Major or Mild Frontotemporal Neurocognitive Disorder

  • Ana Hategan
  • James A. Bourgeois
  • Calvin H. Hirsch


Frontotemporal neurocognitive disorder (NCD) constitutes the leading form of NCD in patients younger than age 65. It can lead to the behavioral-variant frontotemporal NCD or pure cognitive changes, as in primary progressive aphasia. Although patients with behavioral variant have relatively preserved memory and language function, they display major deficits in insight, judgment, working memory, and executive functions. Patients with primary progressive aphasia most commonly have difficulty with naming and/or word finding. Other common presenting symptoms include hesitancy or nonfluent speech production, motor speech abnormalities (such as dysarthria), impaired language comprehension, and repetition. Primary progressive aphasia has been divided into three separate subsyndromes: nonfluent/agrammatic, semantic, and logopenic variants. The clinical presentation is determined by the anatomical areas involved and the pathognomonic atrophy. An accurate clinical diagnosis helps to predict probable neuropathology, which is essential for targeted treatment planning. In this chapter, we review the primary symptomatology of these frontotemporal NCD variants, diagnostic and treatment challenges, and comorbidity complexity that needs to be considered in differential diagnosis.


Frontotemporal neurocognitive disorder Frontotemporal dementia Behavioral variant Primary progressive aphasia Nonfluent/agrammatic Semantic Logopenic 


  1. 1.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington: American Psychiatric Publishing; 2013. p. 614–5.CrossRefGoogle Scholar
  2. 2.
    World Health Organisation. ICD-10 Classifications of Mental and Behavioural Disorder. Clinical descriptions and diagnostic guidelines. Geneva: World Health Organization; 1992.Google Scholar
  3. 3.
    Kirshner HS. Frontotemporal dementia and primary progressive aphasia, a review. Neuropsychiatr Dis Treat. 2014;10:1045–55.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Seltman RE, Matthews BR. Frontotemporal lobar degeneration: epidemiology, pathology, diagnosis and management. CNS Drugs. 2012;26(10):841–70.CrossRefPubMedGoogle Scholar
  5. 5.
    Knopman DS, Roberts RO. Estimating the number of persons with frontotemporal lobar degeneration in the US population. J Mol Neurosci. 2011;45:330–5.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Baborie A, Griffiths TD, Jaros E, et al. Frontotemporal dementia in elderly individuals. Arch Neurol. 2012;69(8):1052–60.CrossRefPubMedGoogle Scholar
  7. 7.
    Onyike CU, Diehl-Schmid J. The epidemiology of frontotemporal dementia. Int Rev Psychiatry. 2013;25(2):130–7.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Bird TD, Knopman D, van Swieten J, et al. Epidemiology and genetics of frontotemporal dementia/Pick’s disease. Ann Neurol. 2003;54(5, Suppl):S29–31.CrossRefPubMedGoogle Scholar
  9. 9.
    Goldman JS, Farmer J, Wood EM, et al. Comparison of family histories in FTLD subtypes and related taupathies. Neurology. 2005;65:1817–9.CrossRefPubMedGoogle Scholar
  10. 10.
    Rademakers R, Eriksen JL, Baker M, et al. Common variation in the miR-659 binding-site of GRN is a major risk factor for TDP43-positive frontotemporal dementia. Hum Mol Genet. 2008;17:3631–42.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Rascovsky K, Hodges JR, Knopman D, et al. Sensitivity of revised diagnostic criteria for the behavioral variant of frontotemporal dementia. Brain. 2011;134:2456–77.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Gorno-Tempini ML, Hillis AE, Weintraub S, et al. Classification of primary progressive aphasia and its variants. Neurology. 2011;76:1006–14.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Mesulam MM, Wieneke C, Thompson C, Rogalski E, Weintraub S. Quantitative classification of primary progressive aphasia at early and mild impairment stages. Brain. 2012;135(Pt 5):1537–53.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Freitas S, Simões MR, Alves L, et al. Montreal Cognitive Assessment (MoCA): validation study for frontotemporal dementia. J Geriatr Psychiatry Neurol. 2012;25(3):146–54.Google Scholar
  15. 15.
    Dubois B, Slachevsky A, Litvan I, Pillon B. The FAB: a frontal assessment battery at bedside. Neurology. 2000;55(11):1621–6.CrossRefPubMedGoogle Scholar
  16. 16.
    Manoochehri M, Huey ED. Diagnosis and management of behavioral issues in frontotemporal dementia. Curr Neurol Neurosci Rep. 2012;12(5):528–36.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    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
  18. 18.
    Fastenau PS, Denburg NL, Mauer BA. Parallel short forms for the Boston Naming Test: psychometric properties and norms for older adults. J Clin Exp Neuropsychol. 1998;20(6):828–34.CrossRefPubMedGoogle Scholar
  19. 19.
    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
  20. 20.
    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
  21. 21.
    Burnett J, Dyer CB, Naik AD. Convergent validation of the Kohlman Evaluation of Living Skills as a screening tool of older adults’ ability to live safely and independently in the community. Arch Phys Med Rehabil. 2009;90(11):1948–52.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Hornberger M, Piguet O, Graham AJ, Nestor PJ, Hodges JR. How preserved is episodic memory in behavioral variant frontotemporal dementia? Neurology. 2010;74(6):472–9.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Hutchinson AD, Mathias JL. Neuropsychological deficits in frontotemporal dementia and Alzheimer’s disease: a meta-analytic review. J Neurol Neurosurg Psychiatry. 2007;78(9):917–28.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Hogan DB, Bailey P, Carswell A, Clarke B, Cohen C, Forbes D, et al. Management of mild to moderate Alzheimer’s disease and dementia. Alzheimers Dement. 2007;3(4):355–84.CrossRefPubMedGoogle Scholar
  25. 25.
    Whitwell JL, Weigand SD, Boeve BF, et al. Neuroimaging signatures of frontotemporal dementia genetics: C9ORF72, tau, progranulin and sporadics. Brain. 2012;135(3):794–806.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Warren JD, Rohrer JD, Rossor MN. Frontotemporal dementia. BMJ. 2013;347:f4827.
  27. 27.
    Jicha GA, Nelson PT. Management of frontotemporal dementia: targeting symptom management in such a heterogeneous disease requires a wide range of therapeutic options. Neurodegener Dis Manag. 2011;1(2):141–56.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Lopez OL, Gonzalez MP, Becker JT, Reynolds CF, Sudilovsky A, DeKosky ST. Symptoms of depression and psychosis in Alzheimer’s disease and frontotemporal dementia. Neuropsychiatry Neuropsychol Behav Neurol. 1996;9:154–61.Google Scholar
  29. 29.
    Grossman M. The non-fluent/agrammatic variant of primary progressive aphasia. Lancet Neurol. 2012;11(6):545–55.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Nardell M, Tampi RR. Pharmacological treatments for frontotemporal dementias: a systematic review of randomized controlled trials. Am J Alzheimers Dis Other Demen. 2014;29(2):123–32.CrossRefPubMedGoogle Scholar
  31. 31.
    Ikeda M, Tanabe H, Horino T, et al. Care for patients with Pick’s disease—by using their preserved procedural memory. Seishin Shinkeigaku Zasshi. 1995;97:179–92.PubMedGoogle Scholar
  32. 32.
    Merrilees J. A model for management of behavioral symptoms in frontotemporal lobar degeneration. Alzheimer Dis Assoc Disord. 2007;21(4):S64–9.CrossRefPubMedGoogle Scholar
  33. 33.
    Brett L, Traynor V, Stapley P. Effects of physical exercise on health and well-being of individuals living with a dementia in nursing homes: a systematic review. J Am Med Dir Assoc. 2016;17(2):104–16.CrossRefPubMedGoogle Scholar
  34. 34.
    Portugal Mda G, Marinho V, Laks J. Pharmacological treatment of frontotemporal lobar degeneration: systematic review. Rev Bras Psiquiatr. 2011;33(1):81–90.CrossRefPubMedGoogle Scholar
  35. 35.
    Mendez MF, Shapira JS, McMurtray A, Licht E. Preliminary findings: behavioral worsening on donepezil in patients with frontotemporal dementia. Am J Geriatr Psychiatry. 2007;15(1):84–7.Google Scholar
  36. 36.
    Inouye SK, van Dyck CH, Alessi CA, et al. Clarifying confusion: the confusion assessment method. A new method for detection of delirium. Ann Intern Med. 1990;11:941–8.CrossRefGoogle Scholar
  37. 37.
    Hategan A, Bourgeois JA, Saperson K, Chiu S. The chief psychiatric complaints. In: Hategan A, Bourgeois JA, Hirsch CH, editors. On-call geriatric psychiatry: handbook of principles and practice. Cham: Springer; 2016.CrossRefGoogle Scholar
  38. 38.
    Wylie MA, Shnall A, Onyike CU, Huey ED. Management of frontotemporal dementia in mental health and multidisciplinary settings. Int Rev Psychiatry. 2013;25(2):230–6.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Chow TW, Binns MA, Cummings JL, et al. Apathy symptom profile and behavioral associations in frontotemporal dementia vs. Alzheimer’s disease. Arch Neurol. 2009;66(7):888–93.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Padala PR, Burke WJ, Bhatia SC, Petty F. Treatment of apathy with methylphenidate. J Neuropsychiatry Clin Neurosci. 2007;19(1):81–3.CrossRefPubMedGoogle Scholar
  41. 41.
    Landes AM, Sperry SD, Strauss ME, Geldmacher DS. Apathy in Alzheimer’s disease. J Am Geriatr Soc. 2001;49(12):1700–7.CrossRefPubMedGoogle Scholar
  42. 42.
    Mendez MF, Fras IA, Kremen SA, Tsai PH. False reports from patients with frontotemporal dementia: delusions or confabulations? Behav Neurol. 2011;24(3):237–44.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Alladi S, Xuereb J, Bak T, et al. Focal cortical presentations of Alzheimer’s disease. Brain. 2007;130:2636–45.CrossRefPubMedGoogle Scholar
  44. 44.
    Budson AE, Solomon PR. New diagnostic criteria for Alzheimer’s disease and mild cognitive impairment for the practical neurologist. Pract Neurol. 2012;12(2):88–96.CrossRefPubMedGoogle Scholar
  45. 45.
    Keable A, Fenna K, Yuen HM, et al. Deposition of amyloid β in the walls of human leptomeningeal arteries in relation to perivascular drainage pathways in cerebral amyloid angiopathy. Biochim Biophys Acta. 2016;1862(5):1037–46.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Schott JM, Warren JD. Alzheimer’s disease: mimics and chameleons. Pract Neurol. 2012;12(6):358–66.CrossRefPubMedGoogle Scholar
  47. 47.
    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
  48. 48.
    Reus VI, Fochtmann LJ, Eyler AE, et al. APA’s practice guideline on the use of antipsychotics to treat agitation or psychosis in patients with dementia. Am J Psychiatry. 2016;173(5):543–6.CrossRefPubMedGoogle Scholar
  49. 49.
    Bak TH. Motor neuron disease and frontotemporal dementia: one, two, or three diseases? Ann Indian Acad Neurol. 2010;13(Suppl2):S81–8.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Hodges J. Familial frontotemporal dementia and amyotrophic lateral sclerosis associated with the C9ORF72 hexanucleotide repeat. Brain. 2012;135(3):652–5. CrossRefPubMedGoogle Scholar
  51. 51.
    Mesulam M, Wieneke C, Rogalski E, Cobia D, Thompson C, Weintraub S. Quantitative template for subtyping primary progressive aphasia. Arch Neurol. 2009;66(12):1545–51.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Reed DA, Johnson NA, Thompson C, Weintraub S, Mesulam MM. A clinical trial of bromocriptine for treatment of primary progressive aphasia. Ann Neurol. 2004;56(5):750.CrossRefPubMedGoogle Scholar
  53. 53.
    Effects of Tolcapone on Frontotemporal Dementia. Available at Accessed 19 Feb 2017.
  54. 54.
    Dolder CR, Davis LN, McKinsey J. Use of psychostimulants in patients with dementia. Ann Pharmacother. 2010;44(10):1624–32.CrossRefPubMedGoogle Scholar
  55. 55.
    Jesso S, Morlog D, Ross S, et al. The effects of oxytocin on social cognition and behaviour in frontotemporal dementia. Brain. 2011;134:2493–501.CrossRefPubMedGoogle Scholar
  56. 56.
    Finger EC, MacKinley J, Blair M, et al. Oxytocin for frontotemporal dementia: a randomized dose-finding study of safety and tolerability. Neurology. 2015;84(2):174–81.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Liljegren M, Naasan G, Temlett J, et al. Criminal behavior in frontotemporal dementia and Alzheimer disease. JAMA Neurol. 2015;72(3):295–300.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Ana Hategan
    • 1
  • James A. Bourgeois
    • 2
  • Calvin H. Hirsch
    • 3
  1. 1.Department of Psychiatry and Behavioural NeurosciencesMcMaster UniversityHamiltonCanada
  2. 2.Baylor Scott and White Department of PsychiatryTexas A&M University College of MedicineTempleUSA
  3. 3.Division of General MedicineUniversity of California Davis Medical CenterSacramentoUSA

Personalised recommendations