Pick’s disease (PiD) was discovered by Arnold Pick in 1892. The meaning of the term “pick’s disease” has changed dramatically over the years. In the past, it was used to describe Frontotemporal dementia (FTD) but now it represents a histopathological (the study of tissues and cells under a microscope) subtype of FTD. FTD belongs to an even broader pathology called frontotemporal lobe degeneration (FTLD). FTD is any form of dementia in which frontal and temporal lobes of the brain degenerate. It is characterized by the presence of intraneuronal inclusions in the form of pick bodies and ballooned cells in the brain called pick cells. These inclusions contain aggregates of abnormal tau protein.
Tau protein in PiD is 3-repeat, meaning the Tau protein exists in various isoforms and large amounts of 3-repeat have profound axonal transport defects and locomotor impairments. PiD is a primary tauopathy (deposition of abnormal levels of Tau protein). Healthy tau protein helps in the assembly of microtubules in the neurons. It is coded by the MAPT gene. Like all other types of dementia, it is a neurodegenerative disease. Atrophy in the PiD brain is limited to frontal and temporal lobes. This atrophy results in the formation of a characteristic knife-edge-like shape of the brain. Damage to the frontal lobe results in behavioral decline while damage to the temporal lobes results in language decline. The age of onset of PiD ranges from 40 to 75 years. PiD is more prevalent in men than in women. FTD is divided into clinical subtypes such as behavior called behavioral variant of Frontotemporal dementia (bvFTD) and diminished language skills called primary progressive aphasia (PPA). bvFTD presents the most common set of symptoms in PiD. Most cases of PiD have a sporadic origin. Characteristic symptoms of PiD include abrupt mood change, compulsive behavior, stereotypic and immoral behaviors, difficulty in speech, disinhibition, and apathy.
Caregiving in PiD is particularly difficult due to the inappropriate behavior of patients towards caregivers. PiD patients show stereotypic, sexually inappropriate, and impulsive behavior. PiD patients also suffer from anomia; a condition in which a person has difficulty remembering the names of objects and places. Akinesia and rigidity may occur in the later stages of the disease. Diagnosis of living PiD patients is difficult because of the lack of specific biomarkers for pick bodies. Antibodies can be used in the diagnosis of PiD. Cognitive and behavioral tests are currently the best option for diagnosing PiD. Despite all these options, many PiD patients are misdiagnosed. Brain imaging can be used to visualize atrophy. Most patients suffering from PiD have mixed pathology in which other neurodegenerative diseases are also involved. Frontotemporal lobar atrophy is a prominent sign of PiD. Knife-edge-like cortical atrophy can be observed upon gross examination.
The risk of PiD increases with age. High education, regular physical exercise, and a healthy diet can be effective in the prevention of all types of dementia including PiD. There are three stages of PiD. These are called initial, steady and terminal stages. Symptoms get worse with advancing stages. Males suffering from PiD show aggressive behavior. No treatment can slow down or reverse the progression of PiD. Different drugs can be used to manage the symptoms and the treatment is highly individualized. Cholinesterase inhibitors are used for the behavioral management of PiD. The drugs being used to manage symptoms of PiD are intended for symptomatic treatment of other disorders such as AD. Much work needs to be done to understand the pathophysiology of PiD in order to develop disease-modifying treatments.
Written by: Numair Arshad & Lawrence D. Jones, Ph.D.