AUTHOR AND EDITOR INFORMATION

Section 1 of 13  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Acknowledgments
• Multimedia
• References

INTRODUCTION

Section 2 of 13  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Acknowledgments
• Multimedia
• References

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 bodies^{10, 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

Section 3 of 13  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Acknowledgments
• Multimedia
• References

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.

DIFFERENTIALS

Section 4 of 13  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Acknowledgments
• Multimedia
• References

Other Problems to be Considered

Adult polyglucosan body disease
Chronic meningitis
Hashimoto encephalopathy
Hemochromatosis (controversial)
Neurosarcoidosis
Other frontal lobe tumors
Dementia in Parkinson disease
Dementia in progressive supranuclear palsy
Creutzfeldt-Jakob disease
Olfactory groove meningioma
Tertiary neurosyphilis
Sequential bilateral thalamic strokes

WORKUP

Section 5 of 13  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Acknowledgments
• Multimedia
• References

Lab Studies

• As for any dementia evaluation, initial workup includes a vitamin B-12 level, thyroid function studies, antinuclear antibodies¹⁶, and possibly fluorescent treponemal antibody testing for syphilis. The American Academy of Neurology in their practice guidelines for the evaluation of dementia indicate that the incidence of syphilis as a cause of dementia is so low in the typical American patient that routine screening for syphilis is not necessary.⁵ However, index of suspicion should be high in patients with HIV and in patients from geographic regions where the prevalence of syphilis is high.
• • If prominent inattention is observed, the patient may have a toxic and/or metabolic encephalopathy rather than a true dementia. In such patients, obtain a urine toxicology screen, serum chemistry panel, complete blood count and differential count, liver function tests, ammonia level, and erythrocyte sedimentation rate.
  • If the patient has parkinsonism or a movement disorder, the following tests can be added:
  • • Ceruloplasmin (serum) and serum or urinary copper to exclude Wilson disease
    • Manual peripheral blood smear for acanthocytes
    • Genetic testing is not commercially available for screening for mutations associated with frontotemporal dementias, but may be obtained from research laboratories.
• Second-line workup includes cerebrospinal fluid examination (for chronic meningitis or elevated pressure) and HIV serology.
• • As Alzheimer disease is almost always in the differential diagnosis, cerebrospinal fluid analysis for Abeta1-42 may be indicated (see Procedures).
  • If prominent inattention is present, obtain a metastatic cancer workup, electroencephalogram (EEG), and Lyme disease serology.
  • Consider consultation by a social worker, geriatric case manager, or nurse practitioner.
• Third-line workup includes the following:
• • Obtain evaluation by neuropsychologist, behavioral neurologist, or neuropsychiatrist.
  • Consider and discuss brain biopsy in very select patients.

Imaging Studies

• Brain computed tomography (CT) or magnetic resonance imaging (MRI)
• • Order CT scan if MRI is contraindicated for the patient (eg, the patient has a pacemaker or metallic ocular implants).
  • If not contraindicated, order an MRI. Metastatic lesions and subcortical infarction (eg, caudate, thalamic) can easily be missed on CT scan. Frontal lobe atrophy out of proportion to atrophy in other brain regions can sometimes be detected. Some patients with frontotemporal dementia may have increased T2 signal in frontal lobe white matter, especially on FLAIR sequences.⁸
• Functional brain image (eg, single-photon emission computed tomography [SPECT] scan) or physiologic imaging with positron emission tomography (PET scan) may be appropriate in some patients.
• • In some patients with relatively isolated social-behavioral dysfunction, employers or others may require evidence of a medical disorder. Such patients may appear cognitively normal on objective neuropsychological tests, yet may be unable to function due to acquired brain disease.
  • A SPECT scan may demonstrate relative hypometabolism in frontal and temporal areas (when other neuroimaging is normal), thus providing evidence of brain dysfunction.

Procedures

• Lumbar puncture (cerebrospinal fluid examination) may be appropriate. Some memory disorder specialists perform this examination in every patient with frontal lobe or atypical dementia.
• • Check pressure, cultures, cryptococcal antigen, and large-volume tap for cytology or acid-fast bacillus (AFB) if the clinical situation warrants such testing. Elevated levels of phosphorylated tau protein and low levels of Abeta1-42 are found in CSF of patients with Alzheimer disease. Data on levels of tau and beta-amyloid in CSF from patients with frontotemporal dementias has been inconsistent.^{25, 26} Markers for Creutzfeldt-Jakob disease, CNS Whipple disease, progressive multifocal leukoencephalopathy (PML), and herpes encephalitis also can be ordered from the spinal fluid.
  • Brain biopsy may be considered in exceptional circumstances if the diagnosis is in doubt and a treatment depends on the results. Occasionally, spinal fluid markers can obviate the need for a brain biopsy, even in these patients. Some of the factors mitigating for a brain biopsy include the following:
    • If diagnosis is in doubt (eg, faced with second- or third-line autoimmune therapy for neurosarcoidosis)
    • If a familial frontotemporal dementia is suspected
    • If the family desires
    • If treatment with significant adverse effects is being considered

Histologic Findings

See Pathophysiology.

TREATMENT

Section 6 of 13  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Acknowledgments
• Multimedia
• References

Medical Care

• On first evaluation, discontinue medications that can impair memory or cause confusion (eg, anticholinergic drugs, sedatives, benzodiazepines).
• • Consider empiric treatment for symptoms that are consistent with depression and/or sleep disorders.
  • Consider administering thiamine empirically (100-300 mg IV/IM).
  • As dysfunction of cortical cholinergic systems does not occur in Pick disease, use of acetyltransferase inhibitors makes less sense than it does in the treatment of Alzheimer disease or dementia with Lewy bodies. Nonetheless, class II studies have suggested they might be of some benefit.
  • The few published studies assessing the efficacy of memantine in frontotemporal dementias have had equivocal results.
  • Some research has indicated that drugs that modulate the serotonergic system may be helpful for treating behavioral symptoms in frontotemporal dementias.
• On second evaluation, treat any systemic conditions that were identified and discuss performing a lumbar puncture and HIV testing with the patient and family.
• • If prominent inattention is present and epilepsy is considered, consider further second-line workup, including EEG or an empiric trial of an anticonvulsant.
  • Consider referral to a case manager, geriatric nurse practitioner, or other dementia resource person or group for social-family issues.
• On third evaluation, perform a lumbar puncture, treat any conditions identified on testing, and consider consultation with a behavioral neurologist or geriatric psychiatrist.
• • Share dementia information and reading material with the family.
  • Consider a brain biopsy if the diagnosis is in doubt or if substantial benefit results for the patient and/or family with a tissue diagnosis.

Consultations

• Geriatric or psychiatric case manager (social worker) or nurse practitioner
• Neuropsychologist, behavioral neurologist, geriatric psychiatrist, or neuropsychiatrist
• For patients with progressive aphasia, speech pathologist for family and patient education and, in rare cases, referral for a computerized communication assistive device

Diet

High sugar content foods may need to be restricted in some patients with carbohydrate craving, which may indicate Klüver-Bucy syndrome.

Activity

No restrictions on activity are necessary.

MEDICATION

Section 7 of 13  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Acknowledgments
• Multimedia
• References

Unfortunately, no available drugs arrest or reverse the condition. Currently, practitioners use a combination of neuroprotective and symptomatic therapies. Research studies suggest that a number of agents may actively inhibit neurodegeneration in animals, cellular models, or other disorders (see Scott and Barrett, 2007 for a review²⁷), but none of these drugs are currently standard for this disease.

Drug Category: Vitamins

Cofactors necessary in metabolic reactions and essential for normal DNA synthesis, with some vitamins providing antioxidant effects.

Drug Category: Antidepressants

Although SSRIs have been suggested for behavioral symptoms in these patients (eg, crave sweets, hypersexual)^{28, 29}, exercise care in using these agents in patients with parkinsonism, who may develop adverse effects of akathisia or dyskinesias.

Agents with mixed noradrenergic and serotonergic action may be helpful in treating patients with depression and frontal cognitive disorder.

Drug Category: Cholinergic agents

Cholinergic therapy may be helpful for patients with aphasia³⁰, and preliminary studies indicate cholinesterase inhibitors may be useful for aphasia in Pick disease³¹ and for other dementia-related symptoms in these patients³².

Drug Category: Dopaminergic agents

Although these agents may worsen sexual or behavioral disinhibition, they may improve executive function, perseveration, and abulia.^{33, 34, 35}

FOLLOW-UP

Section 8 of 13  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Acknowledgments
• Multimedia
• References

Further Inpatient Care

• The second and third steps of the 3-step dementia workup also can be accomplished as an inpatient procedure.
• • This is completed over 2 days with initial contact made by a case manager.
  • It is particularly useful if the diagnosis is unclear, since referral for brain biopsy may be expedited.

Further Outpatient Care

• Periodic follow-up care is indicated to manage problem behaviors or clinical problems of the patient, to support the caregiver, or to re-evaluate the diagnosis if it is in doubt.
• If paranoia, depression, or other behavioral problems manifest, pharmacologic treatments can be tailored to address these problems.

Complications

• After diagnostic lumbar puncture, some patients with Pick disease and cerebral atrophy can develop a subdural hematoma.
• Observe for headache or change in mental status for several days after this procedure (some physicians admit for 23-h observation). If a subdural hematoma is suspected, perform a CT scan with and without contrast or an MRI scan with contrast.

Prognosis

• Like most dementias, Pick disease is slowly progressive, leading to increased vocational and personal disability.
• Some patients can progress slowly over extremely long periods.
• Some may develop artistic or other talents during the course of their dementia, perhaps related to disinhibition of "creative" brain areas. Musical or artistic tastes also may change (eg, sudden interest in music intended for much younger listeners).
• Some may be capable of acquiring new knowledge or skills such as learning to use a computer-assisted simple communication system.

Patient Education

• For excellent patient education resources, visit eMedicine's Dementia Center. Also, see eMedicine's patient education articles Pick Disease and Dementia Medication Overview.

MISCELLANEOUS

Section 9 of 13  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Acknowledgments
• Multimedia
• References

Medical/Legal Pitfalls

• Patients with progressive dementia should undergo neuroimaging sensitive enough to detect a structural lesion (eg, MRI in most patients, rather than a CT scan). Serologic testing for syphilis also should be strongly considered. Interim progression of these potentially treatable disorders can result in legal culpability.

Special Concerns

• Consultation with a nurse practitioner or case manager experienced with dementia is indicated. If needed, such a person can be located through a local chapter of the Alzheimer's Association or the state Department of Aging.
• • While the patient is able to participate, a family contact (eg, durable power of attorney) can be designated to decide care-giving and/or end-of-life issues.
  • The nurse or case manager also can assist caregivers with stress management, teach behavioral techniques, refer to day programs, and assess a patient who may need to be admitted for short- or long-term management of behavioral problems.
• In situations where a strong family history of frontotemporal dementia or Pick disease is present, unaffected family members may desire genetic testing. It cannot be overstressed that this should only be performed after informed genetic counseling, preferably in a specialty center familiar with the genetics of dementing disorders. In this setting, testing may be of benefit.³⁶

FURTHER READING

Section 10 of 13  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Acknowledgments
• Multimedia
• References

See Medscape CME activity Alzheimer's Disease and Dementia.

ACKNOWLEDGMENTS

Section 11 of 13  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Acknowledgments
• Multimedia
• References

The author would like to thank Shaan Khurshid for help in research and preparation of the most recent revision of this article. 

MULTIMEDIA

Section 12 of 13  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Acknowledgments
• Multimedia
• References

Media file 1:  Motor perseveration in a patient with Pick disease. The patient is asked to copy the loops (as demonstrated by the examiner in the first line).
	View Full Size Image
Media type:  Image

REFERENCES

Section 13 of 13

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Acknowledgments
• Multimedia
• 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].

Article Last Updated: Jun 18, 2008