Table 1.

Personalized medicine approaches by PD subtype

Subtype		Therapeutic strategy
Age	Young onset	• Monitor for emergence of motor fluctuations and dyskinesias • Consider dopamine agonists to delay motor complications
	Older onset	• Caution when using dopamine agonists, anti-cholinergics, or deep brain stimulation • Consider the role of co-pathology (e.g., Alzheimer’s disease or cerebrovascular disease), if atypical cognitive or motor features appear
Motor	Tremor dominant	• May consider anti-cholinergic drugs, clozapine, or deep brain stimulation for levodopa-refractory tremor affecting quality of life
	Akinetic-rigid	• Early referral to physical therapy to reduce fear of falling and prevent falls • Consider GPi as a deep brain stimulation target (vs. STN) for significant gait impairment
Nonmotor	Cholinergic: Early cognitive decline and falls	• Consider intervention with cholinesterase inhibitors, e.g., rivastigmine (E) • Avoid anti-cholinergics from the onset or drugs with anti-cholinergic potential as well as dopamine agonists, unless specifically required • Early bone health screening to ensure optimal management of osteoporosis due to higher risk of falls and fractures • Physiotherapy and exercise programs focused on gait and falls prevention
	Noradrenergic: dysautonomia, esp. delayed gastric emptying and constipation	• Monitor for postural hypotension, treat as required, e.g., droxidopa (E) • Monitor for constipation, treat as required, e.g., polyethylene glycol (E), lubiprostone (E), probiotics (LE) • Screen for delayed gastric emptying. • Consider use of nonoral dopaminergic therapies • Screen and counsel for RBD • Lifestyle advice for peripheral sympathetic dysfunction such as peripheral pain and thermoregulatory function
	Serotonergic: somnolence, fatigue	• Avoid dopamine agonists with a D3 activity (e.g., pramipexole, ropinirole) • Consider proactive recognition and treatment of fatigue, e.g., rasagiline (E) • Evaluate and treat sleep-disordered breathing (continuous positive airway pressure, E), if present • Lifestyle advice regarding driving and other hazardous occupations, in which sleepiness could be a problem
Genetic subtypes	GBA-PD	• Avoid use of anti-cholinergics and dopamine agonists in cognitive impairment • Cautious use of deep brain stimulation given poorer outcomes
	LRRK2-PD	• As in idiopathic PD

E = efficacious; LE = likely efficacious (according to the International Parkinson’s and Movement Disorders Society Evidence-Based Medicine Review [55])