Grow Youthful: How to Slow Your Aging and Enjoy Extraordinary Health
Grow Youthful: How to Slow Your Aging and Enjoy Extraordinary Health

Alzheimer's disease

What is Alzheimer's disease?

Symptoms of Alzheimer's disease

Risk factors for Alzheimer's disease

Root causes of Alzheimer's disease

Prevention / remedies / treatment / recovery from Alzheimer's disease

References

What is Alzheimer's disease?

Alzheimer's disease is the most common cause of dementia. It is a virus infection, bacteria infection, modern lifestyle and diet-caused disease, and it is mostly preventable if treated early.

About 34 million people around the world suffer from Alzheimer's disease. It is one of the fastest-growing degenerative diseases, and its prevalence is expected to triple over the next 40 years. Conventional medicine says that dementia is just a normal part of aging or a condition for which nothing can be done other than treating the symptoms. Conventional doctors maintain the disease worsens as it progresses, and eventually leads to death. However, with awareness of the real causes and use of appropriate treatments, you can substantially lower your risk of developing this dreadful disease.

In Australia, dementia is the second leading cause of death and Alzheimer's is the most frequent cause of dementia. 1.8% of the entire population suffer from some form of dementia, and it is growing at a rate of more than 3% each year. Similar statistics apply in other developed countries. (19)

Alzheimer's disease is most commonly diagnosed in people over the age of 65, but it can occur much earlier. The average life expectancy after diagnosis is seven years. Less than three percent of individuals live for more than fourteen years after diagnosis.

Symptoms of Alzheimer's disease

Early symptoms of Alzheimer's disease are often mistakenly thought to be manifestations of stress or aging. Early symptoms to look out for, in order of progression, are:

  1. Impaired olfaction (reduced sense of smell). Later taste may deteriorate, followed by the other senses of touch, sight and sound.
  2. Loss of sense of balance).
  3. Difficulty with eloquent language, not remembering a full range of words. Communication not as clear as it used to be. Lags and pauses in conversation compared to previously.
  4. Navigation impaired. Poor navigation both in the home, and around the town or city which used to be easy and familiar.
  5. Constipation.
  6. Personality changes.
  7. Mood changes, mostly being frustration with lost function and abilities.
  8. Poor memory. Not remembering recent events. Memories over weeks, months and even recent years are slipping.
  9. Thinking and problem solving ability deteriorates.
  10. Awareness, attention and focus are decreased.
  11. Repeating things when speaking.
  12. Sleep disorders are a symptom of Alzheimer's disease as well as a cause. Agitation during the night may affect as many as a quarter of AD patients during some stage of their illness. (42, 43, 44, 66) A study (45) over a period of twelve years found that men who napped for more than an hour a day at the beginning of the study were two to three times more likely to develop Parkinson's disease within 11 years. A subsequent study (46) published by the same authors on 18 June 2019 extended those results to suggest that napping may also precede the risk of dementia and cognitive decline more broadly.

Longer term symptoms vary with each individual, and sometimes may not be diagnosed for years. Dementia normally occurs between 5 to 20 years after the manifestation of the first early symptoms. As the disease advances, symptoms may include:

Risk factors for Alzheimer's disease

Risk factor 1 below is of overwhelming importance. In addition, a study showed that as many as half of Alzheimer's disease cases worldwide and in the USA are associated with risk factors 2-8, which are all modifiable. (1)

  1. Infection by a variety of microorganisms such as herpes simplex virus (30, 47), Chlamydia pneumoniae,Chlamydophila pneumoniae, several types of spirochaete bacteria (such as Borrelia of Lyme disease), Desulfovibrio bacteria, (68) fungal infections and some protozoa infections. Tooth loss, tooth decay, periodontitis and gum disease are leading causes of infection. (14, 17, 38) A study in 2015 found over a ten-fold increased occurrence of Alzheimer's disease when there is detectable evidence of spirochetal bacteria infection. (18) Another study (38) published in 2019 found the gum disease bacteria Porphyromonas gingivalis to be closely associated with Alzheimer's disease and other forms of dementia.

    Some bacteria such as Coprococcus protect against Alzheimer's, and people who lack these protective bacteria are at significantly higher risk. (68)
  2. Cognitive inactivity or low educational attainment. Basically, mental laziness. In particular, social isolation is the major risk factor. (6) Not learning new things, or not subjecting yourself to novel situations is also bad.
  3. Lack of sleep. (24, 25, 33, 34, 35, 37, 55, 66) Sleep is a detoxification process. In particular, the brain requires a sufficient and deep period of sleep every 24 hours.

    Beta amyloid is a protein peptide found in the brain every day, this is a normal process. At night, beta amyloids are flushed out of the brain during a phase known as slow wave sleep, a deep sleep phase which occurs early in the night. It is highly efficient at flushing out beta amyloids compared to other phases of sleep.

    Beta amyloid levels in the brain accumulate if there is insufficient slow wave sleep. A study published in 2017 (21) showed that chronically disrupted sleep promotes amyloid plaque accumulation and inflammation in the brain. This effect was specific for lack of slow wave activity, and not for sleep duration or efficiency. There is a build-up of B-amyloid after just one night of sleep deprivation. (37)

    Beta amyloid accumulation is strongly associated with Alzheimer's disease. High levels of beta amyloid accumulation are found in an autopsy of the brains of people who have died from Alzheimer's. However, it is likely that Alzheimer's causes the accumulation, rather than the beta amyloids causing Alzheimer's. (53, 54)
  4. Physical inactivity. (16, 28, 40, 41)
  5. Pollution. A 2020 study of over 18,000 American seniors found a 10% variation in the incidence of Alzheimer's depending on the level of air pollution where they lived, when all other factors were statistically accounted for. (48)
  6. Hypertension (high blood pressure).
  7. Obesity. (41)
  8. Depression.
  9. Iron excess. Iron tends to accumulate in the body as it is not excreted and very difficult to remove except through blood loss. Women lose iron in their blood during their monthly period, but men have no such outlet. Most adult men and post-menopausal women suffer from a toxic excess of iron. High levels of iron can cause mental problems including Alzheimer's and Parkinson's diseases, decreased insulin sensitivity, diabetes, heart disease and a wide range of degenerative diseases.
  10. Under-methylation, also known as histadelia.
  11. Smoking.

Root causes of Alzheimer's disease

  1. Insulin resistance. Alzheimer's disease is a form of diabetes manifested in the brain. Insulin resistance leads to the formation of insoluble amyloid-beta protein fragments, which eventually form amyloid plaques in the brain. One of the consequences of these amyloid plaques is further insulin resistance. Thus, insulin resistance and amyloid plaque formation form a vicious cycle in which initial insulin resistance leads to plaque amyloid development, which leads to further insulin resistance. (58) Metabolic syndrome is a strong risk factor for Alzheimer's. Therefore high levels of sugar in the diet and frequent eating are a cause of Alzheimer's. (22, 23, 41, 49, 56, 57, 60, 64)
  2. Toxins. Accumulation of a variety of toxins to which the brain and nervous system are exposed.

    Lack of slow wave sleep, a deep sleep phase which occurs early in the night, is strongly associated with the accumulation of beta amyloids, a pathological protein which accumulates in the brains of all those with Alzheimer's disease. (21, 66)

    Pharmaceutical drugs. A 2018 study examined the risk of new-onset dementia among nearly 350,000 older adults in the UK. It found that those who used certain types of anticholinergics (used to treat diseases like depression, Parkinson's disease and urinary incontinence) for a year or more, had a 30% increase in the risk of later developing dementia. (29, 32)

    Lysosomal dysfunction. Lysosomes are the garbage system of the cell. Lysosomes degrade and digest material taken up from outside the cell and digest obsolete parts of the cell itself. If lysosomes are not working properly then autophagy is impaired or impossible. (53, 54)

    Foods are a common and major source of toxins, usually accompanied by a variety of digestive problems. Sugar and artificial sweeteners are a direct cause of Alzheimer's (20), and also feed the above spirochaete bacteria. (50, 51, 52)

    Air pollution. (48)

    A range of estrogen-like hormones and chemicals (xenoestrogens) in the environment.

    A range of other toxic pollutants in our homes, everyday environment, personal care products and water are so diverse and so unique to each person, that it is difficult to connect the dots between the toxin and the ailment.
  3. Intra-cellular infection with pathogenic microbes. Amyloid plaque may be an anti-microbial agent, (59, 61, 62) and the accumulation of plaque may occur when there is a disruption of the brain microbiome. (62, 63) In other words, Alzheimer's is a reaction to an infection that disrupts the brain biome. Usually a small bacteria such as small spirochaete bacteria, and most commonly a Borrelia species that causes Lyme disease. Over time they will co-infect with other bacteria, viruses, fungi or protozoa. Borrelia and other small bacteria live inside cells, and some shed their own cellular walls to better hide from the immune system. Thousands of these microorganisms can live inside a single cell; eventually the cell walls burst and they spread to a new cellular host. Outside of cells, they also build biofilm for protection. B. garinii mostly affect the brain and central nervous system, although B. burgdorferi which are associated with Lyme disease also have a near universal association. (10, 11, 12, 13, 14, 15, 17, 18)

    There is little agreement that Lyme disease occurs in Australia, but Alzheimer's is as prevalent as it is in America. In Australia, ticks often carry Rickettsia bacteria. So it seems that a variety of other bacteria, particularly those with a spirochaete structure, affect the brain, nerves and immune system. For example, Toxoplasma gondii infection is associated with schizophrenia, epilepsy, Parkinson's, Alzheimer's, cancer, mood disorders and cognitive impairment. (3, 39) Chlamydia pneumoniae has been found in the brains of nearly all multiple sclerosis patients and the majority of Alzheimer's patients. (4, 5, 14, 17, 18)

    A 2016 study (8) found a strong relationship between periodontitis (gum disease) and Alzheimer's. This was reinforced by a study (38) published in 2019 which found the gum disease bacteria Porphyromonas gingivalis to be closely associated with Alzheimer's disease and other forms of dementia. Gum infection is more common in the elderly, and the problem is self-reinforcing causing a reduced ability to take care of oral hygiene as the disease progresses. (17)

    A 2018 study (30) found a significant connection between Alzheimer's and the herpes virus. This was confirmed by another study published in 2020. (47)

    A study published in 2023 found that Coprococcus bacteria are protective against Alzheimer's, and that Desulfovibrio are a cause of Alzheimer's. In this study, healthy young rats showed cognitive decline and other Alzheimer's symptoms less than ten days after receiving Desulfovibrio bacteria from human Alzheimer's patients. (68)
  4. Brain / mental inactivity and lack of stimulation.

Prevention / remedies / treatment / recovery from Alzheimer's disease

Here are some changes that you can make to your diet and lifestyle that will substantially reduce your risk of getting Alzheimer's. As I explain in Grow Youthful, this type of lifestyle will also make you look younger, feel younger and more energised, will slow your aging, and prevent many other degenerative diseases.

References

1. Barnes D.E., Yaffe K. The projected effect of risk factor reduction on Alzheimer's disease prevalence. Lancet Neurol. 2011 Sep;10(9):819-28.

2. Bijal Trivedi. Eat Your Way to Dementia. New Scientist, 1 September 2012.

3. Fekadu A. et al. Toxoplasmosis as a cause for behaviour disorders - overview of evidence and mechanisms. Folia Parasitol (Praha). 2010 June; 57(2):105-13.

4. Balin BJ. et al. Chlamydophila pneumoniae and the etiology of late-onset Alzheimer's disease. J Alzheimers Dis. May 2008; 13(4):371-80.

5. Christine J Hammond, Loretta R Hallock, Raymond J Howanski, Denah M Appelt, C Scott Little, Brian J Balin. Immunohistological detection of Chlamydia pneumoniae in the Alzheimer's disease brain. BMC Neuroscience 2010, 11:121 doi:10.1186/1471-2202-11-121.

6. Michelle Carlson et al. Civic Engagement May Stave Off Brain Atrophy, Improve Memory. Meaningful activities experienced with others may reverse the normal brain shrinkage associated with the aging process. Retrieved online 14 Apr 2015. Johns Hopkins Bloomberg School of Public Health.

7. Kazuki Hyodo, Ippeita Dan, Yasushi Kyutoku, Kazuya Suwabe, Kyeongho Byun, Genta Ochi, Morimasa Kato, Hideaki Soya. The association between aerobic fitness and cognitive function in older men mediated by frontal lateralization. NeuroImage, Volume 125, 15 January 2016, Pages 291-300.

8. Mark Ide, Marina Harris, Annette Stevens, Rebecca Sussams, Viv Hopkins, David Culliford, James Fuller, Paul Ibbett, Rachel Raybould, Rhodri Thomas, Ursula Puenter, Jessica Teeling, V. Hugh Perry, Clive Holmes. Periodontitis and Cognitive Decline in Alzheimer's Disease. Published 10 March 2016. PLoS ONE 11(3): e0151081. doi:10.1371/journal.pone.0151081.

9. Raji CA, Merrill DA, Eyre H, Mallam S, Torosyan N, Erickson KI, Lopez OL, Becker JT, Carmichael OT, Gach HM, Thompson PM, Longstreth WT, Kuller LH. Longitudinal Relationships between Caloric Expenditure and Gray Matter in the Cardiovascular Health Study. J Alzheimers Dis. 11 March 2016, viewed online.

10. Miklossy, Judith. Alzheimer's disease - a spirochetosis? Neuroreport. 1993 Jul;4(7):841-8.

11. Judith Miklossy. Alzheimer's disease - a neurospirochetosis. Analysis of the evidence following Koch's and Hill's criteria. Journal of Neuroinflammation. 20118:90. DOI: 10.1186/1742-2094-8-90. Published: 4 August 2011.

12. MacDonald A B. Plaques of Alzheimer's disease originate from cysts of Borrelia burgdorferi, the Lyme disease spirochete. Med Hypotheses. 2006;67(3):592-600. Epub 2006 May 3. PMID: 16675154.

13. MacDonald A B. Alzheimer's disease Braak Stage progressions: reexamined and redefined as Borrelia infection transmission through neural circuits. Med Hypotheses. 2007;68(5):1059-64. Epub 2006 Nov 17. PMID: 17113237.

14. Itzhaki, Ruth F. Lathe, Richard Balin, Brian J. Ball, Melvyn J. Bearer, Elaine L. Bullido, Maria J. Carter, Chris Clerici, Mario Cosby, S. Louise Field, Hugh Fulop, Tamas Grassi, Claudio Griffin, W. Sue T. Haas, Jurgen Hudson, Alan P. Kamer, Angela R. Kell, Douglas B. Licastro, Federico Letenneur, Luc Lovheim, Hugo Mancuso, Roberta Miklossy, Judith Lagunas, Carola Otth Palamara, Anna Teresa Perry, George Preston, Christopher Pretorius, Etheresia Strandberg, Timo Tabet, Naji Taylor-Robinson, Simon D. and Whittum-Hudson, Judith A. Microbes and Alzheimer's Disease. Journal of Alzheimer's Disease. Published online 8 March 2016. doi:10.3233/JAD-160152.

15. MacDonald AB, Miranda JM. Concurrent neocortical borreliosis and Alzheimer's disease. Hum Pathol. 1987 Jul;18(7):759-61.

16. Muscari, A., Giannoni, C., Pierpaoli, L., Berzigotti, A., Maietta, P., Foschi, E., Ravaioli, C., Poggiopollini, G., Bianchi, G., Magalotti, D., Tentoni, C. and Zoli, M. Chronic endurance exercise training prevents aging-related cognitive decline in healthy older adults: a randomized controlled trial. (2010),Int. J. Geriat. Psychiatry, 25: 1055-1064. doi:10.1002/gps.2462. Published 23 December 2009.

17. Deborah K. Shoemark, Shelley J. Allen. The Microbiome and Disease: Reviewing the Links between the Oral Microbiome, Aging, and Alzheimer's Disease. Journal of Alzheimer's Disease 43 (2015) 725-738. DOI 10.3233/JAD-141170.

18. Maheshwari P, Eslick GD. Bacterial infection and Alzheimer's disease: a meta-analysis. J Alzheimers Dis. 2015;43(3):957-66. doi: 10.3233/JAD-140621.

19. Alzheimer's Australia website, news item dated 31 March 2015.

20. Matthew P. Pase, Jayandra J. Himali, Alexa S. Beiser, Hugo J. Aparicio, Claudia L. Satizabal, Ramachandran S. Vasan, Sudha Seshadri, Paul F. Jacques. Sugar and Artificially Sweetened Beverages and the Risks of Incident Stroke and Dementia. Stroke. 2017;STROKEAHA.116.016027. Published 20 April 2017.

21. Yo-El S. Ju Sharon J. Ooms Courtney Sutphen Shannon L. Macauley Margaret A. Zangrilli Gina Jerome Anne M. Fagan Emmanuel Mignot John M. Zempel Jurgen A.H.R. Claassen David M. Holtzman. Slow wave sleep disruption increases cerebrospinal fluid amyloid-B levels. Brain, awx148. Published: 10 July 2017.

22. Suzanne M. de la Monte, Jack R. Wands. Alzheimer's Disease Is Type 3 Diabetes - Evidence Reviewed. J Diabetes Sci Technol. 2008 Nov; 2(6): 1101-1113. Published online November 2008. doi: 10.1177/193229680800200619. PMCID: PMC2769828.

23. Fanfan Zheng, Li Yan, Zhenchun Yang, Baoliang Zhong, Wuxiang Xie. HbA1c, diabetes and cognitive decline: the English Longitudinal Study of Ageing. Diabetologia. Published online 25 January 2018.

24. Erik S. Musiek, Meghana Bhimasani, Margaret A. Zangrilli, John C. Morris, David M. Holtzman, Yo-ElS, Ju. Circadian Rest-Activity Pattern Changes in Aging and Preclinical Alzheimer Disease. JAMA Neurol. Published online 29 January 2018. doi:10.1001/jamaneurol.2017.4719.

25. Yen Ying Lim, Pawel Kalinowski, Robert H. Pietrzak, Simon M. Laws, Samantha C. Burnham, David Ames, Victor L. Villemagne, Christopher J. Fowler, Stephanie R. Rainey-Smith, Ralph N. Martins, Christopher C. Rowe, Colin L. Masters, Paul T. Maruff. Association of β-Amyloid and Apolipoprotein E e4 With Memory Decline in Preclinical Alzheimer Disease. JAMA Neurol. Published online 22 January 2018. doi:10.1001/jamaneurol.2017.4325.

26. Helena Horder, Lena Johansson, XinXin Guo, Gunnar Grimby, Silke Kern, Svante Ostling, Ingmar Skoog. Midlife cardiovascular fitness and dementia: A 44-year longitudinal population study in women. Neurology, 14 March 2018. DOI: 10.1212/WNL. 5290.

27. Martha Clare Morris, Yamin Wang, Lisa L. Barnes, David A. Bennett, Bess Dawson-Hughes, Sarah L. Booth. Nutrients and bioactives in green leafy vegetables and cognitive decline. Neurology Dec 2017, 10.1212/WNL.4815.

28. Prabha Siddarth, Alison C. Burggren, Harris A. Eyre, Gary W. Small, David A. Merrill. Sedentary behavior associated with reduced medial temporal lobe thickness in middle-aged and older adults. Published 12 April 2018 in PLOS One.

29. Kathryn Richardson, Chris Fox, Ian Maidment, Nicholas Steel, Yoon K Loke, Antony Arthur, Phyo K Myint, Carlota M Grossi, Katharina Mattishent, Kathleen Bennett, Noll L Campbell, Malaz Boustani, Louise Robinson, Carol Brayne, Fiona E Matthews, George M Savva. Anticholinergic drugs and risk of dementia: case-control study. BMJ 2018;361:k1315. Published 25 April 2018.

30. Ben Readhead, Jean-Vianney, Haure-Mirande, Cory C. Funk, Matthew A. Richards, Paul Shannon, Vahram Haroutunian, Mary Sano, Winnie S. Liang, Noam D. Beckmann, Nathan D. Price, Eric M. Reiman, Eric E. Schadt, Michelle E. Ehrlich, Sam Gandy, Joel T. Dudley. Multiscale Analysis of Independent Alzheimer's Cohorts Finds Disruption of Molecular, Genetic, and Clinical Networks by Human Herpesvirus. Neuron, Volume 99, Issue 1, 11 July 2018, Pages 64-82.

31. Abdelhamid AS, Brown TJ, Brainard JS, Biswas P, Thorpe GC, Moore HJ, Deane KHO, AlAbdulghafoor FK, Summerbell CD, Worthington HV, Song F, Hooper L. Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database of Systematic Reviews. 18 July 2018. Issue 7. Art. No.: CD003177. DOI: 10.1002/14651858.CD003177.pub3.

32. Erin M. Hill-Burns, Justine W. Debelius, James T. Morton, William T. Wissemann, Matthew R. Lewis, Zachary D. Wallen, Shyamal D. Peddada, Stewart A. Factor, Eric Molho, Cyrus P. Zabetian, Rob Knight, Haydeh Payami. Parkinson's disease and Parkinson's disease medications have distinct signatures of the gut microbiome. Movement Disorders, 14 February 2017.

33. Kate E. Sprecher, Barbara B. Bendlin, Annie M. Racine, Ozioma C. Okonkwo, Bradley T. Christian, Rebecca L. Koscik, Mark A. Sager, Sanjay Asthana, Sterling C. Johnson, Ruth M. Benca. Amyloid Burden Is Associated With Self-Reported Sleep In Non-Demented Late Middle-Aged Adults. Neurobiol Aging. 2015 Sep; 36(9): 2568-2576. PMID: 26059712.

34. Kate E. Sprecher, Rebecca L. Koscik, Cynthia M. Carlsson, Henrik Zetterberg, Kaj Blennow, Ozioma C. Okonkwo, Mark A. Sager, Sanjay Asthana, Sterling C. Johnson, Ruth M. Benca, Barbara B. Bendlin. Poor sleep is associated with CSF biomarkers of amyloid pathology in cognitively normal adults. Neurology. 2017 Aug 1; 89(5): 445-453. doi: 10.1212/WNL.4171. PMCID: PMC5539733. PMID: 28679595.

35. Omonigho M. Bubu, Michael Brannick, James Mortimer, Ogie Umasabor-Bubu, Yuri V. Sebastiao, Yi Wen, Skai Schwartz, Amy R. Borenstein, Yougui Wu, David Morgan, William M. Anderson. Sleep, Cognitive impairment, and Alzheimer's disease: A Systematic Review and Meta-Analysis. Sleep, Volume 40, Issue 1, 1 January 2017, zsw032.

36. Simons LA, Simons J, McCallum J, Friedlander Y. Lifestyle factors and risk of dementia: Dubbo Study of the elderly. Med J Aust. 2006 Jan 16;184(2):68-70.

37. Ehsan Shokri-Kojori, Gene-Jack Wang, Corinde E. Wiers, Sukru B. Demiral, Min Guo, Sung Won Kim, Elsa Lindgren, Veronica Ramirez, Amna Zehra, Clara Freeman, Gregg Miller, Peter Manza, Tansha Srivastava, Susan De Santi, Dardo Tomasi, Helene Benveniste, Nora D. Volkow. B-Amyloid accumulation in the human brain after one night of sleep deprivation. PNAS, 24 April 2018. 115 (17) 4483-4488.

38. Stephen S. Dominy, Casey Lynch, Florian Ermini, Malgorzata Benedyk, Agata Marczyk, Andrei Konradi, Mai Nguyen, Ursula Haditsch, Debasish Raha, Christina Griffin, Leslie J. Holsinger, Shirin Arastu-Kapur, Samer Kaba, Alexander Lee, Mark I. Ryder, Barbara Potempa, Piotr Myde, Annelie Hellvard, Karina Adamowicz, Hatice Hasturk, Glenn D. Walker, Eric C. Reynolds, Richard L. M. Faull, Maurice A. Curtis, Mike Dragunow, Jan Potempa. Porphyromonas gingivalis in Alzheimer's disease brains: Evidence for disease causation and treatment with small-molecule inhibitors. Science Advances 23 Jan 2019. Vol. 5, no. 1, eaau3333. DOI: 10.1126/sciadv.aau3333.

39. Huan M. Ngo, Ying Zhou, Hernan Lorenzi, Kai Wang, Taek-Kyun Kim, Yong Zhou, Kamal El Bissati, Ernest Mui, Laura Fraczek, Seesandra V. Rajagopala, Craig W. Roberts, Fiona L. Henriquez, Alexandre Montpetit, Jenefer M. Blackwell, Sarra E. Jamieson, Kelsey Wheeler, Ian J. Begeman, Carlos Naranjo-Galvis, Ney Alliey-Rodriguez, Roderick G. Davis, Liliana Soroceanu, Charles Cobbs, Dennis A. Steindler, Kenneth Boyer, A. Gwendolyn Noble, Charles N. Swisher, Peter T. Heydemann, Peter Rabiah, Shawn Withers, Patricia Soteropoulos, Leroy Hood, Rima McLeod. Toxoplasma Modulates Signature Pathways of Human Epilepsy, Neurodegeneration & Cancer. Nature, 13 September 2017, Scientific Reports, volume 7, Article number: 11496.

40. Mychael V. Lourenco, Rudimar L. Frozza, Guilherme B. de Freitas, Hong Zhang, Grasielle C. Kincheski, Felipe C. Ribeiro, Rafaella A. Goncalves, Julia R. Clarke, Danielle Beckman, Agnieszka Staniszewski, Hanna Berman, Lorena A. Guerra, Leticia Forny-Germano, Shelby Meier, Donna M. Wilcock, Jorge M. de Souza, Soniza Alves-Leon, Vania F. Prado, Marco A. M. Prado, Jose F. Abisambra, Fernanda Tovar-Moll, Paulo Mattos, Ottavio Arancio, Sergio T. Ferreira, Fernanda G. De Felice. Exercise-linked FNDC5/irisin rescues synaptic plasticity and memory defects in Alzheimer's models. 7 January 2019. Nature Medicinevolume 25, 165-175.

41. Ilianna Lourida, Eilis Hannon, Thomas J. Littlejohns, Kenneth M. Langa, Elina Hypponen, Elzbieta Kuzma, David J. Llewellyn. Association of Lifestyle and Genetic Risk With Incidence of Dementia. JAMA. Published online 14 July 2019. doi:10.1001/jama.2019.9879.

42. Donald L. Bliwise. Sleep disorders in Alzheimer's disease and other dementias. Clinical Cornerstone, Volume 6, Issue 1, Supplement A, 2004, Pages S16-S28.

43. Tamara Bhandari. Decreased deep sleep linked to early signs of Alzheimer's disease. Washington University School of Medicine. Published online 9 January 2019 at sciencedaily.

44. Lucey BP, McCullough A, Landsness EC, Toedebusch CD, McLeland JS, Zaza AM, Fagan AM, McCue L, Xiong C, Morris JC, Benzinger TLS, Holtzman DM. Reduced non-rapid eye movement sleep is associated with tau pathology in early Alzheimer's disease. Science Translational Medicine, Jan. 9, 2019 DOI: 10.1126/scitranslmed.aau6550.

45. Leng Y, Goldman SM, Cawthon PM, Stone KL, Ancoli-Israel S, Yaffe K. Excessive daytime sleepiness, objective napping and 11-year risk of Parkinson's disease in older men. Int J Epidemiol. 2018 Oct 1;47(5):1679-1686. doi: 10.1093/ije/dyy098.

46. Yue Leng, Susan Redlineb, Katie L. Stone, Sonia Ancoli-Israel, Kristine Yaffe. Objective napping, cognitive decline, and risk of cognitive impairment in older men. Published online on 18 June 2019 in Alzheimer's and Dementia.

47. Dana M. Cairns, Nicolas Rouleau, Rachael N. Parker, Katherine G. Walsh, Lee Gehrke, David L. Kaplan. A 3D human brain-like tissue model of herpes-induced Alzheimer's disease. Science Advances, 06 May 2020: Vol. 6, no. 19, eaay8828. DOI: 10.1126/sciadv.aay8828.

48. Leonardo Iaccarino, Renaud La Joie, Orit H. Lesman-Segev, Eunice Lee, Lucy Hanna, Isabel E. Allen, Bruce E. Hillner, Barry A. Siegel, Rachel A. Whitmer, Maria C. Carrillo, Constantine Gatsonis, Gil D. Rabinovici. Association Between Ambient Air Pollution and Amyloid Positron Emission Tomography Positivity in Older Adults With Cognitive Impairment. JAMA Neurol. Published online 30 November 2020. doi:10.1001/jamaneurol.2020.3962.

49. Ryan A Wirt et al. Altered theta rhythm and hippocampal-cortical interactions underlie working memory deficits in a hyperglycemia risk factor model of Alzheimer's disease. Communications Biology, September 2021. DOI: 10.1038/s42003-021-02558-4.

50. Celik E, Sanlier N. Effects of nutrient and bioactive food components on Alzheimer's disease and epigenetic. Crit Rev Food Sci Nutr. 2019;59(1):102-113. doi: 10.1080/10408398.2017.1359488. Epub 2017 Oct 11. PMID: 28799782.

51. Norwitz NG, Saif N, Ariza IE, Isaacson RS. Precision Nutrition for Alzheimer's Prevention in ApoE4 Carriers. Nutrients. 2021 Apr 19;13(4):1362. doi: 10.3390/nu13041362. PMID: 33921683; PMCID: PMC8073598.

52. Paz-Y-Mino CA, Garcia-Cardenas JM, Lopez-Cortes A, Salazar C, Serrano M, Leone PE. Positive Association of the Cathepsin D Ala224Val Gene Polymorphism With the Risk of Alzheimer's Disease. Am J Med Sci. 2015 Oct;350(4):296-301. doi: 10.1097/MAJ.555. PMID: 26351775.

53. Filocamo M, Morrone A. Lysosomal storage disorders: Molecular basis and laboratory testing. Hum Genomics 5, 156 (2011). doi.org/10.1186/1479-7364-5-3-156.

54. Uddin MS, Stachowiak A, Mamun AA, Tzvetkov NT, Takeda S, Atanasov AG, Bergantin LB, Abdel-Daim MM, Stankiewicz AM. Autophagy and Alzheimer's Disease: From Molecular Mechanisms to Therapeutic Implications. Front Aging Neurosci. 2018 Jan 30;10:04. doi: 10.3389/fnagi.2018.00004. PMID: 29441009; PMCID: PMC5797541.

55. Severine Sabia, Aline Dugravot, Damien Leger, Celine Ben Hassen, Mika Kivimaki, Archana Singh-Manoux. Association of sleep duration at age 50, 60, and 70 years with risk of multimorbidity in the UK: 25-year follow-up of the Whitehall II cohort study. Published 18 October 2022, PLOS Medicine.

56. Jason Pitt, Kyle C. Wilcox, Vanessa Tortelli, Luan Pereira Diniz, Maira S. Oliveira, Cassandra Dobbins, Xiao-Wen Yu, Sathwik Nandamuri, Flavia C. A. Gomes, Nadia DiNunno, Kirsten L. Viola, Fernanda G. De Felice, Sergio T. Ferreira, William L. Klein. Neuroprotective astrocyte-derived insulin/insulin-like growth factor 1 stimulates endocytic processing and extracellular release of neuron-bound Aβ oligomers. Molecular Biology of the Cell, Vol 28, No 20. Published Online 9 Aug 2017.

57. Shieh JC, Huang PT, Lin YF. Mol Neurobiol. 2020 Apr;57(4):1966-1977. doi: 10.1007/s12035-019-01858-5. Epub 2020 Jan 3. PMID: 31900863.

58. Moreira PI, Santos MS, Sena C, Seica R, Oliveira CR. Insulin protects against amyloid beta-peptide toxicity in brain mitochondria of diabetic rats. Neurobiol Dis. 2005 Apr;18(3):628-37. doi: 10.1016/j.nbd.2004.10.017. PMID: 15755688.

59. Moreira PI, Santos MS, Sena C, Nunes E, Seica R, Oliveira CR. CoQ10 therapy attenuates amyloid beta-peptide toxicity in brain mitochondria isolated from aged diabetic rats. Exp Neurol. 2005 Nov;196(1):112-9. doi: 10.1016/j.expneurol.2005.07.012. Epub 2005 Aug 29. PMID: 16126199.

60. Duarte AI, Moreira PI, Oliveira CR. Insulin in central nervous system: more than just a peripheral hormone. J Aging Res. 2012;2012:384017. doi: 10.1155/2012/384017. Epub 2012 Feb 21. PMID: 22500228; PMCID: PMC3303591.

61. Maheshwari P, Eslick GD. Bacterial infection and Alzheimer's disease: a meta-analysis. J Alzheimers Dis. 2015;43(3):957-66. doi: 10.3233/JAD-140621. PMID: 25182736.

62. Westfall S, Dinh DM, Pasinetti GM. Investigation of Potential Brain Microbiome in Alzheimer's Disease: Implications of Study Bias. J Alzheimers Dis. 2020;75(2):559-570. doi: 10.3233/JAD-191328. PMID: 32310171.

63. Link CD. Is There a Brain Microbiome? Neurosci Insights. 2021 May 27;16:26331055211018709. doi: 10.1177/26331055211018709. PMID: 34104888; PMCID: PMC8165828.

64. Richard J. Johnson, Dean R. Tolan, Dale Bredesen, Maria Nagel, Laura G. Sanchez-Lozada, Mehdi Fini, Scott Burtis, Miguel A. Lanaspa, David Perlmutter. Could Alzheimer's disease be a maladaptation of an evolutionary survival pathway mediated by intracerebral fructose and uric acid metabolism? 11 January 2023, American Journal of Clinical Nutrition. DOI: 10.1016/j.ajcnut.2023.01.002.

65. Ghahremani, M, Smith, EE, Chen, H-Y, Creese, B, Goodarzi, Z, Ismail, Z. Vitamin D supplementation and incident dementia: Effects of sex, APOE, and baseline cognitive status. Alzheimer's Dement. 2023; 15:e12404. doi.org/10.1002/dad2.12404.

66. Zavecz Z, Shah VD, Murillo OG, et al. NREM sleep as a novel protective cognitive reserve factor in the face of Alzheimer's disease pathology. BMC Med 21, 156 (2023). doi.org/10.1186/s12916-023-02811-z.

67. Klevay LM. Alzheimer's disease as copper deficiency. Med Hypotheses 70, no. 4 (2008): 802-7.

68. Stefanie Grabrucker, Moira Marizzoni, Edina Silajdzic, Nicola Lopizzo, Elisa Mombelli, Sarah Nicolas, Sebastian Dohm-Hansen, Catia Scassellati, Davide Vito Moretti, Melissa Rosa, Karina Hoffmann, John F Cryan, Olivia F O'Leary, Jane A English, Aonghus Lavelle, Cora O'Neill, Sandrine Thuret, Annamaria Cattaneo, Yvonne M Nolan. Microbiota from Alzheimer's patients induce deficits in cognition and hippocampal neurogenesis. Brain, 2023, awad303.

69. Matsuzaki K, Nakajima A, Guo Y, Ohizumi Y. A Narrative Review of the Effects of Citrus Peels and Extracts on Human Brain Health and Metabolism. Nutrients. 2022 Apr 28;14(9):1847. doi: 10.3390/nu14091847. PMID: 35565814; PMCID: PMC9103913.