Apathy or Depression: Which One Is It? - Parkinson's Foundation
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
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 vholt@pdf.org or call
(212) 923-4700
Apathy or Depression
Which One Is It?
Dawn Bowers, Ph.D., ABPP-CN
Professor
University of Florida
University of Florida J. Robert Cade, Inventor
of Gatorade
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 • Tips for improving apathy
Neuropsychiatric Features of
Parkinson’s Disease
Frightened
Depression
Apathy
Anxiety
Happy
Basal Ganglia Loops
Disgusted
20% reducation amygdala volume
30-45% reduction dopamine binding
Apathy vs. Depression
Depression Apathy
THESIS: Depression = Mood disorder
Apathy = Motivational disorder
signature of PD progression
Motivation – from the Latin “movere”, to move
What is Apathy ? Disorder of motivation Examples of apathetic behavior: 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
Apathy as a Syndrome
(Marin, 1991)
Cognitive
Loss of interest, curiosity
Emotion
Apathy
Reduced emotional reactivity,
Lack of motivation; reward
Failure to initiate goal-
directed behavior
Behavioral
Reduced initiative; Needs others
to structure activities
(Marin, 1991) Motivation: To move, activate, energize, from Latin, ‘movere’
Apathy: Why is it important? In many neurologic diseases (AD, stroke, PD), apathy is associated with: • Reduced daily functioning (ADL’s & IADL’s) • Increased caregiver stress/distress • Poor illness outcome • Poor treatment compliance • Worse rehabilitation outcome
Average Time Spent in Various Activities by
People with Parkinson’s with & without Apathy
Over a 5 Day Period
Apathy Group Not Apathy Group
Beata Ferencz, 2009
Master’s thesis – UF & U. MaastrichtMeasuring Apathy in PD
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
MDC Consensus panel, Leentjens et al., 2008), recommend #2 & #6Apathy Scale
Starkstein et al., 1992
• 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?
• 3
Versions:
Self-‐report,
clinician
raBng,
family
raBng
• Reasonable
psychometrics
• Criterion
validity
-‐
novelty
toy
task
• Test-‐retest
Most widely used in PD Ferencz, et al., 2012Lille Apathy Rating Scale (LARS)
Sockeel et al., 2006
33 item semi-structured interview tapping 9 domains, items are scored
yes-not except 1st three items; takes 20 minutes to administer
9 DOMAINS 4 Composite Subscales
Everyday productivity
Interests Intellectual Curiosity
Taking initiative Emotion
Novelty seeking Action Initiation (AI)
Voluntary actions Self-Awareness (SA)
Emotional responses
Concern TOTAL SCORE
Social life -36 (normal) to +36 (abnormal)
Self-awarenessAssessing Apathy using Item 4 from
the UPDRS
0= normal
1= more passive
2= less initiative/disinterest
3= routine events affected
4= withdrawn, total lack
N=301 Idiopathic PD
Easy, but it lacks right mix of
sensitivity/specificity
Correlates with AS, but has
mediocre ROC, miss too many
folks at 0 and 1
Bottom Line: Don’t use
UPDRS = unified parkinson’s disease rating scale Kirsch-Darrow et al., 2009)Our Recommendation
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
MDC Consensus panel, Leentjens et al., 2008), recommend #2 & #6, also 3Prevalence-Incidence of Apathy
in PD
• Prevalence/incidence depends on how apathy is
assessed – estimates range from 12% to 70% across
studies
• Tricky, since no formally recognized diagnostic criteria
for apathy
• Recent meta-analysis: almost 40% across 23 studies;
apathy associated with lower MMSE, higher UPDRS, older
age (den Brok et al. 2015)Proposed Apathy Diagnostic Criteria
Starkstein & Leentjens, 2008; adapted from Marin, 1991
A. Lack of motivation relative to previous level of
functioning or societal norms
B. Presence of at least 1 symptom from each of 3 domains
must be present for at least 4 weeks
1. Diminished goal-directed behavior
e.g., requires others to structure activity, lack of effort
2. Diminished goal-directed Cognition
e.g., lack of interest in new experiences, decreased curiosity
3. Diminished emotion reactivity
e.g., emotional blunting, decreased physiological reactivityProposed Diagnostic Criteria
Starkstein & Leentjens, 2008; adapted from Marin, 1991 continued
C. Symptoms cause clinically significant distress
or impairment in social, occupational, & other
areas of functioning
D. Symptoms not due to reduced level of
consciousness or direct physiological effects
of substance (meds, drug abuse, etc.)Depression in PD
Depressive Disorders Mood Fluctuations
• e.g. major depression, • e.g. shifts from dysphoric to
dysthymia euphoric
• last from weeks to years • change many times daily
• can occur at any stage of • occurs mostly in patients who
illness have developed motor
fluctuationsDiagnosing Depression • Clinical interview • Depression Scales • Self-Rating (Beck; Geriatric Depression Scale) • Clinician Ratings (Hamilton, MADRS) • DSM-V criteria • Structured Clinical Interview (SCID)
DiagnosBc
Criteria
for
Major
Depression
At least 5 of 9 symptoms, including either or both 1 & 2
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
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 PDCourtesy of H Fernandez
Telling Depression & Apathy Apart
Unique & Overlapping Symptoms
Depression Apathy
symptoms symptoms
Overlap
Sadness Anhedonia Decreased initiative
Worthlessness Less enthusiasm Less interest in starting
Guilt about usual new activities
Hopelessness interests
Less interest in world
Increased slowness
Helplessness Emotional indifference
Pessimism Decreased emotional
Suicidal ideation reactivity
Unique & Overlapping Symptoms in Apathy and Depression
Zahodne et al., 2012; Pagonabarraga et al, 2015Why 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 apathyApathy 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 • Mesolimbic
• Mesocortical
in brain’s motivation circuitry • Nigro-striatal
(mesolimbic, D2)
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 thisApathy is Higher with Greater
Disease Severity (Hoehn Yahr)
Apathy Scale Score
*
*
Hoehn Yahr Stage
Kirsch et al (2006)Apathy Worsens with Motor Disease
Progression
N=186 idiopathic PD; Tested over 18 month period
Motor Score
Apathy Depression
Zahodne et al., 2011Apathy & Depression in PD
Relationship to Cognitive Status
100
Percentage of Patients who were apathetic or depressed
80
80%
Not
Demented
N=111
60
51% 48% Unknown
% of Ss
36% N=80
40
Demented
24% 26% N=35
20
0
Apathy Depression AS & BDI-II cutoffs
Kellison et al., 2007Predicting Apathy in Non-demented
People with Parkinson’s
N-111 nondemented people with Parkinson’s
Apathy Scale (AS)
Stroop Interference, Age, & BDI-II
Kirsch-Darrow, 2009Differential Influence of Apathy &
Depression on …
Cognition
Behavior
Emotion PsychophysiologyBehavior: Novelty Toy Task
Ferencz et al (2012)
Lab based task of % Time Playing
exploration with Toys
100
80
% time (10 min)
60 81%
40 *
20 38%
0
Apathy Nonapathy
GROUP
Ferencz, et al., 2012Emotion Reactivity
Psychophysiology blunting
• Skin conductance, startle
• Hypoarousal
Electrophysiology blunting
• Reduced ERP to emotion pix
• Reduced novelty detection (P300)
Bowers et al., 2006; Miller et al., 2009, Dietz et al, 2015; Kaufman et al., 2016To Recap
•
Apathy
common
in
PD,
disBnct
from
depression
•
Occurs
in
both
demented
and
non-‐demented
PD
• Best
cogniBve
predictors
of
apathy
in
non-‐demented
PD
are
“frontal”
tasks
such
as
the
Stroop
•
Associated
with
physiologic
blunBng
to
emoBonal
pictures
•
Related
to
disease
severity
and
age.
Implication Apathy is an intrinsic part of
Parkinson’s diseaseApathy in PD:
What we don’t know
• Is apathy merely a signature for disease
progression?
• How to best treat apathy? What are the best
approaches for bolstering motivation and drive?
• Pharmacologic
• NonpharmacologicApathy Treatment
Adcock et al, Neuron, 2016
Pix from KQED News, NPRApathy Treatment
No “silver bullet”
Pharmacologic
Nonpharmacologic
• Stimulation (rTMS)
• Behavioral approachesPharmacologic
• 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
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)
Brain Stimulation – repetitive Transcranial Magnetic Stimulation
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
Sham rTMS
Apathetic PD
N=24
Real rTMS
Primary outcome: Apathy Scale Score
Fernandez, Bowers et al.The Restore Study (rTMS)
Brain Stimulation – repetitive Transcranial Magnetic Stimulation
Results: Terrific! Apathy Improved
Dramatic improvement in
Sham rTMS apathy, as measured by AS
Apathetic PD and LARS
N=24
Real rTMS
But true for both groups
WHY? Behavioral Activation?
Placebo?
Fernandez, Bowers et al.Behavioral Approaches for
Improving Apathy
1. Dance Therapy
2. Music Therapy
3. Exercise
4. Cognitive Training
5. Behavioral Activation - PAL programCognitive 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 remindersParkinson’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/stressGetting Motivated - Best Practices 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
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 pressOther Tips for Behavioral
Activation
UF Brain Activity Guide
Outings
Crafts & Hobbies
Music
Nature
In the Home
Verbal Skills
Games
Reminiscing
dawnbowers@phhp.ufl.eduBottom 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
medications, particularly dopamine agonists (if
possible)
• 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…Thank You! • 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!
“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
53
Questions and Discussion
54
Resources from PDF
Fact
Sheets
Online
Seminars
• CombaBng
• A
Closer
Look
at
Depression
Anxiety
and
Depression
in
Parkinson's
Disease
• Under-‐recognized
Nonmotor
Symptoms
of
Parkinson's
Disease
Parkinson’s
HelpLine
•Available
at
(800)
457-‐6676
or
info@pdf.org
•Monday
through
Friday
•9:00
AM
–
5:00
PM
ET
55
You can also read
