Alzheimer's disease (AD)

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Introduction

Classifcation:

Etiology

Epidemiology

  • 4 million persons in USA affected
    • 4th leading cause of death; 46,000 deaths/year
    • deaths due to Alzheimer's disease rose 71% from 2000-2013[29] & from 3.7% in 2009 to 4.7% in 2021[46]
    • deaths due to Alzheimer disease 36.9 per 100,000 in 1st quarter of 2017[34]
  • 35% of dementia pure AD; 15% mixed AD/vascular dementia
  • 5% age 65-74; 15-25% age 75-84; 35-50% > 85 years of age
  • prevalence of 42% by age 82 years[33]
  • 70% of women & 17% of men > age 90 (ADAMS study, 2006)
  • prevalence of neuropathologically-defined AD may be substantially higher than clinically-defined AD (2x)[8]
  • < 1/2 of patients or their caregivers with Alzheimer's disease acknowledge being told of the diagnosis[28]
  • costliest disease to society
    • cost of care for patients with Alzheimer's disease & other types of dementia in 2015 are estimated at $226 billion[29]

Pathology

see pathology of Alzheimer's disease

Genetics

see genetics of Alzheimer's disease

History

Clinical manifestations

grossly, function is lost in Alzheimer's disease in a reversal of the order that it was acquired during development.[22]

also see dementia for general features

* may also be present with early-onset AD

Diagnostic criteria

Laboratory

Diagnostic procedures

Radiology

Complications

Differential diagnosis

Management

Notes

More general terms

More specific terms

Additional terms

References

  1. ↑ Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 1053-55
  2. ↑ Jump up to: 2.0 2.1 2.2 2.3 2.4 2.5 Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 16, 17. American College of Physicians, Philadelphia 1998, 2006, 2012, 2015
    Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  3. ↑ Prescriber's Letter 7(2):10, Feb. 2000
  4. ↑ Role of cholinergic therapy in treatment of Alzheimer's disease & other dementias, Farlow, M et al, 2001
  5. ↑ Journal Watch 21(15):125, 2001 Kivipelto M, Helkala EL, Laakso MP, Hanninen T, Hallikainen M, Alhainen K, Soininen H, Tuomilehto J, Nissinen A. Midlife vascular risk factors and Alzheimer's disease in later life: longitudinal, population based study. BMJ. 2001 Jun 16;322(7300):1447-51. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11408299
  6. ↑ UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
  7. ↑ Jump up to: 7.0 7.1 McPherson, S. Director, Neuropsychology Laboratory UCLA ADRC
  8. ↑ Jump up to: 8.0 8.1 Polvikoski et al, Prevalence of Alzhmeimer' disease in very elderly people: a prospective neuropathological study Neurology 56:1690, 2001 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11425935
  9. ↑ Selkoe D. Alzheimer's disease: genes, proteins, and therapy. Physiological Reviews 81:741, 2001 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11274343
  10. ↑ Journal Watch 22(7):56-57, 2002 Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D'Agostino RB, Wilson PW, Wolf PA. Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. N Engl J Med. 2002 Feb 14;346(7):476-83. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11844848
  11. ↑ Prescriber's Letter 9(4):22 2002
  12. ↑ Journal Watch 23(12):93, 2003 Tan ZS, Seshadri S, Beiser A, Wilson PW, Kiel DP, Tocco M, D'Agostino RB, Wolf PA. Plasma total cholesterol level as a risk factor for Alzheimer disease: the Framingham Study. Arch Intern Med. 2003 May 12;163(9):1053-7. PMID: https://www.ncbi.nlm.nih.gov/pubmed/12742802
  13. ↑ Jump up to: 13.0 13.1 Journal Watch 24(10):80-81, 2004 Larson EB, Shadlen MF, Wang L, McCormick WC, Bowen JD, Teri L, Kukull WA. Survival after initial diagnosis of Alzheimer disease. Ann Intern Med. 2004 Apr 6;140(7):501-9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15068977
  14. ↑ Smith GE et al, A plateau in pre-Alzheimer memory decline: Evidence for compensatory mechanisms. Neurology 2007, 69:133 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17620545
  15. ↑ Jump up to: 15.0 15.1 Olichney JM et al, Cognitive decline is faster in Lewy body variant than in Alzheimer's disease. Neurology 1998, 51:351 PMID: https://www.ncbi.nlm.nih.gov/pubmed/9710002
  16. ↑ Jump up to: 16.0 16.1 Riemersma-van der Lek RF et al, Effect of bright light and melatonin on cognitive and noncognitive function in elderly residents of group care facilities: A randomized controlled trial. JAMA 2008, 299:2642 PMID: https://www.ncbi.nlm.nih.gov/pubmed/18544724
  17. ↑ Jump up to: 17.0 17.1 17.2 17.3 17.4 17.5 17.6 17.7 Geriatric Review Syllabus, 7th edition Parada JT et al (eds) American Geriatrics Society, 2010
    Geriatric Review Syllabus, 9th edition (GRS9) Medinal-Walpole A, Pacala JT, Porter JF (eds) American Geriatrics Society, 2016
  18. ↑ Alzheimer Disease International World Alzheimer Report 2013. Journey of Caring. An analysis of long-term care for dementia. http://www.alz.co.uk/research/WorldAlzheimerReport2013.pdf
  19. ↑ Jump up to: 19.0 19.1 Vos SJB et al. Preclinical Alzheimer's disease and its outcome: A longitudinal cohort study. Lancet Neurol 2013 Oct; 12:957 PMID: https://www.ncbi.nlm.nih.gov/pubmed/2401237
  20. ↑ Montine TJ et al. Recommendations of the Alzheimer's Disease-Related Dementias Conference. Neurology 2014 Jul 30; PMID: https://www.ncbi.nlm.nih.gov/pubmed/25080517
  21. ↑ Jump up to: 21.0 21.1 21.2 Studies Suggest People with Early AD Can Still Learn http://www.alzheimers.org/nianews/nianews67.html
  22. ↑ Jump up to: 22.0 22.1 Arendt T. Neurodegeneration and plasticity. Int J Dev Neurosci. 2004 Nov;22(7):507-14. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15465280
  23. ↑ Jump up to: 23.0 23.1 Jorm AF, Masaki KH, Davis DG, Hardman J, Nelson J, Markesbery WR, Petrovitch H, Ross GW, White LR. Memory complaints in nondemented men predict future pathologic diagnosis of Alzheimer disease. Neurology. 2004 Nov 23;63(10):1960-1. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15557525
  24. ↑ Jump up to: 24.0 24.1 24.2 Liguori C et al. Orexinergic system dysregulation, sleep impairment, and cognitive decline in Alzheimer disease. JAMA Neurol 2014 Oct 13; PMID: https://www.ncbi.nlm.nih.gov/pubmed/25322206
    Ferini-Strambi L. Possible role of orexin in the pathogenesis of Alzheimer disease. JAMA Neurol 2014 Oct 13 PMID: https://www.ncbi.nlm.nih.gov/pubmed/25317720
  25. ↑ Jump up to: 25.0 25.1 Masters MC et al. "Noncognitive" symptoms of early Alzheimer disease: A longitudinal analysis. Neurology 2015 Jan 14 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25589671 <Internet> http://www.neurology.org/content/early/2015/01/13/WNL.0000000000001238
  26. ↑ Jump up to: 26.0 26.1 Peters ME et al. Neuropsychiatric symptoms as predictors of progression to severe Alzheimer's dementia and death: The Cache County Dementia Progression Study. Am J Psychiatry 2015 Jan 13 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25585033 <Internet> http://psychiatryonline.org/doi/abs/10.1176/appi.ajp.2014.14040480
  27. ↑ Jump up to: 27.0 27.1 N Engl J Med Knowledge+ Question of the Week. March 17, 2015
    Mayeux R. Clinical practice. Early Alzheimer's disease. N Engl J Med 2010 Jun 19; 362:2194. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20558370
    Knopman DS et al. Practice parameter: diagnosis of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2001 May 9; 56:1143 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11342678
  28. ↑ Jump up to: 28.0 28.1 Alzheimer's News, 3/24/15 New Alzheimer's Association report finds less than half of people with Alzheimer's disease say they were told the diagnosis. http://www.alz.org/news_and_events_facts_figs_told_diagnosis.asp
  29. ↑ Jump up to: 29.0 29.1 29.2 U.S. Department of Health and Human Services (HHS) White House Conference on Aging: Combating Alzheimer's and Other Dementias. July 13, 2015 http://www.hhs.gov/news/press/2015pres/07/20150713b.html
  30. ↑ Alzheimers Association 2015 Alzheimer's disease facts and figures The Journal of the Alzheimer's Association. March 2015 11(3):332 http://www.alzheimersanddementia.com/article/S1552-5260%2815%2900058-8/fulltext
  31. ↑ Jump up to: 31.0 31.1 Balsis S, Carpenter BD, Storandt M. Personality change precedes clinical diagnosis of dementia of the Alzheimer type. J Gerontol B Psychol Sci Soc Sci. 2005 Mar;60(2):P98-P101. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15746024
  32. ↑ Jump up to: 32.0 32.1 Mittelman MS, Haley WE, Clay OJ, Roth DL. Improving caregiver well-being delays nursing home placement of patients with Alzheimer disease. Neurology. 2006 Nov 14;67(9):1592-9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17101889
  33. ↑ Jump up to: 33.0 33.1 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: https://www.ncbi.nlm.nih.gov/pubmed/28766695
  34. ↑ Jump up to: 34.0 34.1 Ahmad FB, Bastian B. Quarterly provisional estimates for selected indicators of mortality, 2016-Quarter 2, 2017. National Center for Health Statistics. National Vital Statistics System, Vital Statistics Rapid Release Program. 2017. https://www.cdc.gov/nchs/nvss/vsrr/mortality-dashboard.htm
  35. ↑ Jump up to: 35.0 35.1 Jack CR Jr, Bennett DA, Blennow K et al NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers & Dementia. April 2018, 14(4):535-562 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29653606 <Internet> http://www.alzheimersanddementia.com/article/S1552-5260(18)30072-4/fulltext
    Jack CR Jr, Bennett DA, Blennow K et al A/T/N: An unbiased descriptive classification scheme for Alzheimer disease biomarkers. Neurology. 2016 Aug 2;87(5):539-47. Epub 2016 Jul 1. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27371494 Free PMC Article
  36. ↑ Jump up to: 36.0 36.1 MedPage Today Staff. February 15, 2018 Sea Change for Alzheimer's Drug Development (FDA) Agency may approve drugs for 'preclinical' disease solely on biomarker effects. https://www.medpagetoday.com/neurology/alzheimersdisease/71185
    U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER) Early Alzheimer's Disease: Developing Drugs for Treatment Guidance for Industry. Draft Guidance. February 2018 https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM596728.pdf
  37. ↑ Brooks M. First Alzheimer's Guidelines for Clinical Practice Released. Medscape Medical News. WebMD, Inc. July 23, 2018. https://www.medscape.com/viewarticle/899674
    First Practice Guidelines for Clinical Evaluation of Alzheimer's Disease and Other Dementias for Primary and Specialty Care. Alzheimer's Association. Chicago. July 22, 2018. https://www.alz.org/aaic/releases_2018/AAIC18-Sun-clinical-practice-guidelines.asp
  38. ↑ Jump up to: 38.0 38.1 Stetka B In Alzheimer's Disease, It's Not Always Memory That Goes Medscape - Jul 10, 2020. https://www.medscape.com/viewarticle/933537
  39. ↑ Jump up to: 39.0 39.1 ScienceDaily. Aug 19, 2020 Brain remapping dysfunction causes spatial memory impairment in Alzheimer's disease. A step towards a treatment of wandering behaviors in dementia patients.
  40. ↑ Jump up to: 40.0 40.1 Lutsep HL Fast Five Quiz: Memory Loss and Cognitive Impairment Medscape. April 28, 2021 https://reference.medscape.com/viewarticle/949619
  41. ↑ Jump up to: 41.0 41.1 George J Early Alzheimer's Trajectories May Vary Widely. High heterogeneity could influence clinical trial results, simulation shows. MedPage Today June 4, 2021 https://www.medpagetoday.com/neurology/alzheimersdisease/92934
    Jutten RJ, Sikkes SAM, Van der Flier WM et al Finding treatment effects in Alzheimer trials in the face of disease progression heterogeneity. Neurology 2021. May 31 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34550903 Free PMC article. https://n.neurology.org/content/96/22/e2673
    Buckley RF, Knopman DS Cognitive heterogeneity in Alzheimer clinical trials: harnessing noise to achieve meaningfulness. Neurology 2021. May 31 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34550902 https://n.neurology.org/content/96/22/1017
    Jutten RJ, Sikkes SAM, Amariglio RE Identifying Sensitive Measures of Cognitive Decline at Different Clinical Stages of Alzheimer's Disease. J Int Neuropsychol Soc. 2021 May;27(5):426-438 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33046162 Free PMC article.
  42. ↑ Jump up to: 42.0 42.1 42.2 Schaffert J, LoBue C, Hynan LS et al Predictors of Life Expectancy in Autopsy-Confirmed Alzheimer's Disease. Journal of Alzheimer's Disease 2022;86(1)271-281 PMID: https://www.ncbi.nlm.nih.gov/pubmed/35034898 https://content.iospress.com/articles/journal-of-alzheimers-disease/jad215200
  43. ↑ Jump up to: 43.0 43.1 43.2 Creavin ST et al Clinical judgement by primary care physicians for the diagnosis of all- cause dementia or cognitive impairment in symptomatic people. Cochrane Library. 2022. June 16. PMID: https://www.ncbi.nlm.nih.gov/pubmed/35709018 PMCID: PMC9202995 Free PMC article https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD012558.pub2/full
  44. ↑ Dolphin H, Dyer AH, Morrison L, Shenkin SD, Welsh T, Kennelly SP. New horizons in the diagnosis and management of Alzheimer's Disease in older adults. Age Ageing. 2024 Feb 1;53(2):afae005. PMID: https://www.ncbi.nlm.nih.gov/pubmed/38342754 PMCID: PMC10859247 Free PMC article. Review.
  45. ↑ Jump up to: 45.0 45.1 45.2 45.3 45.4 Atri A, Dickerson BC, Clevenger C et al Alzheimer's Association clinical practice guideline for the Diagnostic Evaluation, Testing, Counseling, and Disclosure of Suspected Alzheimer's Disease and Related Disorders (DETeCD-ADRD): Executive summary of recommendations for primary care. Alzheimers Dement. 2024 Dec 23. PMID: https://www.ncbi.nlm.nih.gov/pubmed/39713942 https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.14333
    Dickerson BC, Atri A, Clevenger C et al The Alzheimer's Association clinical practice guideline for the Diagnostic Evaluation, Testing, Counseling, and Disclosure of Suspected Alzheimer's Disease and Related Disorders (DETeCD-ADRD): Executive summary of recommendations for specialty care. Alzheimers Dement. 2024 Dec 23. PMID: https://www.ncbi.nlm.nih.gov/pubmed/39713957
  46. ↑ Jump up to: 46.0 46.1 CDC National Vital Statistics System. Deaths: Leading Causes for 2021. https://www.cdc.gov/nchs/data/nvsr/nvsr73/nvsr73-04.pdf
  47. ↑ NINDS Alzheimer's Disease Information Page https://www.ninds.nih.gov/Disorders/All-Disorders/Alzheimers-Disease-Information-Page
  48. ↑ ADEAR: Alzheimer's Disease Fact Sheet http://adear.niapublications.org/pubs/adfact.html

Patient information

Alzheimer's disease patient information

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