Contents

Search

prevention of Alzheimer's disease/dementia

Management: - there is no good evidence that anything prevents the pathology of Alzheimer's disease [11,20,45,50] - also see prevention of cognitive impairment - a healthy lifestyle may delay symptoms of Alzheimer's disease & prolong life expectancy [75] - risk-factor prevention should target modifiable cardiovascular risk [42,45,79] - sedentary life style - diet - insulin resistance & type 2 diabetes - obesity (midlife) - metabolic syndrome - hypertension (midlife) - hypercholesterolemia - smoking - renal disease - depression - low education - hearing loss - angiotensin receptor blockers may reduce indidence of dementia in patients with chronic hypertension [53] - blood pressure control reduces risk of Alzheimer's dementia [54] - intensive blood pressure control (target systolic BP < 120 mm Hg vs < 140 mm Hg) does not reduce brain MRI markers of AD [62] - use of diuretics to control hypertension linked to less neuropathology [65] - cardiovascular fitness at midlife may reduce risk for dementia [47] - higher Life's simple 7 scores at midlife associated with lower risk for dementia [80] === exercise & physical fitness === - exercise reduces the risk of dementia [7,13,19,45,53] & the risk of AD [20,50) - aerobic exercise that improves cardiorespiratory fitness benefits cognition in healthy older adults more than other forms of exercise (GRS11) [28] - 150 minutes of moderate-intensity aerobic physical activity per week, or 75 minutes of vigorous-intensity activity per week (WHO) - 30 minutes of exercise twice a week insufficient (GRS11) [28] - this statement may contradict other evidence presented here - social network more important if exercise insufficient (GRS11) [28] - moderate intensity aerobic training or stretching, balance, & range-of-motion exercise may prevent cognitive decline in persons with mild cognitive impairment [83] - dementia is less common among people who are more fit before age 65 [26] - physical fitness associated with lower risk of dementia [71] - exercise does not reduce risk of dementia [40] - vigorous, regular exercise may slow disease progression in biomarker-positive amnestic MCI & mild Alzheimer's disease [89] - exercise training may improve memory in elderly with intact cognition or mild cognitive impairment due to Alzheimer's disease [93] - an intensive program of exercise & functional activity training did not improve activities of daily living, physical activity, or quality of life; reduce falls; or improve any other secondary health outcomes in elderly (80 years) with mild cognitive impairment or early dementia, despite good compliance [100] === cognition, socialization, sleep, stress & mood === - physical & mental activity lower risk for dementia [85] - midlife cognitive & physical activity decreases dementia risk in women [52] - risk-factor prevention should also target depression, psychological & physiologic stress, traumatic brain injury, sleep-disordered breathing & alcohol abuse [42] - slow-wave sleep & sleep efficiency diminish accumulation of beta-amyloid deposition in susequent years [60] (see glymphatic clearance) - sleep & circadian function may be a modifiable risk factor for AD [82] - ability to cope with stress correlates with lower tau burden [58] - marriage confers lower risk of dementia [44] - positive beliefs about aging halfs 4 year risk of dementia in high-risk individuals, including those with apoE4 allele [46] but does protect against either neurodegenerative or vascular brain pathology (i.e. neurofibrillary tangles or senile plaques) [12] - active cognitive lifestyle does not protect against pathology of Alzheimer's disease, but may exert beneficial effects on cortical ribbon thickness of heteromodal prefrontal cortex (Brodman's area 9) [23] - education lowers the risk or delays onset of dementia - higher education & a complex job with social interaction might help protect against Alzheimer's disease [36,50] - cognitive training may be of benefit [19,45] - memory training programs of no benefit [28] - participation in new stimulating activities contributes to cognitive fitness & might delay cognitive decline [29] - exercise & computer classes seem to generate equivalent beneficial effects [29] - midlife & late-life social & cognitive activities diminish likelihood of late-life cognitive decline [72,73] - internet use may prevent or delay dementia in older adults [95] === diet & supplements === - Mediterranean diet in combination with exercise reduces the risk of dementia [18,53] & may reduce risk of Alzheimer's disease [50] - most studies describe Mediterranean diet rich in olive oil - omega-6 fatty acids as present in olive oil reduce oxidative stress & mitigate cognitive decline in older adults [69] - cognitive decline may be attenuated 63% with combination of high physical activity & high fruit & vegetable intake [81] - MIND diet may reduce risk of Alzheimer's disease [35] - adherence to a MIND diet is associated with a reduced risk of dementia in middle-age & older adults [92] - MIND diet & Mediterranean diet are associated with less postmortem Alzheimer's disease pathology (beta-amyloid < neurofibrillary tangles), correlating with green-leafy vegetables [91] - in a 20-year follow-up study, neither adherence to conventional dietary recommendations nor to modified Mediterranean diet were associated with reduced risk for developing all-cause dementia, Alzheimer's dementia, or vascular dementia [87] - dietary fiber, especially soluble fiber, linked to lower risk of dementia [70] - potatoes, but not fruits or vegetables show similar association [70] - flavonoids (from red wine may reduce incidence of dementia [6] - flavonols may reduce risk of Alzheimer's disease [55] - higher serum levels of lutein+zeaxanthin & beta-cryptoxanthin associated with lower risk of dementia [78] - omega-3 fatty acids - docosahexaenoic acid (omega-3 fatty acid) - may be neuroprotective [8] - does not slow decline of mild to moderate AD (2 g/day) [14] - higher dietary intake of omega-3 fatty acids is associated with lower plasma levels of Abeta40 & Abeta42 [22] - a diet low in inflammatory foods & high in fruits, vegetables & legumes may reduced risk of dementia (see dietary inflammatory index) [66] - weekly seafood consumption may diminish risk of dementia in people heterozygous for apo E4 [34] - low saturated fat intake & high monounsaturated fat intake are beneficial for cognition in elderly women [24] - coffee drinking may be associated with a decreased risk of AD [30,51] - 1-6 cups of tea/day may reduce risk of Alzheimer's disease 16-19% & reduce risk of vascular dementia 25-29% [77] - curcumin in curry may have benefit [9] - no strong evidence linking it to prevention of dementia or to attenuation of cognitive decline (GRS11) [28] - mushrooms may diminish risk (RR=0.81 >= 3x/week) [43] - evidence insufficient to recommend any over-the-counter supplements for prevention of Alzheimer's disease [45] - multivitamin for 3 years is associated with a 60% slowing of cognitive aging [67] - vitamin E plus vitamin C in combination reduced risk of Alzheimer's disease; RR = 0.22 for users > 5 years [5] - dose of vitamins not controlled, but estimate is - vitamin E: up to 1000 IU/day - vitamin C: 500-1000 mg/day - a diet rich in vitamin E may diminish risk of dementia [17] - vitamin E 2000 IU may increase mortality in patients with Alzheimer's disease [63] - supplementation with vitamin E & selenium, taken alone or in combination not associated with a decreased incidence of dementia in asymptomatic older men [39] - niacin may be associated with a diminish risk of AD [10] - vitamin B12 alone without folate or vitamin B6 may be of benefit [12], see investigational treatment of AD - combination of vitamin B12 400 ug, folate 2 mg, vitamin B6 25 mg of no benefit [16] - folic acid & vitamin B12 supplementation in elderly with elevated serum homocysteine of no benefit [33] - higher vitamin D intake may decrease risk of dementia [59] - vitamin D supplementation reduces risk of dementia (40%) [90] - Gingko biloba of no benefit [25] === pharmaceuticals & alcohol === - non-steroidal anti-inflammatory agents (NSAIDs) a) epidemiologic studies associate NSAID use with diminished risk of AD [1]; RR 0.27 for long-term users > 24 months [4] b) risk may be attenuated with certain NSAIDs, but not others [2,3] 1] rofecoxib 25 mg/day of no benefit [3] 2] naproxen 220 mg BID of no benefit [3] c) concurrent role of NSAID as gamma-secretase inhibitor rather than anti-inflammatory agent may confer benefit d) tarenflurbil (Flurizan) R-flurbiprofen, a gamma-secretase inhibitor without NSAID activity of no benefit for delaying onset of AD [21] e) NSAIDs diminish salivary Abeta42, a presumptive marker of amyloid-beta deposition in brain [48] f) no evidence to support use of low-dose aspirin or other NSAID of any class (celecoxib, rofecoxib or naproxen) for prevention of dementia; however there is evidence of harm (Cochrone review) [57] - Crenezumab in clinical trial for prevention of familial AD - citalopram reduces Abeta production in CSF (humans) [31] - for patients with modifiable risk for AD, a multidisciplinary intervention may be beneficial [32] - modification of cardiovascular risk factors - nutritional advice - physical activity - cognitive training - social activities - long-term increased lithium exposure in drinking water may be associated with a lower incidence of dementia [41] - hormone replacement therapy - NOT currently indicated for prevention or treatment of Alzheimer's disease or other dementias - may lower risk of Alzheimer's disease if started within 5 years of menopause [38] - reduces risk for Alzheimer's disease only after 10 years of self-reported use [37] - alcohol consumption 1-7 drinks weekly associated with lowest risk of dementia, abstinence or more associated with higher risk [49] - TNF inhibitors may lower risk of Alzheimer's disease & related dementia in patients with rheumatoid arthritis & cardiovascular disease [74] - tau aggregation inhibitors - tau aggregation inhibitor hydromethylthionine mesylate (HMTM) improves cognition over 18 months in elderly with mild cognitive impairment [98] - tau aggregation inhibitor (LMTM) of no benefit in patients with mild-to-moderate Alzheimer's disease [99] - semaglutide may reduce risk of Alzheimer's disease in patients with diabetes mellitus type-2 (RR=0.3-0.6) [1-2] === vaccine === - Herpes zoster vaccine Zostavax reduced new diagnosis of dementia within 7 years (RR=0.8) [94] === other === - dentures mitigate increased risk of dementia associated with tooth loss [64] - correction of sensory impairment - visual impairment is a potentially modifiable risk factor for dementia [76] - cataract extraction associated with reduced risk of dementia (RR=0.71) [68] - hearing impairment is a potentially modifiable risk factor for dementia - hearing aids & cochlear implants may attenuate cognitive decline [88] - may reduce 3 year cognitive decline in older adults at increased risk [97] - not likely to benefit persons at low risk of cognitive decline [97] - lean mass might be a possible modifiable protective factor [96] Notes: - leisure activity may not protect against AD [61] - PDE-5 inhibitors - not effective in preventing Alzheimer's disease & related dementias [86] - may reduce risk of Alzheimer's disease (RR=0.56-0.82) depending on dose [101]

Related

Alzheimer's disease (AD) cognitive resilience etiology/risk of Alzheimer's disease guidelines for Alzheimer's disease management investigational therapies for treatment of Alzheimer's disease predictors of Alzheimer's disease

Specific

warning signs of Alzheimer's disease

General

prevention of cognitive impairment

References

  1. Journal Watch 21(24):193, 2001 in 't Veld et al, NEJM 345:1515,2001
  2. Journal Watch 21(24):194, 2001 Weggen et al, Nature 414:212, 2001
  3. Journal Watch 23(14):109, 2003 Aisen PS, Schafer KA, Grundman M, Pfeiffer E, Sano M, Davis KL, Farlow MR, Jin S, Thomas RG, Thal LJ; Alzheimer's Disease Cooperative Study. Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial. JAMA. 2003 Jun 4;289(21):2819-26. PMID: 12783912 - Szekely CA, Thorne JE, Zandi PP, Ek M, Messias E, Breitner JC, Goodman SN. Nonsteroidal anti-inflammatory drugs for the prevention of Alzheimer's disease: a systematic review. Neuroepidemiology. 2004 Jul-Aug;23(4):159-69. Review. PMID: 15279021 - Launer LJ. Nonsteroidal anti-inflammatory drugs and Alzheimer disease: what's next? JAMA. 2003 Jun 4;289(21):2865-7. No abstract available. Erratum in: JAMA. 2003 Sep 3;290(9):1154. PMID: 12783919
  4. Journal Watch 23(18):145, 2003 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. 2003 Jul 19;327(7407):128. Review. PMID: 12869452 http://bmj.com/cgi/content/full/327/7407/12
  5. Zandi PP, Anthony JC, Khachaturian AS, Stone SV, Gustafson D, Tschanz JT, Norton MC, Welsh-Bohmer KA, Breitner JC; Cache County Study Group. Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: the Cache County Study. Arch Neurol. 2004 Jan;61(1):82-8. PMID: 14732624 http://archneur.ama-assn.org/cgi/content/abstract/61/1/82
  6. Commenges D, Scotet V, Renaud S, Jacqmin-Gadda H, Barberger- Gateau P, Dartigues JF. Intake of flavonoids and risk of dementia. Eur J Epidemiol. 2000 Apr;16(4):357-63. PMID: 10959944
  7. Larson EB, Wang L, Bowen JD, McCormick WC, Teri L, Crane P, Kukull W. Exercise is associated with reduced risk for incident dementia among persons 65 years of age and older. Ann Intern Med. 2006 Jan 17;144(2):73-81. Summary for patients in: Ann Intern Med. 2006 Jan 17;144(2):I20. PMID: 16418406 - [No authors listed] Summaries for patients. Exercise in people age 65 years and older is associated with lower risk for dementia. Ann Intern Med. 2006 Jan 17;144(2):I20. No abstract available. PMID: 16418403
  8. Lukiw WJ, Cui JG, Marcheselli VL, Bodker M, Botkjaer A, Gotlinger K, Serhan CN, Bazan NG. A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease. J Clin Invest. 2005 Oct;115(10):2774-83. PMID: 16151530 - Morris MC, Evans DA, Tangney CC, Bienias JL, Wilson RS. Fish consumption and cognitive decline with age in a large community study. Arch Neurol. 2005 Dec;62(12):1849-53. Epub 2005 Oct 10. PMID: 16216930
  9. Chen M, Du ZY, Zheng X et al. Use of curcumin in diagnosis, prevention, and treatment of Alzheimer's disease. Neural Regen Res. 2018;13(4):742-752 PMID: 29722330 PMCID: PMC5950688 Free PMC article - Kuszewski JC, Wong RHX, Howe PRC. Can curcumin counteract cognitive decline? Clinical trial evidence and rationale for combining omega-3 Adv Nutr. 2018;9(2):105-113 PMID: 29659685 PMCID: PMC5916424 Free PMC article https://academic.oup.com/advances/article/9/2/105/4969259
  10. Morris MC, Evans DA, Bienias JL, Scherr PA, Tangney CC, Hebert LE, Bennett DA, Wilson RS, Aggarwal N. Dietary niacin and the risk of incident Alzheimer's disease and of cognitive decline. J Neurol Neurosurg Psychiatry. 2004 Aug;75(8):1093-9. PMID: 15258207
  11. NATIONAL INSTITUTES OF HEALTH STATE-OF-THE-SCIENCE CONFERENCE STATEMENT NIH State-of-the-Science Conference: Preventing Alzheimer's Disease and Cognitive Decline April 26-28, 2010 PMID: 20547888 http://consensus.nih.gov/2010/docs/alz/alz_stmt.pdf
  12. EClipSE Collaborative Members. Education, the brain and dementia: Neuroprotection or compensation? Brain 2010 Aug; 133:2210. PMID: 20826429
  13. Erickson KI et al Physical activity predicts gray matter volume in late adulthood: the Cardiovascular Health Study. Neurology 2010 Oct 19; 75:1415 PMID: 20944075 http://www.neurology.org/cgi/content/abstract/WNL.0b013e3181f88359v1 - Liang KY et al. Exercise and Alzheimer's disease biomarkers in cognitively normal older adults. Ann Neurol 2010 Sep; 68:311. PMID: 20818789
  14. Quinn JF et al Docosahexaenoic Acid Supplementation and Cognitive Decline in Alzheimer Disease JAMA. 2010;304(17):1903-1911 PMID: 21045096 http://jama.ama-assn.org/cgi/content/full/304/17/1903
  15. Hooshmand B et al Homocysteine and holotranscobalamin and the risk of Alzheimer disease: A longitudinal study. Neurology 2010 Oct 19; 75:1408. PMID: 20956786
  16. Ford AH et al Vitamins B(12), B(6), and folic acid for cognition in older men. Neurology. 2010 Oct 26;75(17):1540-7. Epub 2010 Sep 22. PMID: 20861451
  17. Devore EE et al Dietary antioxidants and long-term risk of dementia. Arch Neurol. 2010 Jul;67(7):819-25. PMID: 20625087
  18. Scarmeas N et al Physical Activity, Diet, and Risk of Alzheimer Disease JAMA. 2009;302(6):627-637. PMID: 19671904 http://jama.ama-assn.org/cgi/content/full/302/6/627 - Feart C et al Adherence to a Mediterranean Diet, Cognitive Decline, and Risk of Dementia JAMA. 2009;302(6):638-648. PMID: 19671905 http://mail.google.com/mail/?hl=en&tab=wm#inbox/1230e5270aa617fe - Knopman DS et al Mediterranean Diet and Late-Life Cognitive Impairment A Taste of Benefit JAMA. 2009;302(6):686-687 PMID: 19671912 http://mail.google.com/mail/?hl=en&tab=wm#inbox/1230e5270aa617fe
  19. Plassman BL, Williams JW Jr, Burke JR, et al. Systematic review: Factors associated with risk for and possible prevention of cognitive decline in later life. Ann Intern Med Aug 3, 2010; 153(3):182-193. PMID: 20547887
  20. Buchman AS et al Total daily physical activity and the risk of AD and cognitive decline in older adults Neurology April 18, 2012 PMID: 22517108 http://www.neurology.org/content/early/2012/04/18/WNL.0b013e3182535d35.abstract
  21. Green RC et al. Effect of tarenflurbil on cognitive decline and activities of daily living in patients with mild Alzheimer disease: A randomized controlled trial. JAMA 2009 Dec 16; 302:2557. PMID: 20009055 - Montine TJ and Larson EB. Late-life dementias: Does this unyielding global challenge require a broader view? JAMA 2009 Dec 16; 302:2593. PMID: 20009062
  22. Gu Y et al Nutrient intake and plasma beta-amyloid Neurology, May 1, 2012, 78 (18) PMID: 22551728 http://www.neurology.org/content/early/2012/05/02/WNL.0b013e318258f7c2.abstract
  23. Valenzuela MJ et al. Multiple biological pathways link cognitive lifestyle to protection from dementia. Biol Psychiatry 2012 May 1; 71:783. PMID: 22055015 - Doraiswamy PM. Is the idle mind a devil's workshop? Biol Psychiatry 2012 May 1; 71:765. PMID: 22482886
  24. Okereke OI et al. Dietary fat types and 4-year cognitive change in community- dwelling older women. Ann Neurol 2012 May 17 PMID: 22605573 http://onlinelibrary.wiley.com/doi/10.1002/ana.23593/abstract
  25. Vellas B et al Long-term use of standardised ginkgo biloba extract for the prevention of Alzheimer's disease (GuidAge): a randomised placebo-controlled trial The Lancet Neurology, Early Online Publication, 6 September 2012 http://www.thelancet.com/journals/laneur/article/PIIS1474-4422%2812%2970206-5/abstract
  26. DeFina LF et al. The association between midlife cardiorespiratory fitness levels and later-life dementia: A cohort study. Ann Intern Med 2013 Feb 5; 158:162. PMID: 23381040
  27. Barnes DE, Yaffe K. The projected effect of risk factor reduction on Alzheimer's disease prevalence. Lancet Neurol. 2011 Sep;10(9):819-28. Review. PMID: 21775213
  28. Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013 - Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022
  29. Klusmann V, Evers A, Schwarzer R Complex mental and physical activity in older women and cognitive performance: a 6-month randomized controlled trial. J Gerontol A Biol Sci Med Sci. 2010 Jun;65(6):680-8 PMID: 20418350
  30. Eskelinen MH, Kivipelto M Caffeine as a protective factor in dementia and Alzheimer's disease. J Alzheimers Dis. 2010;20 Suppl 1:S167-74 PMID: 20182054
  31. Yager J Might SSRIs Reduce the Risk for Alzheimer Disease? NEJM Journal Watch. May 27, 2014 Massachusetts Medical Society (subscription needed) http://www.jwatch.org - Sheline YI et al. An antidepressant decreases CSF Abeta production in healthy individuals and in transgenic AD mice. Sci Transl Med 2014 May; 6:236re4 PMID: 24828079 http://stm.sciencemag.org/content/6/236/236re4?ijkey=4d44f88a853621ff2f0f2212954925a3b3d7adf8&keytype2=tf_ipsecsha
  32. Alzheimer's Association, July 13, 2014 FINGER Study http://www.alz.org/aaic/_downloads/AAIC-2014-FINGER-Study.pdf
  33. van der Zwaluw NL et al Results of 2-year vitamin B treatment on cognitive performance. Secondary data from an RCT. Neurology. Nov 12, 2014 PMID: 25391305 http://www.neurology.org/content/early/2014/11/12/WNL.0000000000001050
  34. Morris MC, Brockman J, Schneider JA et al Association of Seafood Consumption, Brain Mercury Level, and APOE e4 Status With Brain Neuropathology in Older Adults. JAMA. 2016 Feb 2;315(5):489-497 PMID: 26836731 - Kroger E, Laforce R Jr Fish Consumption, Brain Mercury, and Neuropathology in Patients With Alzheimer Disease and Dementia. JAMA. 2016 Feb 2;315(5):465-466 PMID: 26836728
  35. Jacobs AR Can the MIND Diet Reduce Alzheimer's Risk? Medscape. March 8, 2016 http://www.medscape.com/viewarticle/858958
  36. Alzheimer's Association News Release Alzheimer's Association International Conference. July 22-28, 2016 Toronto, Canada FORMAL EDUCATION AND COMPLEX WORK MAY REDUCE THE NEGATIVE EFFECTS OF BAD DIET AND CEREBROVASCULAR DISEASE ON COGNITION http://www.multivu.com/players/English/7865351-aaic-2016-cognitive-training/docs/press-release-1311562930.pdf
  37. Imtiaz B, Tuppurainen M, Rikkonen T et al. Postmenopausal hormone therapy and Alzheimer disease: A prospective cohort study. Neurology 2017 Feb 15 PMID: 28202700 http://www.neurology.org/content/early/2017/02/15/WNL.0000000000003696
  38. Shao H et al Hormone therapy and Alzheimer disease dementia New findings from the Cache County Study PMID: 23100399 Neurology, Oct 24 2012 http://www.neurology.org/content/early/2012/10/24/WNL.0b013e318271f823.abstract - Henderson VW and Rocca WA Estrogens and Alzheimer disease risk: Is there a window of opportunity? Neurology, October 24, 2012 PMID: 23100400 http://www.neurology.org/content/early/2012/10/24/WNL.0b013e318271f88f.excerpt
  39. Slomski A. Vitamin E and Selenium Fail to Prevent Dementia in Men. JAMA. 2017;317(20):2054 PMID: 28535233 http://jamanetwork.com/journals/jama/article-abstract/2627967
  40. Sabia S et al Physical activity, cognitive decline, and risk of dementia: 28 year follow-up of Whitehall II cohort study. BMJ 2017;357:j2709 PMID: 28642251 Free full text http://www.bmj.com/content/357/bmj.j2709
  41. Kessing LV, Gerds TA, Knudsen NN et al Association of lithium in drinking water with the incidence of dementia. JAMA Psychiatry. 2017 Aug 23 PMID: 28832877 Free PMC article - McGrath JJ, Berk M. Could Lithium in Drinking Water Reduce the Incidence of Dementia? JAMA Psychiatry. 2017 Aug 23. PMID: 28832875
  42. Barclay LL Alzheimer's Prevention: A Summary of What We Know Medscape - Aug 23, 2017. http://www.medscape.com/viewarticle/884615 - Galvin JE. Prevention of Alzheimer's Disease: Lessons Learned and Applied. J Am Geriatr Soc. 2017 Aug 2. PMID: 28766695
  43. Zhang S, Tomata Y, Sugiyama K, Sugawara Y, Tsuji I. Mushroom Consumption and Incident Dementia in Elderly Japanese: The Ohsaki Cohort 2006 Study. J Am Geriatr Soc. 2017 Jul;65(7):1462-1469. Epub 2017 Mar 13. PMID: 28295137
  44. Kneisel K. Married Folks Seem to Have Lower Dementia Risk. Widowed, lifelong singles tend to be underdiagnosed in routine clinical practice. MedPage Today Nov 28, 2017 https://www.medpagetoday.com/geriatrics/dementia/69529 - Sommerlad A, Ruegger J, Singh-Manoux A, Lewis G, Livingston G. Marriage and risk of dementia: systematic review and meta- analysis of observational studies. J Neurol Neurosurg Psychiatry 2017 PMID: 29183958 - Chen CPLH, Mok VCT. Marriage and risk of dementia: systematic review and meta- analysis of observational studies. J Neurol Neurosurg Psychiatry 2017 PMID: 29183957 Free Article
  45. Yaffe K Modifiable Risk Factors and Prevention of Dementia. What Is the Latest Evidence? JAMA Intern Med. Published online December 18, 2017 PMID: 29255907 https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2665382 - Brasure M, Desai P, Davila H et al Physical Activity Interventions in Preventing Cognitive Decline and Alzheimer-Type Dementia: A Systematic Review. Ann Intern Med. 2017. Dec 19. PMID: 29255839 http://annals.org/aim/article-abstract/2666417/physical-activity-interventions-preventing-cognitive-decline-alzheimer-type-dementia-systematic - Fink HA, Jutkowitz E, McCarten JR et al Pharmacologic Interventions to Prevent Cognitive Decline, Mild Cognitive Impairment, and Clinical Alzheimer-Type Dementia: A Systematic Review. Ann Intern Med. 2017. Dec 19. PMID: 29255847 http://annals.org/aim/article-abstract/2666418/pharmacologic-interventions-prevent-cognitive-decline-mild-cognitive-impairment-clinical-alzheimer - Butler M, Nelson VA, Davila H et al Over-the-Counter Supplement Interventions to Prevent Cognitive Decline, Mild Cognitive Impairment, and Clinical Alzheimer- Type Dementia: A Systematic Review. Ann Intern Med. 2017. Dec 19. PMID: 29255909 http://annals.org/aim/article-abstract/2666419/over-counter-supplement-interventions-prevent-cognitive-decline-mild-cognitive-impairment - Butler M, McCreedy E, Nelson VA et al Does Cognitive Training Prevent Cognitive Decline?: A Systematic Review. Ann Intern Med. 2017. Dec 19. PMID: 29255842 http://annals.org/aim/article-abstract/2666420/does-cognitive-training-prevent-cognitive-decline-systematic-review - Larson EB Prevention of Late-Life Dementia: No Magic Bullet. Ann Intern Med. 2017. Dec 19. PMID: 29255884 http://annals.org/aim/article-abstract/2666421/prevention-late-life-dementia-magic-bullet
  46. Levy BR, Slade MD, Pietrzak RH, Ferrucci L. Positive age beliefs protect against dementia even among elders with high-risk gene. PLoS One 2018 Feb 7; 13:e0191004 PMID: 29414991 Free PMC Article http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0191004
  47. Horder H, Johansson L, Guo X et al Midlife cardiovascular fitness and dementia. A 44-year longitudinal population study in women. Neurology. March 14, 2018 PMID: 29540588 http://n.neurology.org/content/early/2018/03/14/WNL.0000000000005290 - Spartano NL, Ngandu T Fitness and dementia risk Further evidence of the heart-brain connection. Neurology. March 14, 2018 PMID: 29540586 http://n.neurology.org/content/early/2018/03/14/WNL.0000000000005282
  48. Science News. March 26, 2018 Neuroscientists say daily ibuprofen can prevent Alzheimer's disease. https://www.sciencedaily.com/releases/2018/03/180326140239.htm - McGeer PL, McGeer E. Conquering Alzheimer's Disease by Self Treatment. J Alzheimers Dis. 2018 Mar 16. PMID: 29562519 - McGeer PL, Guo JP, Lee M, Kennedy K, McGeer EG. Alzheimer's Disease Can Be Spared by Nonsteroidal Anti- Inflammatory Drugs. J Alzheimers Dis. 2018;62(3):1219-1222. PMID: 29103042 Free PMC Article
  49. Sabia S, Fayosse A, Dumurgier J et al Alcohol consumption and risk of dementia: 23 year follow-up of Whitehall II cohort study. BMJ 2018;362:k2927 PMID: 30068508 Free full text https://www.bmj.com/content/362/bmj.k2927 - Yasar S Relation between alcohol consumption in midlife and dementia in late life. BMJ 2018;362:k3164 PMID: 30068510 https://www.bmj.com/content/362/bmj.k3164https://www.bmj.com/content/362/bmj.k3164
  50. Medical Knowledge Self Assessment Program (MKSAP) 18, 19, American College of Physicians, Philadelphia 2018, 2021
  51. University Health Network Drinking coffee may reduce your chances of developing Alzheimer's, Parkinson's. Science News. Nov 5, 2018 https://www.sciencedaily.com/releases/2018/11/181105160825.htm
  52. Najar J, Ostling S, Gudmundsson P et al. Cognitive and physical activity and dementia: A 44-year longitudinal population study of women. Neurology. 2019 Mar 19;92(12):e1322-e1330. Epub 2019 Feb 20. PMID: 30787164
  53. Hulisz D, Hein DJ Does an ARB a Day Keep Dementia at Bay? Medscape - Jul 26, 2019. https://www.medscape.com/viewarticle/915949
  54. Ding J, Davis-Plourde KL, Sedaghat S et al Antihypertensive medications and risk for incident dementia and Alzheimer's disease: a meta-analysis of individual participant data from prospective cohort studies. Lancet Neurology. Nov 6, 2019 PMID: 31706889 https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(19)30393-X/fulltext - Peters R, Anderson CS Advancing dementia prevention through effective blood pressure control. Lancet Neurology. Nov 6, 2019 PMID: 31706888 https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(19)30407-7/fulltext
  55. George J More Flavonol, Less Alzheimer's - Prospective study points to phyotochemicals as possible neuroprotective agents. MedPage Today Jan 29, 2020 https://www.medpagetoday.com/neurology/alzheimersdisease/84603 - Holland T, Agarwal P, Wang Y et al Dietary flavonols and risk of Alzheimer dementia, Neurology 2020, Jan 29. PMID: 31996451
  56. WHO guidelines for prevention of dementia https://www.who.int/mental_health/neurology/dementia/english_foreward_executive_summary_dementia_guidelines.pdf
  57. Jordan F, Quinn TJ, McGuinness B et al Aspirin and other non-steroidal anti-inflammatory drugs for the prevention of dementia. Cochrane Database Syst Rev. 2020 Apr 30;4:CD011459 PMID: 32352165 https://www.cochrane.org/CD011459/aspirin-and-other-non-steroidal-anti-inflammatory-drugs-prevention-dementia
  58. Arenaza-Urquijo EM, Przybelski SA, Machulda MM et al. Better stress coping associated with lower tau in amyloid-positive cognitively unimpaired older adults. Neurology 2020 Apr 14; 94:e1571. PMID: 31964689 https://n.neurology.org/content/94/15/e1571
  59. Zhao C, Tsapanou A, Manly J et al Vitamin D intake is associated with dementia risk in the Washington Heights- Inwood Columbia Aging Project (WHICAP) Alzheimer's & Dementia, Sept 13, 2020 PMID: 32921000 https://alz-journals.onlinelibrary.wiley.com/doi/abs/10.1002/alz.12096
  60. Winer JP, Mander BA, Kumar A et al Sleep Disturbance Forecasts beta-Amyloid Accumulation across Subsequent Years. Current Biology 2020. Sept 3. PMID: 32888482 PMCID: PMC7642104 https://www.cell.com/current-biology/pdf/S0960-9822(20)31171-4.pdf
  61. Kneisel K Protective Effects of Leisure Activity on Dementia Risk Called Into Question - Previous short-term studies may reflect consequences of preclinical dementia. MedPage Today 2020, Nov 21 https://www.medpagetoday.org/neurology/dementia/89827 - Sommerlad A, et al Leisure activity participation and risk of dementia: an 18-year follow-up of the Whitehall II study. Neurology 2020, Nov 17;95(20):e2803-e2815 PMID: 33115773 - Henderson VW, Elias MF Leisure activity for dementia prevention: more work to be done. Neurology 2020. Nov 17;95(20):895-896 PMID: 33115774
  62. Nasrallah IM, Gaussoin SA, Pomponio R et al. Association of intensive vs standard blood pressure control with magnetic resonance imaging biomarkers of Alzheimer disease: Secondary analysis of the SPRINT MIND randomized trial. JAMA Neurol 2021 Mar 8; [e-pub]. PMID: 33683313 PMCID: PMC7941253 (available on 2022-03-08) https://jamanetwork.com/journals/jamaneurology/article-abstract/2776960
  63. Miller ER 3rd, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2005 Jan 4;142(1):37-46. PMID: 15537682 Free article
  64. Qi X, Zhu Z, Plassman BL, Wu B Dose-Response Meta-Analysis on Tooth Loss With the Risk of Cognitive Impairment and Dementia. JAMDA 2021. July 8 PMID: 34579934 PMCID: PMC8479246 (available on 2022-10-01) https://www.jamda.com/article/S1525-8610(21)00473-4/fulltext
  65. Anderson P Antihypertensives Tied to Lower Alzheimer's Pathology. Medscape. October 25, 2021. https://www.medscape.com/viewarticle/961531
  66. George J Dementia Linked to Inflammatory Foods - hree times greater risk of dementia tied to diets low in fruit, vegetables, legumes. MedPage Today November 12, 2021 https://www.medpagetoday.com/neurology/dementia/95626 - Charisis S, Ntanasi E, Yannakoulia M et al Diet Inflammatory Index and Dementia Incidence: A Population-Based Study. Neurology. 2021. Nov 10 PMID: 34759053 https://n.neurology.org/content/early/2021/11/10/WNL.0000000000012973
  67. Anderson P Multivitamins, but Not Cocoa, Tied to Slowed Brain Aging. Medscape. November 11, 2021. https://www.medscape.com/viewarticle/962772 - ClinicalTrials.gov COcoa Supplement and Multivitamin Outcomes Study for the Mind (COSMOS-Mind). https://clinicaltrials.gov/ct2/show/NCT03035201 - Manson JE Multivitamins Slow Cognitive Aging in Older Adults. Medscape. December 10, 2021 https://www.medscape.com/viewarticle/963748
  68. Lee CS, Gibbons LE, Lee AY et al Association Between Cataract Extraction and Development of Dementia. JAMA Intern Med. Published online December 6, 2021 PMID: 34870676 PMCID: PMC8649913 Free PMC article https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2786583 - Slomski A Cataract Surgery May Stave Off Dementia Among Older Patients. JAMA. 2022;327(5):416 https://jamanetwork.com/journals/jama/fullarticle/2788544
  69. Anderson P Dietary Fat Tied to Better Cognition in Older Adults. Medscape Feb 3, 2022 https://www.medscape.com/viewarticle/967806 - Liu D, Zhou L, Yang M et al Oxidative Stress Mediates the Association Between Dietary Fat Intake and Cognition in US Older Adults. Am J Geriatric Psychiatry 2022. Jan 14 PMID: 35151552 https://www.sciencedirect.com/science/article/abs/pii/S106474812200001X
  70. Swift Yasgur B Dietary Fiber Tied to Lower Dementia Risk Medscape. March 07, 2022 https://www.medscape.com/viewarticle/969760 - Yamagishi K, Maruyama K, Nagao M et al Dietary fiber intake and risk of incident disabling dementia: the Circulatory Risk in Communities Study Nutr Neurosci. 2022 Feb 6:1-8. PMID: 35125070 https://www.tandfonline.com/doi/full/10.1080/1028415X.2022.2027592
  71. Brooks M Physical Fitness Tied to Lower Alzheimer's Risk. Medscape. March 8, 2022 https://www.medscape.com/viewarticle/969905
  72. Roberts RO et al Risk and protective factors for cognitive impairment in persons aged 85 years and older. Neurology. April 8, 2015 PMID: 25854867 http://www.neurology.org/content/early/2015/04/08/WNL.0000000000001537 - Galvin JE Too much of a good thing may still be good for your brain. Neurology. April 8, 2015 PMID: 25854870 http://www.neurology.org/content/early/2015/04/08/WNL.0000000000001547
  73. Xu H, Yang R, Qi X et al Association of Lifespan Cognitive Reserve Indicator With Dementia Risk in the Presence of Brain Pathologies. JAMA Neurol. Published online July 14, 2019. PMID: 31302677 https://jamanetwork.com/journals/jamaneurology/fullarticle/2738336
  74. George J Is Alzheimer's Risk Lower With TNF Inhibitors? For arthritis patients with cardiovascular disease, the answer may be yes. MedPage Today April 8, 2022 https://www.medpagetoday.com/neurology/alzheimersdisease/98138
  75. George J Longevity Without Alzheimer's Tied to Lifestyle. More years of life did not mean more years with dementia. MedPage Today April 13, 20 https://www.medpagetoday.com/neurology/alzheimersdisease/98199 - Dhana K, Evans DA, Rajan KB et al Healthy lifestyle and the risk of Alzheimer dementia. Findings from 2 longitudinal studies. Neurology. 2020 95(4) July 28 PMID: 32554763 PMCID: PMC7455318 Free PMC article https://n.neurology.org/content/95/4/e374 - Dhana K, Franco OH, Ritz EM et al Healthy lifestyle and life expectancy with and without Alzheimer's dementia: population based cohort study. BMJ. 2022 Apr 13;377:e068390 PMID: 35418416
  76. Ehrlich JR, Goldstein J, Swenor BK et al Addition of Vision Impairment to a Life-Course Model of Potentially Modifiable Dementia Risk Factors in the US. JAMA Neurol. Published online April 25, 2022 PMID: 35467745 https://jamanetwork.com/journals/jamaneurology/fullarticle/2791268 - Deal J, Rohas JC Visual Impairment as a Modifiable Risk Factor in Dementia Prevention and Management. JAMA Neurol. Published online April 25, 2022 PMID: 35467705 https://jamanetwork.com/journals/jamaneurology/fullarticle/2791267
  77. Hu HY, Wu BS, Ou YN et al Tea consumption and risk of incident dementia: A prospective cohort study of 377,392 UK Biobank participants. Transl Psychiatry, 2022, 12, 171 PMID: 35474192 PMCID: PMC9042826 Free PMC article
  78. George J Dementia Risk Tied to Antioxidant Levels. Two types of carotenoids linked with less likelihood of developing dementia over time. MedPage Today May 4, 2022 https://www.medpagetoday.com/neurology/dementia/98551 - Beydoun MA, Beydoun AH, Fanelli-Kuczmarski MT et al Association of Serum Antioxidant Vitamins and Carotenoids With Incident Alzheimer Disease and All-Cause Dementia Among US Adults. Neurology May 4, 2022 PMID: 35508396 https://n.neurology.org/content/early/2022/05/04/WNL.0000000000200289
  79. George J Large Share of Alzheimer's, Dementia Cases Tied to 8 Modifiable Risk Factors. Midlife, early-life risk factors now more common, differ by sex, race/ethnicity. MedPage Today May 9, 2022 https://www.medpagetoday.com/neurology/dementia/98615 - Nianogo RA, Rosenwohl-Mack A, Yaffe K et al Risk Factors Associated With Alzheimer Disease and Related Dementias by Sex and Race and Ethnicity in the US. JAMA Neurol. Published online May 9, 2022. PMID: 35532912 https://jamanetwork.com/journals/jamaneurology/article-abstract/2792227
  80. Tin A, Bressler J, Simino J et al Genetic Risk, Midlife Life's Simple 7, and Incident Dementia in the Atherosclerosis Risk in Communities Study. Neurology 2022. May 25. PMID: 35613930 https://n.neurology.org/content/early/2022/05/25/WNL.0000000000200520
  81. Wang RS, Wang BL, Huang YN, Wan TTH The combined effect of physical activity and fruit and vegetable intake on decreasing cognitive decline in older Taiwanese adults. Scientific Reports. 2022 volume 12: June 14 PMID: 35701477 PMCID: PMC9198009 Free PMC article https://www.nature.com/articles/s41598-022-14219-5
  82. Musiek ES, Ju YES Targeting Sleep and Circadian Function in the Prevention of Alzheimer Disease. JAMA Neurol. Published online July 11, 2022. PMID: 35816332 https://jamanetwork.com/journals/jamaneurology/fullarticle/2793873
  83. George J Regular Exercise Program May Stall Cognitive Decline. Trial shows promise for people with mild cognitive impairment. MedPage Today August 3, 2022 https://www.medpagetoday.com/meetingcoverage/aaic/100054
  84. Musiek ES, Ju YES Targeting Sleep and Circadian Function in the Prevention of Alzheimer Disease. JAMA Neurol. 2022;79(9):835-836. https://jamanetwork.com/journals/jamaneurology/fullarticle/2793873
  85. Zhu J et al. Physical and mental activity, disease susceptibility, and risk of dementia: A prospective cohort study based on UK Biobank. Neurology 2022 Jul 27; 99:e799. PMID: 35896434 PMCID: PMC9484730 Free PMC article https://n.neurology.org/content/99/8/e799
  86. Desai RJ, Mahesri M, Lee SB et al No association between initiation of phosphodiesterase-5 inhibitors and risk of incident Alzheimer's disease and related dementia: results from the Drug Repurposing for Effective Alzheimer's Medicines (DREAM) study. Brain Communications. 2022. Oct 4 PMID: 36330433 https://academic.oup.com/braincomms/advance-article/doi/10.1093/braincomms/fcac247/6731685
  87. Glans I, Sonestedt E, Nagga K et al Association Between Dietary Habits in Midlife With Dementia Incidence Over a 20-Year Period. Neurology. 2022 Oct 12:10.1212/WNL.0000000000201336. PMID: 36224029
  88. Yeo BSY, Song HJJMD, Toh EMS et al Association of Hearing Aids and Cochlear Implants With Cognitive Decline and Dementia. A Systematic Review and Meta-analysis. JAMA Neurol. Published online December 5, 2022. PMID: 36469314 https://jamanetwork.com/journals/jamaneurology/fullarticle/2799139 - Denham MW, Weitzman RE, Golub JS Hearing Aids and Cochlear Implants in the Prevention of Cognitive Decline and Dementia - Breaking Through the Silence. JAMA Neurol. Published online December 5, 2022 PMID: 36469311 https://jamanetwork.com/journals/jamaneurology/fullarticle/2799142
  89. George J Their Alzheimer's Disease Didn't Worsen. Why? Case reports find one healthy habit in common. MedPage Today February 3, 2023 https://www.medpagetoday.com/neurology/alzheimersdisease/102961 - Devanand DP, Masurkar AV, Wisniewski T. Vigorous, regular physical exercise may slow disease progression in Alzheimer's disease. Alzheimer's & Dementia. 2023. Feb 3. PMID: 36722738 https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.12946
  90. Ghahremani M, Smith EE, Chen HY et al Vitamin D supplementation and incident dementia: Effects of sex, APOE, and baseline cognitive status. Alzheimer' & Dementia 2023 Mar 1;15(1):e12404. PMID: 36874594 PMCID: PMC9976297 Free PMC article https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/dad2.12404
  91. George J Autopsies Show Relationship Between Alzheimer's Pathology and Diet in Older Adults. Green leafy vegetable intake inversely correlated with pathology in postmortem brain tissue. MedPage Today March 8, 2023 https://www.medpagetoday.com/neurology/alzheimersdisease/103459 - Agarwal P, Leurgans SE, Agrawal S et al Association of Mediterranean-DASH Intervention for Neurodegenerative Delay and Mediterranean Diets With Alzheimer Disease Pathology. Neurology. 2023. March 8. PMID: 36889921 https://n.neurology.org/content/early/2023/03/08/WNL.0000000000207176
  92. George J Dementia Risk and Diet Investigated. Analysis probes multiple studies about the MIND diet approach. MedPage Today May 3, 2023 https://www.medpagetoday.com/neurology/dementia/104321 - Chen H, Dhana K, Huang Y et al Association of the Mediterranean Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) Diet With the Risk of Dementia. JAMA Psychiatry. Published online May 3, 2023 PMID: 37133875 https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2804268
  93. Won J, Nielson KA, Smith JC. Large-Scale Network Connectivity and Cognitive Function Changes After Exercise Training in Older Adults with Intact Cognition and Mild Cognitive Impairment. J Alzheimers Dis Rep. 2023 7(1):399-413 PMID: 37220620 PMCID: PMC10200248 Free PMC article https://content.iospress.com/articles/journal-of-alzheimers-disease-reports/adr220062
  94. Reardon S Does shingles vaccination cut dementia risk? Large study hints at a link. Analysis of nearly 300,000 people finds an association between the shingles jab and a lower rate of dementia - but questions linger. Nature. 2023. June 6 https://www.nature.com/articles/d41586-023-01824-1 - Eyting M et al Causal evidence that herpes zoster vaccination prevents a proportion of dementia cases. MedRxiv. 2023. May 25. https://www.medrxiv.org/content/10.1101/2023.05.23.23290253v1
  95. Swift Yasgur B Internet Use a Modifiable Dementia Risk Factor in Older Adults? Medscape. May 17, 2023 https://www.medscape.com/viewarticle/992111 - Cho G, Betensky RA, Chang VW. Internet usage and the prospective risk of dementia: A population-based cohort study. J Am Geriatr Soc. 2023 PMID: 37132331 https://agsjournals.onlinelibrary.wiley.com/doi/epdf/10.1111/jgs.18394
  96. Daghlas I, Nassan M, Gill D et al Genetically proxied lean mass and risk of Alzheimer's disease: mendelian randomisation study. BMJ Medicine 2023. 2(1) https://bmjmedicine.bmj.com/content/2/1/e000354
  97. Lin FR, Pike JR, Albert MS et al Hearing intervention versus health education control to reduce cognitive decline in older adults with hearing loss in the USA (ACHIEVE): a multicentre, randomised controlled trial. Lancet 2023. July 17. PMID: 37478886 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)01406-X/fulltext
  98. Brooks M Oral Tau Inhibitor Continues to Show Promise in Alzheimer's Medscape. July 21, 2023 https://www.medscape.com/viewarticle/994646
  99. Gauthier S et al. Efficacy and safety of tau-aggregation inhibitor therapy in patients with mild or moderate Alzheimer's disease: A randomised, controlled, double-blind, parallel-arm, phase 3 trial. Lancet 2016 Nov 15; 388:2873. PMID: 27863809 Free PMC Article - Rafii MS. Targeting tau protein in Alzheimer's disease. Lancet 2016 Nov 15; 388:2842 PMID: 27863808
  100. Harwood RH, Goldberg SE, Brand A et al. Promoting Activity, Independence, and Stability in Early Dementia and mild cognitive impairment (PrAISED): randomised controlled trial. BMJ. 2023 Aug 29;382:e074787. PMID: 37643788 PMCID: PMC10463053 Free PMC article. https://www.bmj.com/content/382/bmj-2023-074787
  101. George J Erectile Dysfunction Drugs Tied to Less Alzheimer's Risk. Large U.K. study tracked health records of 270,000 men. MedPage Today February 7, 2024 https://www.medpagetoday.com/neurology/dementia/108626 - Adesuyan M, Jani YH, Alsugeir D et al Phosphodiesterase Type 5 Inhibitors in Men With Erectile Dysfunction and the Risk of Alzheimer Disease. A Cohort Study. Neurology. 2024. Feb 27;102(4):e209131. Epub Feb 7 PMID: 38324745 https://www.neurology.org/doi/10.1212/WNL.0000000000209131
  102. Wang W, Wang Q, Qi X et al Associations of semaglutide with first-time diagnosis of Alzheimer's disease in patients with type 2 diabetes: Target trial emulation using nationwide real-world data in the US. Alzheimers Dement. 2024 Oct 24. PMID: 39445596