Common Major and Mild Neurocognitive Disorders: Alzheimer Disease, Frontotemporal, Lewy Body, and Vascular Types

  • Ana Hategan
  • James A. Bourgeois
  • Tracy Cheng
  • Julie Young


Major and mild neurocognitive disorders are often managed by physicians in multiple specialties including primary practice, psychiatry, geriatric medicine, and neurology. Major and mild neurocognitive disorders are classified according to the known etiological or pathological entities underlying the cognitive impairment. For certain types, the diagnosis depends on the presence of a potentially causative entity, such as Parkinson disease, other parkinsonism, vascular disease, or traumatic brain injury. For other etiologies, such as Alzheimer disease, frontotemporal lobar degeneration, and Lewy body disease, the diagnosis is based primarily on the cognitive, behavioral, and functional symptoms. The differentiation among these multiple types of neurocognitive disorders becomes more evident at the level of major neurocognitive disorder than at the level of mild neurocognitive disorder, but characteristic features can be present at the mild level as well. For many types, international expert groups have developed specialized consensus criteria based on clinicopathological correlation with underlying brain pathology. This section reviews the diagnostic guidelines, clinical presentations, differential diagnosis, and treatment considerations of the four main types: neurocognitive disorder due to Alzheimer disease, frontotemporal neurocognitive disorder, neurocognitive disorder due to Lewy bodies, and vascular neurocognitive disorder.


Major or mild neurocognitive disorder Dementia Cognitive impairment Amnestic phenotype Alzheimer disease Neurocognitive disorder due to Alzheimer disease Frontotemporal lobar degeneration Lewy body disease Vascular neurocognitive disorder Atypical Alzheimer disease 


  1. 1.
    Roberts RO, Geda YE, Knopman DS, et al. The incidence of MCI differs by subtype and is higher in men: the Mayo Clinic Study of Aging. Neurology. 2012;78(5):342–51.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Ismail Z, Smith EE, Geda Y, et al. Neuropsychiatric symptoms as early manifestations of emergent dementia: provisional diagnostic criteria for mild behavioral impairment. Alzheimers Dement. 2016;12(2):195–202.CrossRefPubMedGoogle Scholar
  3. 3.
    Ismail Z, Agüera-Ortiz L, Brodaty H, et al. The mild behavioral impairment checklist (MBI-C): a rating scale for neuropsychiatric symptoms in pre-dementia populations. J Alzheimers Dis. 2017;56(3):929–38.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Woolley JD, Khan BK, Murthy NK, Miller BL, Rankin KP. The diagnostic challenge of psychiatric symptoms in neurodegenerative disease; rates of and risk factors for prior psychiatric diagnosis in patients with early neurodegenerative disease. J Clin Psychiatry. 2011;72(2):126–33.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Taragano FE, Allegri RF, Krupitzki H, et al. Mild behavioral impairment and risk of dementia: a prospective cohort study of 358 patients. J Clin Psychiatry. 2009;70:584–92.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Rosenberg PB, Mielke MM, Appleby BS, Oh ES, Geda YE, Lyketsos CG. The association of neuropsychiatric symptoms in MCI with incident dementia and Alzheimer’s disease. Am J Geriatr Psychiatry. 2013;21(7):685–95. Scholar
  7. 7.
    Peters M, Rosenberg P, Steinberg M, et al. Neuropsychiatric symptoms as risk factors for progression from CIND to dementia: the Cache County Study. Am J Geriatr Psychiatry. 2013;21(11):1116–24. Scholar
  8. 8.
    Pink A, Stokin GB, Bartley MM, et al. Neuropsychiatric symptoms, APOE ε4, and the risk of incident dementia: a population-based study. Neurology. 2015;84(9):935–43.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Petersen RC. Early diagnosis of Alzheimer’s disease: is MCI too late? Curr Alzheimer Res. 2009;6(4):324–30.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Köhler S, Thomas AJ, Barnett NA, O’Brien JT. The pattern and course of cognitive impairment in late-life depression. Psychol Med. 2010;40(4):591–602.CrossRefPubMedGoogle Scholar
  11. 11.
    Singh-Manoux A, Dugravot A, Fournier A, Abell J, Ebmeier K, Kivimäki M, Sabia S. Trajectories of depressive symptoms before diagnosis of dementia: a 28-year follow-up study. JAMA Psychiatry. 2017;74(7):712–8.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Mirza SS, de Bruijn RF, Direk N, et al. Depressive symptoms predict incident dementia during short- but not long-term follow-up period. Alzheimers Dement. 2014;10(5 Suppl):S323–9.e1.CrossRefPubMedGoogle Scholar
  13. 13.
    Almeida OP, Hankey GJ, Yeap BB, Golledge J, Flicker L. Depression as a modifiable factor to decrease the risk of dementia. Transl Psychiatry. 2017;7(5):e1117.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington: American Psychiatric Publishing; 2013.CrossRefGoogle Scholar
  15. 15.
    Clark LR, Stricker NH, Libon DJ, et al. Yes/No versus forced-choice recognition memory in mild cognitive impairment and Alzheimer’s disease: patterns of impairment and associations with dementia severity. Clin Neuropsychol. 2012;26(7):1201–16.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Budson AE, Solomon PR. New diagnostic criteria for Alzheimer’s disease and mild cognitive impairment for the practical neurologist. Pract Neurol. 2012;12:88–96.CrossRefPubMedGoogle Scholar
  17. 17.
    Dubois B, Feldman HH, Jacova C, et al. Advancing research diagnostic criteria for Alzheimer’s disease: the IWG-2 criteria. Lancet Neurol. 2014;13(6):614–29.CrossRefPubMedGoogle Scholar
  18. 18.
    Molin P, Rockwood K. The new criteria for Alzheimer’s disease—implications for geriatricians. Can Geriatr J. 2016;19(2):66–73.PubMedPubMedCentralGoogle Scholar
  19. 19.
    Hategan A, Xiong GL. Major or mild neurocognitive disorder due to Alzheimer disease. In: Hategan, et al., editors. Geriatric psychiatry: a case-based textbook. Springer; 2018, p. 369–401.Google Scholar
  20. 20.
    Patterson C, Feightner JW, Garcia A, Hsiung G-YR, MacKnight C, Sadovnick AD. Diagnosis and treatment of dementia: 1. Risk assessment and primary prevention of Alzheimer disease. CMAJ. 2008;178(5):548–56.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Rahayel S, Frasnelli J, Joubert S. The effect of Alzheimer’s disease and Parkinson’s disease on olfaction: a meta-analysis. Behav Brain Res. 2012;231(1):60–74.CrossRefPubMedGoogle Scholar
  22. 22.
    Velayudhan L, Pritchard M, Powell JF, Proitsi P, Lovestone S. Smell identification function as a severity and progression marker in Alzheimer’s disease. Int Psychogeriatr. 2013;25(7):1157–66.CrossRefPubMedGoogle Scholar
  23. 23.
    Wehling EI, Lundervold AJ, Nordin S, Wollschlaeger D. Longitudinal changes in familiarity, free and cued odor identification, and edibility judgments for odors in aging individuals. Chem Senses. 2016;41(2):155–61.PubMedGoogle Scholar
  24. 24.
    Lafaille-Magnan ME, Poirier J, Etienne P, et al. PREVENT-AD Research Group. Odor identification as a biomarker of preclinical AD in older adults at risk. Neurology. 2017;89(4):327–35.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Growdon ME, Schultz AP, Dagley AS, et al. Odor identification and Alzheimer disease biomarkers in clinically normal elderly. Neurology. 2015;84(21):2153–60.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Doty RL, Shaman P, Dann M. Development of the University of Pennsylvania Smell Identification Test: a standardized microencapsulated test of olfactory function. Physiol Behav. 1984;32(3):489–502.CrossRefPubMedGoogle Scholar
  27. 27.
    Doty RL, Frye RE, Agrawal U. Internal consistency reliability of the fractionated and whole University of Pennsylvania Smell Identification Test. Percept Psychophys. 1989;45(5):381–4.CrossRefPubMedGoogle Scholar
  28. 28.
    Da Silva MNM, Millington RS, Bridge H, James-Galton M, Plant GT. Visual dysfunction in posterior cortical atrophy. Front Neurol. 2017;8:389. Scholar
  29. 29.
    Benson DF, Davis RJ, Snyder BD. Posterior cortical atrophy. Arch Neurol. 1988;45(7):789–93.CrossRefPubMedGoogle Scholar
  30. 30.
    Tang-Wai DF, Graff-Radford NR, Boeve BF, et al. Clinical, genetic, and neuropathologic characteristics of posterior cortical atrophy. Neurology. 2004;63(7):1168–74.CrossRefPubMedGoogle Scholar
  31. 31.
    Caine D. Posterior cortical atrophy: a review of literature. Neurocase. 2004;10(5):382–5.CrossRefPubMedGoogle Scholar
  32. 32.
    Schmidt C, Wolff M, Weitz M, Bartlau T, Korth C, Zerr I. Rapidly progressive Alzheimer disease. Arch Neurol. 2011;68(9):1124–30.CrossRefPubMedGoogle Scholar
  33. 33.
    Schott JM, Warren JD. Alzheimer’s disease: mimics and chameleons. Pract Neurol. 2012;12(6):358–66.CrossRefPubMedGoogle Scholar
  34. 34.
    Blennow K, de Leon MJ, Zetterberg H. Alzheimer’s disease. Lancet. 2006;368(9533):387–403.CrossRefPubMedGoogle Scholar
  35. 35.
    Rogan S, Lippa CF. Alzheimer’s disease and other dementias: a review. Am J Alzheimers Dis Other Demen. 2002;17:11–7.CrossRefPubMedGoogle Scholar
  36. 36.
    Trzepacz PT, Hochstetler H, Wang S, Walker B, Saykin AJ, Alzheimer’s Disease Neuroimaging Initiative. Relationship between the Montreal Cognitive Assessment and Mini-mental State Examination for assessment of mild cognitive impairment in older adults. BMC Geriatr. 2015;15:107.–015–0103–3.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Hollis AM, Duncanson H, Kapust LR, Xi PM, O’Connor MG. Validity of the mini-mental state examination and the montreal cognitive assessment in the prediction of driving test outcome. J Am Geriatr Soc. 2015;63(5):988–92.CrossRefPubMedGoogle Scholar
  38. 38.
    Gauthier S, Patterson C, Chertkow H, et al. Recommendations of the 4th Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (CCCDTD4). Can Geriatr J. 2012;15(4):120–6.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Lee L, Molnar F. Driving and dementia: efficient approach to driving safety concerns in family practice. Can Fam Physician. 2017;63(1):27–31.PubMedPubMedCentralGoogle Scholar
  40. 40.
    Roy M, Molnar F. Systematic review of the evidence for Trails B cut-off scores in assessing fitness-to-drive. Can Geriatr J. 2013;16(3):120–42.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Papandonatos GD, Ott BR, Davis JD, Barco PP, Carr DB. The clinical utility of the trail making tests as predictors of driving performance in older adults. J Am Geriatr Soc. 2015;63(11):2358–64.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Marshall GA, Amariglio RE, Sperling RA, Rentz DM. Activities of daily living: where do they fit in the diagnosis of Alzheimer’s disease? Neurodegener Dis Manag. 2012;2(5):483–91.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Livingston G, Sommerlad A, Orgeta V, et al. Dementia prevention, intervention, and care. Lancet. 2017;390(10113):2673–734. pii: S0140-6736(17)31363-6.CrossRefPubMedGoogle Scholar
  44. 44.
    Hsiung GY, Sadovnick AD. Genetics and dementia: risk factors, diagnosis, and management. Alzheimers Dement. 2007;3(4):418–27.CrossRefPubMedGoogle Scholar
  45. 45.
    Campion D, Dumanchin C, Hannequin D, et al. Early-onset autosomal dominant Alzheimer disease: prevalence, genetic heterogeneity, and mutation spectrum. Am J Hum Genet. 1999;65(3):664–70.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Sleegers K, Roks G, Theuns J, et al. Familial clustering and genetic risk for dementia in a genetically isolated Dutch population. Brain. 2004;127(Pt 7):1641–9.CrossRefPubMedGoogle Scholar
  47. 47.
    Rademakers R, Cruts M, Van Broeckhoven C. Genetics of early-onset Alzheimer dementia. Sci World J. 2003;3:497–519.CrossRefGoogle Scholar
  48. 48.
    Cupples LA, Farrer LA, Sadovnick AD, Relkin N, Whitehouse P, Green RC. Estimating risk curves for first-degree relatives of patients with Alzheimer’s disease: the REVEAL study. Genet Med. 2004;6(4):192–6.CrossRefPubMedGoogle Scholar
  49. 49.
    Patterson C, Feightner J, Garcia A, MacKnight C. General risk factors for dementia: a systematic evidence review. Alzheimers Dement. 2007;3(4):341–7.CrossRefPubMedGoogle Scholar
  50. 50.
    National Academies of Sciences, Engineering, and Medicine. Preventing cognitive decline and dementia: a way forward. Washington, DC: The National Academies Press; 2017. Accessed 3 Nov 2017.CrossRefGoogle Scholar
  51. 51.
    Alexopoulos GS, Meyers BS, Young RC, Campbell S, Silbersweig D, Charlson M. ‘Vascular depression’ hypothesis. Arch Gen Psychiatry. 1997;54(10):915–22.CrossRefPubMedGoogle Scholar
  52. 52.
    Aizenstein HJ, Baskys A, Boldrini M, et al. Vascular depression consensus report—a critical update. BMC Med. 2016;14(1):161.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Diniz BS, Butters MA, Albert SM, Dew MA, Reynolds CF 3rd. Late-life depression and risk of vascular dementia and Alzheimer’s disease: systematic review and meta-analysis of community-based cohort studies. Br J Psychiatry. 2013;202(5):329–35.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Gorelick PB, Scuteri A, Black SE, et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2011;42(9):2672–713.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Burhan AM, Moradizadeh M, Marlatt N. Major or mild vascular neurocognitive disorder. In: Hategan, et al., editors. Geriatric psychiatry: a case-based textbook. Springer; 2018, p. 445–66.Google Scholar
  56. 56.
    Olney NT, Spina S, Miller BL. Frontotemporal dementia. Neurol Clin. 2017;35(2):339–74.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Dubois B, Slachevsky A, Litvan I, Pillon B. The FAB: a frontal assessment battery at bedside. Neurology. 2000;55(11):1621–6.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Milan G, Lamenza F, Iavarone A, et al. Frontal Behavioural Inventory in the differential diagnosis of dementia. Acta Neurol Scand. 2008;117(4):260–5.CrossRefPubMedGoogle Scholar
  59. 59.
    De Deyn PP, Engelborghs S, Saerens J, et al. The Middelheim Frontality Score: a behavioural assessment scale that discriminates frontotemporal dementia from Alzheimer’s disease. Int J Geriatr Psychiatry. 2005;20:70–9.CrossRefPubMedGoogle Scholar
  60. 60.
    Bora E, Velakoulis D, Walterfang M. Meta-analysis of facial emotion recognition in behavioral variant frontotemporal dementia: comparison with Alzheimer disease and healthy controls. J Geriatr Psychiatry Neurol. 2016;29(4):205–11.CrossRefPubMedGoogle Scholar
  61. 61.
    Nasreddine ZS, Phillips NA, Bédirian V, et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005;53(4):695–9.CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    McKeith IG, Galasko D, Kosaka K, et al. Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology. 1996;47:1113–24.CrossRefPubMedGoogle Scholar
  63. 63.
    McKeith IG, Dickson DW, Lowe J, et al. Diagnosis and management of dementia with Lewy bodies third report of the DLB consortium. Neurology. 2005;65(12):1863–72.CrossRefPubMedGoogle Scholar
  64. 64.
    Kales HC, Gitlin LN, Lyketsos CG. Assessment and management of behavioral and psychological symptoms of dementia. BMJ. 2015;350:h369.CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Massoud F, Leger G. Pharmacological treatment of Alzheimer disease. Can J Psychiatry. 2011;56(10):579–88.CrossRefPubMedGoogle Scholar
  66. 66.
    Reisberg B, Ferris SH, de Leon MJ, Crook T. The Global Deterioration Scale for assessment of primary degenerative dementia. Am J Psychiatry. 1982;139(9):1136–9.CrossRefPubMedGoogle Scholar
  67. 67.
    Yorkshire and the Humber Clinical Networks. The assessment of cardiac status before prescribing acetyl cholinesterase inhibitors for dementia. First published April 2016. Reviewed October 2017. Accessed 8 Oct 2017.
  68. 68.
    Rowland JP, Rigby J, Harper AC, Rowland R. Cardiovascular monitoring with acetylcholinesterase inhibitors: a clinical protocol. Adv Psychiatr Treat. 2007;13(3):178–84.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Ana Hategan
    • 1
  • James A. Bourgeois
    • 2
    • 3
  • Tracy Cheng
    • 4
  • Julie Young
    • 5
  1. 1.Department of Psychiatry and Behavioural NeurosciencesMcMaster UniversityHamiltonCanada
  2. 2.Department of PsychiatryBaylor Scott and White Health Central Texas DivisionDallasUSA
  3. 3.Department of PsychiatryTexas A&M University Health Science Center, College of MedicineTempleCanada
  4. 4.St. Joseph’s Healthcare Hamilton, McMaster UniversityHamiltonUSA
  5. 5.Mercy San Juan Medical CenterFarmingtonUSA

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