Recent Advances in the Management of Parkinsonism

Recent Advances in the Management of Parkinsonism Fifteen–Twenty High-Yield Points Baseline — established management

Levodopa remains the main and often the only treatment for PD in the elderly. It is combined with a peripheral decarboxylase inhibitor — Madopar (levodopa + benserazide) or Sinemet (carbidopa + levodopa).

Start low and increase very gradually; most patients are controlled on 300–600 mg/day in the first years, given three or four times daily, preferably 30 minutes before meals. Dispersible Madopar achieves faster peak levels and is used for early-morning akinesia.

Dopamine agonists, anticholinergics and (largely) MAO-B inhibitors are avoided in older patients — agonists because of hallucinations, somnolence, impulse-control disorders and orthostatic hypotension; anticholinergics such as trihexyphenidyl because of confusion, urinary retention and glaucoma.

COMT inhibitors (entacapone, tolcapone) prolong the levodopa effect and are useful in older patients with motor fluctuations or dyskinesia. Tolcapone requires monitoring for hepatotoxicity.

Non-motor symptoms have specific best-evidence treatments: venlafaxine for depression, clozapine or pimavanserin for hallucinations, rivastigmine for dementia and apathy, droxidopa/midodrine/fludrocortisone for orthostatic hypotension, domperidone for nausea, botulinum toxin for severe drooling, and macrogol with fibre and hydration for constipation.

Clozapine requires blood count monitoring and must be stopped permanently if the neutrophil count falls below 1500/mm3. Domperidone requires ECG monitoring for QT prolongation.

Non-pharmacological care is integral: early functional rehabilitation timed to peak levodopa effect, speech therapy for dysarthria and drooling, swallowing assessment, home support, and structured patient and caregiver education.

The central therapeutic problem in advanced PD is pulsatile stimulation of striatal dopamine receptors by short-acting oral levodopa. Every recent advance addresses this by achieving continuous dopaminergic stimulation.

Extended-release oral levodopa formulations reduce dosing frequency and smooth plasma levels.

Continuous subcutaneous infusion of levodopa prodrugs and of apomorphine delivers 24-hour dopaminergic stimulation without the need for surgery.

Intrajejunal levodopa-carbidopa gel via PEG-J remains a standard device-aided therapy for advanced disease.

Deep brain stimulation of STN or GPi gives sustained improvement in levodopa-responsive symptoms and reduces dyskinesia; recent observational data show equal efficacy and no excess adverse events in patients over 70.

MR-guided focused ultrasound and gamma knife offer incisionless lesioning for medication-refractory tremor.

Technology in PD — wearable sensors and digital monitoring — is an established area of development for objective measurement of fluctuations.

Dopamine transporter (loflurane) SPECT separates degenerative parkinsonism (abnormal) from drug-induced parkinsonism, vascular parkinsonism, essential tremor and AD (all normal).

No treatment has yet been shown to be disease-modifying. Selegiline and rasagiline were proposed for neuroprotection but this remains unproven.

Strategies "beyond dopamine" — targeting α-synuclein aggregation, LRRK2, GBA and neuroinflammation — are the main direction of current research.

Exercise is an effective intervention in PD and is included in all recent position statements on exercise prescription in older adults.