Alzheimer's disease natural history, complications and prognosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2]


Alzheimer's disease (AD) is a slow-progressing condition that involves complications such as the inability to take care of oneself. If left untreated, Alzheimer's disease progresses from pre-clinical stage to advanced dementia. Common complications of Alzheimer's disease include anosmia, bedsores, psychosis, malnutrition and dehydration. There is no cure for Alzheimer's disease currently and the treatment focuses on symptomatic management of the disease.

Natural History

If left untreated, Alzheimer's disease (AD) may progress through three stages:[1]

  • (i) Preclinical stage:
  • (II) Mild cognitive impairment (MCI) :
    • MCI denotes the period during which there is observable evidence of cognitive impairment, often also reported by an informant; however, the impairment is not enough to limit daily activities
  • (III) Alzheimer's disease dementia:
    • The transition or prodromal stage between normal ageing and dementia or mild cognitive impairment (MCI) is a heterogeneous entity.
    • Advanced dementia may display the following features:
      • Becoming unaware of the time and place
      • Difficulty recognizing relatives and friends
      • Increased need for assisted self-care
      • Difficulty walking
      • Behavioural changes that may escalate and include aggression


Potential complications of Alzheimer's disease include:[2][3][4]


  • Individual prognosis is difficult to assess due to the variability of the duration of the disease. AD develops for an indeterminate period of time before becoming fully apparent, and it can progress undiagnosed for years
  • The early stages of Alzheimer's disease are most difficult to diagnose. A definitive diagnosis is usually made once cognitive impairment compromises everyday activities, although the patient may still be living independently
  • People with Alzheimer's disease progress from mild cognitive problems, such as memory loss, through increasing stages of cognitive and non-cognitive disturbances, eliminating any possibility of independent living[3]
  • Life expectancy of the population with the disease is reduced[5][6][7]
  • The mean life expectancy following diagnosis is approximately seven years[8]
  • Fewer than 3% of patients live more than fourteen years[8]
  • Disease features significantly associated with reduced survival are an increased severity of cognitive impairment, decreased functional level, history of falls, and disturbances in the neurological examination
  • Other coincident diseases such as heart problems, diabetes, or history of alcohol abuse are also related with shortened survival[6][9][10]
  • While the earlier the age of onset the higher the total survival years, life expectancy is particularly reduced when compared to the healthy population among those who are younger[7]
  • Men have a less favorable survival prognosis than women[8][11]
  • Pneumonia and dehydration are the most frequent immediate causes of death, while cancer is a less frequent cause of death than in the general population.[5][11]


  1. Tarawneh R, Holtzman DM (2012). "The clinical problem of symptomatic Alzheimer disease and mild cognitive impairment". Cold Spring Harb Perspect Med. 2 (5): a006148. doi:10.1101/cshperspect.a006148. PMC 3331682. PMID 22553492.
  2. Kukull WA, Brenner DE, Speck CE, Nochlin D, Bowen J, McCormick W, Teri L, Pfanschmidt ML, Larson EB (1994). "Causes of death associated with Alzheimer disease: variation by level of cognitive impairment before death". J Am Geriatr Soc. 42 (7): 723–6. PMID 8014346.
  3. 3.0 3.1 Förstl H, Kurz A (1999). "Clinical features of Alzheimer's disease". Eur Arch Psychiatry Clin Neurosci. 249 (6): 288–90. PMID 10653284.
  4. Devanand DP (1997). "Behavioral complications and their treatment in Alzheimer's disease". Geriatrics. 52 Suppl 2: S37–9. PMID 9307585.
  5. 5.0 5.1 Mölsä PK, Marttila RJ, Rinne UK. "Survival and cause of death in Alzheimer's disease and multi-infarct dementia". Acta Neurologica Scandinavica. 74 (2): 103–7. PMID 3776457. |access-date= requires |url= (help)
  6. 6.0 6.1 Bowen JD, Malter AD, Sheppard L; et al. "Predictors of mortality in patients diagnosed with probable Alzheimer's disease". Neurology. 47 (2): 433–9. PMID 8757016.
  7. 7.0 7.1 Dodge HH, Shen C, Pandav R, DeKosky ST, Ganguli M. "Functional transitions and active life expectancy associated with Alzheimer disease". Arch. Neurol. 60 (2): 253–9. PMID 12580712.
  8. 8.0 8.1 8.2 Mölsä PK, Marttila RJ, Rinne UK. "Long-term survival and predictors of mortality in Alzheimer's disease and multi-infarct dementia". Acta Neurologica Scandinavica. 91 (3): 159–64. PMID 7793228. |access-date= requires |url= (help)
  9. Larson EB, Shadlen MF, Wang L; et al. "Survival after initial diagnosis of Alzheimer disease". Ann. Intern. Med. 140 (7): 501–9. PMID 15068977.
  10. Jagger C, Clarke M, Stone A. "Predictors of survival with Alzheimer's disease: a community-based study". Psychol Med. 25 (1): 171–7. PMID 7792352.
  11. 11.0 11.1 Ganguli M, Dodge HH, Shen C, Pandav RS, DeKosky ST. "Alzheimer disease and mortality: a 15-year epidemiological study". Arch. Neurol. 62 (5): 779–84. doi:10.1001/archneur.62.5.779. PMID 15883266.

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