Pick Disease Health Article

Definition

Pick disease is a rare neurodegenerative disorder that affects pre-senile adults. It is characterized by atrophy of the tissues in the frontal and temporal lobes of the brain and by the presence of aggregated tau protein that accumulates in Pick bodies in the neurons of the affected regions. Named for the German physician who studied patients who with the disease, Pick disease is grouped together with other non-Alzheimer's dementias, under the category of frontotemporal dementia (FTD), which is now the preferred term for Pick disease. FTD is classified by the Diagnostic and Statistical Manual of Mental disorders, Fourth Edition (DSM-IV) as a Dementia Due to Other General Medical Conditions.

Description

The disease is named after the German physician, Arnold Pick, but it was not named by him. German psychiatrist and pathologist Alois Alzheimer named the illness in 1923 following post-mortem examinations of Pick's patients. One of these patients was a 71-year old man who died following progressive mental deterioration. His autopsy revealed atrophy of the frontal cortex. This feature is seen nearly universally among patients with FTD. The disease is also referred to as frontotemporal lobar degeneration, progressive aphasia and semantic dementia.

The disease may be inherited through mutations associated with chromosomes 17, 9 and 3, or develop sporadically.

Demographics

Alzheimer's disease and other non-Alzheimer's dementias are much more common than FTD. The average age of onset is 54 years, and most cases arise between the ages of 40 and 60. Few diagnoses are made in individuals older than 75 years of age, but FTD has been diagnosed in people as young as 20.

At autopsy, 8–10% of all cases of pre-senile dementia meet the diagnostic criteria for FTD disease, although some estimates put the incidence of the disease in the United States at as much as 15% of individuals with dementia. Epidemiological studies have estimated that FTD affects as few as one in 100,000 people. The familial incidence of FTD disease may be higher in Europe; a Dutch study indicated a prevalence of 28 per 100,000 individuals. The incidence increases with age, affecting 10.7 per 100,000 in the 50–60-year age range and 28 per 100,000 in the 60–70-year age range. FTDs account for about 3% of dementias. One-fifth to one-half of individuals diagnosed with FTD has a first-degree relative that has also been diagnosed with dementia.

Discrepancies in neuropathological diagnosis have led some groups to suspect that its incidence is much greater than previously indicated. There is some suggestion that as imaging techniques improve the disease is becoming more frequently recognized in younger patients.

Causes and Symptoms

The molecular cause of Pick disease are a series of mutations linked to chromosomes 17, 9 and 3. One of these mutations is located on the long arm of chromosome 17 (17q35) at the locus known to hold the gene for the tau protein, and accounts for between 9–14% of all FTDs. This gene has also been implicated in Alzheimer's disease. Mutations on chromosomes 9 and 3 have not yet been identified. The gene encodes a scaffold protein that maintains the shape of brain neurons by stabilizing cellular microtubules. Mutations to the tau protein cause it to form clumps and limit its ability to assemble microtubules. The aggregates that form in the neurons of the affected regions of the brain are called Pick bodies. As in Alzheimer's disease, the tau protein is hyperphoshorylated in FTD.

The brain regions most severely affected by the tau mutation are the frontal and temporal lobes. These parts of the brain control reasoning and judgment, behavior and speech. In addition to the accumulation of tau protein, these regions atrophy over the course of the disease.

The clinical features of frontotemporal dementia includes changes in the patient's behavior, and may include additional emotional, neurological and language symptoms. Patients show poor reasoning, judgment and mental flexibility, but memory may not be affected.

Initially, patients become disinhibited and restless, and lose the ability to control their actions or to chose socially acceptable behavior. As the condition progresses, repetitive and ritualistic behaviors, such as hand rubbing or clapping, develop. Hyperoral behaviors are often associated with this phase, and may include overeating, hoarding or fixations on specific foods.

Later, apathy, uncaring and unsympathetic attitudes, and mood changes may develop. The patient may also develop language difficulties, including aphasia and reduced reading and writing comprehension, dysarthria and echolalia. Most patients with FTD eventually become mute.

Some patients with FTD will develop ALS, also known as Lou Gehrig's disease, parkinsonian, or psychiatric symptoms.