
  13. 13.
    Panza F, Solfrizzi V, Imbimbo BP, Tortelli R, Santamato A, Logroscino G. Amyloid-based immunotherapy for Alzheimer's disease in the time of prevention trials: the way forward. Expert Rev Clin Immunol. 2014;10:405–19.PubMedGoogle Scholar
  14. 14.
    Panza F, Solfrizzi V, Frisardi V, Capurso C, D’Introno A, Colacicco AM, et al. Disease-modifying approach to the treatment of Alzheimer's disease: from alpha-secretase activators to gamma-secretase inhibitors and modulators. Drugs Aging. 2009;26:537–55.PubMedGoogle Scholar
  15. 15.
    Panza F, Logroscino G, Imbimbo BP, Solfrizzi V. Is there still any hope for amyloid-based immunotherapy for Alzheimer's disease? Curr Opin Psychiatry. 2014;27:128–37.PubMedGoogle Scholar
  16. 16.
    Grant WB. Dietary links to Alzheimer's disease: 1999 Update. J Alzheimers Dis. 1999;1:197–201.PubMedGoogle Scholar
  17. 17.
    Solfrizzi V, Panza F, Capurso A. The role of diet in cognitive decline. J Neural Transm. 2003;110:95–110.PubMedGoogle Scholar
  18. 18.
    Luchsinger JA, Mayeux R. Dietary factors and Alzheimer's disease. Lancet Neurol. 2004;3:579–87.PubMedGoogle Scholar
  19. 19.
    Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al. Cardiovascular Health Study Collaborative Research Group. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56:M146–56.PubMedGoogle Scholar
  20. 20.
    Walston J, Hadley EC, Ferrucci L, Guralnik JM, Newman AB, Studenski SA, et al. Research agenda for frailty in older adults: toward a better understanding of physiology and etiology: summary from the American Geriatrics Society/National Institute on Aging Research Conference on Frailty in Older Adults. J Am Geriatr Soc. 2006;54:991–1001.PubMedGoogle Scholar
  21. 21.•
    Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet. 2013;381:752–62. A recent and comprehensive review on frailty in older people, addressing the epidemiology, pathophysiology, assessment of frailty, and the development of interventions potentially effective for this clinical syndrome. PubMedGoogle Scholar
  22. 22.•
    Kelaiditi E, van Kan GA, Cesari M. Frailty: role of nutrition and exercise. Curr Opin Clin Nutr Metab Care. 2014;17:32–9. This is the most recent review on prevention of frailty in older people, comprehensively addressing the role of nutrition and exercise on frailty, supporting preventive strategies against disability in older person. PubMedGoogle Scholar
  23. 23.
    Avila-Funes JA, Amieva H, Barberger-Gateau P, Le Goff M, Raoux N, Ritchie K, et al. Cognitive impairment improves the predictive validity of the phenotype of frailty for adverse health outcomes: the Three-City Study. J Am Geriatr Soc. 2009;57:453–61.PubMedGoogle Scholar
  24. 24.
    Rockwood K, Howlett SE, MacKnight C, Beattie BL, Bergman H, Hébert R, et al. Prevalence, attributes, and outcomes of fitness and frailty in community-dwelling older adults: Report from the Canadian Study of Health and Aging. J Gerontol A Biol Sci Med Sci. 2004;59A:1310–7.Google Scholar
  25. 25.
    Rockwood K, Song X, MacKnight C, Bergman H, Hogan DB, McDowell I, et al. A global clinical measure of fitness and frailty in elderly people. Can Med Assoc J. 2005;173:489–95.Google Scholar
  26. 26.
    Eeles EM, White SV, O’Mahony SM, Bayer AJ, Hubbard RE. The impact of frailty and delirium on mortality in older inpatients. Age Ageing. 2012;41:412–6.PubMedGoogle Scholar
  27. 27.
    Panza F, Solfrizzi V, Frisardi V, Maggi S, Sancarlo D, Addante F, et al. Different models of frailty in predementia and dementia syndromes. J Nutr Health Aging. 2011;15:711–9.PubMedGoogle Scholar
  28. 28.
    Harrison FE. A critical review of vitamin C for the prevention of age-related cognitive decline and Alzheimer's disease. J Alzheimers Dis. 2012;29:711–26.PubMedCentralPubMedGoogle Scholar
  29. 29.
    Viña J, Lloret A, Giraldo E, Badia MC, Alonso MD. Antioxidant pathways in Alzheimer's disease: possibilities of intervention. Curr Pharm Des. 2011;17:3861–4.PubMedGoogle Scholar
  30. 30.
    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.PubMedGoogle Scholar
  31. 31.
    Darvesh AS, Carroll RT, Bishayee A, Geldenhuys WJ, Van der Schyf CJ. Oxidative stress and Alzheimer's disease: dietary polyphenols as potential therapeutic agents. Expert Rev Neurother. 2010;10:729–45.PubMedGoogle Scholar
  32. 32.
    Hu N, Yu JT, Tan L, Wang YL, Sun L, Tan L. Nutrition and the risk of Alzheimer's disease. Biomed Res Int. 2013;2013:524820.PubMedCentralPubMedGoogle Scholar
  33. 33.
    Shah R. The role of nutrition and diet in Alzheimer’s disease: a systematic review. J Am Med Dir Assoc. 2013;14:398–402.PubMedGoogle Scholar
  34. 34.
    Galasko DR, Peskind E, Clark CM, Quinn JF, Ringman JM, Jicha GA, et al. Antioxidants for Alzheimer disease: a randomized clinical trial with cerebrospinal fluid biomarker measures. Arch Neurol. 2012;69:836–41.PubMedCentralPubMedGoogle Scholar
  35. 35.
    Wald DS, Kasturiratne A, Simmonds M. Effect of folic acid, with or without other B vitamins, on cognitive decline: meta-analysis of randomized trials. Am J Med. 2010;123:522–7.PubMedGoogle Scholar
  36. 36.
    Presse N, Belleville S, Gaudreau P, Greenwood CE, Kergoat MJ, Morais JA, et al. Vitamin K status and cognitive function in healthy older adults. Neurobiol Aging. 2013;34:2777–83.PubMedGoogle Scholar
  37. 37.
    Coley N, Andrieu S, Gardette V, Gillette-Guyonnet S, Sanz C, Vellas B, et al. Dementia prevention: methodological explanations for inconsistent results. Epidemiol Rev. 2008;30:35–66.PubMedGoogle Scholar
  38. 38.
    Frisardi V, Panza F, Seripa D, Imbimbo BP, Vendemiale G, Pilotto A, et al. Nutraceutical properties of Mediterranean diet and cognitive decline: possible underlying mechanisms. J Alzheimers Dis. 2010;22:715–40.PubMedGoogle Scholar
  39. 39.
    Solfrizzi V, Frisardi V, Capurso C, D'Introno A, Colacicco AM, Vendemiale G, et al. Dietary fatty acids in dementia and predementia syndromes: epidemiological evidence and possible underlying mechanisms. Ageing Res Rev. 2010;9:184–99.PubMedGoogle Scholar
  40. 40.
    Cunnane SC, Plourde M, Pifferi F, Bégin M, Féart C, Barberger-Gateau P. Fish, docosahexaenoic acid and Alzheimer's disease. Prog Lipid Res. 2009;48:239–56.PubMedGoogle Scholar
  41. 41.
    Solfrizzi V, Colacicco AM, D’Introno A, Capurso C, Torres F, Rizzo C, et al. Dietary intake of unsaturated fatty acids and age-related cognitive decline: a 8.5-year follow-up of the Italian Longitudinal Study on Aging. Neurobiol Aging. 2006;27:1694–704.PubMedGoogle Scholar
  42. 42.
    Naqvi AZ, Harty B, Mukamal KJ, Stoddard AM, Vitolins M, Dunn JE. Monounsaturated, trans, and saturated Fatty acids and cognitive decline in women. J Am Geriatr Soc. 2011;59:837–43.PubMedCentralPubMedGoogle Scholar
  43. 43.
    Fotuhi M, Mohassel P, Yaffe K. Fish consumption, long-chain omega-3 fatty acids and risk of cognitive decline or Alzheimer disease: a complex association. Nat Clin Pract Neurol. 2009;5:140–52.PubMedGoogle Scholar
  44. 44.
    van de Rest O, Geleijnse JM, Kok FJ, van Staveren WA, Hoefnagels WH, Beekman AT, et al. Effect of fish-oil supplementation on mental well-being in older subjects: a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr. 2008;88:706–13.PubMedGoogle Scholar
  45. 45.
    van de Rest O, Geleijnse JM, Kok FJ, van Staveren WA, Dullemeijer C, Olderikkert MG, et al. Effect of fish oil on cognitive performance in older subjects: a randomized, controlled trial. Neurology. 2008;71:430–8.PubMedGoogle Scholar
  46. 46.
    Quinn JF, Raman R, Thomas RG, Yurko-Mauro K, Nelson EB, Van Dyck C, et al. Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: a randomized trial. JAMA. 2010;304:1903–11.PubMedCentralPubMedGoogle Scholar
  47. 47.••
    Martínez-Lapiscina EH, Clavero P, Toledo E, San Julián B, Sanchez-Tainta A, Corella D, et al. Virgin olive oil supplementation and long-term cognition: the PREDIMED-NAVARRA randomized, trial. J Nutr Health Aging. 2013;17:544–52. This key paper suggested that Mediterranean diet supplemented with extra virgin olive oil (1 l/week) for 6.5 years improved cognitive performance, while a supplement of mixed nuts (30 g/ day) had no effect. Persons taking extra virgin olive oil were less likely to develop mild cognitive impairment. PubMedGoogle Scholar
  48. 48.
    Friedland RP. Fish consumption and the risk of Alzheimer disease: is it time to make dietary recommendations? Arch Neurol. 2003;60:923–4.PubMedGoogle Scholar
  49. 49.•
    Crichton GE, Bryan J, Murphy KJ, Buckley J. Review of dairy consumption and cognitive performance in adults: findings and methodological issues. Dement Geriatr Cogn Disord. 2010;30:352–61. Comprehensive and unique review on the possible association between dairy intake and cognitive functioning. PubMedGoogle Scholar
  50. 50.
    Yamada M, Kasagi F, Sasaki H, Masunari N, Mimori Y, Suzuki G. Association between dementia and midlife risk factors: the radiation effects research foundation adult health study. J Am Geriatr Soc. 2003;51:410–4.PubMedGoogle Scholar
  51. 51.
    Kliem KE, Givens DI. Dairy products in the food chain: their impact on health. Annu Rev Food Sci Technol. 2011;2:21–36.PubMedGoogle Scholar
  52. 52.
    Kerola T, Kettunen R, Nieminen T. The complex interplay of cardiovascular system and cognition: how to predict dementia in the elderly? Int J Cardiol. 2011;150:123–9.PubMedGoogle Scholar
  53. 53.
    Henderson ST. High carbohydrate diets and Alzheimer's disease. Med Hypotheses. 2004;62:689–700.PubMedGoogle Scholar
  54. 54.
    Seneff S, Wainwright G, Mascitelli L. Nutrition and Alzheimer's disease: the detrimental role of a high carbohydrate diet. Eur J Intern Med. 2011;22:134–40.PubMedGoogle Scholar
  55. 55.
    Luchsinger JA, Tang MX, Mayeux R. Glycemic load and risk of Alzheimer's disease. J Nutr Health Aging. 2007;11:238–41.PubMedGoogle Scholar
  56. 56.
    Loef M, Walach H. Fruit, vegetables and prevention of cognitive decline or dementia: a systematic review of cohort studies. J Nutr Health Aging. 2012;16:626–30.PubMedGoogle Scholar
  57. 57.
    Barranco Quintana JL, Allam MF, Serrano Del Castillo A, Fernandez-Crehuet NR. Alzheimer’s disease and coffee: a quantitative review. Neurol Res. 2007;29:91–5.PubMedGoogle Scholar
  58. 58.
    Santos C, Costa J, Santos J, Vaz-Carneiro A, Lunet N. Caffeine intake and dementia: systematic review and meta-analysis. J Alzheimers Dis. 2010;20 Suppl 1:S187–204.PubMedGoogle Scholar
  59. 59.•
    Arab L, Khan F, Lam H. Epidemiologic evidence of a relationship between tea, coffee, or caffeine consumption and cognitive decline. Adv Nutr. 2013;4:115–22. A recent and in depth review of tea, coffee, and caffeine consumption and cognition. PubMedCentralPubMedGoogle Scholar
  60. 60.
    Panza F, Frisardi V, Seripa D, Logroscino G, Santamato A, Imbimbo BP, et al. Alcohol consumption in mild cognitive impairment and dementia: harmful or neuroprotective? Int J Geriatr Psychiatry. 2012;27:1218–38.PubMedGoogle Scholar
  61. 61.
    Peters R, Peters J, Warner J, Beckett N, Bulpitt C. Alcohol, dementia and cognitive decline in the elderly. a systematic review. Age Ageing. 2008;37:505–12.PubMedGoogle Scholar
  62. 62.
    Anstey KJ, Mack HA, Cherbuin N. Alcohol consumption as a risk factor for dementia and cognitive decline: meta-analysis of prospective studies. Am J Geriatr Psychiatry. 2009;17:542–55.PubMedGoogle Scholar
  63. 63.
    Neafsey EJ, Collins MA. Moderate alcohol consumption and cognitive risk. Neuropsychiatr Dis Treat. 2011;7:465–84.PubMedCentralPubMedGoogle Scholar
  64. 64.
    Luchsinger JA, Noble JM, Scarmeas N. Diet and Alzheimer's disease. Curr Neurol Neurosci Rep. 2007;7:366–72.PubMedGoogle Scholar
  65. 65.
    Samieri C, Jutand MA, Féart C, Capuron L, Letenneur L, Barberger-Gateau P. Dietary patterns derived by hybrid clustering method in older people: association with cognition, mood, and self-rated health. J Am Diet Assoc. 2008;108:1461–71.PubMedGoogle Scholar
  66. 66.
    Sofi F, Macchi C, Abbate R, Gensini GF, Casini A. Effectiveness of the Mediterranean diet: can it help delay or prevent Alzheimer's disease? J Alzheimers Dis. 2010;20:795–801.PubMedGoogle Scholar
  67. 67.
    Eskelinen MH, Ngandu T, Tuomilehto J, Soininen H, Kivipelto M. Midlife healthy-diet index and late-life dementia and Alzheimer's disease. Dement Geriatr Cogn Dis Extra. 2011;1:103–12.PubMedCentralPubMedGoogle Scholar
  68. 68.•
    Lourida I, Soni M, Thompson-Coon J, Purandare N, Lang IA, Ukoumunne OC, et al. Mediterranean diet, cognitive function, and dementia: a systematic review. Epidemiology. 2013;24:479–89. A comprehensive and systematic review synthesizing the available evidence on the association between adherence to Mediterranean diet and cognitive function or dementia. PubMedGoogle Scholar
  69. 69.
    Kesse-Guyot E, Andreeva VA, Jeandel C, Ferry M, Hercberg S, Galan P. A healthy dietary pattern at midlife is associated with subsequent cognitive performance. J Nutr. 2012;142:909–15.PubMedGoogle Scholar
  70. 70.
    Allès B, Samieri C, Féart C, Jutand MA, Laurin D, Barberger-Gateau P. Dietary patterns: a novel approach to examine the link between nutrition and cognitive function in older individuals. Nutr Res Rev. 2012;25:207–22.PubMedGoogle Scholar
  71. 71.•
    Ozawa M, Ninomiya T, Ohara T, Doi Y, Uchida K, Shirota T, et al. Dietary patterns and risk of dementia in an elderly Japanese population: the Hisayama Study. Am J Clin Nutr. 2013;97:1076–82. A Japanese population-based study suggesting that a higher adherence to a Japanese-style diet with a dietary pattern characterized by a high intake of soybeans and soybean products, vegetables, algae, and milk and dairy products and a low intake of rice may be associated with reduced risk of dementia. PubMedGoogle Scholar
  72. 72.•
    Tangney CC. DASH and Mediterranean-type dietary patterns to maintain cognitive health. Curr Nutr Rep. 2014;3:51–61. Complete and very updated review on the principal dietary patterns linked to the protection against dementia and late-life cognitive decline. Google Scholar
  73. 73.
    Solfrizzi V, Panza F. Mediterranean diet and cognitive decline. A lesson from the whole-diet approach: what challenges lie ahead? J Alzheimers Dis. 2014;39:283–6.PubMedGoogle Scholar
  74. 74.
    Hu FB. Dietary pattern analysis: a new direction in nutritional epidemiology. Curr Opin Lipidol. 2002;13:3–9.PubMedGoogle Scholar
  75. 75.
    Hooijmans CR, Rutters F, Dederen PJ, et al. Changes in cerebral blood volume and amyloid pathology in aged Alzheimer APP/PS1 mice on a docosahexaenoic acid (DHA) diet or cholesterol enriched Typical Western Diet (TWD). Neurobiol Dis. 2007;28:16–29.PubMedGoogle Scholar
  76. 76.
    Studzinski CM, Li F, Bruce-Keller AJ, et al. Effects of short-term Western diet on cerebral oxidative stress and diabetes related factors in APP x PS1 knock-in mice. J Neurochem. 2009;108:860–6.PubMedCentralPubMedGoogle Scholar
  77. 77.
    Gustaw-Rothenberg K. Dietary patterns associated with Alzheimer's disease: population based study. Int J Environ Res Public Health. 2009;6:1335–40.PubMedCentralPubMedGoogle Scholar
  78. 78.
    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.PubMedCentralPubMedGoogle Scholar
  79. 79.
    Akbaraly TN, Singh-Manoux A, Marmot MG, Brunner EJ. Education attenuates the association between dietary patterns and cognition. Dement Geriatr Cogn Disord. 2009;27:147–54.PubMedCentralPubMedGoogle Scholar
  80. 80.
    Appel LJ, Brands MW, Daniels SR, Karanja N, Elmer PJ, Sacks FM, et al. Dietary approaches to prevent and treat hypertension: a scientific statement from the American Heart Association. Hypertension. 2006;47:296–308.PubMedGoogle Scholar
  81. 81.
    Sacks FM, Campos H. Dietary therapy in hypertension. N Engl J Med. 2010;362:2102–12.Google Scholar
  82. 82.••
    Smith PJ, Blumenthal JA, Babyak MA, Craighead L, Welsh-Bohmer KA, Browndyke JN, et al. Effects of the dietary approaches to stop hypertension diet, exercise, and caloric restriction on neurocognition in overweight adults with high blood pressure. Hypertension. 2010;55:1331–8. A trial designed to improve cardiovascular outcomes in a high-risk U.S. population sample in which repeated cognitive testing has occurred over a short 4-month period. Cognitive improvements were noted in both Dietary Approaches to Stop Hypertension (DASH) active treatments; a DASH dietary modification or a DASH dietary modification plus weight loss against usual care. PubMedCentralPubMedGoogle Scholar
  83. 83.
    Norton MC, Dew J, Smith H, Fauth E, Piercy KW, Breitner JC, et al. Lifestyle behavior pattern is associated with different levels of risk for incident dementia and Alzheimer's disease: the Cache County study. J Am Geriatr Soc. 2012;60:405–12.PubMedCentralPubMedGoogle Scholar
  84. 84.••
    Wengreen H, Munger RG, Cutler A, Quach A, Bowles A, Corcoran C, et al. Prospective study of dietary approaches to stop hypertension–and Mediterranean-style dietary patterns and age-related cognitive change: the cache county study on memory, health and aging. Am J Clin Nutr. 2013;98:1272–81. Dietary Approaches to Stop Hypertension and Mediterranean diet scores were assessed in relation to repeated cognitive measures. Higher scores of each pattern were consistently associated higher cognitive function over an 11-year period in a U.S. cohort of 3,861 men and women. Google Scholar
  85. 85.
    Feart C, Samieri C, Barberger-Gateau P. Mediterranean diet and cognitive function in older adults. Curr Opin Clin Nutr Metab Care. 2010;13:14–8.PubMedCentralPubMedGoogle Scholar
  86. 86.
    Psaltopoulou T, Sergentanis TN, Panagiotakos DB, Sergentanis IN, Kosti R, Scarmeas N. Mediterranean diet and stroke, cognitive impairment, depression: a meta-analysis. Ann Neurol. 2013;74:580–91.PubMedGoogle Scholar
  87. 87.
    Singh B, Parsaik AK, Mielke MM, Erwin PJ, Knopman DS, Petersen RC, et al. Association of Mediterranean diet with mild cognitive impairment and Alzheimer's disease: a systematic review and meta-analysis. J Alzheimers Dis. 2014;39:271–82.PubMedGoogle Scholar
  88. 88.
    McMillan L, Owen L, Kras M, Scholey A. Behavioural effects of a 10-day Mediterranean diet. Results from a pilot study evaluating mood and cognitive performance. Appetite. 2011;56:143–7.PubMedGoogle Scholar
  89. 89.••
    Martínez-Lapiscina EH, Clavero P, Toledo E, Estruch R, Salas-Salvadó J, San Julián B, et al. Mediterranean diet improves cognition: the PREDIMED-NAVARRA randomised trial. J Neurol Neurosurg Psychiatry. 2013;84:1318–25. This key paper was the first long-term prevention randomized trial that compared two interventions with Mediterranean diet (MeDi) versus a low-fat diet. An intervention with MeDi with supplementation with either extra-virgin olive oil or nuts appeared to improve cognition compared with a low-fat diet in a 6.5-year follow-up. PubMedGoogle Scholar
  90. 90.•
    Robertson DA, Savva GM, Kenny RA. Frailty and cognitive impairment-A review of the evidence and causal mechanisms. Ageing Res Rev. 2013;12:840–51. A very comprehensive review on the relationship between frailty and cognitive impairment, also focusing on the possible mechanisms behind this association. PubMedGoogle Scholar
  91. 91.
    Rockwood K. Frailty and its definition: a worthy challenge. J Am Geriatr Soc. 2005;53:1069–70.PubMedGoogle Scholar
  92. 92.
    Buchner DM, Wagner EH. Preventing frail health. Clin Geriatr Med. 1992;8:1–17.PubMedGoogle Scholar
  93. 93.
    Hamerman D. Toward an understanding of frailty. Ann Intern Med. 1999;130:945–50.PubMedGoogle Scholar
  94. 94.
    Rockwood K, Hogan DB, MacKnight C. Conceptualisation and measurement of frailty in elderly people. Drugs Aging. 2000;17:295–302.PubMedGoogle Scholar
  95. 95.
    Markle-Reid M, Browne G. Conceptualizations of frailty in relation to older adults. J Adv Nurs. 2003;44:58–68.PubMedGoogle Scholar
  96. 96.
    Hogan DB, MacKnight C, Bergman H. Models, definitions, and criteria of frailty. Aging Clin Exp Res. 2003;15:1–29.PubMedGoogle Scholar
  97. 97.
    Levers MJ, Estabrooks CA, Ross Kerr JC. Factors contributing to frailty: literature review. J Adv Nurs. 2006;56:282–91.PubMedGoogle Scholar
  98. 98.
    Schuurmans H, Steverink N, Lindenberg S, Frieswijk N, Slaets JP. Old or frail: what tells us more? J Gerontol A Biol Sci Med Sci. 2004;59:M962–5.PubMedGoogle Scholar
  99. 99.
    Gobbens RJ, Luijkx KG, Wijnen-Sponselee MT, Schols JM. In search of an integral conceptual definition of frailty: opinions of experts. J Am Med Dir Assoc. 2010;11:338–43.PubMedGoogle Scholar
  100. 100.
    Sourial N, Wolfson C, Bergman H, Zhu B, Karunananthan S, Quail J, et al. A correspondence analysis revealed frailty deficits aggregate and are multidimensional. J Clin Epidemiol. 2010;63:647–54.PubMedCentralPubMedGoogle Scholar
  101. 101.
    Sourial N, Bergman H, Karunananthan S, Wolfson C, Guralnik J, Payette H, et al. Contribution of frailty markers in explaining differences among individuals in five samples of older persons. J Gerontol A Biol Sci Med Sci. 2012;67:1197–204.PubMedCentralPubMedGoogle Scholar
  102. 102.
    de Vries NM, Staal JB, van Ravensberg CD, Hobbelen JS, Olde Rikkert MG, Nijhuis-van der Sanden MW. Outcome instruments to measure frailty: a systematic review. Ageing Res Rev. 2011;10:104–14.PubMedGoogle Scholar
  103. 103.
    Rockwood K, Fox RA, Stolee P, Robertson D, Beattie BL. Frailty in elderly people: an evolving concept. Can Med Assoc J. 1994;150:489–95.Google Scholar
  104. 104.
    Rockwood K, Mitnitski A. Frailty in relation to the accumulation of deficits. J Gerontol A Biol Sci Med Sci. 2007;62:722–7.PubMedGoogle Scholar
  105. 105.•
    Rodríguez-Mañas L, Féart C, Mann G, Viña J, Chatterji S, Chodzko-Zajko W, et al. Searching for an operational definition of frailty: a Delphi method based consensus statement: the frailty operative definition-consensus conference project. J Gerontol A Biol Sci Med Sci. 2013;68:62–7. A modified Delphi process was used to attempt to achieve a consensus on the operational definition of frailty. PubMedCentralPubMedGoogle Scholar
  106. 106.
    Studenski S, Hayes RP, Leibowitz RQ, Bode R, Lavery L, Walston J, et al. Clinical Global Impression of Change in Physical Frailty: development of a measure based on clinical judgment. J Am Geriatr Soc. 2004;52:1560–6.PubMedGoogle Scholar
  107. 107.
    Bergman H, Ferrucci L, Guralnik J, Hogan DB, Hummel S, Karunananthan S, et al. Frailty: an emerging research and clinical paradigm issues and controversies. J Gerontol A Biol Sci Med Sci. 2007;62:731–7.PubMedCentralPubMedGoogle Scholar
  108. 108.
    Fulop T, Larbi A, Witkowski JM, McElhaney J, Loeb M, Mitnitski A, et al. Aging, frailty and age-related diseases. Biogerontology. 2010;11:547–663.Google Scholar
  109. 109.
    Jones DM, Song X, Rockwood K. Operationalizing a frailty index from a standardized comprehensive geriatric assessment. J Am Geriatr Soc. 2004;52:1929–33.PubMedGoogle Scholar
  110. 110.
    Jones D, Song X, Mitnitski A, Rockwood K. Evaluation of a frailty index based on a comprehensive geriatric assessment in a population based study of elderly Canadians. Aging Clin Exp Res. 2005;17:465–71.PubMedGoogle Scholar
  111. 111.
    Rockwood K, Andrew M, Mitnitski A. A comparison of two approaches to measuring frailty in elderly people. J Gerontol A Biol Sci Med Sci. 2007;62:738–43.PubMedGoogle Scholar
  112. 112.
    Cigolle CT, Ofstedal MB, Tian Z, Blaum CS. Comparing models of frailty: the health and retirement study. J Am Geriatr Soc. 2009;57:830–9.PubMedGoogle Scholar
  113. 113.
    Pilotto A, Rengo F, Marchionni N, Sancarlo D, Fontana A, Panza F, et al. Comparing the prognostic accuracy for all-cause mortality of frailty instruments: a multicentre 1-year follow-up in hospitalized older patients. PLoS One. 2012;7:e29090.PubMedCentralPubMedGoogle Scholar
  114. 114.
    Rockwood K, Abeysundera MJ, Mitnitski A. How should we grade frailty in nursing home patients? J Am Med Dir Assoc. 2007;8:595–603.PubMedGoogle Scholar
  115. 115.
    Armstrong JJ, Stolee P, Hirdes JP, Poss JW. Examining three frailty conceptualizations in their ability to predict negative outcomes for home-care clients. Age Ageing. 2010;39:755–8.PubMedGoogle Scholar
  116. 116.
    Mitnitski A, Fallah N, Rockwood K. A multistate model of cognitive dynamics in relation to frailty in older adults. Ann Epidemiol. 2011;21:507–16.PubMedGoogle Scholar
  117. 117.
    Mitnitski A, Fallah N, Rockwood MR, Rockwood K. Transitions in cognitive status in relation to frailty in older adults: a comparison of three frailty measures. J Nutr Health Aging. 2011;15:863–7.PubMedGoogle Scholar
  118. 118.
    Song X, Mitnitski A, Rockwood K. Nontraditional risk factors combine to predict Alzheimer disease and dementia. Neurology. 2011;77:227–34.PubMedCentralPubMedGoogle Scholar
  119. 119.
    Pilotto A, Sancarlo D, Panza F, Paris F, D'Onofrio G, Cascavilla L, et al. The Multidimensional Prognostic Index (MPI) based on a comprehensive geriatric assessment predicts short- and long-term mortality in hospitalized older patients with dementia. J Alzheimers Dis. 2009;18:191–9.PubMedCentralPubMedGoogle Scholar
  120. 120.
    Dramé M, Novella JL, Jolly D, Lanièce I, Somme D, Heitz D, et al. Rapid cognitive decline, one-year institutional admission and one-year mortality: analysis of the ability to predict and inter-tool agreement of four validated clinical frailty indexes in the SAFEs cohort. J Nutr Health Aging. 2011;15:699–705.PubMedGoogle Scholar
  121. 121.
    Doba N, Tokuda Y, Goldstein NE, Kushiro T, Hinohara S. A pilot trial to predict frailty syndrome: the Japanese Health Research Volunteer Study. Exp Gerontol. 2012;47:638–43.PubMedGoogle Scholar
  122. 122.••
    Kelaiditi E, Cesari M, Canevelli M, van Kan GA, Ousset PJ, Gillette-Guyonnet S, et al. Cognitive frailty: rational and definition from an (I.A.N.A./I.A.G.G.) international consensus group. J Nutr Health Aging. 2013;17:726–34. An international consensus group comprised of investigators from the International Academy of Nutrition and Aging (IANA) and the International Association of Gerontology and Geriatrics (IAGG) proposed a definition for “cognitive frailty” in older adults. PubMedGoogle Scholar
  123. 123.
    Jacobs JM, Cohen A, Ein-Mor E, Maaravi Y, Stessman J. Frailty, cognitive impairment and mortality among the oldest old. J Nutr Health Aging. 2011;15:678–82.PubMedGoogle Scholar
  124. 124.
    Ávila-Funes JA, Pina-Escudero SD, Aguilar-Navarro S, Gutierrez-Robledo LM, Ruiz-Arregui L, Amieva H. Cognitive impairment and low physical activity are the components of frailty more strongly associated with disability. J Nutr Health Aging. 2011;15:683–9.PubMedGoogle Scholar
  125. 125.
    Ní Mhaoláin AM, Gallagher D, Crosby L, Ryan D, Lacey L, Coen R, et al. Correlates of frailty in Alzheimer's disease and mild cognitive impairment. Age Ageing. 2011;40:630–3.PubMedGoogle Scholar
  126. 126.
    O'Halloran AM, Fan CW, Kenny RA, Pénard N, Galli A, Robertson IH. Variability in sustained attention and risk of frailty. J Am Geriatr Soc. 2011;59:2390–2.PubMedGoogle Scholar
  127. 127.
    Solfrizzi V, Scafato E, Frisardi V, Sancarlo D, Seripa D, Logroscino G, et al. Frailty syndrome and all-cause mortality in demented patients: the Italian Longitudinal Study on Aging. Age (Dordr). 2012;34:507–17.Google Scholar
  128. 128.
    Jürschik P, Nunin C, Botigué T, Escobar MA, Lavedán A, Viladrosa M. Prevalence of frailty and factors associated with frailty in the elderly population of Lleida, Spain: the FRALLE survey. Arch Gerontol Geriatr. 2012;55:625–31.PubMedGoogle Scholar
  129. 129.
    Macuco CR, Batistoni SS, Lopes A, Cachioni M, da Silva Falcão DV, Neri AL, et al. Mini-Mental State Examination performance in frail, pre-frail, and non-frail community dwelling older adults in Ermelino Matarazzo, São Paulo, Brazil. Int Psychogeriatr. 2012;24:1725–31.PubMedGoogle Scholar
  130. 130.
    Yassuda MS, Lopes A, Cachioni M, Falcao DV, Batistoni SS, Guimaraes VV, et al. Frailty criteria and cognitive performance are related: data from the FIBRA study in Ermelino Matarazzo, São Paulo, Brazil. J Nutr Health Aging. 2012;16:55–61.PubMedGoogle Scholar
  131. 131.
    Langlois F, Vu TT, Kergoat MJ, Chassé K, Dupuis G, Bherer L. The multiple dimensions of frailty: physical capacity, cognition, and quality of life. Int Psychogeriatr. 2012;24:1429–36.PubMedGoogle Scholar
  132. 132.
    Shimada H, Makizako H, Doi T, Yoshida D, Tsutsumimoto K, Anan Y, et al. Combined prevalence of frailty and mild cognitive impairment in a population of elderly Japanese people. J Am Med Dir Assoc. 2013;14:518–24.PubMedGoogle Scholar
  133. 133.
    Han ES, Lee Y, Kim J. Association of cognitive impairment with frailty in community-dwelling older adults. Int Psychogeriatr. 2014;26:155–63.PubMedGoogle Scholar
  134. 134.
    Ottenbacher KJ, Ostir GV, Peek MK, Snih SA, Raji MA, Markides KS. Frailty in older Mexican Americans. J Am Geriatr Soc. 2005;53:1524–31.PubMedCentralPubMedGoogle Scholar
  135. 135.
    Gill TM, Williams CS, Richardson ED, Tinetti ME. Impairments in physical performance and cognitive status as predisposing factors for functional dependence among nondisabled older persons. J Gerontol A Biol Sci Med Sci. 1996;51A:M283–8.Google Scholar
  136. 136.
    Strawbridge WJ, Shema SJ, Balfour JL, Higby HR, Kaplan GA. Antecedents of frailty over three decades in an older cohort. J Gerontol B Psychol Sci Soc Sci. 1998;53B:S9–16.Google Scholar
  137. 137.
    Buchman AS, Boyle PA, Wilson RS, Tang Y, Bennett DA. Frailty is associated with incident Alzheimer’s disease and cognitive decline in the elderly. Psychosom Med. 2007;69:483–9.PubMedGoogle Scholar
  138. 138.
    Samper-Ternent R, Al Snih S, Raji MA, Markides KS, Ottenbacher KJ. Relationship between frailty and cognitive decline in older Mexican Americans. J Am Geriatr Soc. 2008;56:1845–52.PubMedCentralPubMedGoogle Scholar
  139. 139.
    Boyle PA, Buchman AS, Wilson RS, Leurgans SE, Bennett DA. Physical frailty is associated with incident mild cognitive impairment in community-based older persons. J Am Geriatr Soc. 2010;58:248–55.PubMedCentralPubMedGoogle Scholar
  140. 140.
    Sarkisian CA, Gruenewald TL, John Boscardin W, Seeman TE. Preliminary evidence for subdimensions of geriatric frailty: the MacArthur study of successful aging. J Am Geriatr Soc. 2008;56:2292–7.PubMedCentralPubMedGoogle Scholar
  141. 141.
    Auyeung TW, Lee JS, Kwok T, Woo J. Physical frailty predicts future cognitive decline - a four-year prospective study in 2737 cognitively normal older adults. J Nutr Health Aging. 2011;15:690–4.PubMedGoogle Scholar
  142. 142.
    Bilotta C, Bergamaschini L, Nicolini P, Casè A, Pina G, Rossi SV, et al. Frailty syndrome diagnosed according to the Study of Osteoporotic Fractures criteria and mortality in older outpatients suffering from Alzheimer's disease: a one-year prospective cohort study. Aging Ment Health. 2012;16:273–80.PubMedGoogle Scholar
  143. 143.
    Bilotta C, Nicolini P, Casè A, Pina G, Rossi S, Vergani C. Frailty syndrome diagnosed according to the Study of Osteoporotic Fractures (SOF) criteria and adverse health outcomes among community-dwelling older outpatients in Italy. A one-year prospective cohort study. Arch Gerontol Geriatr. 2012;54:e23–8.PubMedGoogle Scholar
  144. 144.
    Kulmala J, Nykänen I, Mänty M, Hartikainen S. Association between Frailty and Dementia: a population-based study. Gerontology. 2014;60:16–21.PubMedGoogle Scholar
  145. 145.
    Buchman AS, Schneider JA, Leurgans S, Bennett DA. Physical frailty in older persons is associated with Alzheimer disease pathology. Neurology. 2008;71:499–504.PubMedCentralPubMedGoogle Scholar
  146. 146.
    Solfrizzi V, Scafato E, Frisardi V, Seripa D, Logroscino G, Maggi S, et al. Frailty syndrome and the risk of vascular dementia: the Italian Longitudinal Study on Aging. Alzheimers Dement. 2013;9:113–22.PubMedGoogle Scholar
  147. 147.
    Avila-Funes JA, Carcaillon L, Helmer C, Carrière I, Ritchie K, Rouaud O, et al. Is frailty a prodromal stage of vascular dementia? Results from the Three-City Study. J Am Geriatr Soc. 2012;60:1708–12.PubMedGoogle Scholar
  148. 148.
    Gray SL, Anderson ML, Hubbard RA, LaCroix A, Crane PK, McCormick W, et al. Frailty and incident dementia. J Gerontol A Biol Sci Med Sci. 2013;68:1083–90.PubMedGoogle Scholar
  149. 149.
    Raji MA, Al Snih S, Ostir GV, Markides KS, Ottenbacher KJ. Cognitive status and future risk of frailty in older Mexican Americans. J Gerontol A Biol Sci Med Sci. 2010;65:1228–34.PubMedGoogle Scholar
  150. 150.
    Aranda MP, Ray LA, Snih SA, Ottenbacher KJ, Markides KS. The protective effect of neighborhood composition on increasing frailty among older Mexican Americans: a barrio advantage? J Aging Health. 2011;23:1189–217.PubMedCentralPubMedGoogle Scholar
  151. 151.
    Woods AJ, Cohen RA, Pahor M. Cognitive frailty: frontiers and challenges. J Nutr Health Aging. 2013;17:741–3.PubMedGoogle Scholar
  152. 152.
    Panza F, D'Introno A, Colacicco AM, Capurso C, Parigi AD, Capurso SA, et al. Cognitive frailty: predementia syndrome and vascular risk factors. Neurobiol Aging. 2006;27:933–40.PubMedGoogle Scholar
  153. 153.•
    Cano C, Samper-Ternent R, Al Snih S, Markides K, Ottenbacher KJ. Frailty and cognitive impairment as predictors of mortality in older Mexican Americans. J Nutr Health Aging. 2012;16:142–7. A population-based study with a 10-year follow-up investigating a cognitive frailty model linked to increased all-cause mortality in older adults.PubMedCentralPubMedGoogle Scholar
  154. 154.
    Milaneschi Y, Tanaka T, Ferrucci L. Nutritional determinants of mobility. Curr Opin Clin Nutr Metab Care. 2010;13:625–9.PubMedCentralPubMedGoogle Scholar
  155. 155.
    Inzitari M, Doets E, Bartali B, Benetou V, Di Bari M, Di Visser M. International Association Of Gerontology And Geriatrics (IAGG) Task Force For Nutrition In The Elderly. Nutrition in the age-related disablement process. J Nutr Health Aging. 2011;15:599–604.PubMedGoogle Scholar
  156. 156.
    Lee JS, Auyeung TW, Leung J, Kwok T, Leung PC, Woo J. Physical frailty in older adults is associated with metabolic and atherosclerotic risk factors and cognitive impairment independent of muscle mass. J Nutr Health Aging. 2011;15:857–62.PubMedGoogle Scholar
  157. 157.
    Bartali B, Frongillo EA, Bandinelli S, Lauretani F, Semba RD, Fried LP, et al. Low nutrient intake is an essential component of frailty in older persons. J Gerontol A Biol Sci Med Sci. 2006;61:589–93.PubMedCentralPubMedGoogle Scholar
  158. 158.
    Ble A, Cherubini A, Volpato S, Bartali B, Walston JD, Windham BG, et al. Lower plasma vitamin E levels are associated with the frailty syndrome: the InCHIANTI study. J Gerontol A Biol Sci Med Sci. 2006;61:278–83.PubMedGoogle Scholar
  159. 159.
    de Jong N, Chin A, Paw MJ, de Groot LC, de Graaf C, Kok FJ, et al. Functional biochemical and nutrient indices in frail elderly people are partly affected by dietary supplements but not by exercise. J Nutr. 1999;129:2028–36.PubMedGoogle Scholar
  160. 160.
    Morley JE. Developing novel therapeutic approaches to frailty. Curr Pharm Des. 2009;15:3384–95.PubMedGoogle Scholar
  161. 161.
    Cesari M. Perspective: protein supplementation against sarcopenia and frailty – future perspectives from novel data. J Am Med Dir Assoc. 2013;14:62–3.PubMedGoogle Scholar
  162. 162.•
    Tamura BK, Bell CL, Masaki KH, Amella EJ. Factors associated with weight loss, low BMI, and malnutrition among nursing home patients: A systematic review of the literature. J Am Med Dir Assoc. 2013;14:649–55. A systematic review on factors associated with weight loss and poor nutrition in long term care to target high-risk institutionalized patients. PubMedGoogle Scholar
  163. 163.
    Morley JE. Cognition and nutrition. Curr Opin Clin Nutr Metab Care. 2014;17:1–4.PubMedGoogle Scholar
  164. 164.
    Cesari M, Pahor M, Bartali B, Cherubini A, Penninx BW, Williams GR, et al. Antioxidants and physical performance in elderly persons: the Invecchiare in Chianti (InCHIANTI) study. Am J Clin Nutr. 2004;79:289–94.PubMedGoogle Scholar
  165. 165.
    Semba RD, Bartali B, Zhou J, Blaum C, Ko CW, Fried LP. Low serum micronutrient concentrations predict frailty among older women living in the community. J Gerontol A Biol Sci Med Sci. 2006;61:594–9.PubMedGoogle Scholar
  166. 166.
    Michelon E, Blaum C, Semba RD, Xue QL, Ricks MO, Fried LP. Vitamin and carotenoid status in older women: associations with the frailty syndrome. J Gerontol A Biol Sci Med Sci. 2006;61:600–7.PubMedGoogle Scholar
  167. 167.
    Bartali B, Semba RD, Frongillo EA, Varadhan R, Ricks MO, Blaum CS, et al. Low micronutrient levels as a predictor of incident disability in older women. Arch Intern Med. 2006;166:2335–40.PubMedCentralPubMedGoogle Scholar
  168. 168.
    Annweiler C, Schott AM, Berrut G, Fantino B, Beauchet O. Vitamin D-related changes in physical performance: a systematic review. J Nutr Health Aging. 2009;13:893–8.PubMedGoogle Scholar
  169. 169.
    Bischoff-Ferrari HA, Dawson-Hughes B, Staehelin HB, Orav JE, Stuck AE, Theiler R, et al. Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials. BMJ. 2009;339:b3692.PubMedCentralPubMedGoogle Scholar
  170. 170.•
    Talegawkar SA, Bandinelli S, Bandeen-Roche K, Chen P, Milaneschi Y, Tanaka T, et al. A higher adherence to a mediterranean-style diet is inversely associated with the development of frailty in community-dwelling elderly men and women. J Nutr. 2012;142:2161–6. A population-based study with a 6-year follow-up showing that higher adherence to a Mediterranean-style diet at baseline was associated with a lower risk for frailty. Among frailty components, a higher adherence to a Mediterranean-style diet at baseline was associated with lower odds of low physical activity as well as low walking speed. PubMedCentralPubMedGoogle Scholar
  171. 171.
    Bollwein J, Diekmann R, Kaiser MJ, et al. Dietary quality is related to frailty in community-dwelling older adults. J Gerontol A Biol Sci Med Sci. 2013;68:483–9.PubMedGoogle Scholar
  172. 172.
    Féart C, Pérès K, Samieri C, Letenneur L, Dartigues JF, Barberger-Gateau P. Adherence to a Mediterranean diet and onset of disability in older persons. Eur J Epidemiol. 2011;26:747–56.PubMedGoogle Scholar
  173. 173.
    Milaneschi Y, Bandinelli S, Corsi AM, Lauretani F, Paolisso G, Dominguez LJ, et al. Mediterranean diet and mobility decline in older persons. Exp Gerontol. 2011;46:303–8.PubMedCentralPubMedGoogle Scholar
  174. 174.
    Shahar DR, Houston DK, Hue TF, Lee JS, Sahyoun NR, Tylavsky FA, et al. Adherence to mediterranean diet and decline in walking speed over 8 years in community-dwelling older adults. J Am Geriatr Soc. 2012;60:1881–8.PubMedCentralPubMedGoogle Scholar
  175. 175.
    de Vries NM, van Ravensberg CD, Hobbelen JS, Olde Rikkert MG, Staal JB, Nijhuis-van der Sanden MW. Effects of physical exercise therapy on mobility, physical functioning, physical activity and quality of life in community-dwelling older adults with impaired mobility, physical disability and/or multi-morbidity: a meta-analysis. Ageing Res Rev. 2012;11:136–49.PubMedGoogle Scholar
  176. 176.
    Clegg A, Barber S, Young J, Forster A, Iliffe S. Do home-based exercise interventions improve outcomes for frail older people? Findings from a systematic review. Rev Clin Gerontol. 2012;22:68–78.Google Scholar
  177. 177.
    Smit E, Crespo CJ, Michael Y, Ramirez-Marrero FA, Brodowicz GR, Bartlett S, et al. The effect of vitamin D and frailty on mortality among noninstitutionalized US older adults. Eur J Clin Nutr. 2012;66:1024–8.PubMedGoogle Scholar
  178. 178.
    Smit E, Winters-Stone KM, Loprinzi PD, Tang AM, Crespo CJ. Lower nutritional status and higher food insufficiency in frail older US adults. Br J Nutr. 2013;110:172–8.PubMedGoogle Scholar
  179. 179.
    Bollwein J, Volkert D, Diekmann R, Kaiser MJ, Uter W, Vidal K, et al. Nutritional status according to the mini nutritional assessment (MNA1) and frailty in community dwelling older persons: a close relationship. J Nutr Health Aging. 2013;17:351–6.PubMedGoogle Scholar
  180. 180.
    Serra-Prat M, Mans E, Palomera E, Clave P. Gastrointestinal peptides, gastrointestinal motility, and anorexia of aging in frail elderly persons. Neurogastroenterol Motil. 2013;25:291–345.PubMedGoogle Scholar
  181. 181.•
    Allen VJ, Methven L, Gosney MA. Use of nutritional complete supplements in older adults with dementia: systematic review and meta-analysis of clinical outcomes. Clin Nutr. 2013;32:950–7. A meta-analysis showing that oral nutritional supplements may increase weight and improve cognition in persons with dementia. PubMedGoogle Scholar
  182. 182.
    Stange I, Bartram M, Liao Y, Poeschl K, Kolpatzik S, Uter W, et al. Effects of a low-volume, nutrient- and energy-dense oral nutritional supplement on nutritional and functional status: a randomized, controlled trial in nursing home residents. J Am Med Dir Assoc. 2013;14:628.e1–8.Google Scholar
  183. 183.
    Fiatarone MA, O’Neill EF, Ryan ND, Clements KM, Solares GR, Nelson ME, et al. Exercise training and nutritional supplementation for physical frailty in very elderly people. N Engl J Med. 1994;330:1769–75.PubMedGoogle Scholar
  184. 184.
    Kim C-O, Lee K-R. Preventive effect of protein-energy supplementation on the functional decline of frail older adults with low socioeconomic status: a community-based randomized controlled study. J Gerontol A Biol Sci Med Sci. 2013;68:309–16.PubMedGoogle Scholar
  185. 185.••
    Chan DC, Tsou HH, Yang RS, Tsauo JY, Chen CY, Hsiung CA, et al. A pilot randomized controlled trial to improve geriatric frailty. BMC Geriatr. 2012;12:58. One of the first pilot randomized controlled trials examining the effects of both nutritional consultation and exercise in frail older adults, although both interventions on frailty status were only short-term effective (3 months). PubMedCentralPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Francesco Panza
    • 1
    • 2
  • Vincenzo Solfrizzi
    • 3
  • Rosanna Tortelli
    • 1
    • 2
  • Francesco Resta
    • 3
  • Carlo Sabbà
    • 3
  • Giancarlo Logroscino
    • 1
    • 2
  1. 1.Neurodegenerative Disease Unit, Department of Basic Medicine, Neuroscience, and Sense OrgansUniversity of Bari Aldo MoroBariItaly
  2. 2.Department of Clinical Research in NeurologyUniversity of Bari Aldo Moro, “Pia Fondazione Cardinale G. Panico,” TricaseLecceItaly
  3. 3.Geriatric Medicine-Memory Unit and Rare Disease CentreUniversity of Bari Aldo MoroBariItaly

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