Enumerate the motor and non-motor symptoms of Parkinson's disease. What treatment modalities are available and what is the side effect profile of the drugs used, with special reference to the geriatric population? RECURS

Definition. Parkinson's disease is the second most common neurodegenerative disease, caused by loss of substantia nigra neurons with striatal dopamine depletion and α-synuclein Lewy bodies. Prevalence is about 1% over age 65.

Cardinal motor symptoms. Bradykinesia (obligatory), 4–6 Hz rest tremor, rigidity and postural instability. Onset is asymmetric or unilateral and becomes bilateral as the disease progresses.

Other motor symptoms. Difficulty in moving, writing and walking; flexed posture of limbs and trunk; reduced step length and height with reduced arm swing; falls; expressionless face; freezing; dysarthria and dysphagia in advanced disease.

Non-motor — neuropsychiatric and cognitive. Bradyphrenia (slowness of mental function); depression in about 50%; anxiety, mainly generalised anxiety disorder and obsessive–compulsive disorder; visual hallucinations and delusions; PD-related dementia only after several years — cognitive impairment is never a sign of early PD.

Non-motor — autonomic. Dominated by orthostatic hypotension (fall of 20 mmHg systolic or 10 mmHg diastolic within three minutes of standing, often worsened by antiparkinsonian drugs) and constipation in about 50%. Also sweating, drooling, sexual dysfunction, urinary frequency, urgency and dysuria, and delayed gastric emptying in at least 70%.

Non-motor — other. Hyposmia, insomnia, REM sleep behaviour disorder, pain and fatigue. In advanced disease, insomnia, pain, sweats, dysphagia, dysarthria, drooling and urinary dysfunction cluster together.

Levodopa — the mainstay in the elderly. It is the main and often the only treatment for PD in older people, given with a peripheral decarboxylase inhibitor as Madopar (levodopa + benserazide) or Sinemet (carbidopa + levodopa). Effective for tremor, bradykinesia and rigidity. Start low, increase very gradually; usual early control on 300–600 mg/day in 3–4 doses 30 minutes before meals; dispersible form for early-morning akinesia.

Side effect profile of levodopa. Nausea, vomiting, anorexia, orthostatic hypotension; sedation, nightmares, vivid dreams, hallucinations, delusions and delirium (dose-related, especially in the old); and after several years motor fluctuations (delayed on, wearing-off, on–off) with dyskinesias — chorea, athetosis and dystonia.

Other drug classes and their geriatric restrictions. Dopamine agonists are not used in older people with PD and anticholinergics are never used. COMT inhibitors, amantadine and MAO-B inhibitors are adjuncts (see table).

Non-drug modalities and non-motor treatment. Bilateral deep brain stimulation of the STN or GPi for cognitively intact patients with refractory motor complications; rehabilitation started early and timed to the peak effect of levodopa; speech therapy for dysarthria, drooling and swallowing; home support, caregiver education and psychological support. Non-motor symptoms are treated only after adjusting levodopa — venlafaxine for depression, clozapine or pimavanserin for psychosis, rivastigmine for dementia and apathy, droxidopa or midodrine for orthostatic hypotension, macrogol for constipation, domperidone for nausea. Side Effect Profile of Antiparkinsonian Drugs (revision table)

New levodopa delivery systems (2024–25). Crexont (extended-release carbidopa/levodopa capsules) was FDA-approved in August 2024, Vyalev (foslevodopa/foscarbidopa) — the first 24-hour continuous subcutaneous infusion — in October 2024, and Onapgo (subcutaneous apomorphine infusion) in February 2025. Tavapadon, a novel D1/D5 partial agonist, gave an extra 1.1 hours of daily "on" time in Phase 3 TEMPO-3 and is under FDA review.

Adaptive deep brain stimulation (February 2025). The FDA approved Medtronic BrainSense Adaptive DBS on the basis of the ADAPT-PD randomised crossover trial — the first closed-loop system, which titrates stimulation in real time to sensed beta-band local field potentials for patients with motor fluctuations. Contemporary data also show DBS outcomes in patients over 70 are comparable to younger patients, so age alone is no longer a contraindication.