LBDA Webinar Bradley Boeve

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


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


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


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


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


Ne

uro

psy

chia

tric

fe

atu

res Visual hallucinations

Illusions

Delusions

Capgras syndrome

Depression

Anxiety

Agitation/aggressive behaviorM

anag

em

en

t


Therapies:

Aricept, Razadyne, Exelon

SSRIs/SNRIs, melatonin

Seroquel, Zyprexa

Provigil, Nuvigil


NO HALDOL


A B C

A

B

CDA

MOTOR ISSUES

The Parkinson’s disease-like features (parkinsonism) primarily relate to the reduction in DA


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


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


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


Therapies:

Clonazepam, Melatonin

Provigil, Nuvigil


Trazodone, Ambien

Chloral hydrate

Nasal CPAP

Oxygen, Temazepam

Mirapex, Sinemet


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


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

https://www.lbda.org/content/treatment-options

Dementia With Lewy BodiesACTIVE CLINICAL TRIALS

https://www.lbda.org/node/2786

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)


Fun

ctio

nin

g

Age



Rx

DLB



Fun

ctio

nin

g

Age



Rx

DLB



Fun

ctio

nin

g

Age



Rx

DLB


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. ____________________

Health & Medicine

LBDA Webinar Bradley Boeve