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Comprehensive Approach to DLB Management
Bradley F. Boeve, MDDivision of Behavioral Neurology
Department of Neurology Mayo Clinic
Rochester, Minnesota
Comprehensive Approach to DLB ManagementDisclosures
Financial Interests/Other Relationships
Dr. Boeve currently serves as an investigator for clinical trials sponsored by GE Healthcare and Axovant. He does not receive any personal compensation for his involvement in these trials. He also receives research support from the National Institutes of Health (U01 AG045390, U54 NS092089, P50 AG016574, UO1 AG006786, RO1 AG041797), and the Mangurian Foundation.
Off-label and/or Investigational Use
Dr. Boeve will discuss the use of several medications that are not FDA-approved for the indications that are reviewed, which include the use of melatonin, clonazepam, cholinesterase inhibitors, carbidopa/levodopa, dopamine agonists, selective serotonin reuptake inhibitors, atypical neuroleptics, anti-amyloid/tau/alpha-synuclein immunotherapies, memantine, sedative/hypnotics, and psychostimulants for the management of cognitive impairment, neuropsychiatric disorders, parkinsonism, sleep disorders, and autonomic dysfunction. He may also discuss neuroimaging studies that are not FDA-approved for the indications that are reviewed, which include ioflupane SPECT (DaTscan), FDG-PET, amyloid PET and tau PET imaging in the assessment of patients with cognitive impairment and/or parkinsonism.
Dementia With Lewy BodiesOverview
QUESTION:
Which of the following statements is TRUE:
1. All of the symptoms in DLB reflect problems in the brain.
2. Almost all of symptoms of DLB primarily reflect problems related to the chemical known as dopamine.
3. The degrees of neuronal death and brain atrophy are greater in DLB compared to Alzheimer’s disease.
4. The primary way to manage the problematic symptoms in DLB is to use medications.
5. The diagnosis of DLB is not easy, and the management of DLB is highly complex.
Dementia with Lewy BodiesOverview
Dementia with Lewy BodiesOverview
Dementia With Lewy BodiesManagement
Consider symptoms
as they relate to:
Cognitive impairment
Neuropsychiatric features
Motor featuresSleep disorders
Autonomic dysfunction Ask patient/family to
prioritize the most troublesome issues
they seek to change:
• 1. ____________________
• 2. ____________________
• 3. ____________________
Dementia With Lewy BodiesOverview
QUESTION:
Which of the following is LEAST likely to be beneficial for individuals with DLB:
1. Cholinesterase inhibitors (eg, Aricept, Exelon, Razadyne)
2. Traditional neuroleptics (eg, Haldol)
3. Education + counseling
4. Exercise
5. Melatonin
Dementia With Lewy BodiesBrain-Behavior Relationships
A B C
A
B
C
Dementia With Lewy BodiesBrain-Behavior Relationships
Ach
DA
5-HT
HCT
glutamate (Glu)
glycine (Gly)
ABBREVIATIONS
Ach acetylcholine – basal forebrain
HCT hypocretin-1 - hypothalamus
DA dopamine – substantia nigra
5-HT serotonin – raphe nucleus
Glu and Gly Neurotransmitters – dorsal pons
Dementia With Lewy BodiesBrain-Behavior Relationships
A B C
Ach
DA
5-HT
HCT
A
B
C
COGNITIVE ISSUES
Largely due to reduced Ach
Reductions in other brain chemicals contributes to
cognitive impairment
Some degree of neuron cell loss too
Dementia With Lewy BodiesManagement
Co
gnit
ive
imp
airm
en
t
Varying degrees of memory impairment
Verbal blocking
Executive dysfunction
Bradyphrenia
Spatial/geographic disorientation
Visual misidentification
Fluctuations M
anag
em
en
t
Education and counseling
Therapies:
Aricept, Razadyne, Exelon
Namenda
Sinemet, Mirapex, Neupro
Provigil, Nuvigil
Methylphenidate, Adderall
Dementia With Lewy BodiesBrain-Behavior Relationships
A B C
A
B
C
Ach
DA
5-HT
NEUROPSYCHIATRIC ISSUES
Hallucinations and delusions related to
DA imbalance
Depression related to low 5-HT +/- NE
Apathy – many causes
Dementia With Lewy BodiesManagement
Ne
uro
psy
chia
tric
fe
atu
res Visual hallucinations
Illusions
Delusions
Capgras syndrome
Depression
Anxiety
Agitation/aggressive behaviorM
anag
em
en
t
Education and counseling
Therapies:
Aricept, Razadyne, Exelon
SSRIs/SNRIs, melatonin
Seroquel, Zyprexa
Provigil, Nuvigil
Methylphenidate, Adderall
NO HALDOL
Dementia With Lewy BodiesBrain-Behavior Relationships
A B C
A
B
CDA
MOTOR ISSUES
The Parkinson’s disease-like features (parkinsonism) primarily relate to the reduction in DA
Dementia With Lewy BodiesManagement
Mo
tor
dys
fun
ctio
nTremor
Bradykinesia
Rigidity
Myoclonus
Shuffling gait
Stooped posture
Difficulty with fine motor skills
Masked facies
Sialorrhea (drooling)
Man
age
me
nt
Education and counseling, PT, OT,
devices
Therapies:
Sinemet
Mirapex, Requip
Neupro patch
Clonazepam, Neurontin
Dementia With Lewy BodiesBrain-Behavior Relationships
A B C
A
B
C
DA
5-HT
HCT
SLEEP ISSUES
Daytime sleepiness, insomnia, and
fragmented sleep relate in part to the loss in HCT
Acting out dreams (RBD) relates to changes in the
dorsal pons
Reduced DA and 5-HT also affects sleep
Glu, Gly
Dementia With Lewy BodiesManagement
Sle
ep
dis
ord
ers
REM sleep behavior disorder
Excessive daytime somnolence
Insomnia
Obstructive sleep apnea
Central sleep apnea
Restless legs syndrome
Periodic limb movement in sleep
Man
age
me
nt
Education and counseling
Therapies:
Clonazepam, Melatonin
Provigil, Nuvigil
Methylphenidate, Adderall
Trazodone, Ambien
Chloral hydrate
Nasal CPAP
Oxygen, Temazepam
Mirapex, Sinemet
Dementia With Lewy BodiesBrain-Behavior Relationships
AUTONOMIC ISSUES
Many autonomic changes related to changes in the
spinal cord and peripheral nerves in and around the:
nose heart stomach intestines bladder sex organs
Dementia With Lewy BodiesManagement
Au
ton
om
ic d
ysfu
nct
ion
Rhinorrhea
Orthostatic hypotension
Impotence
Urinary incontinence
Constipation Man
age
me
nt
Education and counseling, PT, OT, nonRx measures
Therapies:
Nasal sprays: Flonase, Atrovent
Midodrine, Florinef, salt
Viagra, Cialis
Enablex, Gelnique, Sanctura
Senokot, MiraLAX
Dementia With Lewy BodiesPros and Cons of Medications
Feature AChEI MemantineAtypical
NeurolepticsSSRIs/SNRIs Dopaminergics Sleep Meds Stimulants
Cognitive Impairment
Often improvesSometimes improves
Usually neutral, but can worsen
Usually neutral Usually neutralClonazepam -usually neutral but can worsen
Sometimes improves
Neuro-Psychiatric Features
Often improves VH and delusions and apathy
Sometimes improves
Often improves VH/delusions if dosed appropriately and tolerated
Usually Improves depression; Sometimes improves VH and delusions
Often worsens VH and delusions
Melatonin -sometimes improves VH
Sometimes improves VH
Parkinsonism Rarely worsens Usually neutral Rarely worsens Usually neutralUsually improves, but effects modest
Usually neutral Usually neutral
Sleep - daytime alertness
Often improves Usually neutralOften worsens hypersomnia
Usually neutral Sometimes worsens
Can improve alertness by improving sleep continuity
Often improves
Sleep - RBD Usually neutralSometimes improves
Sometimes improves
Sometimes worsensSometimes improves
Melatonin and Clonazepam usually improve RBD
Usually neutral
Autonomic dysfunction
Sometimes improves OH and constipation
Usually neutralOften worsens OH and ED
Sometimes worsens OH and ED
Often worsens OH Usually neutralCan improve OH, but can worsen supine hypertension
Greater optimism Modest optimism Caution Greater Caution
Legend
Dementia With Lewy BodiesPros and Cons of Medications
Issue/Concern AChEI MemantineAtypical
NeurolepticsSSRIs/SNRIs Dopaminergics Sleep Meds Stimulants
ClinicalNausea, Diarrhea,
SyncopeNCS
Diabetes, StrokeOrthostatism
NCSOrthostatism
or syncope
NCSIncreased BP, Increased HR, Vascular event
Laboratory NCS NCSHyperglycemia, Reduced WBC
NCS NCS NCS NCS
ECGBradycardia, Heart
blockNCS
Prolong QT, Arrhythmia
Prolong QT, Arrhythmia
NCS NCSTachycardia, Arrhythmia
Caution NCS = not clinically significant
Legend
Dementia With Lewy BodiesRESOURCES
https://www.lbda.org/content/treatment-options
Dementia With Lewy BodiesACTIVE CLINICAL TRIALS
https://www.lbda.org/node/2786
Dementia With Lewy BodiesFUTURE PROSPECTS
Fun
ctio
nin
g
Age
REM sleep behavior disorder (RBD)
Asymptomatic/minimally symptomatic
DLB
Prodromal DLB(eg, MCI+RBD)
Dementia With Lewy BodiesFUTURE PROSPECTS
Fun
ctio
nin
g
Age
REM sleep behavior disorder (RBD)
Asymptomatic/minimally symptomatic
Rx
DLB
Prodromal DLB(eg, MCI+RBD)
Dementia With Lewy BodiesFUTURE PROSPECTS
Fun
ctio
nin
g
Age
REM sleep behavior disorder (RBD)
Asymptomatic/minimally symptomatic
Rx
DLB
Prodromal DLB(eg, MCI+RBD)
Dementia With Lewy BodiesFUTURE PROSPECTS
Fun
ctio
nin
g
Age
REM sleep behavior disorder (RBD)
Asymptomatic/minimally symptomatic
Rx
DLB
Prodromal DLB(eg, MCI+RBD)
Dementia With Lewy BodiesSUMMARY
Optimize management of problematic symptoms and quality of life for patients and their families through education, empowerment,
and the use of medication and non-medication approaches
Issues:
Cognitive impairment
Neuropsychiatric features
Motor features Sleep disordersAutonomic dysfunction
Ask patient/family to prioritize the most
troublesome issues they seek to change:
• 1. ____________________
• 2. ____________________
• 3. ____________________