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Advances in Gerontology

Erschienen in:

01.06.2022

Is Ketogenic Diet Therapy a Remedy for Alzheimer’s Disease or Mild Cognitive Impairments?: A Narrative Review of Randomized Controlled Trials

verfasst von: H. Şimşek, A. Uçar

Erschienen in: Advances in Gerontology | Ausgabe 2/2022

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Abstract

Alzheimer’s disease (AD) is the most common form of dementia and is estimated to increase further due to the aging of the world population. Since preventive strategies or effective treatment for AD have not been defined yet, studies on metabolism and nutritional approaches have gained attention. A present literature review aimed to provide a summary of current evidence on the neuroprotective roles of ketogenic diets. A literature search was conducted on the MEDLINE, EMBASE, and CENTRAL databases for clinical trials that published in English and focused ketogenic therapy in AD or mild cognitive impairment. The neuroprotective potential of ketone bodies is based on mitochondrial dysfunction, suppression of oxidative damage and inflammation, reduction of the negative effects of impaired glucose metabolism in the brain, and effects at the genomic level. Clinical studies mainly provide evidence of improved verbal memory, attention, and total cognitive function. But optimal procedures have not yet been clarified. Also, ketogenic diet practices in older adults may pose several risks in long term. Therefore, further clinical research will shed more light on the neuroprotective effect, safety, and sustainability of the ketogenic diet, which is promising in the protection or improvement of cognitive functions.

2020 Alzheimer’s Disease Facts and Figures, Alzheimer’s Association report, Alzheimer’s Dement., 2020, vol. 16, no. 3, pp. 391–460.

Augustin, K.A., Khabbush, S., Williams, S., et al., Mechanisms of action for the medium-chain triglyceride ketogenic diet in neurological and metabolic disorders, Lancet Neurol., 2018, vol. 17, no. 1, pp. 84–93.PubMedCrossRef

Barnard, N.D., Bush, A.I., Ceccarelli, A., et al., Dietary and lifestyle guidelines for the prevention of Alzheimer’s disease, Neurobiol. Aging, 2014, vol. 35, no. 2, pp. S74–S78.PubMedCrossRef

Bough, K.J., Wetherington, J., Hassel, B., et al., Mitochondrial biogenesis in the anticonvulsant mechanism of the ketogenic diet, Ann. Neurol., 2006, vol. 60, no. 2, pp. 223–235.PubMedCrossRef

Brandt, J., Buchholz, A., Henry-Barron, B., et al., Preliminary report on the feasibility and efficacy of the modified Atkins diet for treatment of mild cognitive impairment and early Alzheimer’s disease, J. Alzheimer’s Dis., 2019, vol. 68, no. 3, pp. 969–981.CrossRef

Broom, G.M., Shaw, I.C., and Rucklidge, J.J., The ketogenic diet as a potential treatment and prevention strategy for Alzheimer’s disease, Nutrition, 2019, vol. 60, no. 2, pp. 118–121.PubMedCrossRef

Busche, M.A., Wegmann, S., Dujardin, S., et al., Tau impairs neural circuits, dominating amyloid-β effects, in Alzheimer models in vivo, Nat. Neurosci., 2019, vol. 22, no. 1, pp. 57–64.PubMedCrossRef

Craft, S., Neth, B.J., Mintz, A., et al., O4-05-03: ketogenic diet effects on brain ketone metabolism and Alzheimer’s disease CSF biomarkers, Alzheimer’s Dementia, 2016, vol. 12, no. 2, pp. Р342–P343.CrossRef

Cummings, J.L., Morstorf, T., and Zhong, K., Alzheimer’s disease drug-development pipeline: few candidates, frequent failures, Alzheimers Res. Ther., 2014, vol. 3, no. 4, p. 37.CrossRef

10.

Cunnane, S.C., Courchesne-Loyer, A., St-Pierre, V., et al., Can ketones compensate for deteriorating brain glucose uptake during aging? Implications for the risk and treatment of Alzheimer’s disease, Ann. N.Y. Acad. Sci., 2016.

11.

Davies, P. and Maloney, A.J., Selective loss of central cholinergic neurons in Alzheimer’s disease, Lancet, 1976, vol. 25, no. 8000, p. 1403.CrossRef

12.

Duran-Aniotz, C. and Hetz, C., Glucose metabolism: a sweet relief of Alzheimer’s disease, Current Biol., 2016, vol. 12, no. 17, pp. 806–809.CrossRef

13.

Edwards, I.G.A., Gamez, N., Escobedo, G., et al., Modifiable risk factors for Alzheimer’s disease, Front. Aging Neurosci., 2019, vol. 11, no. 146, pp. 1–18.

14.

Fan, L., Mao, C., Hu, X., et al., New insights into the pathogenesis of Alzheimer’s disease, Front. Neurol., 2019, vol. 10, no. 10, p. 1312.PubMedCrossRef

15.

Ferreira, S.T. and Klein, W.L., The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease, Neurobiol. Learning Memory, 2011, vol. 96, no. 4, pp. 529–543.CrossRef

16.

Fortier, M., Castellano, C.A., Croteau, E., et al., A ketogenic drink improves brain energy and some measures of cognition in mild cognitive impairment, Alzheimer’s Dement., 2019, vol. 15, no. 5, pp. 625–634.CrossRef

17.

Fortier, M., Castellano, C.A., and St-Pierre, V., A ketogenic drink improves cognition in mild cognitive impairment: results of a 6-month RCT, Alzheimer’s Dement., 2021, vol. 17, no. 3, pp. 543–552.CrossRef

18.

Grabacka, M., Pierzchalska, M., Dean, M., and Reiss, K., Regulation of ketone body metabolism and the role of PPAR-α, Int. J. Mol. Sci., 2016, vol. 17, no. 12, p. 2093.PubMedCentralCrossRef

19.

Hampel, H., Mesulam, M.M., Cuello, A.C., et al., The cholinergic system in the pathophysiology and treatment of Alzheimer’s disease, Brain, 2018, vol. 141, no. 7, pp. 1917–1933.PubMedPubMedCentralCrossRef

20.

Hardy, J. and Allsop, D., Amyloid deposition as the central event in the aetiology of Alzheimer’s disease, Trends Pharmacol. Sci., 1991, vol. 12, no. 10, pp. 383–388.PubMedCrossRef

21.

National Institutes of Health (NIH), www.nia.nih.gov/ health/how-alzheimers-disease-treated.

22.

Hebert, L.E., Weuve, J., Scherr, P.A., et al., Alzheimer disease in the United States (2010–2050) estimated using the 2010 census, Neurology, 2013, vol. 80, no. 19, pp. 1778–1783.PubMedPubMedCentralCrossRef

23.

Henderson, S.T., Vogel, J.L., Barr, L.J., et al., Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer’s disease: a randomized, double-blind, placebo-controlled, multicenter trial, Nutr. Metab., 2009, vol. 10, no. 6, p. 31.CrossRef

24.

Huang, L.-K., Chao, S.-P., and Hu, C.-J., Clinical trials of new drugs for Alzheimer disease, J. Biomed. Sci., 2020, vol. 27, no. 1, p. 18.PubMedPubMedCentralCrossRef

25.

Jensen, N.J., Wodschow, H.Z., Nilsson, M., et al., Effects of ketone bodies on brain metabolism and function in neurodegenerative diseases, Int. J. Mol. Sci., 2020, vol. 21, no. 22, p. 8767.PubMedCentralCrossRef

26.

Yao, J. and Brinton, R.D., Targeting mitochondrial bioenergetics for Alzheimer’s prevention and treatment, Curr. Pharm. Design, 2011, vol. 17, no. 31, pp. 3474–3479.CrossRef

27.

Kashiwaya, Y., Takeshima, T., Mori, N., et al., D-β-hydroxybutyrate protects neurons in models of Alzheimer’s and Parkinson’s disease, Proc. Natl. Acad. Sci. U. S. A., 2000, vol. 97, no. 10, pp. 5440–5444.PubMedPubMedCentralCrossRef

28.

Knight, R., Khondoker, M., Magill, N., et al., A systematic review and meta-analysis of the effectiveness of acetylcholinesterase inhibitors and memantine in treating the cognitive symptoms of dementia, Dement. Geriatr. Cogn. Disord., 2018, vol. 45, nos. 3–4, pp. 131–151.PubMedCrossRef

29.

Koepsell, H., Glucose transporters in brain in health and disease, Pflüegers Arch., 2020, vol. 472, no. 9, pp. 1299–1343.CrossRef

30.

Krikorian, R., Shidler, M.D., Dangelo, K., et al., Dietary ketosis enhances memory in mild cognitive impairment, Neurobiol. Aging, 2012, vol. 33, no. 2, p. 425.PubMedCrossRef

31.

Kuehn, B.M., In Alzheimer research, glucose metabolism moves to center stage, JAMA, 2020, vol. 323, no. 4, pp. 297–299.PubMedCrossRef

32.

Kumar, A., Sidhu, J., Goyal, A., et al., Alzheimer Disease, Treasure Island (FL): StatPearls Publishing, 2021.

33.

Liu, P.-P., Xie, Y., Meng, X.-Y., et al., History and progress of hypotheses and clinical trials for Alzheimer’s disease, Signal Transduct. Target. Ther., 2019, vol. 23, no. 4, p. 29.CrossRef

34.

Liu, Y., Liu, F., Iqbal, K., et al., Decreased glucose transporters correlate to abnormal hyperphosphorylation of tau in Alzheimer disease, FEBS Lett., 2008, vol. 582, no. 2, pp. 359–364.PubMedPubMedCentralCrossRef

35.

Livingston, G., Huntley, J., Sommerlad, A., et al., Dementia prevention, intervention, and care: 2020 report of the lancet commission, Lancet, 2020, vol. 396, no. 10248, pp. 413–446.PubMedPubMedCentralCrossRef

36.

Ludwig, D.S., The ketogenic diet: evidence for optimism but high-quality research needed, J. Nutr., 2020, vol. 150, no. 6, pp. 1354–1359.PubMedCrossRef

37.

Marei, H.E., Althani, A., Suhonen, J., et al., Recent perspective about the amyloid cascade hypothesis and stem cell-based therapy in the treatment of Alzheimer’s disease, in Front. Clin. Drug Res., Bentham, 2016.

38.

McDonald, T.J.W. and Cervenka, M.C., Ketogenic diets for adult neurological disorders, Neurotherapeutics, 2018, vol. 15, no. 4, pp. 1018–1031.PubMedPubMedCentralCrossRef

39.

McNally, M.A. and Hartman, A.L., Ketone bodies in epilepsy, J. Neurochem., 2012, vol. 121, no. 1, pp. 28–35.PubMedPubMedCentralCrossRef

40.

Möller, H.J. and Graeber, M.B., The case described by Alois Alzheimer in 1911. Historical and conceptual perspectives based on the clinical record and neurohistological sections, Eur. Arch. Psychiatry Clin. Neurosci., 1998, vol. 248, no. 3, pp. 111–122.PubMedCrossRef

41.

Nichols, E., Szoeke, C.E., Vollset, S.E., et al., Global, regional, and national burden of Alzheimer’s disease and other dementias, 1990–2016: a systematic analysis for the global burden of disease study 2016, Lancet Neurol., 2019, vol. 18, no. 1, pp. 88–106.CrossRef

42.

Ohnuma, T., Toda, A., Kimoto, A., et al., Benefits of use, and tolerance of, medium-chain triglyceride medical food in the management of Japanese patients with Alzheimer’s disease: a prospective, open-label pilot study, Clin. Interv. Aging, 2016, vol. 8, no. 11, p. 29.CrossRef

43.

Omar, S.H., Mediterranean and mind diets containing olive biophenols reduces the prevalence of Alzheimer’s disease, Int. J. Mol. Sci., 2019, vol. 20, no. 11, p. 2797.PubMedCentralCrossRef

44.

Ota, M., Matsuo, J., Ishida, I., et al., Effects of a medium-chain triglyceride-based ketogenic formula on cognitive function in patients with mild-to-moderate Alzheimer’s disease, Neurosci. Lett., 2019, vol. 18, no. 690, pp. 232–236.CrossRef

45.

Phillips, M.C.L., Deprez, L.M., Mortimer, G.M.N., et al., Randomized crossover trial of a modified ketogenic diet in Alzheimer’s disease, Alzheimer’s Res. Ther., 2021, vol. 13, no. 1, p. 51.CrossRef

46.

Pinto, A., Bonucci, A., Maggi, E., et al., Anti-oxidant and anti-inflammatory activity of ketogenic diet: new perspectives for neuroprotection in Alzheimer’s disease, Antioxidants (Basel), 2018, vol. 7, no. 5, р. 63.

47.

Rabinovici, G.D., Late-onset Alzheimer Disease, Continuum (Minneapolis: Minn.), 2019, vol. 25, no. 1, рр. 14–33.CrossRef

48.

Raina, P., Santaguida, P., Ismaila, A., et al., Effectiveness of cholinesterase inhibitors and memantine for treating dementia: evidence review for a clinical practice guideline, Ann. Int. Med., 2008, vol. 148, no. 5, pp. 379–397.PubMedCrossRef

49.

Rebello, C.J., Keller, J.N., Liu, A.G., et al., Pilot feasibility and safety study examining the effect of medium chain triglyceride supplementation in subjects with mild cognitive impairment: a randomized controlled trial, Biochim. Biophys. Acta, Clin., 2015, vol. 16, no. 3, pp. 123–125.

50.

Reger, M.A., Henderson, S.T., Hale, C., et al., Effects of β-hydroxybutyrate on cognition in memory-impaired adults, Neurobiol. Aging, 2004, vol. 25, no. 3, pp. 311–314.PubMedCrossRef

51.

Republic of Turkey Ministry of Health. Türkiye Beslenme Rehberi (TÜBER). 2015 [05/05/2021]. Accessed: https://dosyasb.saglik.gov.tr/Eklenti/10915,tuber-turkiye-beslenme-rehberipdf.pdf.

52.

Roehl, K. and Sewak, S.L., Practice paper of the Academy of Nutrition and Dietetics: classic and modified ketogenic diets for treatment of epilepsy, J. Acad. Nutr. Diet, 2017, vol. 117, no. 8, pp. 1279–1292.PubMedCrossRef

53.

Rusek, M., Pluta R., Ulamek-Koziol, M., et al., Ketogenic diet in Alzheimer’s disease, Int. J. Mol. Sci., 2019, vol. 20, no. 16, p. 3892.PubMedCentralCrossRef

54.

Serrano-Pozo, A., Das, S., and Hyman, B.T., APOE and Alzheimer’s disease: advances in genetics, pathophysiology, and therapeutic approaches, Lancet Neurol., 2021, vol. 20, no. 1, pp. 68–80.PubMedPubMedCentralCrossRef

55.

Shen, L. and Jia, J., An overview of genome-wide association studies in Alzheimer’s disease, Neurosci. Bull., 2016, vol. 32, no. 2, pp. 183–190.PubMedPubMedCentralCrossRef

56.

Soria Lopez, J.A., González, H.M., and Léger, G.C., Alzheimer’s disease, Handb. Clin. Neurol., 2019, no. 167, pp. 231–255.

57.

Sridharan, B. and Lee, M.J., Ketogenic diet: a promising neuroprotective composition for managing Alzheimer’s diseases and its pathological mechanisms, Curr. Mol. Med., 2021. https://doi.org/10.2174/1566524021666211004104703

58.

Taylor, M.K., Sullivan, D.K., Swerdlow, R.H., et al., A high-glycemic diet is associated with cerebral amyloid burden in cognitively normal older adults, Am. J. Clin. Nutr., 2017, vol. 106, no. 6, pp. 1463–1470.PubMedPubMedCentralCrossRef

59.

Taylor, M.K., Swerdlow, R.H., Burns, J.M., et al., An experimental ketogenic diet for Alzheimer disease was nutritionally dense and rich in vegetables and avocado, Curr. Dev. Nutr., 2019, vol. 3, no. 4, article ID nzz003.

60.

Tiwari, S., Atluri, V., Kaushik, A., et al., Alzheimer’s disease: pathogenesis, diagnostics, and therapeutics, Int. J. Nanomed., 2019, vol. 19, no. 14, pp. 5541–5554.CrossRef

61.

Torosyan, N., Sethanandha, C., Grill, J.D., et al., Changes in regional cerebral blood flow associated with a 45-day course of the ketogenic agent, caprylidene, in patients with mild to moderate Alzheimer’s disease: results of a randomized, double-blinded, pilot study, Exp. Gerontol., 2018, vol. 1, no. 11, pp. 118–121.CrossRef

62.

Van der Auwera, I., Wera, S., Van Leuven, F., et al., A ketogenic diet reduces amyloid beta 40 and 42 in a mouse model of Alzheimer’s disease, Nutr. Metab., 2005, vol. 17, no. 2, p. 28.CrossRef

63.

Veyrat-Durebex, C., Reynier, P., Procaccio, V., et al., How can a ketogenic diet improve motor function?, Front. Mol. Neurosci., 2018, vol. 26, no. 11, p. 15.CrossRef

64.

Wheless, J.W., History of the ketogenic diet, Epilepsia, 2008, vol. 49, no. 8, pp. 3–5.PubMedCrossRef

65.

Williams, T., Borchelt, D.R., and Chakrabarty, P., Therapeutic approaches targeting apolipoprotein E function in Alzheimer’s disease, Mol. Neurodegener., 2020, vol. 15, no. 1, p. 8.PubMedPubMedCentralCrossRef

66.

Wlodarek, D., Role of ketogenic diets in neurodegenerative diseases (Alzheimer’s disease and Parkinson’s disease), Nutrients, 2019, vol. 11, no. 1, p. 169.PubMedCentralCrossRef

67.

World Health Organization. Dementia. 2020 [01/04/2021]. www.who.int/news-room/fact-sheets/detail/dementia.

68.

Youm, Y.H., Nguyen, K.Y., Grant, R.W., et al., The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease, Nat. Med., 2015, vol. 21, no. 3, pp. 263–269.PubMedPubMedCentralCrossRef

Titel: Is Ketogenic Diet Therapy a Remedy for Alzheimer’s Disease or Mild Cognitive Impairments?: A Narrative Review of Randomized Controlled Trials
verfasst von: H. Şimşek
A. Uçar
Publikationsdatum: 01.06.2022
Verlag: Pleiades Publishing
Erschienen in: Advances in Gerontology / Ausgabe 2/2022
Print ISSN: 2079-0570
Elektronische ISSN: 2079-0589
DOI: https://doi.org/10.1134/S2079057022020175

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