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An overview of Pick’s disease

Pick’s disease (PiD) is a rare neurodegenerative disease of the frontal lobes of the brain, characterized by the presence of pick bodies in the neurons or ballooned cells called pick cells. It is a histopathological type of frontotemporal dementia. Frontotemporal dementia belongs to an even broader disorder called frontotemporal lobe degeneration [1]. In the clinical setting, FTD is often divided into behavioral variant frontotemporal dementia (bvFTD), primary progressive aphasia (PPA), and movement disorders.

Pick's disease

The characteristic pick bodies are stained black with silver salts because of their argyrophilic (having an affinity for silver) nature. These inclusions contain aggregates of abnormal tau protein. For this reason, it is referred to as tauopathy. Healthy tau protein helps in the assembly of microtubules in the neurons. It is coded by the MAPT gene [2]. Six isoforms of tau are coded by this gene. These isoforms are categorized into two types depending on the number of repeats in them. Three isoforms are 3R while three are 4R. The relative level of these two groups of isoforms can have important implications in neurodegenerative diseases. Tau protein in PiD belongs to the 3R type. Hyperphosphorylated tau (containing extra phosphoryl groups) protein forms insoluble inclusions called pick bodies. Pick bodies are spherical and contain other proteins as well.

Atrophy (decrease in size) in the PiD brain is limited to the 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.

Global perspective

It is difficult to know the exact prevalence of PiD because of the challenges in its diagnosis. A careful estimate gives the prevalence of PiD to be around 1 in 100,000 people [3]. The mean duration is 8-9 years. The age of onset of PiD ranges from 40 to 75 years. PiD is more prevalent among men than in women. The male-to-female ratio of PiD is 14:3.

Indian perspective

The number of all dementia-related cases is expected to increase in India as the nation moves towards an older population phase. According to a famous report, the cases of dementia are expected to rise by 300% between 2001 to 2040 [4]. According to a study in South India, FTD is the second most common type of dementia in India after Alzheimer’s disease.

Signs and Symptoms

Since PiD is a pathological grade of FTD, its symptoms are described in the context of the variants of FTD. Characteristic symptoms of PiD include:

  • Abrupt mood change

  • Compulsive behavior

  • Stereotypic and immoral behaviors

  • Difficulty in speech

  • Disinhibition

  • 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) and akinesia (loss of voluntary muscle control) and rigidity (inflexibility) may occur in the later stages of the disease.

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.


Diagnosis of alive 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. Brain imaging can be used to visualize atrophy. Despite all these options, many PiD patients are misdiagnosed.

Distinguishing PiD from Alzheimer’s Disease is critical because both these diseases are presenile dementia (occur before the age of 65). PHF-1 is an important biomarker of pick bodies [5]. Hyperphosphorylated and aggregated tau proteins can be detected through antibodies.

It is possible to diagnose the underlying pathology in patients suffering from familial bvFTD, but the pathology of sporadic bvFTD can only be diagnosed by autopsy. Despite all these methods, cognitive and behavioral tests are currently the best option for diagnosing PiD. Certain signs indicate whether a patient suffering from bvFTD has tau-positive or tau-negative pathology. Distinctive symptoms such as poor planning and judgment indicate the presence of tau-pathology in patients with bvFTD. Whereas symptoms such as depression, weakened personal conduct, delusions, and appetite changes suggest the presence of pathology other than tauopathy.


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 and memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, are used for the cognitive management of PiD. The drugs being used to manage symptoms of PiD are intended for symptomatic treatment of other disorders such as AD.

  • Parkinsonia symptoms are managed through levodopa. Levodopa is not as effective in PiD as in Parkinson’s disease but it is still preferred.

  • A wide set of neuroleptics, antidepressants, and antidepressants are used to manage behavioral symptoms. Just as these symptoms vary from individual to individual, the prescribed medication is also highly specialized.

Quality of life management

Like other forms of neurodegenerative disease, caregiving in PiD is not easy. Watching loved ones slowly devoured by PiD is distressing for family members. PiD patients are particularly difficult to deal with due to their stereotypic and immoral social behavior. Patients may show inappropriate and often sexual attitudes towards caregivers.

These challenges can be managed through proper training of caregivers and mood-stabilizing drugs. Firstly, the caregivers are advised not to create such situations that trigger unwanted responses from the patient. The family members are often asked to ask politely with the patient. Secondly, the doctor can prescribe antidepressants and antipsychotics that can help with these disturbing behaviors. In addition, non-pharmacological options such as occupational therapy and speech therapy are also effective in improving quality of life [6]. Patients are often encouraged to take part in healthy activities and social activities. Well-lit home with minimal noise and distraction techniques such as doing puzzles and listening to music is also helpful.

While these options can improve the quality of life of the patients, more work needs to be done to understand the pathophysiology of PiD and develop better diagnostic methods and disease-modifying treatment.


1. L. Riedl, I. R. Mackenzie, H. Förstl, A. Kurz, and J. Diehl-Schmid, “Frontotemporal lobar degeneration: current perspectives,” Neuropsychiatr Dis Treat, vol. 10, pp. 297–310, 2014, doi: 10.2147/NDT.S38706.

2. D. F. V. Pîrşcoveanu et al., “Tau protein in neurodegenerative diseases - a review,” Rom J Morphol Embryol, vol. 58, no. 4, pp. 1141–1150, 2017.

3. D. M. McFarland, “The journey through Pick’s Disease with a loved one: a personal account,” Int Nurs Rev, vol. 57, no. 1, pp. 142–144, Mar. 2010, doi: 10.1111/j.1466-7657.2009.00743.x.

4. C. P. Ferri et al., “Global prevalence of dementia: a Delphi consensus study,” Lancet, vol. 366, no. 9503, pp. 2112–2117, Dec. 2005, doi: 10.1016/S0140-6736(05)67889-0.

5. T. T. Rohn, R. J. Day, L. W. Catlin, R. J. Brown, A. J. Rajic, and W. W. Poon, “Immunolocalization of an amino-terminal fragment of apolipoprotein E in the Pick’s disease brain,” PLoS One, vol. 8, no. 12, p. e80180, 2013, doi: 10.1371/journal.pone.0080180.

6. S. Shinagawa et al., “Non-pharmacological management for patients with frontotemporal dementia: a systematic review,” J Alzheimers Dis, vol. 45, no. 1, pp. 283–293, 2015, doi: 10.3233/JAD-142109.



IIT Guwahati
University of Manchester
Rhenix Lifesciences
American university of Sharjah
IIT Delhi
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