eMedicine Specialties > Neurology > Behavioral Neurology and Dementia

Pick Disease

Author: Anna M Barrett, MD, Associate Professor of Physical Medicine and Rehabilitation and Neurology and Neurosciences, University of Medicine and Dentistry of New Jersey, New Jersey Medical School; Director, Stroke Rehabilitation Research Program, Kessler Medical Rehabilitation Research and Education Center
Contributor Information and Disclosures

Updated: Jun 18, 2008

Introduction

Background

Pick disease (named after Arnold Pick) is a progressive dementia defined by clinical and pathologic criteria. Unlike Alzheimer disease, which typically presents with impairment of recent memory associated with entorhinal cortex and hippocampal dysfunction, Pick disease typically affects the frontal and/or anterolateral temporal lobes. First described in 1892, with the defining pathologic characteristics first reported by Alois Alzheimer in 1911, Pick disease is now considered by some to be part of a "complex" of neurodegenerative disorders with similar or related histopathologic and clinical features.1,2

Nomenclature history

Frontotemporal dementia (of which Pick disease is an example) is a broader term including Pick disease. Frontal lobe dementia is a term signifying neuropsychological features localizing to the frontal lobes. Clinically, Pick disease may be identical or very similar to frontal lobe degeneration.3

Some cases diagnosed premorbidly as Pick disease are shown pathologically to be progressive subcortical gliosis.4 Other cases may be diagnosed pathologically as dementia lacking distinctive histopathology.5 A clinical/genetic nosology includes frontotemporal dementia linked to chromosome 17.6 Primary progressive aphasia is a focal atrophy syndrome that may be associated with Pick, Alzheimer, or other pathology; clinically the deficit appears restricted to the frontal and/or temporal lobes.7

In a recent clinicopathological series, only 5% of patients with clinically diagnosed frontotemporal dementia had classical Pick disease with Pick bodies at postmortem evaluation.8

Pathophysiology

Pick disease is defined pathologically by severe atrophy, neuronal loss, and gliosis. Classified as a tauopathy, Pick disease is always accompanied by the occurrence of tau-positive inclusions.9 Swollen (ballooned) neurons (Pick cells) and argentophilic neuronal inclusions known as Pick bodies10,11 disproportionally affect the frontal and temporal cortical regions.

Images of these abnormal findings can be viewed online at Internet Pathology Laboratory, University of Utah, CNS Degenerative Diseases.

Frequency

United States

Frontotemporal dementias as a group are the fourth most common cause of dementia. In most parts of the United States, among patients younger than 60 years, the frontotemporal dementias are the first or second most common cause of dementia. In patients older than 60 years, the incidence and prevalence of Alzheimer disease begins to take off and Alzheimer disease becomes by far the most prevalent form of dementia.8

Pick disease is sometimes used to refer to the clinical phenotype of the frontotemporal dementias. This group of disorders has a variety of pathological substrates, the most prevalent is frontotemporal lobar degeneration with ubiquitin inclusions. Pick disease itself (as defined by the presence of tau-positive, silver staining, cytoplasmic inclusions) accounted for only 5% of all cases of frontotemporal dementias in a recent pathological series.8

International

Familial forms of Pick disease may occur more frequently in Europe (particularly in Scandinavian nations). In a recent study in the Netherlands, the prevalence was only 28 per 100,000 persons.12

Mortality/Morbidity

  • The disorder is progressive and invariably leads to increasing disability. The disease runs a shorter course than Alzheimer disease, on average about 6 years.13,14
  • In some individuals whose main symptoms are a disturbance of speech and language (primary progressive aphasia), the clinical course can be slow. The patient's ability to function at home may be spared for 10 or more years after onset.

Race

  • Familial forms of Pick-complex dementias, linked to chromosome arm 17q, may be particularly common in people of Scandinavian origin/descent.
  • It may represent as many as 17% of dementias in these populations.

Sex

More men than women may be affected.13,15

Age

  • Pick disease occurs in a younger age group than dementia of the Alzheimer type.
  • Peak incidence occurs in individuals aged 55-65 years, and in most patients, Pick disease often presents when younger than 70 years.

Clinical

History

  • The onset of behavioral and cognitive dysfunction in individuals with Pick disease is insidious.
  • The primary impairment in cognition normally does not involve an abnormal level of consciousness or distractibility. Such a finding is more consistent with an attentional dementia16 or a confusional state and/or dementia.
  • Clinical course during the first 2 years is as follows:
    • Psychiatric abnormalities that seem to respect the pattern of the classic frontal lobe syndromes are present.17
      • Patients with orbitofrontal dysfunction become aggressive and socially inappropriate. They may steal or demonstrate obsessive or repetitive stereotyped behaviors.
      • Patients with dorsomedial or dorsolateral frontal dysfunction may demonstrate a lack of concern, apathy, or decreased spontaneity.
      • Patients may be depressed early in the disease.
      • These mood changes can predate amnesia.
    • Speech and language abnormalities often begin early and progress rapidly.
      • Patients usually have relatively little limb apraxia and/or visuospatial dysfunction, thus distinguishing them from patients with diffuse bihemispheric impairment.
      • Even memory impairment is relatively less severe than speech/language and behavioral changes.
    • Incontinence can occur early. In contrast, continence generally is preserved in mild-to-moderate Alzheimer disease.
    • Parkinsonism, with its concomitant history of rigidity and gait impairment, can occur. Severe parkinsonism suggests an alternate diagnosis such as corticobasal ganglionic degeneration, diffuse Lewy body disease, or progressive supranuclear palsy.

Physical

The general physical examination often shows the patient to be unkempt at an earlier stage than in comparably impaired patients with Alzheimer disease.

  • Abnormal spontaneous behaviors observed during examination may include the following:
    • Witzelsucht or inappropriate jocularity
    • Echolalia (repeating the examiner's words), echopraxia (imitating the examiner's gestures)18,19 , and other disinhibited approach or utilization behaviors
  • General neurologic examination may include some of the following abnormalities:
    • Primitive reflexes such as grasp, suck, and snout (not palmomental reflex, which is often present in healthy individuals20 )
    • Akinesia, plastic rigidity, or paratonia on motor examination21
    • Resting tremor (uncommon; its presence suggests Parkinson disease or a Parkinson-plus syndrome)
  • Mental status/neuropsychological examination may reveal the following:
    • Verbal output that is often nonfluent
      • Most patients have difficulty in naming common objects or pictures (anomia).
      • Spontaneous speech can be sparse yet fluent in character, with preserved grammar (logopenia).
    • Perseveration (cognitive and motor; see Media file 1)
    • Relatively preserved visuospatial and visual orientation skills

Causes

  • The specific cause of Pick disease is unknown.
  • In families with an inherited frontal lobe dementia (some of which pathologically or clinically were indistinguishable from Pick disease), linkage to markers on band 17q21-22 coding tau protein has been reported 22,6 as have presenilin-1 mutations 14q21.23,24
    • These familial disorders are heterogenous in different family members.
    • Some members may present primarily with amyotrophy, others with primary supranuclear gaze palsy, Parkinsonism, schizophrenialike thought disorder, or progressive aphasia and/or apraxia.

More on Pick Disease

Overview: Pick Disease
Differential Diagnoses & Workup: Pick Disease
Treatment & Medication: Pick Disease
Follow-up: Pick Disease
Multimedia: Pick Disease
References
Further Reading
[ CLOSE WINDOW ]

References

  1. Kertesz A, Hudson L, Mackenzie IR, Munoz DG. The pathology and nosology of primary progressive aphasia. Neurology. Nov 1994;44(11):2065-72. [Medline].

  2. Kertesz A. Pick Complex: an integrative approach to frontotemporal dementia: primary progressive aphasia, corticobasal degeneration, and progressive supranuclear palsy. Neurologist. Nov 2003;9(6):311-7. [Medline].

  3. Miller BL, Ikonte C, Ponton M, Levy M, Boone K, Darby A, et al. A study of the Lund-Manchester research criteria for frontotemporal dementia: clinical and single-photon emission CT correlations. Neurology. Apr 1997;48(4):937-42. [Medline].

  4. Neumann MA, Cohn R. Progressive subcortical gliosis, a rare form of presenile dementia. Brain. Jun 1967;90(2):405-18. [Medline].

  5. Knopman DS, Mastri AR, Frey WH 2nd, Sung JH, Rustan T. Dementia lacking distinctive histologic features: a common non- Alzheimer degenerative dementia. Neurology. Feb 1990;40(2):251-6. [Medline].

  6. Foster NL, Wilhelmsen K, Sima AA, Jones MZ, D'Amato CJ, Gilman S. Frontotemporal dementia and parkinsonism linked to chromosome 17: a consensus conference. Conference Participants. Ann Neurol. Jun 1997;41(6):706-15. [Medline].

  7. Weintraub S, Rubin NP, Mesulam MM. Primary progressive aphasia. Longitudinal course, neuropsychological profile, and language features. Arch Neurol. Dec 1990;47(12):1329-35. [Medline].

  8. Graff-Radford NR, Woodruff BK. Frontotemporal dementia. Semin Neurol. Feb 2007;27(1):48-57. [Medline].

  9. Forman MS, Farmer J, Johnson JK, Clark CM, Arnold SE, Coslett HB, et al. Frontotemporal dementia: clinicopathological correlations. Ann Neurol. Jun 2006;59(6):952-62. [Medline].

  10. Jellinger KA. Neuropathological criteria for Pick disease and frontotemporal lobe dementia. In: Cruz-Sanchez et al, eds. Neuropathological Diagnostic Criteria. Amsterdam: IOS Press; 1995:35-54.

  11. Jackson M, Lowe J. The new neuropathology of degenerative frontotemporal dementias. Acta Neuropathol (Berl). 1996;91(2):127-34. [Medline].

  12. Stevens M, van Duijn CM, Kamphorst W, de Knijff P, Heutink P, van Gool WA, et al. Familial aggregation in frontotemporal dementia. Neurology. Jun 1998;50(6):1541-5. [Medline].

  13. Hodges JR, Davies R, Xuereb J, Kril J, Halliday G. Survival in frontotemporal dementia. Neurology. Aug 12 2003;61(3):349-54. [Medline].

  14. Rascovsky K, Salmon DP, Lipton AM, Leverenz JB, DeCarli C, Jagust WJ, et al. Rate of progression differs in frontotemporal dementia and Alzheimer disease. Neurology. Aug 9 2005;65(3):397-403. [Medline].

  15. Ratnavalli E, Brayne C, Dawson K, Hodges JR. The prevalence of frontotemporal dementia. Neurology. Jun 11 2002;58(11):1615-21. [Medline].

  16. Nadeau SE. Multi-infarct dementia, subcortical dementia, and hydrocephalus. South Med J. May 1991;84(5 Suppl 1):S41-52. [Medline].

  17. Gregory CA, Hodges JR. Frontotemporal dementia: use of consensus criteria and prevalence of psychiatric features. Neuropsychiatry Neuropsychol Behav Neurol. 1996;9(3):145-153.

  18. Lhermitte F. 'Utilization behaviour' and its relation to lesions of the frontal lobes. Brain. Jun 1983;106 (Pt 2):237-55. [Medline].

  19. Shimomura T, Mori E. Obstinate imitation behaviour in differentiation of frontotemporal dementia from Alzheimer's disease. Lancet. Aug 22 1998;352(9128):623-4. [Medline].

  20. Sjogren M, Wallin A, Edman A. Symptomatological characteristics distinguish between frontotemporal dementia and vascular dementia with a dominant frontal lobe syndrome. Int J Geriatr Psychiatry. Jun 1997;12(6):656-61. [Medline].

  21. Beversdorf DQ, Heilman KM. Facilitory paratonia and frontal lobe functioning. Neurology. Oct 1998;51(4):968-71. [Medline].

  22. Lynch T, Sano M, Marder KS, Bell KL, Foster NL, Defendini RF, et al. Clinical characteristics of a family with chromosome 17-linked disinhibition-dementia-parkinsonism-amyotrophy complex. Neurology. Oct 1994;44(10):1878-84. [Medline].

  23. Rogaeva EA, Fafel KC, Song YQ, Medeiros H, Sato C, Liang Y, et al. Screening for PS1 mutations in a referral-based series of AD cases: 21 novel mutations. Neurology. Aug 28 2001;57(4):621-5. [Medline].

  24. Raux G, Gantier R, Thomas-Anterion C, Boulliat J, Verpillat P, Hannequin D, et al. Dementia with prominent frontotemporal features associated with L113P presenilin 1 mutation. Neurology. Nov 28 2000;55(10):1577-8. [Medline].

  25. Grossman M, Farmer J, Leight S, Work M, Moore P, Van Deerlin V. Cerebrospinal fluid profile in frontotemporal dementia and Alzheimer's disease. Ann Neurol. May 2005;57(5):721-9. [Medline].

  26. Verbeek MM, Pijnenburg YA, Schoonenboom NS, Kremer BP, Scheltens P. Cerebrospinal fluid tau levels in frontotemporal dementia. Ann Neurol. Oct 2005;58(4):656-7; author reply 657. [Medline].

  27. Scott KR and Barrett AM. Dementia Syndromes: Evaluation and Treatment. Expert Review of Neurotherapeutics. 2007;7:407-422.

  28. Litvan I. Therapy and management of frontal lobe dementia patients. Neurology. Jun 2001;56(11 Suppl 4):S41-5. [Medline].

  29. Swartz JR, Miller BL, Lesser IM, Schuman S. Frontotemporal dementia: treatment response to serotonin selective reuptake inhibitors. J Clin Psychiatry. May 1997;58(5):212-6. [Medline].

  30. Tanaka Y, Miyazaki M, Albert ML. Effects of increased cholinergic activity on naming in aphasia. Lancet. Jul 12 1997;350(9071):116-7. [Medline].

  31. Kertesz A, Blair M, Davidson W. A Pilot Study of the Safety and Efficacy of Galantamine for Pick Complex/Frontotemporal Dementia (FTD). Abstracts of the 130th Annual Meeting of the American Neurological Association. 2005;61.

  32. Lampl Y, Sadeh M, Lorberboym M. Efficacy of acetylcholinesterase inhibitors in frontotemporal dementia. Ann Pharmacother. Nov 2004;38(11):1967-8. [Medline].

  33. Imamura T, Takanashi M, Hattori N, Fujimori M, Yamashita H, Ishii K, et al. Bromocriptine treatment for perseveration in demented patients. Alzheimer Dis Assoc Disord. Jun 1998;12(2):109-13. [Medline].

  34. McDowell S, Whyte J, D''Esposito M. Differential effect of a dopaminergic agonist on prefrontal function in traumatic brain injury patients. Brain. Jun 1998;121 (Pt 6):1155-64. [Medline].

  35. Drayton SJ, Davies K, Steinberg M, Leroi I, Rosenblatt A, Lyketsos CG. Amantadine for executive dysfunction syndrome in patients with dementia. Psychosomatics. May-Jun 2004;45(3):205-9. [Medline].

  36. Steinbart EJ, Smith CO, Poorkaj P, Bird TD. Impact of DNA testing for early-onset familial Alzheimer disease and frontotemporal dementia. Arch Neurol. Nov 2001;58(11):1828-31. [Medline].

  37. Coleman LW, Digre KB, Stephenson GM, Townsend JJ. Autopsy-proven, sporadic pick disease with onset at age 25 years. Arch Neurol. May 2002;59(5):856-9. [Medline].

  38. Freedman M. Frontotemporal dementia: recommendations for therapeutic studies, designs, and approaches. Can J Neurol Sci. Mar 2007;34 Suppl 1:S118-24. [Medline].

  39. Ghika-Schmid F, Ghika J, Regli F, Dworak N, Bogousslavsky J, Stadler C, et al. Hashimoto's myoclonic encephalopathy: an underdiagnosed treatable condition?. Mov Disord. Sep 1996;11(5):555-62. [Medline].

  40. Kertesz A, Munoz DG. Pick's Disease and Pick Complex. NY: Wiley-Liss: 1998.

  41. Kilgard MP, Merzenich MM. Cortical map reorganization enabled by nucleus basalis activity. Science. Mar 13 1998;279(5357):1714-8. [Medline].

  42. Lebert F, Stekke W, Hasenbroekx C, Pasquier F. Frontotemporal dementia: A randomised, controlled trial with trazodone. In: Dementia & Geriatric Cognitive Disorders. Vol 17(4). Jun 2004: 355-59.

  43. Litvan I, Agid Y, Sastry N, Jankovic J, Wenning GK, Goetz CG, et al. What are the obstacles for an accurate clinical diagnosis of Pick's disease? A clinicopathologic study. Neurology. Jul 1997;49(1):62-9. [Medline].

  44. Neary D, Snowden JS, Gustafson L. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology. Dec 1998;51(6):1546-54. [Medline].

  45. Perry RJ, Miller BL. Behavior and treatment in frontotemporal dementia. Neurology. Jun 2001;56(11 Suppl 4):S46-51. [Medline].

  46. Pick A. Ueber die Beziehungen der senilen Hirnatrophie zur Aphasie. Pragmatische Medizinsche Wehnschrift. 1892;17:165-167.

  47. Roman GC, Tatemichi TK, Erkinjuntti T, Cummings JL, Masdeu JC, Garcia JH, et al. Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology. Feb 1993;43(2):250-60. [Medline].

[ CLOSE WINDOW ]

Further Reading

See Medscape CME activity Alzheimer's Disease and Dementia.

[ CLOSE WINDOW ]

Keywords

dementia lacking distinctive histopathology, frontal lobe degeneration, frontal lobe dementia, frontotemporal dementia, FTD, frontotemporal dementia linked to chromosome 17, primary progressive aphasia, progressive subcortical gliosis, Pick disease, Pick's disease, progressive dementia

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Anna M Barrett, MD, Associate Professor of Physical Medicine and Rehabilitation and Neurology and Neurosciences, University of Medicine and Dentistry of New Jersey, New Jersey Medical School; Director, Stroke Rehabilitation Research Program, Kessler Medical Rehabilitation Research and Education Center
Anna M Barrett, MD is a member of the following medical societies: American Academy of Neurology, American Society of Neurorehabilitation, and International Neuropsychological Society
Disclosure: Nothing to disclose.

Medical Editor

Daniel H Jacobs, MD, Associate Professor of Neurology, University of Central Florida College of Medicine
Daniel H Jacobs, MD is a member of the following medical societies: American Academy of Neurology, American Society of Neurorehabilitation, and Society for Neuroscience
Disclosure: Teva Pharmaceutical Grant/research funds Consulting; Biogen Idex Grant/research funds Independent contractor; Serono EMD Royalty Speaking and teaching; Pfizer Royalty Speaking and teaching; Berlex Royalty Speaking and teaching

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Richard J Caselli, MD, Professor, Department of Neurology, Mayo Medical School, Rochester, MN; Chair, Department of Neurology, Mayo Clinic of Scottsdale
Richard J Caselli, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Medical Association, American Neurological Association, and Sigma Xi
Disclosure: Nothing to disclose.

CME Editor

Matthew J Baker, MD, Consulting Staff, Collier Neurologic Specialists, Naples Community Hospital
Matthew J Baker, MD is a member of the following medical societies: American Academy of Neurology
Disclosure: Nothing to disclose.

Chief Editor

Howard A Crystal, MD, Professor, Departments of Neurology and Pathology, State University of New York Downstate; Consulting Staff, Department of Neurology, University Hospital and Kings County Hospital Center
Howard A Crystal, MD is a member of the following medical societies: American Academy of Neurology and American Neurological Association
Disclosure: Pfizer Honoraria Speaking and teaching; Myriad Honoraria Consulting

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.