What is Pick's Disease?
Pick's disease is a specific neuropathological entity within the spectrum of frontotemporal lobar degeneration (FTLD-tau), characterized by abnormal tau protein accumulation forming distinctive Pick bodies in neurons, primarily affecting the frontal and temporal lobes and causing progressive behavioral, personality, and language deterioration. 1
Neuropathological Definition
Pick's disease refers specifically to the pathological finding of Pick bodies (argyrophilic, spherical intraneuronal tau inclusions), distinguishing it from the broader clinical syndrome of frontotemporal dementia (FTD). 1
The disease is classified as FTLD-tau, meaning many neuropathologists consider it part of frontotemporal lobar degeneration with tau pathology, alongside progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). 1
Pathologically, it shows circumscribed cortical atrophy most prominently in the frontal and temporal poles, with maximal neuronal loss in the limbic system (hippocampus, entorhinal cortex, amygdala). 2
Pick bodies are frequently abundant in the dentate fascia of the hippocampus, and tau-immunoreactive glial inclusions are characteristic findings. 2
Clinical Presentation
The clinical syndrome presents with executive dysfunction, personality changes, and behavioral alterations, with relative preservation of memory early in the disease course, distinguishing it from Alzheimer's disease. 3
Behavioral manifestations typically begin with apathy and disinterest (often mistaken for depression), followed by disinhibition, perseverative behavior, and compulsive actions. 4
Progressive language loss (primary progressive aphasia) can be the presenting feature, with some patients developing semantic dementia where the meaning of nouns and objects is lost. 4
Personality deterioration and memory deficits are often more severe than the visuospatial and apraxic disorders common in Alzheimer's disease. 5, 2
Age and Epidemiology
Pick's disease typically presents in the presenile period, between ages 48-65 years, and is rare after age 75. 3
It accounts for approximately 5% of all dementias and can be familial in some cases, with chromosome 17 localization and tau mutations discovered in familial forms. 4, 6
Diagnostic Approach
Definitive diagnosis requires neuropathological confirmation showing Pick bodies, obtainable only through biopsy or autopsy; clinical diagnosis represents the most likely etiology, not pathological certainty. 3
The diagnostic approach is primarily clinical, requiring identification of a progressive dysexecutive and/or behavioral syndrome combined with neuroimaging showing characteristic frontal and temporal lobe atrophy, followed by exclusion of alternative etiologies. 3
Non-contrast MRI of the brain is the primary imaging modality to identify the characteristic atrophy pattern and exclude alternative diagnoses. 3
FDG-PET/CT shows hypometabolism in frontal and/or temporal regions and can differentiate FTD from Alzheimer's disease with 60% sensitivity and 78.5% positive predictive value. 3
Important Clinical Caveat
There is a probabilistic—not deterministic—relationship between clinical syndrome and pathological diagnosis; the clinical syndrome of frontotemporal dementia can be caused by various pathologies including Pick's disease, PSP, CBD, or TDP-43 proteinopathy. 1
Clinical overlap with other non-Alzheimer degenerative disorders is increasingly recognized, making precise antemortem diagnosis challenging. 4, 2
Serial clinical assessments and repeat neuroimaging help confirm the progressive nature and refine diagnosis over time, documenting progression of cognitive, behavioral, and functional decline. 3