Prevention of dementia explained

The prevention of dementia involves reducing the number of risk factors for the development of dementia, and is a global health priority needing a global response.[1] [2] [3] [4] Initiatives include the establishment of the International Research Network on Dementia Prevention (IRNDP)[5] which aims to link researchers in this field globally, and the establishment of the Global Dementia Observatory[6] a web-based data knowledge and exchange platform, which will collate and disseminate key dementia data from members states. Although there is no cure for dementia, it is well established that modifiable risk factors influence both the likelihood of developing dementia and the age at which it is developed.[1] [7] Dementia can be prevented by reducing the risk factors for vascular disease[1] [8] such as diabetes, high blood pressure, obesity, smoking, physical inactivity and depression. A study concluded that more than a third of dementia cases are theoretically preventable. Among older adults both an unfavorable lifestyle and high genetic risk are independently associated with higher dementia risk.[9] A favorable lifestyle is associated with a lower dementia risk, regardless of genetic risk. In 2020, a study identified 12 modifiable lifestyle factors, and the early treatment of acquired hearing loss was estimated as the most significant of these factors, potentially preventing up to 9% of dementia cases.

Lifestyle

Mental activity

See main article: Brain fitness. "Use it or lose it" might be applied to the brain when it comes to dementia. Intellectual activities help keep the mind in shape in later years. Activities such as reading, learning a new language, playing cards and board games[10] [11] and playing a musical instrument can postpone the onset and slow the progression of both Alzheimer's and vascular dementia.[12] [13] The risk decrease is proportional to frequency of activity,[12] with slower cognitive decline being associated with both late-life and early-life increased cognitive activity.[14]

Apart from spare time activities, a mentally demanding job may prevent dementia, especially during the thirties, forties and fifties.[12]

Mental activity may help to prevent dementia by building up a "brain reserve": additional connections between neurons are created which are more resistant to the deterioration seen in dementia.[12]

Physical activity

See main article: Neurobiological effects of physical exercise. Since vascular dementia is the second most common form of dementia (after Alzheimer's disease), reducing the risk of cerebrovascular disease also reduces the risk of dementia.[15] Thus, physical exercise, having good blood cholesterol, healthy body weight and blood pressure lowers the risk of developing dementia.[12] An active lifestyle can almost halve the risk compared to a sedentary one.[12]

Results of one meta-analysis, which investigated the relationship between physical activity and risk of cognitive decline in people without dementia, showed exercise had a significant and consistent protective effect against cognitive decline, with high levels of physical activity being most protective.[16] Another meta-analysis showed that not only did aerobic exercise reduce the risk of dementia but it may also slow cognitive decline in those with dementia.[17]

The effect of physical activity is not limited to vascular effects. Physical activity can give rise to new neurons in the brain, as well as releasing a substance that can protect them. The protein known as brain-derived neurotrophic factor (BDNF) is known to be important in the development, survival and plasticity of neurons. Regular exercise can boost BDNF levels by 2–3 times.[18]

Diet

Obesity increases the risk of any dementia and Alzheimer's disease in particular.[12] The effect of alcohol on the risk of dementia is a J curve:[19] high alcohol consumption increases the risk of dementia[20] while low alcohol consumption may be protective.[19] [21] However, low alcohol consumption may not protect against vascular dementia and overall cognitive decline.[19] Moderate alcohol consumption can possibly reduce the risk of vascular disease and dementia because it can increase blood levels of HDL cholesterol and weakens blood-clotting agents such as fibrinogen, which offers some protection against heart attacks and small subclinical strokes that together can ultimately damage the brain.[22]

The effects of omega-3 fatty acid in the prevention of dementia is uncertain.[23] Vegetables and nuts may be of benefit,[12] because of their high content of polyunsaturated fats. Non-fish meat, on the other hand, increases the risk of Alzheimer's,[12] because of its high content of saturated fat.

Niacin (vitamin B3) is also believed to prevent dementia as research shows those who have the highest levels of niacin in their blood, are believed to have the lowest risk of developing dementia or having cognitive decline. Niacin is involved with DNA synthesis and repair and also neural cell signaling, it improves circulation and reduces cholesterol levels. In order for niacin to have a positive effect on the brain, it is recommended that patients have 100 to 300 mg per day.

There is evidence for an association between cognitive decline, homocysteine (Hcy) status, and vitamin B status relating especially to B12[24] and also to vitamins B6 and B9.[25] In particular, deficiency of vitamin B12 and/or of folate can cause an increase in Hcy plasma levels, which in turn leads to toxic effects on the vascular and nervous systems.[26]

Vitamin D deficiency correlates with cognitive impairment and dementia; however, the value of vitamin D substitution in cognitive impairment remains doubtful.[27] [28] [29]

Sleep pattern

More than nine hours of sleep per day (including daytime napping) may be associated with an increased risk of dementia.[30] Lack of sleep may also increase risk of dementia by increasing beta-amyloid deposition.[31]

Personality and mental health

Some personality traits such as being neurotic increases the risk of developing Alzheimer's, a type of dementia.[32] [33] [34] Neuroticism is associated with increased brain atrophy and cognitive impairment in life, while conscientiousness has a protective effect by preventing brain atrophy.[35] A meta-analysis found that the openness and agreeableness traits have also some protective effects.[36]

Based on the English Longitudinal Study of Ageing (ELSA), research found that loneliness increased the risk of dementia by one-third. Not having a partner (being single, divorced, or widowed) doubled the risk of dementia. However, having two or three closer relationships reduced the risk by three-fifths.[37] [38]

Depression

Depressive symptoms can be a part of the clinical presentation of dementia, leading to debate as to whether depression is a cause or a symptom of dementia.[39] The evidence remains unclear. However, Livingstone et al. (2014) report that it is "biologically plausible" that depression increases the risk of dementia. There is some evidence that late-life depression increases the risk of dementia however[40] suggesting treating depression in mid-life might delay or prevent dementia.

Medication

Hypertension

Some studies say Alzheimer's and other dementias may be caused by high blood pressure, since it can cause blood vessel damage through constriction.[41] [42] The etiology of vascular dementia includes hypertension, and thus, lowering blood pressure with antihypertensives may have a positive effect in the prevention of dementia, just as physical activity.

However, one study failed to demonstrate a link between high blood pressure and developing dementia. The study, published in the Lancet Neurology journal of July 2008, found that blood pressure lowering medication did not reduce the incidence of dementia to a statistically significant degree. A prospective meta-analysis of the data from this study with other studies suggested that further research might be warranted.[43]

While the results of studies are somewhat inconsistent, it has been recommended that hypertension in mid-life (45–65 years) and older age (65+ years) should be actively treated to reduce the risk of dementia.

Anti-diabetic drugs

Diabetes mellitus is a risk factor for vascular dementia, and is thus the risk is lowered with anti-diabetic drugs.[44]

Besides, Rosiglitazone (Avandia) improves memory and thinking ability for people with mild Alzheimer's disease. The mechanism of the effect may be the ability of the drug to reduce insulin resistance.[12] Thus, less insulin needs to be released to achieve its metabolic effects. Insulin in the bloodstream is a trigger of amyloid beta-production,[44] [45] so decreased insulin levels decrease the level of amyloid beta. This leads to less formation of amyloid plaques seen in Alzheimer's disease.

Steroid hormones

Estrogen may also help in the prevention of dementia but cannot help when dementia is already present and when cognitive function is already impaired. It increases cerebral blood flow and is an anti-inflammatory agent, enhancing activity at the neuronal synapses in the brain. It may also help to increase brain activation in regions that are affected by dementia which is mainly the hippocampus region. Recent evidence on the effects of estrogen do not allow for an unambiguous recommendation for estrogen supplementation and they indicate that the timing of estrogen supplementation may be important, with early postmenopausal use being preferable over its use later in life.[46] [47]

NSAIDs

Non-steroidal anti-inflammatory drugs (NSAIDs) can decrease the risk of developing Alzheimer's and Parkinson's diseases.[12] The length of time needed to prevent dementia varies, but in most studies it is usually between 2 and 10 years.[48] [49] [50] [51] [52] Research has also shown that it must be used in clinically relevant dosages and that so called "baby aspirin" doses are ineffective at treating dementia.[53]

Alzheimer's disease causes inflammation in the neurons by its deposits of amyloid beta peptides and neurofibrillary tangles. These deposits irritate the body by causing a release of e.g. cytokines and acute phase proteins, leading to inflammation. When these substances accumulate over years they contribute to the effects of Alzheimer's.[54] NSAIDs inhibit the formation of such inflammatory substances, and prevent the deteriorating effects.[55] [56] [57]

In 2020 a systematic review conducted by Cochrane of four randomized controlled trials with 23,187 participants concluded that the use of low-dose aspirin and NSAIDS of any type for the prevention of dementia was not supported and that there could be harm.[58]

Vaccine

There is as yet no vaccine against dementia.[12] It has been theorized that a vaccine could activate the body's own immune system to combat the beta amyloid plaques in Alzheimer's disease. One problem to overcome is overreaction from the immune system, leading to encephalitis.[12]

Anticholinergic medication use

Anticholinergic medications are often prescribed to treat health conditions commonly experienced by older people including overactive bladder and many commonly used medications have anticholinergic activity. There has been some observational research that has suggested a linkage between anticholinergic medication use and cognitive decline in older adults. Suggestions to reduce the 'anticholinergic burden', try to modify a person's medications to reduce the use of medications that have anticholinergic activity in a safe way, are often made in dementia guidelines with the goal of improving cognition and/or reducing further decline. The evidence supporting this approach to preventing dementia is weak, however, if safe to do so, and in light of some weaker observational evidence suggesting that these medications may be related to adverse effects or poorer outcomes, it is clinically suggested to prescribe these medications with caution and if safe to do so reduce their use.[59]

See also

Further reading

Notes and References

  1. Livingston G, Huntley J, Sommerlad A, et al . Dementia prevention, intervention, and care: 2020 report of the Lancet Commission . Lancet . 396 . 10248 . 413–446 . August 2020 . 32738937 . 7392084 . 10.1016/S0140-6736(20)30367-6 .
  2. Web site: Development of a draft global action plan on the public health response to dementia. https://web.archive.org/web/20161017004117/http://www.who.int/mental_health/neurology/dementia/action_plan_consultation/en/. dead. 17 October 2016. World Health Organization. 2017-10-31.
  3. Web site: Home World Dementia Council. worlddementiacouncil.org. 2017-10-31.
  4. Web site: Dementia - OECD. www.oecd.org. 2017-10-31.
  5. Web site: International Research Network on Dementia Prevention. 2017-10-31.
  6. Web site: The Global Dementia Observatory. https://web.archive.org/web/20170203142124/http://www.who.int/mental_health/neurology/dementia/GDO/en/. dead. 3 February 2017. World Health Organization. 2017-10-31.
  7. Norton S, Matthews FE, Barnes DE, Yaffe K, Brayne C . Potential for primary prevention of Alzheimer's disease: an analysis of population-based data . The Lancet. Neurology . 13 . 8 . 788–94 . August 2014 . 25030513 . 10.1016/s1474-4422(14)70136-x . 206161840 .
  8. Web site: WHO Media centre fact sheets: Dementia. Fact sheet N°362. April 2012. 21 January 2015.
  9. Lourida I, Hannon E, Littlejohns TJ, Langa KM, Hyppönen E, Kuzma E, Llewellyn DJ . Association of Lifestyle and Genetic Risk With Incidence of Dementia . JAMA . 322 . 5 . 430–437 . July 2019 . 31302669 . 6628594 . 10.1001/jama.2019.9879 .
  10. Altschul DM, Deary IJ . Playing analog games is associated with reduced declines in cognitive function: a 68 year longitudinal cohort study . The Journals of Gerontology. Series B, Psychological Sciences and Social Sciences . November 2019 . 75 . 3 . 474–482 . 31738418 . 10.1093/geronb/gbz149 . 7021446 .
  11. Dartigues JF, Foubert-Samier A, Le Goff M, Viltard M, Amieva H, Orgogozo JM, Barberger-Gateau P, Helmer C . 6 . Playing board games, cognitive decline and dementia: a French population-based cohort study . BMJ Open . 3 . 8 . e002998 . August 2013 . 23988362 . 3758967 . 10.1136/bmjopen-2013-002998 .
  12. Web site: Prevention of Dementia . Dementia: The Growing Crisis in West Virginia . February 2005 . Eugenia . Thoenen . Health Statistics Center Statistical Staff . James . Doria . Fred . King . Thomas N. . Leonard . Tom . Light . Philip . Simmons . 2 October 2009.
  13. Alladi S, Bak TH, Duggirala V, Surampudi B, Shailaja M, Shukla AK, Chaudhuri JR, Kaul S . 6 . Bilingualism delays age at onset of dementia, independent of education and immigration status . Neurology . 81 . 22 . 1938–44 . November 2013 . 24198291 . 10.1212/01.wnl.0000436620.33155.a4 . 18874131 .
  14. Life-span cognitive activity, neuropathologic burden, and cognitive aging (Abstract). 4. 314–321. Wilson . Robert S.. 3 July 2013 . Neurology . 81. etal. 10.1212/WNL.0b013e31829c5e8a. 23825173. 3772831. Explained by Web site: Being a Lifelong Bookworm May Keep You Sharp in Old Age . Koren . Marina . 23 July 2013 . Smithsonian . https://www.webcitation.org/6Ht0xyPkH?url=http://blogs.smithsonianmag.com/science/2013/07/being-a-lifelong-bookworm-may-keep-you-sharp-in-old-age/ . 5 July 2013 . 5 July 2013 . live .
  15. Kuźma E, Lourida I, Moore SF, Levine DA, Ukoumunne OC, Llewellyn DJ . Stroke and dementia risk: A systematic review and meta-analysis . en . Alzheimer's & Dementia . 14 . 11 . 1416–1426 . November 2018 . 30177276 . 6231970 . 10.1016/j.jalz.2018.06.3061 . 2027.42/152961 .
  16. Sofi F, Valecchi D, Bacci D, Abbate R, Gensini GF, Casini A, Macchi C . Physical activity and risk of cognitive decline: a meta-analysis of prospective studies . Journal of Internal Medicine . 269 . 1 . 107–17 . January 2011 . 20831630 . 10.1111/j.1365-2796.2010.02281.x . 2158/392682 . 39115469 . free .
  17. Ahlskog JE, Geda YE, Graff-Radford NR, Petersen RC . Physical exercise as a preventive or disease-modifying treatment of dementia and brain aging . Mayo Clinic Proceedings . 86 . 9 . 876–84 . September 2011 . 21878600 . 3258000 . 10.4065/mcp.2011.0252 .
  18. Web site: Jones. Hilary. Dr. telecare24/co.uk. June 2016.
  19. Chen JH, Lin KP, Chen YC . Risk factors for dementia . Journal of the Formosan Medical Association = Taiwan Yi Zhi . 108 . 10 . 754–64 . October 2009 . 19864195 . 10.1016/S0929-6646(09)60402-2 . free .
  20. Grønbaek M . The positive and negative health effects of alcohol- and the public health implications . Journal of Internal Medicine . 265 . 4 . 407–20 . April 2009 . 19298457 . 10.1111/j.1365-2796.2009.02082.x . free .
  21. Peters R, Peters J, Warner J, Beckett N, Bulpitt C . Alcohol, dementia and cognitive decline in the elderly: a systematic review . Age and Ageing . 37 . 5 . 505–12 . September 2008 . 18487267 . 10.1093/ageing/afn095 . free .
  22. Robert, Levine . Defying dementia: understanding and preventing Alzheimer's and related disorders . Westport: Conn: Praeger . 2006.
  23. Cederholm T, Palmblad J . Are omega-3 fatty acids options for prevention and treatment of cognitive decline and dementia? . Current Opinion in Clinical Nutrition and Metabolic Care . 13 . 2 . 150–5 . March 2010 . 20019606 . 10.1097/MCO.0b013e328335c40b . 46142968 .
  24. Gröber U, Kisters K, Schmidt J . Neuroenhancement with vitamin B12-underestimated neurological significance . Nutrients . 5 . 12 . 5031–45 . December 2013 . 24352086 . 3875920 . 10.3390/nu5125031 . Review . free .
  25. Reay JL, Smith MA, Riby LM . B vitamins and cognitive performance in older adults: review . ISRN Nutrition . 2013 . 650983 . 2013 . 24959550 . 4045270 . 10.5402/2013/650983 . Review . free .
  26. Ansari R, Mahta A, Mallack E, Luo JJ . Hyperhomocysteinemia and neurologic disorders: a review . Journal of Clinical Neurology . 10 . 4 . 281–8 . October 2014 . 25324876 . 4198708 . 10.3988/jcn.2014.10.4.281 . Review .
  27. Schlögl M, Holick MF . Vitamin D and neurocognitive function . Clinical Interventions in Aging . 9 . 559–68 . 2014 . 24729696 . 3979692 . 10.2147/CIA.S51785 . Review . free .
  28. Etgen T, Sander D, Bickel H, Sander K, Förstl H . Vitamin D deficiency, cognitive impairment and dementia: a systematic review and meta-analysis . Dementia and Geriatric Cognitive Disorders . 33 . 5 . 297–305 . 2012 . 22759681 . 10.1159/000339702 . 5303760 . Review . free .
  29. Dickens AP, Lang IA, Langa KM, Kos K, Llewellyn DJ . Vitamin D, cognitive dysfunction and dementia in older adults . CNS Drugs . 25 . 8 . 629–39 . August 2011 . 21790207 . 5097668 . 10.2165/11593080-000000000-00000 .
  30. Benito-León J, Bermejo-Pareja F, Vega S, Louis ED . Total daily sleep duration and the risk of dementia: a prospective population-based study . European Journal of Neurology . 16 . 9 . 990–7 . September 2009 . 19473367 . 10.1111/j.1468-1331.2009.02618.x . 1500708 .
  31. Web site: Lack of sleep may increase Alzheimer's risk. Medical News Today. 22 October 2013 . 21 March 2016.
  32. Terracciano . Antonio . Sutin . Angelina R. . An . Yang . O'Brien . Richard J. . Ferrucci . Luigi . Zonderman . Alan B. . Resnick . Susan M. . Personality and risk of Alzheimer's disease: New data and meta-analysis . Alzheimer's & Dementia . March 2014 . 10 . 2 . 179–186 . 10.1016/j.jalz.2013.03.002. 23706517 . 3783589 .
  33. Web site: Neuroticism and other personality traits in midlife linked to Alzheimer's risk - Alzheimer's Research UK. 1 October 2014. 29 January 2015. https://web.archive.org/web/20141006163420/http://www.alzheimersresearchuk.org/news-detail/11160/Neuroticism-and-other-personality-traits-in-midlife-linked-to-Alzheimers-risk/. 6 October 2014. dead.
  34. Web site: Jealous, Moody Women May Face Higher Alzheimer's Risk, Study Says.
  35. Jackson J, Balota DA, Head D . Exploring the relationship between personality and regional brain volume in healthy aging . Neurobiology of Aging . 32 . 12 . 2162–71 . December 2011 . 20036035 . 2891197 . 10.1016/j.neurobiolaging.2009.12.009 .
  36. Terracciano . Antonio . Sutin . Angelina R. . An . Yang . O'Brien . Richard J. . Ferrucci . Luigi . Zonderman . Alan B. . Resnick . Susan M. . Personality and risk of Alzheimer's disease: New data and meta-analysis . Alzheimer's & Dementia . March 2014 . 10 . 2 . 179–186 . 10.1016/j.jalz.2013.03.002. 23706517 . 3783589 .
  37. 2020-05-27 . Loneliness, but not social isolation, predicts development of dementia in older people . NIHR Evidence . Plain English summary . en . 10.3310/alert_40330. 241649845 .
  38. Rafnsson . Snorri Bjorn . Orrell . Martin . d’Orsi . Eleonora . Hogervorst . Eef . Steptoe . Andrew . 2020-01-01 . Carr . Deborah . Loneliness, Social Integration, and Incident Dementia Over 6 Years: Prospective Findings From the English Longitudinal Study of Ageing . The Journals of Gerontology: Series B . en . 75 . 1 . 114–124 . 10.1093/geronb/gbx087 . 1079-5014 . 6909434 . 28658937.
  39. Livingston G, Sommerlad A, Orgeta V, Costafreda SG, Huntley J, Ames D, Ballard C, Banerjee S, Burns A, Cohen-Mansfield J, Cooper C, Fox N, Gitlin LN, Howard R, Kales HC, Larson EB, Ritchie K, Rockwood K, Sampson EL, Samus Q, Schneider LS, Selbæk G, Teri L, Mukadam N . 6 . Dementia prevention, intervention, and care . Lancet . 390 . 10113 . 2673–2734 . December 2017 . 28735855 . 10.1016/s0140-6736(17)31363-6 . 10026.1/18238 . 27466779 . free .
  40. Diniz BS, Butters MA, Albert SM, Dew MA, Reynolds CF . Late-life depression and risk of vascular dementia and Alzheimer's disease: systematic review and meta-analysis of community-based cohort studies . The British Journal of Psychiatry . 202 . 5 . 329–35 . May 2013 . 23637108 . 3640214 . 10.1192/bjp.bp.112.118307 .
  41. News: Blood pressure drug dementia hope. 28 July 2008. 2 October 2009. BBC News.
  42. Blood Pressure Drugs May Protect Against Alzheimer's. 27 July 2008. Boston University School of Medicine. 2 October 2009.
  43. Peters R, Beckett N, Forette F, Tuomilehto J, Clarke R, Ritchie C, Waldman A, Walton I, Poulter R, Ma S, Comsa M, Burch L, Fletcher A, Bulpitt C . 6 . Incident dementia and blood pressure lowering in the Hypertension in the Very Elderly Trial cognitive function assessment (HYVET-COG): a double-blind, placebo controlled trial . The Lancet. Neurology . 7 . 8 . 683–9 . August 2008 . 18614402 . 10.1016/S1474-4422(08)70143-1 . free . 1959.4/unsworks_82416 . free .
  44. Diabetes and Alzheimer's linked . . 6 November 2008 . 2 October 2009.
  45. Web site: Obesity Today, Alzheimer's Disease Tomorrow?. WebMD. 21 March 2016.
  46. Simpkins JW, Perez E, Wang X, Yang S, Wen Y, Singh M . The potential for estrogens in preventing Alzheimer's disease and vascular dementia . Therapeutic Advances in Neurological Disorders . 2 . 1 . 31–49 . January 2009 . 19890493 . 2771945 . 10.1177/1756285608100427 .
  47. Web site: Anderson P . Timing of Hormone Therapy May Affect Alzheimer's Prevention . Medscape . 25 October 2012 .
  48. Szekely CA, Green RC, Breitner JC, Østbye T, Beiser AS, Corrada MM, Dodge HH, Ganguli M, Kawas CH, Kuller LH, Psaty BM, Resnick SM, Wolf PA, Zonderman AB, Welsh-Bohmer KA, Zandi PP . 6 . No advantage of A beta 42-lowering NSAIDs for prevention of Alzheimer dementia in six pooled cohort studies . Neurology . 70 . 24 . 2291–8 . June 2008 . 18509093 . 2755238 . 10.1212/01.wnl.0000313933.17796.f6 .
  49. Cornelius C, Fastbom J, Winblad B, Viitanen M . Aspirin, NSAIDs, risk of dementia, and influence of the apolipoprotein E epsilon 4 allele in an elderly population . Neuroepidemiology . 23 . 3 . 135–43 . 2004 . 15084783 . 10.1159/000075957 . 39159897 .
  50. Etminan M, Gill S, Samii A . Effect of non-steroidal anti-inflammatory drugs on risk of Alzheimer's disease: systematic review and meta-analysis of observational studies . BMJ . 327 . 7407 . 128–0 . July 2003 . 12869452 . 165707 . 10.1136/bmj.327.7407.128 .
  51. Nilsson SE, Johansson B, Takkinen S, Berg S, Zarit S, McClearn G, Melander A . Does aspirin protect against Alzheimer's dementia? A study in a Swedish population-based sample aged > or =80 years . European Journal of Clinical Pharmacology . 59 . 4 . 313–9 . August 2003 . 12827329 . 10.1007/s00228-003-0618-y . 25373470.
  52. Anthony JC, Breitner JC, Zandi PP, Meyer MR, Jurasova I, Norton MC, Stone SV . Reduced prevalence of AD in users of NSAIDs and H2 receptor antagonists: the Cache County study . Neurology . 54 . 11 . 2066–71 . June 2000 . 10851364 . 10.1212/wnl.54.11.2066 . 24381780 .
  53. Bentham P, Gray R, Sellwood E, Hills R, Crome P, Raftery J . Aspirin in Alzheimer's disease (AD2000): a randomised open-label trial . The Lancet. Neurology . 7 . 1 . 41–9 . January 2008 . 18068522 . 10.1016/S1474-4422(07)70293-4 . 54354338 .
  54. Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM, Cooper NR, Eikelenboom P, Emmerling M, Fiebich BL, Finch CE, Frautschy S, Griffin WS, Hampel H, Hull M, Landreth G, Lue L, Mrak R, Mackenzie IR, McGeer PL, O'Banion MK, Pachter J, Pasinetti G, Plata-Salaman C, Rogers J, Rydel R, Shen Y, Streit W, Strohmeyer R, Tooyoma I, Van Muiswinkel FL, Veerhuis R, Walker D, Webster S, Wegrzyniak B, Wenk G, Wyss-Coray T . 6 . Inflammation and Alzheimer's disease . Neurobiology of Aging . 21 . 3 . 383–421 . 2000 . 10858586 . 3887148 . 10.1016/S0197-4580(00)00124-X .
  55. Tortosa E, Avila J, Pérez M . Acetylsalicylic acid decreases tau phosphorylation at serine 422 . Neuroscience Letters . 396 . 1 . 77–80 . March 2006 . 16386371 . 10.1016/j.neulet.2005.11.066 . 41577779 .
  56. Hirohata M, Ono K, Naiki H, Yamada M . Non-steroidal anti-inflammatory drugs have anti-amyloidogenic effects for Alzheimer's beta-amyloid fibrils in vitro . Neuropharmacology . 49 . 7 . 1088–99 . December 2005 . 16125740 . 10.1016/j.neuropharm.2005.07.004 . 2297/7405 . 20607532 . free .
  57. Thomas T, Nadackal TG, Thomas K . Aspirin and non-steroidal anti-inflammatory drugs inhibit amyloid-beta aggregation . NeuroReport . 12 . 15 . 3263–7 . October 2001 . 11711868 . 10.1097/00001756-200110290-00024 . 71735451 .
  58. Jordan. Fionnuala. Quinn. Terry J.. McGuinness. Bernadette. Passmore. Peter. Kelly. John P.. Tudur Smith. Catrin. Murphy. Kathy. Devane. Declan. 30 April 2020. Aspirin and other non-steroidal anti-inflammatory drugs for the prevention of dementia. The Cochrane Database of Systematic Reviews. 2020. 4 . CD011459. 10.1002/14651858.CD011459.pub2. 1469-493X. 7192366. 32352165.
  59. Taylor-Rowan . Martin . Alharthi . Ahmed A. . Noel-Storr . Anna H. . Myint . Phyo K. . Stewart . Carrie . McCleery . Jenny . Quinn . Terry J. . 2023-12-08 . Anticholinergic deprescribing interventions for reducing risk of cognitive decline or dementia in older adults with and without prior cognitive impairment . The Cochrane Database of Systematic Reviews . 2023 . 12 . CD015405 . 10.1002/14651858.CD015405.pub2 . 1469-493X . 10704558 . 38063254.