Alzheimer’s Disease: Clinical Aspects and Treatments

  • Laura GhezziEmail author


Alzheimer’s disease (AD) is an age-dependent neurodegenerative disorder and the most common cause of dementia with aging. The early stages of AD are characterized by short-term memory loss. Once the disease progresses, patients experience difficulties in sense of direction, oral communication, calculation, ability to learn, and cognitive thinking. In addition, patients may develop language deficits, depression, aggressive behavior, and psychosis during the late stages, and eventually they need total care from caregivers. Currently diagnosis of AD is based either on clinical presentation or on biological biomarkers, in particular radiological and cerebrospinal fluid Amyloid, tau and phospho-tau levels. Here, the main clinical aspects and diagnostic tools for AD are revised; atypical AD presentations and possible diagnostic pitfalls are also discussed.


Alzheimer’s disease Biomarkers Neurodegeneration 


  1. 1.
    Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, et al. Global prevalence of dementia: a Delphi consensus study. Lancet. 2005;366:2112–7.PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Reitz C, Brayne C, Mayeux R. Epidemiology of Alzheimer disease. Nat Rev Neurol. 2011;7(3):137–52.PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Ritchie K, Lovestone S. The dementias. Lancet. 2002;360:1759–66.PubMedCrossRefGoogle Scholar
  4. 4.
    Galimberti D, Scarpini E, Ghezzi L. Immunotherapy against amyloid pathology in Alzheimer’s disease. J Neurol Sci. 2013;333(1–2):50–4.PubMedCrossRefGoogle Scholar
  5. 5.
    Apostolova LG, Cummings JL. Neuropsychiatric manifestations in mild cognitive impairment: a systematic review of the literature. Dement Geriatr Cogn Disord. 2008;25:115–26.PubMedCrossRefGoogle Scholar
  6. 6.
    Arnaiz E, Almkvist O. Neuropsychological features of mild cognitive impairment and preclinical Alzheimer’s disease. Acta Neurol Scand. 2003;179(Suppl):34–41.CrossRefGoogle Scholar
  7. 7.
    Fitzpatrick AL, Kuller LH, Lopez OL, Kawas CH, Jagust W. Survival following dementia onset: Alzheimer’s disease and vascular dementia. J Neurol Sci. 2005;229:43–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Dubois B, Feldman HH, Jacova C, Cummings JL, Dekosky ST, Barberger-Gateau P, et al. Revising the definition of Alzheimer’s disease: a new lexicon. Lancet Neurol. 2010;9(11):1118–27.PubMedCrossRefGoogle Scholar
  9. 9.
    Petersen RC, Roberts RO, Knopman DS, et al. Mild cognitive impairment: ten years later. Arch Neurol. 2009;66(12):1447–55.PubMedCentralPubMedGoogle Scholar
  10. 10.
    McKhann G, Drachman DA, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer’s disease report of the NINCDS–ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s disease. Neurology. 1984;34:939–44.PubMedCrossRefGoogle Scholar
  11. 11.
    Dubois B, Feldman HH, Jacova C, Dekosky ST, Barberger-Gateau P, Cummings J, et al. Research criteria for the diagnosis of Alzheimer’s disease: revising the NINCDS-ADRDA criteria. Lancet Neurol. 2007;6:734–46.PubMedCrossRefGoogle Scholar
  12. 12.
    Hort J, O’Brien JT, Gainotti G, Pirttili T, Popescu BO, Rektorova I, et al. EFNS guidelines for the diagnosis and management of Alzheimer’s disease. Eur J Neurol. 2010;17(10):1236–48.PubMedCrossRefGoogle Scholar
  13. 13.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders (IV-TR). 4th ed, text revised. Washington, DC: American Psychiatric Association; 2000.Google Scholar
  14. 14.
    Bartus RT, Dean III RL, Beer B, Lippa AS. The cholinergic hypothesis of geriatric memory dysfunction. Science. 1982;217:408–14.PubMedCrossRefGoogle Scholar
  15. 15.
    Knowles J. Donepezil in Alzheimer’s disease: an evidence-based review of its impact on clinical and economic outcomes. Core Evid. 2006;1(3):195–219.PubMedCentralPubMedGoogle Scholar
  16. 16.
    Courtney C, Farrell D, Gray R, Hills R, Lynch L, Sellwood E, et al. AD2000 Collaborative Group. Long-term donepezil treatment in 565 patients with Alzheimer’s disease (AD2000): randomised double-blind trial. Lancet. 2004;363:2105–15.PubMedCrossRefGoogle Scholar
  17. 17.
    Birks J, Evans JG, Iakovidou V, Tsolaki M. Rivastigmine for Alzheimer’s disease. Cochrane Database Syst Rev. 2009;2, CD001191.PubMedGoogle Scholar
  18. 18.
    Qaseem A, Snow V, Cross Jr TJ, Forciea MA, Hopkins Jr R, Shekelle P, et al. Current pharmacologic treatment of dementia: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2008;148:370–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Crutch SJ, Lehmann M, Schott JM, Rabinovici GD, Rossor MN, Fox NC. Posterior cortical atrophy. Lancet Neurol. 2012;11:170–8.PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Mendez MF, Ghajarania M, Perryman KM. Posterior cortical atrophy: clinical characteristics and differences compared to Alzheimer’s disease. Dement Geriatr Cogn Disord. 2002;14:33–40.PubMedCrossRefGoogle Scholar
  21. 21.
    Tang-Wai DF, Graff-Radford NR, Boeve BF, Dickson DW, Parisi JE, Crook R, et al. Clinical, genetic, and neuropathologic characteristics of posterior cortical atrophy. Neurology. 2004;63:1168–74.PubMedCrossRefGoogle Scholar
  22. 22.
    Gorno-Tempini ML, Hillis AE, Weintraub S, Kertesz A, Mendez M, Cappa SF, et al. Classification of primary progressive aphasia and its variants. Neurology. 2011;76(11):1006–14.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag London 2014

Authors and Affiliations

  1. 1.Neurology Unit, Department of Pathophysiology and TransplantationUniversity of Milan, Fondazione Cà Granda, IRCCS Ospedale PoliclinicoMilanItaly

Personalised recommendations