Parkinson’s Disease Foundation PD ExpertBriefing: Apathy or Depression: Which One Is It? Led By: Dawn Bowers, Ph.D., Professor of Clinical & Health Psychology and Neurology, University of Florida; Director, Cognitive Neuroscience Laboratory at McKnight Brain Institute in Gainesville, FL, and Neuropsychology Director for the UF Center for Movement Disorders and Neurorestoration. This session was held on: Tuesday, June 14, 2016 at 1:00 PM ET. If you have any questions, please contact: Valerie Holt at [email protected]or call (212) 923-4700
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PD ExpertBriefing Apathy or Depression: Which One Is It?
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Parkinson’s Disease Foundation
PD ExpertBriefing: Apathy or Depression: Which One Is It?
Led By: Dawn Bowers, Ph.D., Professor of Clinical & Health Psychology and Neurology, University of Florida; Director, Cognitive Neuroscience
Laboratory at McKnight Brain Institute in Gainesville, FL, and Neuropsychology Director for the UF Center for Movement Disorders
and Neurorestoration.
This session was held on: Tuesday, June 14, 2016 at 1:00 PM ET.
If you have any questions, please contact: Valerie Holt at [email protected] or call (212) 923-4700
Apathy or Depression
Which One Is It?
Dawn Bowers, Ph.D., ABPP-CN Professor
University of Florida
J. Robert Cade, Inventor of Gatorade
University of Florida
UF Center for Movement Disorders & Neurorestoration
UF Center for Movement Disorders and Neurorestoration
Our Motivation: Our patients, our parents, our children
Plan for Today
• Explain difference between apathy & depression
• Discuss why apathy is such a problem in Parkinson’s disease – the what, why, when & how
• Explain why some treatments for depression actually worsen apathy
Difficulty initiating activity Low activity levels Less interested in trying out or learning new things Lack of effort or reduced productivity Not completing tasks that were started Lack of interest in socializing Not concerned about issues that used to be important Needing someone to remind or prompt
Examples of apathetic behavior:
Cognitive Loss of interest, curiosity
Apathy
Behavioral Reduced initiative; Needs others
to structure activities
Emotion Reduced emotional reactivity,
reward
(Marin, 1991)
(Marin, 1991)
Motivation: To move, activate, energize, from Latin, ‘movere’
Lack of motivation; Failure to initiate goal-directed behavior
Apathy as a Syndrome
Apathy: Why is it important?
In many neurologic diseases (AD, stroke, PD), apathy is associated with:
1. Apathy Evaluation Scale (AES) 2. Apathy Scale (AS) 3. Lille Apathy Rating Scale (LARS) 4. Apathy subscale from FrSBe 5. Item 7 from Brief Neuropsychiatric Inventory 6. Item 4 from UPDRS
• 14 item scale, modified from Marin • Are you interested in learning new things? • Does someone have to tell you what to do each day? • Are you indifferent to things?
1. Sad mood 2. Diminished Interest/ Pleasure 3. Weight/appetite loss or gain 4. Insomnia or hypersomnia 5. Slowing or agitation 6. Fatigue/decreased energy 7. Feelings of worthlessness/guilt 8. Indecision/poor concentration 9. Recurring thought of death
* *
At least 2 weeks in dura5on, disrup5ve , change
DiagnosBc Criteria for Major Depression
At least 5 of 9 symptoms, including either or both 1 & 2
Diagnosis of Depression in PD Can Be Difficult
• Features of PD itself (e.g. bradykinesia, fatigue, insomnia, weight loss, flat affect, concentration problems) can be confused with signs and symptoms of depression
• Syndromic criteria as outlined by DSM may not apply in PD
• Currently available depression rating scales were not designed specifically for use in PD
Why It Is Important to Distinguish Apathy & Depression
Relates to treatment • Use of SSRI’s, common medication for
depression, may actually worsen apathy!!
• Retrospective study at UF, N=181 people with Parkinson’s 42% with apathy, 17% with co-occurring depressive symptoms, only 2% had depression only
• Use of SSRI’s, but not other antidepressants associated with increased apathy
Apathy in PD: What We Know
• Distinct from depression • Largely dopaminergic related • Associated with psychophysiological blunting to
emotional pictures (SCR, startle, ERP) • Associated with worsening motor symptoms in medically
managed PD and worsening cognitive status • Associated with older age
Neural Systems Underlying Apathy
• Dopaminergic depletion in brain’s motivation circuitry (mesolimbic, D2)
• Mesolimbic • Mesocortical • Nigro-striatal
Evidence: • Worse apathy if taken off dopa meds • Especially dopamine (D2) agonists • Neuroimaging – decreased binding of dopamine in ventral striatum • DBS - reduction of dopa-meds results in increased apathy; tx with dopa agonists improves this
Apathy is Higher with Greater Disease Severity (Hoehn Yahr)
Hoehn Yahr Stage
Apa
thy
Scal
e Sc
ore
*
*
Kirsch et al (2006)
Apathy Depression
Motor Score
Zahodne et al., 2011
Apathy Worsens with Motor Disease Progression
N=186 idiopathic PD; Tested over 18 month period
Apathy & Depression in PD Relationship to Cognitive Status
Not Demented N=111 Unknown N=80
Demented N=35
0
20
40
60
80
100
36%
80%
51%
24% 26%
48%
Apathy Depression
% o
f Ss
Kellison et al., 2007
Percentage of Patients who were apathetic or depressed
AS & BDI-II cutoffs
Predicting Apathy in Non-demented People with Parkinson’s A
path
y Sc
ale
(AS)
N-111 nondemented people with Parkinson’s
Stroop Interference, Age, & BDI-II
Kirsch-Darrow, 2009
Differential Influence of Apathy & Depression on …
• Relatively few randomized clinical trials – these are ‘gold standard’ • Most studies involve increasing some variant of dopamine • Only a few have made “apathy” the main focus; for most, apathy is
secondary
Pharmacologic
1. Dopamine agonists • Pramipexole vs. Ropinirole (Julez et al., 2015)*
• Piribedil (D2-D3) • Rotigotine (aka Neupro®)
2. Methylphenidate 3. Rivastigmine (Exelon® patch)- (Devos et al, 2014)*
(cholinergic – nondemented PD)
The Restore Study (rTMS)
To learn whether rTMS would improve apathy in people with Parkinson’s PD participants with apathy randomly assigned to rTMS or to Sham condition; Tx = 2 weeks
Apathetic PD N=24 Real rTMS
Sham rTMS
Primary outcome: Apathy Scale Score
Fernandez, Bowers et al.
Brain Stimulation – repetitive Transcranial Magnetic Stimulation
The Restore Study (rTMS)
Results: Terrific! Apathy Improved
Apathetic PD N=24
Real rTMS
Sham rTMS
Fernandez, Bowers et al.
Brain Stimulation – repetitive Transcranial Magnetic Stimulation
Dramatic improvement in apathy, as measured by AS and LARS But true for both groups
WHY? Behavioral Activation? Placebo?
Behavioral Approaches for Improving Apathy
1. Dance Therapy 2. Music Therapy 3. Exercise 4. Cognitive Training 5. Behavioral Activation - PAL program
Cognitive Training
• Studies in normal aging (ACTIVE TRIAL; VITAL) and mild cognitive impairment; improvements and generalization • Changes in dopamine D1 receptors following working memory training (Klingberg et al., 2009) • Tasks: computer based programs; video games, crossword puzzles, bingo, cards, etc.
• Parkinson’s Disease: Several studies in Parkinson’s disease. Improvement in processing speed; trends for apathy. (Pena et al., 2014)
Parkinson’s Active Living (PAL) Butterfield et al., in press
Behavioral Activation & Goal Setting program • developed specifically for Parkinson’s disease • Targeted outcome = apathy • 6 weeks, telehealth
Key Elements • Identified 5 goals during initial in-person session
2 for Week 1, 3 for Wk 2, 4 for Wk 3, all 5 for remaining Weeks • Developed specific plans & schedules • Weekly telehealth session with program coach • I-Ping reminders
Parkinson’s Active Living (PAL) Butterfield et al., in press
This was single arm ‘unblinded’ study Goals – was this feasible & acceptable?
would this approach improve apathy?
Results: Feasibility: 4 of 32 dropped out (12% attrition) Acceptability: satisfaction 87.5 on 100 scale Apathy significantly improved: AES QOL significantly improved No changes in caregiver burden/stress
Goal Setting - cornerstone of motivation • Specific • Attainable (realistic) • Not too easy • Commitment - self-set goals best • Positive feedback - a reward
Implementation • Specific plans – when, where, how • Prepare for potential setbacks
External Cues • Reminders, schedule
Getting Motivated - Best Practices
Other Tips for Motivation
Be SMART in selecting goals
S - specific goals M - measurable A - attainable R - realistic T - timely
From Butterfield et al, in press
Other Tips for Behavioral Activation
UF Brain Activity Guide
Outings Crafts & Hobbies Music Nature In the Home Verbal Skills Games Reminiscing
Bottom Line Apathy is a motivational disorder whereas Depression is a mood disorder Tip: Sadness, guilt, worrisomeness, hopelessness all point to depression. Not apathy. Tip: Decreased initiation, loss of ‘get up and go’ may point to apathy. Apathy worsens with disease progression and is associated with dopaminergic depletion in the brain’s motivational circuits. It has impact on daily activities, treatment outcomes and caregiver distress.
Bottom Line
Treatment approaches are pharmacologic and behavioral • Tip: Make sure patient is on optimal doses of dopa
• Tip: Avoid SSRI’s if possible • Tip: KEEP MOVING; Use some variant of behavioral
activation and goal setting! • Even if patient cannot do own goal setting, keeping
active (behavioral activation) is critical There is great individual variability – what is not
variable is to keep moving…
• I am happy to take questions
• Thank you to my funding sources at the NIH, Michael J. Fox Foundation, the National Parkinson Foundation, and the state of Florida.
• Thank you to the staff at the Parkinson’s Disease Foundation
• For updates, go to http://movementdisorders.ufhealth.ufl.edu
Thank You!
Thank You!
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“My Parkinson’s diagnosis in 2008 may have closed the door on my piloting career, but it opened a new one to the world of woodworking. Through my craft, I have not only found a way to retain my fine motor skills, I have also regained my
purpose.” Carousel Studio, Bart Kadleck
PDF Creativity and Parkinson’s Project
Questions and Discussion
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Resources from PDF
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Parkinson’s HelpLine • Available at (800) 457-‐6676 or [email protected] • Monday through Friday • 9:00 AM – 5:00 PM ET
Fact Sheets • CombaBng Depression
Online Seminars • A Closer Look at Anxiety and Depression in Parkinson's Disease
• Under-‐recognized Nonmotor Symptoms of Parkinson's Disease