Pick Disease

Pick Disease

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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. (See Etiology.)

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. (See Presentation and Workup.) [1, 2]

Pick disease is one of the disorders classified under the term frontotemporal dementia (FTD). Almost all instances can be pathologically classified by the following abnormal deposited proteins in cells:

FTLD-tau, marked by abnormal accumulation of three microtubule-binding repeats (3R tau), as contrasted with isoforms of cerebral tau with four microtubule-binding repeats (4R tau), found in other neurodegenerative conditions

Associated with progranulin (FTD-TDP), marked by neuronal cytoplasmic inclusions and, frequently, intranuclear inclusions, as well as variable dystrophic neurites, in the frontotemporal cortex

Associated with fused-in-sarcoma (FUS) protein (neuronal intermediate filament inclusion disease, basophilic inclusion body disease, or atypical, with ubiquitin-only immunoreactive changes) [3]

FTLD-UPS NOS: Ubiquitin or P62-positive only immunoreactive inclusions

FTLD-IF NOS: Intermediate filament immunoreactive inclusions

BIBD NOS: Basophilic inclusion body disease

FTLD-niNOS without any immunoreactive inclusions

See Etiology and Workup.

FTD with abnormal tau protein accumulation has been associated with mutations at chromosome 17; TDP-43 associations are linked to band 9p; ubiquinated FUS accumulation is still under intense investigation; other mutations (CHMP-2B) are also identified in rarer cases.

Primary progressive aphasia is a focal atrophy syndrome that may be associated with Pick disease, Alzheimer disease, or other pathology. Two types of primary progressive aphasia are identified: (1) semantic dementia, in which meaning systems are lost from language, and (2) nonfluent primary progressive aphasia. Clinically, the deficit appears restricted to the frontal and/or temporal lobes. [4] Behavioral-variant FTD is the other major FTD syndrome; in this disorder, deficits are nonverbal and primarily affect social, emotional, and self-regulatory skills.

See Figure 1 in Boxer et al (2013) for an illustration of the neuropathologic subtypes of Pick disease/FTD. [5]

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

Pick disease is defined pathologically by severe atrophy, neuronal loss, and gliosis. Frequently, Pick disease is accompanied by the occurrence of tau-positive inclusions. [6] Swollen (ballooned) neurons (Pick cells) and argentophilic neuronal inclusions, known as Pick bodies, [7] can disproportionally affect the frontal and temporal cortical regions. (See Workup.)

Fewer Pick bodies may be present in these regions if the primary symptoms are behavioral (behavioral variant), compared with the primary symptoms of aphasia. [8, 9]

In a clinicopathologic series, only 5% of patients with clinically diagnosed frontotemporal dementia had classic Pick disease with Pick bodies at postmortem evaluation. (See Epidemiology.) [10]

For patient education information, see the Brain and Nervous System Center, as well as Pick Disease and Dementia Medication Overview.

The specific cause of Pick disease is unknown. As many as 50% of patients with frontotemporal dementia have a positive family history of dementia and inherit frontotemporal dementia as an autosomal dominant trait with high penetrance. [3]

In families with an inherited frontal lobe dementia (some of which have been found to be pathologically or clinically indistinguishable from Pick disease), linkage to markers on chromosomes 17, 9, and 3 have been reported. The links between risk factor genes and causative factors is still not fully explored.

These familial disorders are heterogenous in different family members. Some members may present primarily with amyotrophy, and others may present with primary supranuclear gaze palsy, parkinsonism, schizophrenialike thought disorder, or progressive aphasia and/or apraxia.

People with learning disabilities such as dyslexia may be at higher risk of FTD, but it is not known whether this is generally true or if it is true only for certain patterns of learning disability and, whether only certain types of symptoms, such as the syndrome complex of primary progressive aphasia, may be more common in people with a learning disability history.

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, with Alzheimer disease becoming by far the most prevalent form of dementia. [10]

Pick disease is sometimes used to refer to the clinical phenotype of the frontotemporal dementias. This group of disorders has a variety of pathologic substrates, the most prevalent of which is frontotemporal lobar degeneration with ubiquitin inclusions. In one pathologic series, 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. [10]

Familial forms of Pick disease may occur more frequently in Europe (particularly in Scandinavian nations). The estimated frequency ranges from 7-43 cases per 100,000 population. [11] In a study in the Netherlands, the prevalence was 28 per 100,000 persons. [3]

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 this population.

More men than women may be affected by Pick disease.

Pick disease occurs in a younger age group than dementia of the Alzheimer type, with peak incidence occurring in individuals aged 55-65 years. [12, 13]

Like most dementias, Pick disease is slowly progressive, leading to increased vocational and personal disability. However, a small number of people who have behavioral disturbance consistent with the behavioral variant of FTD may not progress—this has been called the phenocopy variant. In past studies, slow or no progression occurs only in patients with nonlinguistic symptoms—none had primary progressive aphasia.

Some patients can progress slowly over extremely long periods. Some may develop artistic or other talents during the course of their dementia, a phenomenon that is perhaps related to disinhibition of “creative” brain areas. Musical or artistic tastes also may change (eg, the patient may develop a sudden interest in music intended for much younger listeners).

Some patients may be capable of acquiring new knowledge or skills, such as the use of a computer-assisted, simple communication system. This relative sparing of ability to “do things” (process-oriented rather than content-oriented memory) may be helpful in implementing behavioral training techniques to optimize social and daily activity competence.

Pick disease runs a shorter course than Alzheimer disease, on average about 6 years. [12, 14] In some individuals whose main symptoms are a disturbance of speech and language (primary progressive aphasia), the clinical course can be slow. In one small series, these patients survived an average of 5 years longer than patients with behavioral symptoms (behavioral variant). [8] A patient with primary progressive aphasia may preserve the ability to function at home for 10 or more years after onset.

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Mackenzie IR, Neumann M, Bigio EH, Cairns NJ, Alafuzoff I, Kril J. Nomenclature and nosology for neuropathologic subtypes of frontotemporal lobar degeneration: an update. Acta Neuropathol. 2010 Jan. 119(1):1-4. [Medline].

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A M Barrett, MD, FAAN, FANA, FASNR Director, Stroke Rehabilitation Research Program, Kessler Foundation; Chief, Neurorehabilitation Program Innovation, Kessler Institute for Rehabilitation; Research Professor of Physical Medicine and Rehabilitation, Rutgers New Jersey Medical School

A M Barrett, MD, FAAN, FANA, FASNR is a member of the following medical societies: American Academy of Neurology, American Society of Neurorehabilitation, International Neuropsychological Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Kessler Foundation<br/>Received research grant from: SPR Therapeutics; DART Neuroscience; Wallerstein Foundation for Geriatric Improvement; NJ Commission on Brain Injury Research; NIDILRR; NIH.

Jasvinder Chawla, MD, MBA Chief of Neurology, Hines Veterans Affairs Hospital; Professor of Neurology, Loyola University Medical Center

Jasvinder Chawla, MD, MBA is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Clinical Neurophysiology Society, American Medical Association

Disclosure: Nothing to disclose.

Daniel H Jacobs, MD, FAAN Associate Professor of Neurology, University of Florida College of Medicine

Daniel H Jacobs, MD, FAAN 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

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Pick Disease

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