What is Pick's disease in older adults?

What is Pick's Disease?

Pick's disease is a specific neuropathological subtype of frontotemporal lobar degeneration (FTLD-tau) characterized by abnormal accumulation of 3-repeat tau protein forming distinctive intraneuronal inclusions called Pick bodies, primarily affecting the frontal and temporal lobes of the brain. 1

Neuropathological Definition

Pick's disease represents one of several tau protein pathologies that fall under the broader umbrella of frontotemporal lobar degeneration (FTLD-tau), which also includes progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). 1 The defining pathological features include:

• Argyrophilic, round intraneuronal inclusions (Pick bodies) composed of abnormal tau proteins, most prominently found in the dentate fascia of the hippocampus 2
• Circumscribed cortical atrophy predominantly affecting frontal and temporal poles, with neuronal loss maximal in limbic structures including hippocampus, entorhinal cortex, and amygdala 2
• Ballooned cortical neurons (Pick cells) and pronounced glial reaction in affected gray and white matter 2
• Tau-immunoreactive glial inclusions with a specific tau protein immunoblotting pattern distinct from Alzheimer's disease 2

Definitive diagnosis requires neuropathological confirmation through biopsy or autopsy; clinical diagnosis represents only the most likely etiology, not pathological certainty. 3

Clinical Presentations in Older Adults

Most Common Syndromes

Behavioral variant frontotemporal dementia (bvFTD) is the most common clinical presentation (57% of cases), characterized by progressive executive dysfunction, personality changes, and behavioral alterations with relative preservation of memory early in the disease course. 4 This distinguishes it from typical Alzheimer's disease. 3

Primary progressive aphasia (PPA) is the second most common presentation (33% of cases), typically manifesting as semantic variant or non-fluent variant PPA. 1, 4 When PPA is due to Pick's disease, it usually presents as semantic variant, though non-fluent variant can occur. 1

Atypical Presentations

Rare presentations include:

• Corticobasal syndrome with asymmetric limb apraxia, rigidity, and cognitive dysfunction 1, 4
• Amnestic dementia mimicking Alzheimer's disease with early memory impairment 5, 4
• Progressive cortical cognitive-somatosensorimotor syndrome with executive dysfunction and asymmetric motor features 1

Age and Demographics

Pick's disease typically presents in the presenile period between ages 48-65 years and is rare after age 75. 3 The median age at disease onset is 54 years, with PPA cases presenting slightly earlier (median 52 years) than bvFTD cases (median 59 years). 4 The disease affects men and women equally. 6

Disease Course and Prognosis

Median disease duration from onset to death is 10 years, with no significant difference between bvFTD (9.5 years) and PPA (13 years) presentations. 4 The disease is progressive and incurable, with personality deterioration and memory deficits often more severe than the visuospatial and apraxic disorders common in Alzheimer's disease. 2

Mixed Pathology Considerations

A critical caveat: only one-third of clinically diagnosed Pick's disease cases show pure Pick pathology at autopsy. 4 The remaining two-thirds demonstrate coexistent pathologies including:

• Alzheimer's disease pathology (29% of cases) 4
• Cerebral amyloid angiopathy (14%) 4
• Combined Alzheimer's and amyloid angiopathy (19%) 4
• Lewy body disease (5%) 4

This is particularly relevant in older adults over age 80, where multiple brain pathologies are the rule rather than the exception. 1

Diagnostic Approach

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

Key Diagnostic Steps:

• Non-contrast brain MRI is the primary imaging modality to identify characteristic atrophy patterns and exclude alternative diagnoses 3
• FDG-PET/CT can differentiate frontotemporal dementia from Alzheimer's disease with 60% sensitivity and 78.5% positive predictive value, showing hypometabolism in frontal and/or temporal regions 3
• Serial clinical assessments and repeat neuroimaging help confirm the progressive nature and refine diagnosis over time 3
• Genetic counseling should be offered if autosomal dominant family history is present, as genetic predisposition is implicated in some cases 3, 6

Clinical Implications

Pick's disease accounts for approximately 5% of all dementias. 7 The most difficult aspects of care involve communication challenges as language deteriorates, requiring nurses and caregivers to adapt communication strategies continuously. 7 The disease is emotionally devastating to families, requiring comprehensive education about nutrition, skin protection, incontinence care, safety, and end-of-life decisions. 7