Description

• A type of progressive frontotemporal dementia typically affecting the frontal and/or anterolateral temporal lobes
• Named after Dr. Arnold Pick, the psychiatrist/neuropathologist who described the clinical syndrome and identified the neuronal inclusions from tau protein accumulation (now known as Pick bodies) that are the characteristic pathology of the condition
• Two types of frontotemporal dementia clinically: (i) behavioral variant, primarily affecting social, emotional, and self-regulatory skill and (ii) primary progressive aphasia, causing speech and language deficits
• Synonym(s): semantic dementia; Arnold Pick disease; Pick disease

Epidemiology

• As a group, the frontotemporal lobe dementias are the fourth most common cause of dementia in the United States.
• One of the more common causes of early-onset (midlife) dementia, frontotemporal dementia occurs at a similar frequency to Alzheimer disease in patients <65 years old.
• Mean age of onset for frontotemporal dementia is about 58 years, with peak incidence in those aged 55 to 65 years. Reported age of onset ranges from 20 to 80 years.
• Estimated frequency ranges from 7 to 43 cases per 100,000 population (1).
• May occur more frequently in Europe (particularly in those of Scandinavian descent)
• More men than women may be affected (although roughly equal).

Etiology and Pathophysiology

• Abnormal tau protein deposition in neurons as seen in other neurodegenerative conditions (2)
• In Pick disease, the FTLD-tau protein involves three microtubule-binding repeats (3R tau) as compared to isoforms of cerebral tau which have four microtubule-binding repeats (4R tau) seen with other disorders.
• Primarily affects the frontal and temporal areas and therefore more associated with personality and behavioral changes than is seen in other types of dementia
• Swollen (ballooned) neurons (Pick cells)
• Argentophilic (silver staining), tau positive, neuronal cytoplasmic inclusions (Pick bodies). Pick bodies are pathognomonic for Pick disease.
• Severe atrophy, neuronal loss, and gliosis
• Above findings predominantly affecting the frontal and temporal cortical regions

Genetics

• As many as 40–50% of patients with frontotemporal dementia have a positive family history of dementia (3).
• No clear inheritance pattern in all cases; can be inherited as an autosomal dominant trait with high penetrance that is observed in 10–25% of cases
• Linkage to chromosomes 3, 9, and 17
• Chromosome 17 mutations have been associated with abnormal tau protein accumulation.

Risk Factors

• Family history of dementia or psychiatric conditions
• Those with learning disabilities such as dyslexia may be at higher risk, although this is uncertain.

General Prevention

No known prevention

Commonly Associated Conditions

• Motor neuron disease/amyotrophic lateral sclerosis (ALS)
• Corticobasal syndrome