Energy and Fatigue

Written by: Kristi Riker OTD, OTR/L

Fatigue in PD is characterized by an abnormal lack of energy and difficulty initiating or sustaining both physical and mental activities. Though this symptom is often overlooked and requires more research, it is highly prevalent, affecting an estimated 36-60% of people with PD. Fatigue often presents as a distinct overwhelming sense of exhaustion that is not proportional to activity level. Fatigue can still be debilitating even with wise management of physical and mental daily tasks. PD fatigue is separate from apathy, depression, and sleepiness, though these often overlap, which can complicate diagnosis, studies, and proper treatment. 

So far, studies have determined multiple potential contributors to fatigue in PD:

• Dopaminergic and Non-Dopaminergic Dysfunction: Disruption does not just occur in dopamine pathways but also in other neurotransmitter systems. Other systems affected include those responsible for transmitting:

  • Serotonin - regulates mood, motivation, sleep/wake cycles

  • Norepinephrine - regulates alertness, attention, mental stamina

  • Acetylcholine - regulates executive functioning, processing speed

  • Glutamate - manages perceived effort of tasks

  • GABA - regulates between excitation and inhibition

  • Hypocretin - regulates wakefulness and energy balance

    
    

• Neuroinflammation: Chronic inflammation in the brain may interfere with energy pathways and neural signaling. It can impair mitochondrial function, which is imperative for energy and it can increase oxidative stress (damages DNA).

  
  

• Genetic Factors: Certain genetic mutations (e.g., GBA, LRRK2, loss of Parkin gene function) correlate with more severe fatigue and may affect mitochondrial function.

  
  

• Metabolic Dysregulation: Altered cellular energy metabolism appears to contribute, possibly through effects on mitochondria and neural energy.

Fatigue treatment is still an evolving area. There is no single FDA-approved medication specifically for Parkinson’s fatigue, so management is typically multifactorial and individualized.

Treatment steps:

• Treat contributing factors: These include depression, anxiety, sleep disorders, blood pressure issues, anemia, thyroid dysfunction, medication side effects, vitamin deficiencies, such as low B12. Treating these first may provide relief and daily energy.

• Medication: Evidence is mixed and results are rarely consistent between individuals. Potential medications include: Rasagiline, Methylphenidate, Modafinil, Levodopa, and antidepressants.

• Exercise: This is the most supported and evidence based treatment for fatigue. Benefits include: improved mitochondrial efficiency, better sleep, improved mood, reduced perceived effort, and increased endurance. Examples of types of exercise that researchers have found to work include: high intensity interval training, aerobic exercise, resistance training, tai chi, dance, and cycling. Even moderate activity can improve energy perception.

• Cognitive Behavioral Therapy: This is an intervention within mental health therapy that focuses on how thoughts, behaviors, emotions, and physical symptoms interact. It is geared towards addressing detrimental fatigue beliefs, modifying avoidance behaviors, improving sleep habits, and increasing activity tolerance. It is especially helpful when fatigue overlaps with anxiety or depression.

• Energy Conservation techniques: Focuses on pacing, task prioritization, environmental modification, breaking activities into steps, and scheduling high-energy tasks during optimal medication windows. This does not eliminate fatigue, but it reduces cycles of energy crashes.

• Sleep optimization: Helps reduce fatigue by evaluating and addressing sleep disorders (REM behavior disorder), insomnia, sleep apnea, and overall sleep hygiene. 

Treatments being researched:

• Anti-inflammatory treatments: Based on findings that chronic inflammation interferes with neurotransmitter signaling and energy metabolism. Current research involves the use of drugs such as NSAIDS and cytokine modulators to target inflammation.

  
  

• Mitochondrial support strategies: Based on the assumption that mitochondrial dysfunction lends to fatigue in PD. Research has been largely experimental and has had mixed results. Experiments have involved use of supplements and agents that support mitochondrial function and reduce oxidative stress.

  
  

• Hypocretin targeted therapies: This neurotransmitter (also called orexin) regulates wakefulness, motivation, and energy balance. Research has centered around drugs that stimulate this neurotransmitter’s receptors to improve alertness.

  
  

• Neuromodulation approaches: These include deep brain stimulation, transcranial direct current stimulation, and transcranial magnetic stimulation. The goal of these is to directly modulate brain circuits linked to energy, motivation, and cognitive stamina.

  
  

• Biomarker-guided treatment selection: Testing is early, but this includes the use of individualized tests such as blood markers, neuroimaging, and genetic profiles to provide individualized therapy.

Fatigue Management Plan

STEP 1: Identify the Type of Fatigue

Ask: When is fatigue the worst? Does medication timing affect it? Does rest improve it?

• Physical fatigue: body feels heavy, low stamina

• Mental fatigue: brain fog, difficulty concentrating

• Motivational fatigue: hard to initiate tasks

• Sleep-related fatigue: unrested despite sleeping

  
  

STEP 2: Rule Out & Treat Contributing Factors

Before assuming “PD fatigue,” screen for:

• Depression, anxiety, insomnia, sleep disorders, etc.

  
  

STEP 3: Optimize Medication Timing

Work with neurology to:

• Align high-demand tasks during “ON” periods

• Avoid scheduling demanding activities during wearing-off

• Consider trial of meds such as Rasagiline or Methylphenidate

  
  

STEP 4: The 4 P’s:

1. Prioritize

• Identify top 1–3 daily “must-do” tasks.

• Let go of nonessential energy drains.

2. Plan

• Schedule high-effort tasks during peak energy.

• Alternate heavy/light activities.

• Break large tasks into smaller segments.

3. Pace

• Stop before exhaustion.

• Use 20–30 minute activity blocks followed by short rest.

• Avoid “boom–bust” cycles.

4. Position

• Sit for tasks when possible.

• Use adaptive equipment.

• Reduce unnecessary walking or carrying.

  
  

STEP 5: Exercise Plan

Evidence supports exercise as one of the strongest fatigue interventions. Regular exercise improves mitochondrial efficiency and reduces perceived effort. Start low, progress gradually.

·         Minimum goal: 3–5 days per week; 20–40 minutes, moderate intensity

·         Include: Aerobic activity (cycling, walking, swimming), resistance training, balance/mobility work, stretching, rock steady boxing!

STEP 6: Sleep Optimization

• Wake up at same time each day

• Reduce daytime naps to less than 30 minutes

• Treat sleep apnea

• Manage REM behavior disorder

• Avoid late caffeine

  
  

STEP 7: Cognitive & Emotional Strategies

• Graded exposure to activity

• Reframing effort perception: 

  • Example: Initial thought - “I don’t have the energy.” ; Reframe: “My brain is signaling high effort. I’ll sit, take breaks, and do half now.”

• Energy journaling:

  •  track daily energy levels, activities completed, rest periods, mood, sleep quality etc. to recognize patterns

• Mindfulness for cognitive overload

  
  

STEP 8: Nutrition & Hydration

• Small frequent meals

• Adequate protein timing (separate from levodopa if advised)

• Stay hydrated (especially with orthostatic symptoms)

• Avoid heavy carb meals midday if they worsen crashes

  
  

STEP 9: Manage Autonomic Load

If orthostatic hypotension contributes:

• Slow positional changes

• Use compression garments

• Adequate salt in diet (if medically appropriate)

• Elevate head of bed

  
  

STEP 10: Weekly Fatigue Tracking

Use a simple scale (0–10) daily and track:

• Sleep hours, exercise, medication timing, stress level, activities completed

Regular exercise – participating 3-5 times a week at Rock Steady is one of the BEST choices you can make for your body in regard to fatigue. Exercise continues to outshine every other non-pharmacological treatment for fatigue. It releases dopamine and improves neural connectivity and activation. It improves mitochondrial function for improved cellular energy, decreases inflammation, enhances sleep quality. Exercise may feel tiring in the short term, but after just a few weeks, it increases baseline energy. So continue what you’re doing! It is making a difference!

Resources:

 Bojtos L, Rodríguez-Antigüedad J, Pagonabarraga J, Martínez-Horta S and Kulisevsky J (2025) Fatigue and neuropsychiatric symptoms in Parkinson’s disease: a narrative review. Front. Neurol. 16:1670644. doi: 10.3389/fneur.2025.1670644

Diaconu S, Monescu V, Filip R, Marian L, Kakucs C, Murasan I, Chaudhuri KR, Jianu DC, Falup-Pecurariu C, Opritoiu B. The Impact of Fatigue on Sleep and Other Non-Motor Symptoms in Parkinson’s Disease. Brain Sciences. 2024; 14(4):397. https://doi.org/10.3390/brainsci14040397

Pitton Rissardo J, Jayasinghe M, Rashidi M, Rashidi F, Moharam H, Khalil I, Dway A, Elhassan WA, Elbadawi MH, Ur Rehman A, Bahar M, Li Y, Fornari Caprara AL, Prathiraja O. Exploring Fatigue in Parkinson's Disease: A Comprehensive Literature Review. Cureus. 2025 Mar 25;17(3):e81129. doi: 10.7759/cureus.81129. PMID: 40276401; PMCID: PMC12019007.

Tinazzi M, Geroin C, Siciliano M, Gandolfi M, Di Vico I, De Micco R, Tessitore A. Pain and fatigue in Parkinson's disease: advances in diagnosis and management. Neurol Sci. 2025 Jun;46(6):2437-2454. doi: 10.1007/s10072-024-07985-9. Epub 2025 Feb 12. PMID: 39937423.