NMU 243 – Early Adult and Mid-Life Cholesterol and Glucose Levels Predict Alzheimer’s disease Later in Life (Framingham study 2022)

Nutrition/Natural Medicine Update No 243 (May 24, 2022)

with Dr. James Meschino

Topic:  Early Adult and Mid-Life Cholesterol and Glucose Levels Predict Alzheimer’s disease Later in Life (Framingham study 2022)

Source: Alzheimer’s & Dementia Journal (March 2022)

 

A study published in the journal Alzheimer’s & Dementia, in March of 2022, has shown that unhealthy blood cholesterol and blood glucose (sugar) levels in early and mid-adulthood are associated with a higher risk of developing Alzheimer’s disease in later life. The study was an extension of the famous Framingham heart study, following 4,932 individuals, which has been studying participants over many years and decades. This arm of the study showed that a 15 mg/dL increase in high-density lipoprotein (HDL) – the good cholesterol, measured during early and middle adulthood was associated with a decreased Alzheimer’s disease risk later in life. As well, a 15 mg/dL increase in glucose (blood sugar) measured during middle adulthood was associated with a 14.5% increased Alzheimer’s disease risk later in life. The study also factored in age, sex, blood pressure, body mass index, smoking history, and educational status. The researchers concluded the following, “Our findings suggest that careful management of cholesterol and glucose beginning in early adulthood can lower Alzheimer’s disease risk.” In their opening comments, they state that Alzheimer’s disease is the fifth leading cause of death among Americans 65 years of age or older.

To date, there are no proven effective disease-modifying therapies to prevent or slow cognitive decline from Alzheimer’s disease. Early identification and treatment of individuals at risk for the common form of Alzheimer’s disease occurring after age 65 have been recognized as an important contributor to reductions in Alzheimer’s disease mortality and delaying the symptoms of the disease. So, in this study, we learned that keeping your glucose and HDL levels in the desirable range are two important ways to reduce the risk of Alzheimer’s disease as you age. Really good targets to shoot for throughout all LMU  adult life include:

• Fasting Glucose level – under 90 mg/dl (5.0 mmol/L)
• Fasting HDL – above 60 mg/dl (1.6 mmol/L)

Some other lifestyle strategies that are shown to help reduce the risk of Alzheimer’s disease include:

• Keeping your total blood cholesterol in the ideal range
• Participate in regular aerobic exercise
• Achieve and maintain an ideal body weight
• Get adequate intake of omega-3 fats (including from supplements)
• Avoid or limit alcohol intake
• Keep your brain active, learning new things or new skills on an ongoing basis
• Avoid head injuries
• Keep your blood pressure in the ideal range
• Drink green tea daily
• Maintain optimal vitamin D blood levels (above 75 nmol/L or 30 ng/ml)
• After the age of 40 or 45 consider taking a supplement containing melatonin one hour before bedtime
• After age 55, I suggest taking a supplement that contains CDP-choline, Huperzine A, Bacopa monnieri and Phosphatidylserine to help maintain brain levels of the memory chemical (neurotransmitter), acetylcholine.

According to published studies, preventing Alzheimer’s disease to the greatest degree possible involves paying attention to a number of dietary and lifestyle factors throughout all of adult life, as I have outlined here. The good news is that these factors are largely under your control and so you should feel empowered knowing that your personal wellness choices from day to day can have a significant impact on lowering your risk as the years tick away. I have included the reference for the 2022 study in the text below, as well as references that support the other Alzheimer’s prevention strategies, I mentioned in this video update.

Main Reference:

Zhang X et al. Midlife lipid and glucose levels are associated with Alzheimer’s disease. Alzheimer’s & Dementia Journal. March 23, 2022. https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.12641

Other Supporting References:

1. http://www.alz.org/alzheimers_disease_facts_and_figures.asp

2. https://www.nia.nih.gov/alzheimers/publication/alzheimers-disease-genetics-fact-sheet

3. http://alzheimers.org.uk/site/scripts/documents_info.php?documentID=161

4. http://www.psychologytoday.com/blog/evolutionary-psychiatry/201109/alzheimersand-

high-blood-sugar

5. http://www.alz.org/national/documents/latino_brochure_diabetes.pdf

6. Cedric Annweiler, Yves Rolland, Anne M Schott, Hubert Blain, Bruno Vellas, Francois R Herrmann, Olivier Beauchet. “Higher Vitamin D Dietary Intake Is Associated With Lower Risk of Alzheimer’s Disease: A 7-Year Follow-up,” J Gerontol A Biol Sci Med Sci., April 13, 2012.(http://biomedgerontology.oxfordjournals.org/content/early/2012/04/13/gerona.gls10 7.abstract)

7. http://www.ox.ac.uk/media/news_stories/2010/100909.html

8. http://journals.lww.com/alzheimerjournal/Abstract/1998/09000/Vitamin_E_and_Vitamin_C_Supplement_Use_and_Risk_of.1.aspx

9. http://journals.lww.com/alzheimerjournal/Citation/2003/10000/Donepezil_Plus_Vitamin_E_as_a_Treatment_in.9.aspx

10. Steve Connor, Gustavo Tenorio, Michael Tom Clandinin, Yves Sauv. DHA supplementation enhances high-frequency, stimulation-induced synaptic transmission

in mouse hippocampus. Applied Physiology, Nutrition, and Metabolism, 20 June 2012

11. Conquer 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

12. Heude B, Ducimetiere P, Berr C. Cognitive decline and fatty acid composition of erythrocyte membranes – the EVA Study. Am J Clin Nutr 2003;77:803-8

13. Tully AM, Roche HM, Doyle R, et al. Low serum cholesteryl esterdocosahexaenoic acid levels in Alzheimer’s disease: a case-control study. Br J Nutr 2003;89:483-9

14. Kalmijn S, van Boxtel MP, Ocke M, Vershcuren WM, Kromhout D, Launer LJ. Dietary intake of fatty acids and fish in relation to cognitive performance at middle age. Neurology 2004;62:275-80

15. Kalmign S, Feskens EJ, Launer LJ, Kromhout D. Polyunsaturated fatty acids, antioxidants,and cognitive function in very old men. Am J Epidemiol 1997;145:33-41

16. He K, Song Y, Daviglus MI, et al. Fish consumption and incidence of stroke: a meta-analysis of cohort studies. Stroke 2004;35:1538-42

17. Connor WE and Connor SL. The importance of fish and docosahexaenoic acid in Alzheimer’s disease. Am J Clin Nutr;85:929-30. 2007

18. Brunner E. Oily fish and omega 3 fat supplements. BMJ;332:739-740.2006

19. Beydoun MA, Kaufman JS, Satia JA, Rousamond W, Folson AR. Plasma n-3 fatty acids and the risk of cognitive decline in older adults: the Atherosclerosis Risk Communities Study.Am J Clin Nutr 85:1103-11. 2007

20. Van Gelder BM, Tijuis 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; 85: 1142-7. 2007

21. Scientific Advisory Committee on Nutrition, Committee on Toxicity. Advice on fish consumption: benefits and risks. London, Stationery Office, 2004.

www.food.gov.uk/multimedia/pdfs/fishreport2004full.pdf (accessed 9 Feb 2006).

22. Feng Z, Zhang JT. Protective effect of melatonin on beta-amyloid-induced apoptosis in rat astroglioma c6 cells and its mechanism. Free Radic Biol Med. 2004 Dec 1;37(11):1790-801.

23. Pandi-Perumal SR, Zisapel N, Srinivasan V, Cardinali DP. Melatonin and sleep in aging population. Exp Gerontol. 2005 Dec;40(12):911-25. Epub 2005 Sep 23.

24. Cardinali DP, Furio AM, Brusco LI. Clinical Aspects of Melatonin Intervention in Alzheimer’s Disease Progression. Curr Neuropharmacol. 2010 September; 8(3): 218–227.

25. Furio AM, Brusco LI, Cardinali DP. Possible Therapeutic Value of Melatonin in Mild Cognitive Impairment: a Retrospective Study. J. Pineal Res. 2007;43:404–409.

26. Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E. Mild Cognitive Impairment: Clinical Characterization and Outcome. Arch. Neurol. 1999;56:303–308

27. Peck JS, LeGoff DB, Ahmed I, Goebert D. Cognitive Effects of Exogenous Melatonin Administration in Elderly Persons: a Pilot Study. Am. J. Geriatr. Psychiatry. 2004;12:432– 436.

28. http://www.ox.ac.uk/media/news_stories/2010/100909.html

29. http://bmjopen.bmj.com/content/2/1/e000850.full

30. Foiravanti M, Yanagi M. Cytidinediphosphocholine (CDP-Choline) for cognitive and behavioral disturbances associated with chronic cerebral disorders in the elderly. Cochrane Syst Revi 2002;(2):000269 In: The Cochrane Library, 1,2002. Oxford: Update Software

31. Present Knowledge in Nutrition (5th edition). The Nutrition Foundation, Inc 1984;Choline:383-399

32. Secades JJ, et al. CDP-Choline: pharmacological and clinical review. Methods Find Exp Clin Pharmacol 1995;17(Suppl B):1-54

33. Zeisel SH, et al. Choline,an essential nutrient for humans. FASEB J 1991;5:20093-2098

34. Cenacchi T, Bertoldin T, Farina C, et al. Cognitive decline in the elderly: A double-blind, placebo-controlled multicenter study on efficacy of phosphatidylserine administration. Aging 1993;5:123-33

35. Crook T, Petrie W, Wells C, Massari DC. Effects of phosphatidylserine in Alzheimer’s disease. Psychopharmacol Bull 1992;28:61-6

36. Crook TH, Tinklenberg J, Yesavage J, Petrie W, Nunzi MG, Massari DC. Effect of phosphatidylserine in age-associated memory impairment. Neurology 1991;41:644-9

37. Engel RR, Satzger W, Gunther W, Kathmann N, Bove D, Gerke S, et al. Double-blind crossover study of phosphatidylserine vs. placebo in subjects with early cognitive deterioration of the Alzheimer type. Eur. Neuropsychopharmacol, 1992;2:149-55

38. Funfgeld EW, Baggen M, Nedwidek P, Richstein B, Mistlberger G. Double-blind study with phosphatidylserine (PS) in parkinsonian patients with senile dementia of Alzheimer’s type (SKAT). Prog Clin Biol Res 1989;317:1235-46

39. Maggioni M, Picotti GB, Bondiolotti GP, Panerai A, Cenacchi T, Nobil P, et al. Effects of phosphatidylserine therapy in geriatric patients with depressive disorders. Acta Psychiatr Scand 1990;81:265-70

40. Nunzi MG, Milan F, Guidolin D, et al. Effects of phosphatidylserine administration on agerelated structural changes in the rat hippocampus and septal complex. Pharmacopsychiat 1989;22:125-8

41. Valzelli L, Kozak W, Zanotti A, Toffano G. Activity of phosphatidylserine on memory retrieval and on exploration in mice. Meth Find Extl Clin Pharmacol 1987;9:657-60

42. Vannucchi MG, Casamenti F, Pepeu G. Decrease of acetylcholine release from cortical slices in aged rats: Investigations into its reversal by phosphatidylserine. J Neurochem 1990;55:819-25

43. Dar A, Channa S. Calcium antagonistic activity of Bacopa monniera on vascular intestinal smooth muscles of rabbit and ginea-pig. J Ethnopharmacol 1999;66(2):167-74

44. Dietary Supplement Information Bureau. www.content.intramedicine.com: Bacopa monnieri

45. Kidd PM. A review of nutrients and botanicals in the integrative management of cognitive dysfunction. Altern Med Rev 1999 Jun;4(3):144-61

46. Mukherjee GD et al. Clinical trial on brahmi. I. J Exp Med Sci 1966;10(1):5-11

47. Stough C, Lloyd J, Clarke J, Downey LA, Hutchison CW, Rodgers T, et la. The chronic effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy human subjects. Psychopharmacology (Berl) 2001 Aug;156(4):481-4

48. Tripathi YB, et al. Bacopa monniera linn. As an antioxidant: Mechanism of action. Indian J Exp Biol 1996 Jun;34(6):523-6

49. Vohora D, Pal SN, Pillai KK. Protection from phenbytoin-induced cognitive deficit by Bacopa monniera, a reputed Indian nootropic plant. J Ethnopharmacol 2000 Aug;71(3):383-90

50. Ashani Y, Peggins JO, Doctor BP. Mechanism of inhibition of cholinesterases by huperzine

A. Biochem Biophys Res Commun, 1992:184:719-26

51. Bai DL, et al. Huperzine A, a potential therapeutic agent for treatment of Alzheimer’s disease. Curr Med Chem, 2000 Mar;7(3):355-74

52. Cheng DH, Ren H, Tang XC. Huperzine A, a novel promising acetylcholinesterase inhibitor. Neuroreport 1996;8:97-101

53. Cheng DH, Tang XC. Comparative studies of huperzine A, E2020, and tacrine on behavior and cholinesterase activites. Pharmacol Biochem Behav 1998;60:377-86

54. Dworkin N. Restoring memory. Psychology Today 2000 Jul/Aug;32(4):p28

55. McCaleb R. Huperzia looks promising for improving memory. HerbalGram, 10/31/1995;35:p14

56. Pirisi, Angela. Plant wisdom: Memory moss. Yoga Journal, 08/31/1999;147:p95

57. Sun QQ, Xu SS, Pan JL, et al. Huperzine-A capsules enhance memory and learning performance in 34 pairs of matched adolescent students. Acta Pharmacol Sin 1999;20:601-3

58. Tang XC. Huperzine A (shuangyiping): A promising drug for Alzheimer’s disease. Chung Kuo Yao Li Hsueh Pao, 1996 Nov;17(6):481-4

59. Wang Z, Ren G, Zhao Y et al. A double-blind study of huperzine A and piracetam in patients with age-associated memory impairment and dementia. In: Kanba S, Richelson E (eds.) Herbal Medicines for Nonpsychiatric Diseases. Tokyo: Seiwa Choten Publishers 1999:39- 50

60. Xu SS, Gao, ZX, Weng Z et al. Efficacy of tablet huperzine-A on memory, cognition, and behavior in Alzheimer’s disease. Chung Kuo Yao Li Hsueh Pao 1995;16:391-5

61. D. Amen MD. Change your brain, change your life. Publisher – Three Rivers Press. 2000.

62. http://www.alz.org/downloads/facts_figures_2012.pdf

63. http://www.hopkinsmedicine.org/health/healthy_aging/healthy_body/blood-pressureand- alzheimers-risk-whats-the-connection

64. http://archneur.jamanetwork.com/article.aspx?articleid=1356776 (Archiv Neurol Sept 10, 2012)

65. Benjamin L. Willis, MD, MPH; Ang Gao, MS; David Leonard, PhD; Laura F. DeFina, MD; Jarett D. Berry, MD, MS. Midlife Fitness and the Development of Chronic Conditions in

Later Life. Arch Int Med. Published online August 27, 2012.

66. Lautenschlager N et al. Effect of Physical Activity on Cognitive Function in Older Adults

at Risk for Alzheimer Disease. JAMA. 2008;300(9):1027-1037.

67. Masato Maesako, Kengo Uemura, Masakazu Kubota, Akira Kuzuya, Kazuki Sasaki, Ayae Kinoshita, et al. “Exercise is more effective than diet control in preventing high fat dietinduced [beta]-amyloid deposition and memory deficit in amyloid precursor protein

transgenic mice.” The Journal of Biological Chemistry, 287, 23024-23033, June 29, 2012

68. Yanyan Wang, Maoquan Li, Xueqing Xu, Min Song, Huansheng Tao, Yun Bai. Green tea epigallocatechin-3-gallate (EGCG) promotes neural progenitor cell proliferation and sonic hedgehog pathway activation during adult hippocampal neurogenesis. Molecular Nutrition & Food Research, 2012; 56 (8): 1292(weblink: http://onlinelibrary.wiley.com/doi/10.1002/mnfr.201200035/abstract)

69. Cedric Annweiler, Yves Rolland, Anne M Schott, Hubert Blain, Bruno Vellas, Francois R Herrmann, Olivier Beauchet. “Higher Vitamin D Dietary Intake Is Associated With Lower Risk of Alzheimer’s Disease: A 7-Year Follow-up,” J Gerontol A Biol Sci Med Sci., April 13, 2012. (http://biomedgerontology.oxfordjournals.org/content/early/2012/04/13/gerona.gls10 7.abstract)

70. http://jamanetwork.com/journals/jamaneurology/fullarticle/2436596

 

Eat Smart, Live Well, Look Great,

Dr. Meschino