380 Ch 379. Parkinson Disease (PD)

Parkinson disease (PD) = 2nd most common neurodegenerative disorder (after AD); prevalence ~ 1% > 60 yo, 5% > 85；clinical hallmark: TRAP — Tremor (rest, asymmetric, pill-rolling 4-6 Hz) + Rigidity (cogwheel) + Akinesia/Bradykinesia + Postural instability (later)；non-motor features critical — REM behavior disorder (prodromal up to 80% develop), hyposmia (very early), constipation, orthostatic hypotension, urinary, sexual dysfunction, depression, anxiety, cognitive decline, fatigue, sleep disorders, pain；pathology: α-synuclein aggregation (Lewy bodies) + loss of dopaminergic neurons in substantia nigra pars compacta + Braak staging (lower brainstem → midbrain → cortex)；MDS clinical criteria 2015: bradykinesia + (rest tremor or rigidity) + supportive + no exclusion；DaT-SCAN differentiates PD from essential tremor + vascular parkinsonism；treatment: levodopa/carbidopa remains gold standard + dopamine agonists (pramipexole, ropinirole, rotigotine patch) + MAO-B inhibitors (selegiline, rasagiline) + COMT inhibitors (entacapone, opicapone)+ amantadine + anticholinergics (limited); motor fluctuations + dyskinesias common after years — advanced therapies (DBS STN/GPi, LCIG levodopa-carbidopa intestinal gel, foslevodopa-foscarbidopa Vyalev SC infusion FDA 2024, focused ultrasound)；no disease-modifying therapy yet — multiple trials of α-synuclein-targeted ongoing。