Table 2.

Symptomatic management of 4R-tauopathy

Symptom	Pharmacologic management	Nonpharmacologic management
Motor symptoms
Bradykinesia/rigidity	Levodopa (trial is recommended) Amantadine (second-line) Dopamine agonist (avoid)	Physical/occupational therapy referral
Dysphagia		Speech language pathologist referral Compensatory modifications Comfort feeding/PEG tube
Dystonia	Botulinum toxin (first-line) GABA agonists (use with caution) Dopaminergic/anticholinergic agents (avoid)	Occupational therapy referral Passive stretching Guided muscle relaxation Strengthen antagonist muscles Surgical consultation (severe cases)
Gait freezing	Levodopa (trial is recommended) Amantadine	Walker-mounted laser pointers Visual and rhythmic cues Arc turning
Hypophonia	Levodopa	Lee Silverman Voice Treatment (BIG) Personal voice amplifier
Imbalance/falls	Levodopa (trial is recommended) Vitamin D, calcium Bisphosphonates	Physical/occupational therapy referral Frequent exercise (treadmill) Multicomponent physical activity programs Assistive devices Bone density screening
Motor speech difficulty		Speech language pathologist referral MBS or FEES Augmentative and alternative communication devices
Myoclonus	Levetiracetam (use with caution) Clonazepam (use with caution) Piracetam, gabapentin, and valproic acid (no evidence for use)
Pseudobulbar affect	Dextromethorphan–quinidine	Pocket education cards
Sialorrhea	Botulinum toxin (use with caution) Glycopyrrolate/scopolamine (avoid)	Speech language pathologist referral Occupational therapy referral
Tremor	Levodopa, amantadine (rest tremor) Botulinum toxin (severe dystonic tremor)	Adaptive devices (weighted silverware)
Visual impairment	Artificial tears (dry eyes) Botulinum toxin (blepharospasm, eyelid apraxia)	Neuro-ophthomology referral (prisms) Occupational therapy referral Eyelid crutches (poorly tolerated) Tinted glasses
Weight loss		High-calorie supplementation Favorite foods
Cognitive symptoms
Executive dysfunction		Safety screen Occupational therapy referral Compensatory technology Cardiovascular exercise Heart-healthy diet Cognitive and social engagement Address sleep or mood difficulty
Aphasia		Speech language pathologist referral Audiology screen Augmentative and alternative communication devices Compensatory communication techniques
Memory dysfunction	Acetylcholinesterase inhibitors (avoid if motor or behavioral problems) Memantine (avoid)	Compensatory technology Establishment of a routine Cardiovascular exercise Heart-healthy diet Cognitive and social engagement Address sleep or mood problems
Behavioral symptoms
Problematic behaviors	SSRIs (avoid paroxetine)	DICE model of behavioral intervention Assess for untreated medical or psychiatric problems Address untreated pain Address sleep or mood problems Environmental modification Establishment of a routine/schedule Increase activity (physical activity and hobbies) Cognitive and social engagement Caregiver education and modeling Tailored activity plan
Anxiety/depression	SSRIs (avoid paroxetine) SNRI/buproprion (second-line) TCAs (typically not used) ECT (refractory cases)	Cognitive behavioral therapy (CBT) Mindfulness yoga Guided meditation
Apathy/inertia	“Activating” antidepressants (e.g., SNRI) Methylphenidate (use with caution) Avoid SSRIs (may worsen apathy)	Regular exercise Scheduled activities
Agitation/aggression	SSRIs (e.g., citalopram) Antipsychotics (avoid if possible) Low-dose lithium (avoid if gait problems)	Music therapy Pet therapy Aromatherapy Massage/touch therapy See “Problematic Behaviors”
Other symptoms
Insomnia/fatigue	Melatonin Suvorexant Trazodone (use with caution) Benzodiazepines (avoid if possible)	Regular physical exercise Sleep hygiene Screen for sleep disordered breathing Establish a routine Strategic napping
Urinary control	Mirabegron Antispasmodics (e.g., tolterodine, trospium, solfenacin, darifenacin) Anticholinergics (e.g., oxybutynin; avoid if possible) Botulinum toxin	Referral to urology Bladder training Pelvic floor exercises Electrical stimulation techniques Adult pads
Constipation	Polyethylene glycol, senna, lactulose Bisacodyl suppository	Increase fluid intake High-fiber diet Regular physical activity