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Pick Disease

The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.

Copyright 1989, 1990, 1996, 1997, 1998, 2000, 2009, 2012

NORD is very grateful to A.M. Barrett, MD, Kessler Foundation Research Center, Professor of Physical Medicine and Rehabilitation, The University of Medicine and Dentistry, New Jersey, for assistance in the preparation of this report.

Synonyms of Pick Disease

Disorder Subdivisions

General Discussion

Pick disease is a form of dementia characterized by behavioral changes such as deterioration of social skills and changes in personality. Intellectual impairment, memory loss and language deterioration may also occur. Most cases of Pick disease are sporadic in nature, but a genetic form of the disease is recognized. Although a progressive form of communication impairment (aphasia) may occur as part of Pick disease, people with Pick disease have other behavioral problems besides language and communication impairment.

Symptoms

Symptoms of Pick disease can include behavioral, emotional and neurological changes as well as deterioration in language skills. Symptoms vary in affected individuals.

Behavioral symptoms can include changes in dietary preferences such as eating only one type of food, eating inedible objects or eating excessively. Repetitive behaviors (for example, collecting worthless objects), impulsive behaviors, neglect for personal hygiene, hyperactivity, and hypersexual behaviors may also occur.

Emotional symptoms may include socially inappropriate behavior, apathy, indifference to loved ones and mood swings. In some people, an early symptom is loss of interest or engagement during important social events (e.g. birthday celebrations). Neurological symptoms may include a movement disorder called Parkinsonism, characterized by decreased facial expression, slow movement, rigidity and instability, and, rarely, hand, head or body tremor. Abnormal eye movements and abnormal muscle postures may also occur as well as muscle weakness and jerks.

Language symptoms may include repetition of words spoken by another person (echolalia), difficulty speaking, lack of speech, trouble finding words, and decreased reading and writing comprehension. The voice may sound slurred or garbled and the cadence of speech may change so that the person with Pick disease is hard to understand. The person with Pick disease may begin to speak too loudly, too softly, or violate conversational rules (for example, may become a close talker, making others uncomfortable). Some people with Pick disease may lose the ability to link spoken or written words with meaning (semantic dementia), as if language has lost its ability to evoke complex thinking and associations in their mind.

Some people may have other mental symptoms including depression, difficulty with skilled hand movements, may become clumsy (for example, when using tools), or may have problems with planning, self-monitoring, and dual-tasking. Most people with Pick disease are unaware of the severity of their own symptoms, and this impaired self-monitoring appears to be separate from psychological denial.

Some people with a form of adult muscular dystrophy (Lou Gehrig disease, amyotrophic lateral sclerosis, or motor neuron disease) may also have symptoms of Pick disease. In this instance, the most severe symptoms are usually loss of drive and motivation.

Causes

Pick disease can be sporadic, hereditary or familial. Approximately 40-75% of individuals affected with Pick disease have the sporadic type that is not thought to run in families. Familial Pick disease is almost nonexistent when the patient has the diagnosis of semantic dementia.

Approximately 10% of those affected have a type of Pick disease that follows autosomal dominant inheritance. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The abnormal gene can be inherited from either parent or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy. The risk is the same for males and females.

Nerve cells in the frontal lobe of the brains from individuals with Pick disease have been found to contain deposits of abnormal Tau protein or a lack of Tau. This protein is involved in the normal function of nerve cells. There are also abnormalities identified affecting other nerve cell proteins, which are often referred to asTDP-43 and FUS. Approximately 25-40% of cases of hereditary Pick disease are caused by an abnormality in the MAPT gene located on chromosome 17. The MAPT gene is responsible for the production of the Tau protein. Pick's disease caused by an abnormality in the MAPT gene is called frontotemporal dementia with parkinsonism-17 (FTDP-17), or FTLD-tau. When the TDP-43 nerve cell protein is implicated, abnormalities have been identified on chromosome 9.

Approximately 20-50% of those affected appear to have a form of Pick disease that is familial, which means that genetic factors are probably involved and family members have an increased risk to develop the disease, but the specific risk is undefined.

Affected Populations

Approximately 10-15% of individuals with dementia are thought to have Pick disease. The genetic and familial forms of Pick disease may occur more often in Scandinavian countries. Pick disease may be under-diagnosed, because it is sometimes confused with Alzheimer disease or with psychiatric disorders like depression or obsessive-compulsive disorder. The typical onset of Pick disease is in the 50's but it has been reported to begin as early as the 20's, and as late as age 80.

Related Disorders

Symptoms of the following disorders can be similar to those of Pick disease. Comparisons may be useful for a differential diagnosis:

Alzheimer disease is a progressive condition of the brain affecting memory, thought and language. The degenerative changes of Alzheimer disease lead to patches or plaques in the brain and the entanglement of nerve fibers (neurofibrillary tangles). Memory loss and behavioral changes occur as a result of these changes in brain tissue. (For more information on this disorder, choose "Alzheimer" as your search term in the Rare Disease Database.)

Huntington's disease is an autosomal dominant genetic disease that is progressive and neurodegenerative and characterized by the gradual development of involuntary muscle movements affecting the hands, feet, face, and trunk and progressive deterioration of cognitive processes and memory (dementia). Neurologic movement abnormalities may include uncontrolled, irregular, rapid, jerky movements (chorea) and athetosis, a condition characterized by relatively slow, writhing involuntary movements. Dementia is typically associated with progressive disorientation and confusion, personality disintegration, impairment of memory control, restlessness, agitation, and other symptoms and findings. In individuals with the disorder, disease duration may range from approximately 10 years up to 25 years or more. Life-threatening complications may result from pneumonia or other infections, injuries related to falls, or other associated developments. . (For more information on this disorder, choose "Huntington" as your search term in the Rare Disease Database.)

Rarely, a structural problem can affect the same areas of the brain affected by Pick disease. This might be caused by a stroke, a brain tumor, or a head injury. An infection, especially viral encephalitis, may sometimes damage these brain regions as well. Even after many years of sexual abstinence, some people can develop a late form of syphilis which can also affect these parts of the brain and cause similar symptoms.

Standard Therapies

Diagnosis
The diagnosis of Pick disease is usually made using a combination of patient history, physical examination and tests that may include neurological examination, neurobehavioral and psychological testing and neuroimaging (CT, MRI, SPECT and PET scans). It is important to consult early with a specialist familiar with dementia and neurological thinking disorders.

Pick disease is characterized by atrophy (shrinkage) of the frontal and temporal lobes of the brain. In individuals with Pick disease, there are also changes in certain nerve cells. Under a microscope, these cells may appear ballooned or inflated and are referred to as "Pick cells." In addition, some nerve cells may contain unusual "inclusion" bodies (Pick inclusion cells). Individuals with Pick's disease do not have the characteristic plaques in the brain that are associated with Alzheimer disease.

Molecular genetic testing is available for the MAPT gene that is associated with frontotemporal dementia with parkinsonism-17 (FTDP-17), and (especially at academic research centers) tests for some of the other genes associated with Pick disease can be performed. It is important that anyone undergoing genetic testing speak with a genetic counselor so the full implications of the results of genetic testing can be discussed and understood.

Treatment
Treatment of Pick disease is symptomatic and supportive. Sedative and antipsychotic medications are sometimes used to treat behavioral symptoms. Behavioral management techniques can be tremendously helpful. Levodopa and other medications conventionally used to treat Parkinson disease can be beneficial in treating Parkinsonism. Medication treatment of depression can be helpful. There are ongoing research studies examining whether medications may enhance mental abilities in Pick disease; at this point, a standard medication regimen to enhance mental abilities has not yet been identified.

Early interdisciplinary care involving social work, psychological, psychiatric and neurological approaches may benefit the sufferer and family and facilitate end-of-life planning. A specialist experienced with the needs of the person with Pick disease and his or her family might be found at an academic dementia clinic, or through the referral of a geriatrician, psychiatrist, or memory disorders specialist. Caregiver support is an especially important part of the care plan.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

Contact for additional information about Pick disease:

A. M. Barrett, MD
Behavioral Neurology/Cognitive RehabilitationProfessor, Physical Medicine & Rehabilitation, UMDNJ-NJMS
Director, Stroke Rehabilitation Research, Kessler Foundation Research Center
Chief, Neurorehabilitation Program Innovation, Kessler Institute of Rehabilitation
1199 Pleasant Valley Way
West Orange, NJ 07079
Phone: (973) 324-3569
Fax: (973) 243-6984

Pick Disease Resources

NORD Member Organizations:

(To become a member of NORD, an organization must meet established criteria and be approved by the NORD Board of Directors. If you're interested in becoming a member, please contact Susan Olivo, Membership Manager, at solivo@rarediseases.org.)

Other Organizations:

References

JOURNAL ARTICLES
Josephs KA, Hodges JR, Snowden JS, et al. Neuropathological background of phenotypical variability in frontotemporal dementia. Acta Neuropathol. 2011;122:137-53.

Snowden J, Neary D, Mann D. Frontotemporal lobar degeneration: clinical and pathological relationships. Acta Neuropathol. 2007;114:31-38.

Forman MS, Farmer J, Johnson JK, et al. Frontotemporal dementia: clinicopathological correlations.
Ann Neurol. 2006;59:952-962.

Josephs KA, Petersen RC, Knopman DS, et al. Clinicopathologic analysis of frontotemporal and corticobasal degenerations and PSP. Neurology. 2006;66:41-48.

Mackenzie IR, Baborie A, Pickering-Brown S, et al. Heterogeneity of ubiquitin pathology in frontotemporal lobar degeneration: classification and relation to clinical phenotype. Acta Neuropathol. 2006;112:539-549.

Kertesz A, McMonagle P, Blair M, Davidson W, Munoz DG. The evolution and pathology of frontotemporal dementia. Brain. 2005;128:1996-2005.

Hodges JR, Davies RR, Xuereb JH, et al. Clinicopathological correlates in frontotemporal dementia. Ann Neurol. 2004;56:399-406.

Neary D, Snowden JS, Gustafson L, et al. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology. 1998;51:1546-1554.

Brun A. Clinical and neuropathological criteria for frontotemporal dementia. The Lund and Manchester Groups. J Neurol Neurosurg Psychiatry. 1994;57:416-418.

INTERNET
Barrett AM. Pick Disease. Emedicine. http://emedicine.medscape.com/article/1135504-overview. Updated January 26, 2012. Accessed April 5, 2012.

van Swieten JC, Rosso SM, and Heutink P. (Updated October 26, 2010). MAPT-Related Disorders. In: GeneReviews at Genetests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1993-2008. Available at http://www.genetests.org. Accessed April 5, 2012.

Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Pick Disease of the Brain. Entry No: 172700. Last Edited April 24, 2006. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed April 5, 2012.

Report last updated: 2012/04/09 00:00:00 GMT+0