Parkinsonism in frontotemporal dementias

Area of Science:

• Neurodegenerative disorders
• Neurology
• Genetics

Background:

• Frontotemporal dementia (FTD) is a heterogeneous neurodegenerative disorder affecting behavior and language.
• FTD shares clinical, genetic, and pathological links with amyotrophic lateral sclerosis (ALS).
• A family history of dementia, motor neuron disease, or parkinsonism is reported in 40% of FTD cases, with C9orf72, MAPT, and PGRN mutations implicated in half of familial cases.

Purpose of the Study:

• To describe the prevalence and phenomenology of parkinsonism in major FTD syndromes and common genetic forms.
• To discuss the evolving nosology and terminology of FTD diagnoses.
• To highlight the significance of parkinsonism as a core FTD feature for clinical management and trial design.

Main Methods:

• Review of literature on parkinsonism in frontotemporal dementia syndromes.
• Analysis of parkinsonism prevalence according to genetic forms of FTD.
• Discussion of clinical characteristics and diagnostic evolution.

Main Results:

• Parkinsonism, particularly akinetic-rigidity, is a common feature in FTD, appearing early in the disease course.
• FTD-associated parkinsonism differs from idiopathic Parkinson's disease, often being symmetric, axial, levodopa-unresponsive, and less frequently associated with tremor.
• Parkinsonism can signify an evolving FTD phenotype, resembling corticobasal syndrome or progressive supranuclear palsy.

Conclusions:

• Parkinsonism is a significant and often early feature in various frontotemporal dementia syndromes and genetic subtypes.
• Understanding FTD-associated parkinsonism is crucial for accurate diagnosis, patient management, and the development of targeted clinical trials.
• The distinct characteristics of FTD parkinsonism necessitate specific diagnostic and therapeutic considerations separate from idiopathic Parkinson's disease.