Comprehensive Approach to DLB Management

Transcription

1 Comprehensive Approach to DLB Management Bradley F. Boeve, MD Division of Behavioral Neurology Department of Neurology Mayo Clinic Rochester, Minnesota

2 Comprehensive Approach to DLB Management Disclosures 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/alphasynuclein 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.

3 Dementia With Lewy Bodies Overview QUESTION: 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. Which of the following statements is TRUE: 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.

4 Dementia with Lewy Bodies Overview

5 Dementia with Lewy Bodies Overview

6 Dementia With Lewy Bodies Management Cognitive impairment Autonomic dysfunction Consider symptoms as they relate to: Neuropsychiatric features Ask patient/family to prioritize the most troublesome issues they seek to change: Sleep disorders Motor features

7 QUESTION: Dementia With Lewy Bodies Overview 1. Cholinesterase inhibitors (eg, Aricept, Exelon, Razadyne) Which of the following is LEAST likely to be beneficial for individuals with DLB: 2. Traditional neuroleptics (eg, Haldol) 3. Education + counseling 4. Exercise 5. Melatonin

8 Dementia With Lewy Bodies Brain-Behavior Relationships A B C A B C

9 Dementia With Lewy Bodies Brain-Behavior Relationships ABBREVIATIONS Ach HCT DA 5-HT Glu and Gly acetylcholine basal forebrain hypocretin-1 - hypothalamus dopamine substantia nigra serotonin raphe nucleus Neurotransmitters dorsal pons Ach DA 5-HT HCT glutamate (Glu) glycine (Gly)

10 Dementia With Lewy Bodies Brain-Behavior Relationships COGNITIVE ISSUES A Largely due to reduced Ach Reductions in other brain chemicals contributes to cognitive impairment Some degree of neuron cell loss too A B C HCT B Ach DA 5-HT C

11 Cognitive impairment Management Varying degrees of memory impairment Dementia With Lewy Bodies Management Verbal blocking Aricept, Razadyne, Exelon Executive dysfunction Bradyphrenia Spatial/geographic disorientation Visual misidentification Fluctuations Education and counseling Therapies: Namenda Sinemet, Mirapex, Neupro Provigil, Nuvigil Methylphenidate, Adderall

12 Dementia With Lewy Bodies Brain-Behavior Relationships NEUROPSYCHIATRIC ISSUES A Hallucinations and delusions related to DA imbalance Depression related to low 5-HT +/- NE Apathy many causes A B C B Ach DA 5-HT C

13 Neuropsychiatric features Dementia With Lewy Bodies Management Management Visual hallucinations Illusions Aricept, Razadyne, Exelon Delusions Capgras syndrome Education and counseling Therapies: SSRIs/SNRIs, melatonin Seroquel, Zyprexa Depression Anxiety Agitation/aggressive behavior NO HALDOL Provigil, Nuvigil Methylphenidate, Adderall

14 Dementia With Lewy Bodies Brain-Behavior Relationships MOTOR ISSUES The Parkinson s disease-like features (parkinsonism) primarily relate to the reduction in DA A A B C B DA C

15 Motor dysfunction Dementia With Lewy Bodies Management Management Tremor Bradykinesia Rigidity Myoclonus Shuffling gait Stooped posture Difficulty with fine motor skills Masked facies Sialorrhea (drooling) Education and counseling, PT, OT, devices Therapies: Sinemet Mirapex, Requip Neupro patch Clonazepam, Neurontin

16 Dementia With Lewy Bodies Brain-Behavior Relationships 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 A A B C HCT B DA 5-HT Glu, Gly C

17 Sleep disorders Dementia With Lewy Bodies Management Management REM sleep behavior disorder Excessive daytime somnolence Insomnia Obstructive sleep apnea Central sleep apnea Restless legs syndrome Periodic limb movement in sleep Education and counseling Therapies: Clonazepam, Melatonin Provigil, Nuvigil Methylphenidate, Adderall Trazodone, Ambien Chloral hydrate Nasal CPAP Oxygen, Temazepam Mirapex, Sinemet

18 Dementia With Lewy Bodies Brain-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

19 Autonomic dysfunction Dementia With Lewy Bodies Management Management Rhinorrhea Orthostatic hypotension Impotence Urinary incontinence Constipation Education and counseling, PT, OT, nonrx measures Therapies: Nasal sprays: Flonase, Atrovent Midodrine, Florinef, salt Viagra, Cialis Enablex, Gelnique, Sanctura Senokot, MiraLAX

20 Feature AChEI Memantine Cognitive Impairment Neuro-Psychiatric Features Often improves Often improves VH and delusions and apathy Sometimes improves Sometimes improves Dementia With Lewy Bodies Pros and Cons of Medications Atypical Neuroleptics Usually neutral, but can worsen Often improves VH/delusions if dosed appropriately and tolerated SSRIs/SNRIs Dopaminergics Sleep Meds Stimulants Usually neutral Usually Improves depression; Sometimes improves VH and delusions Parkinsonism Rarely worsens Usually neutral Rarely worsens Usually neutral Sleep - daytime alertness Sleep - RBD Often improves Usually neutral Usually neutral Sometimes improves Often worsens hypersomnia Sometimes improves Usually neutral Usually neutral Often worsens VH and delusions Usually improves, but effects modest Sometimes worsens Sometimes worsens Sometimes improves Clonazepam - usually neutral but can worsen Melatonin - sometimes improves VH Usually neutral Can improve alertness by improving sleep continuity Melatonin and Clonazepam usually improve RBD Sometimes improves Sometimes improves VH Usually neutral Often improves Usually neutral Autonomic dysfunction Sometimes improves OH and constipation Usually neutral Often worsens OH and ED Sometimes worsens OH and ED Often worsens OH Usually neutral Can improve OH, but can worsen supine hypertension Legend Greater optimism Modest optimism Caution Greater Caution

21 Dementia With Lewy Bodies Pros and Cons of Medications Issue/Concern AChEI Memantine Atypical Neuroleptics SSRIs/SNRIs Dopaminergics Sleep Meds Stimulants Clinical Nausea, Diarrhea, Syncope NCS Diabetes, Stroke Orthostatism NCS Orthostatism or syncope NCS Increased BP, Increased HR, Vascular event Laboratory NCS NCS Hyperglycemia, Reduced WBC NCS NCS NCS NCS ECG Bradycardia, Heart block NCS Prolong QT, Arrhythmia Prolong QT, Arrhythmia NCS NCS Tachycardia, Arrhythmia Legend Caution NCS = not clinically significant

22 Dementia With Lewy Bodies RESOURCES

23 Dementia With Lewy Bodies ACTIVE CLINICAL TRIALS

24 Functioning Dementia With Lewy Bodies FUTURE PROSPECTS REM sleep behavior disorder (RBD) Asymptomatic/minimally symptomatic Prodromal DLB (eg, MCI+RBD) DLB Age

25 Functioning Dementia With Lewy Bodies FUTURE PROSPECTS REM sleep behavior disorder (RBD) Asymptomatic/minimally symptomatic Prodromal DLB (eg, MCI+RBD) DLB Rx Age

26 Functioning Dementia With Lewy Bodies FUTURE PROSPECTS REM sleep behavior disorder (RBD) Asymptomatic/minimally symptomatic Prodromal DLB (eg, MCI+RBD) DLB Rx Age

27 Functioning Dementia With Lewy Bodies FUTURE PROSPECTS REM sleep behavior disorder (RBD) Asymptomatic/minimally symptomatic Prodromal DLB (eg, MCI+RBD) DLB Rx Age

28 Dementia With Lewy Bodies SUMMARY Issues: Cognitive impairment Neuropsychiatric features Motor features Sleep disorders Autonomic dysfunction Ask patient/family to prioritize the most troublesome issues they seek to change: 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