Pharmacological strategies in the Management of alzheimer’s disease

1. Pharmacological strategies in the Management of alzheimer’s disease Daniel Varon, MD Wien Center for Alzheimer’s Disease and Memory Disorders

2. WHAT IS DEMENTIA?

3. CLASSIFICATION OF ABNORMAL COGNITIVE STATES SUBJECTIVE MemoryComplaints No CognitiveorFunctionaldeficits MILD CognitiveImpairment (MCI) Memorycomplaints, somecognitivedeficitsbut NofunctionalDeficits. DEMENTIA Cognitive+ FunctionalDeficits

4. Concept of Dementia NORMAL SUBJECTIVE IMPAIRMENT MILD COGNITIVE IMPAIRMENT DECLINE DEMENTIA TIME

5. Types of dementia

6. Goals of Treatment in Dementia • Improve or preserve ADL function • Reduce caregiver burden • Enhance quality of life • Improve or preserve cognitive function • Improve or preserve behavioral function • Slow deterioration • Manage psychiatric and behavioral symptoms GOALS TARGETS

7. MEDICATIONS IN DEMENTIA SYMPTOMS - COGNITION - Memory, language, orientation, judgment, planning. - BEHAVIOR -Depression, anxiety, agitation, hallucinations, paranoia, aggressiveness. - OTHER - Weight loss, incontinence, gait disturbances, sleep disturbances

8. Treatment NORMAL NATURAL COURSE SUBJECTIVE IMPAIRMENT IDEAL MILD COGNITIVE IMPAIRMENT DECLINE WITH CURRENT TREATMENTS DEMENTIA TIME

9. MEDICATIONS IN DEMENTIA COGNITION Cholinesteraseinhibitors - Aricept – Donepezil - Razadyne – Galantamine - Exelon – Rivastigmine Antagonist of the NMDA glutamate receptor - Namenda – Memantina

10. MEDICATIONS IN DEMENTIA CholinesteraseInhibitors

11. MEDICATIONS IN DEMENTIA ARICEPT – Donepezil Rogers SL, et al. Neurology 1998

12. MEDICATIONS IN DEMENTIA ARICEPT – Donepezil Dose: 5mg dailyfor 4 weeks and thenincreasesto 10mg. Thereis a 23mg formulation. Interactions: - Metabolized in theliver

13. MEDICATIONS IN DEMENTIA RAZADYNE – Galantamine Raskind et al. 2000

14. MEDICATIONS IN DEMENTIA RAZADYNE – Galantamine Dose: 4mg every 12h x 4 weeks 8mg q12h x 4w 12mg every12h Galantamine ER once a day 8, 12, 24mg Interactions: - Metabolized in theliver

15. MEDICATIONS IN DEMENTIA EXELON – Rivastigmine Farlow et al. 2000

16. MEDICATIONS IN DEMENTIA EXELON – Rivastigmine Oral 1.5mg twice a day x 4 weeks 3mg twice a day x 4 weeks 4.5 mg twice a day x 4 weeks 6mg twice a day Patch 4.6mg o 9.5mg Notmetabolized in theliver

17. MEDICATIONS IN DEMENTIA Cholinesteraseinhibitors - Aricept – Donepezil - Razadyne – Galantamine - Exelon – Rivastigmine Sideeffects: - Nausea, vomiting - Diarrhea - Anorexia - Slowheartrate

18. MEDICATIONS IN DEMENTIA NAMENDA – Memantina Reisberg B, et al. NEJM 2003

19. MEDICATIONS IN DEMENTIA NAMENDA – Memantina Dosis: 5mg every 7 days 5mg q12h x 7 days 5mg QAM y 10mg QPM x 7 days 10mg q/12h Interactions: - Notmetabolized in theliver - Excretedthroughthekidneymostlyunchanged (50 - 80%)

20. MEDICATIONS IN DEMENTIA NAMENDA – Memantine

21. Behavioral and Psychological Symptoms of Dementia (BPSD) • Symptoms of disturbed perception, thought content, mood or behavior that frequently occur in patients with dementia. • BPSD leads to increased suffering, early institutionalization, increased cost of care, and causes significant loss in the quality of life for the patient’s caregivers and family. • About two-thirds of people with dementia experience some BPSD at some point during the course of their illness. • The figure may rise to 70-80% among patients with dementia who reside in nursing homes.

22. Common Psychological Changes:Early and Middle Stages of Dementia • Depression • Anxiety • Fear of being alone • Paranoia • Delusions about “imposters” • Accusations of infidelity • Personality changes

23. Behavioral Disturbances:Middles Stages • Wandering • Restlessness • Fidgeting • Pacing • Inappropriate handling of objects • Rummaging • Hoarding • Verbal agitation • Repetitious speech • Verbal aggression • Physical combativeness

24. Appropriate treatment of behavioral symptoms in patients with dementia • Many factors can cause or contribute to behavioral disturbances • Causal and contributing factors must be identified and should inform treatment • Combination of treatment modalities is often necessary to ensure optimal care

25. How does memory impairment lead to behavioral problems? Example Patient is able to dress himself, but can’t remember where his clothes are kept Walks around naked

26. How does language impairment (aphasia) lead to behavioral problems? Example Patient who can’t verbally communicate her dislike of milk Throws milk carton across the room

27. How does impaired recognition (agnosia) lead to behavioral problems? Example Patient can maneuver to pull down his pants, but can’t recognize that a toilet is a receptacle for urination Urinates on floor

28. How does impairment in performance of motor tasks (apraxia) lead to behavioral problems? Example Patient is continent of bladder, but cannot unzip or unbutton to pull down her pants Wets her clothing

29. How does impaired executive functioning lead to behavioral problems? • Example Patient lacks understanding of socially appropriate behavior and is unable to restrain impulses (disinhibition) Talks or behaves in a sexually inappropriate manner in public.

30. Recognize areas of impaired function and areas of preserved function Help compensate for impairment Support residual abilities Initial approach to assessment, management, and prevention

31. What other factors may contribute to behavioral changes in patientswith dementia?

32. Management of Behavioral Disturbances in Dementia • Address unmet physical and psychological needs • Environmental modifications • Treat medical conditions • Treat psychiatric symptoms • Non-pharmacologic interventions • Pharmacologic treatment • Interpersonal strategies / caregiver education

33. Somatic discomfort Pain Constipation Urinary urgency Shortness of breath Dizziness Fatigue Heartburn Headache Medical conditions and somatic discomfort that can lead to behavioral disturbances • Medical condition • Arthritis • Dehydration • Prostatic hypertrophy • COPD • Cerebrovascular disease • CHF • Impaired vision • Impaired hearing • Urinary infection

34. Nonpharmacologic Strategies • Arrange regular exercise • Try to maintain social/family activities • Review photos and souvenirs • Reminisce and tell old stories • Senior centers and day centers • Engaging in tasks and familiar activities within their capacities • Limit expectations

35. Communication Techniques • Use short sentences • Use simple sentence structure, and frequent reminders about content of conversation • Keep concepts focused • Use repetition • Be patient • Be prepared to have the same conversation multiple times • Do not use leading questions if you want to find out information (“You’re hungry, aren’t you?”) • Don’t argue. Don’t expect logic.

36. MEDICATIONS IN DEMENTIA BEHAVIORAL SYMPTOMS

37. MEDICATIONS IN DEMENTIA DEPRESSION SSRI’s - sertraline (Zoloft), citalopram (Celexa), escitalopram (Lexapro). Otherantidepressants - WELLBUTRIN – Bupropion - EFFEXOR – Venlafaxine - CYMBALTA – Duloxetine - REMERON – Mirtazapina

38. MEDICATIONS IN DEMENTIA • DEPRESSION • Antidepressants: • SSRIs: Zoloft – Sertraline Fewinteractions • Celexa – Citalopram EasytotolerateLexapro – Escitalopram • Paxil – Paroxetine More interactions More anticholinergic • Prozac – Fluoxetine Long halflife • More interactions

39. MEDICATIONS IN DEMENTIA Antidepressants: - SSRIs: SelectiveSerotoninReuptakeInhibitors Serotonin - Sideeffects: - Changes in appetite - Nausea - Dizziness - SomnolenceLowsodium (lesscommon) -

40. MEDICATIONS IN DEMENTIA Otherantidepressants: - WELLBUTRIN – Bupropion Notused in patientswithepilepsy - EFFEXOR – Venlafaxine Can increase BP transiently - CYMBALTA – Duloxetine Can cause changes in hepaticfunction Can helpwithchronicpain - REMERON – Mirtazapine Increasessleep and appetite

41. MEDICATIONS IN DEMENTIA PSYCHOSIS - HALLUCINATIONS Visual (Common in LewyBodyDisease ) Auditory Sensory - DELUSIONS (More commonthanhallucinations) Paranoia Confabulation Jealousy

42. MEDICATIONS IN DEMENTIA PSYCHOSIS ATYPICAL (2nd generation) - RISPERDAL – Risperidone - ZYPREXA – Olanzapine - SEROQUEL – Quetiapine - GEODON – Ziprasidone - ABILIFY – Aripiprazole - (Fanapt, Invega, Latuda, Saphris) TYPICAL (1st generation) - HALDOL – Haloperidol ALL ANTIPSYCHOTICS HAVE A BLACK BOX WARNING

43. MEDICATIONS IN DEMENTIA SLEEP ALTERATIONS - Sleep hygiene (initial option) - Trazodone (second option) - Ambien (Zolpidem) - Lunesta (Eszopiclone) - Sonata (Zaleplon) - Temazepam and other benzo’s (last option)

44. MEDICATIONS IN DEMENTIA Urinary incontinence - Behavioral adjustments - Vesicare, Enablex, Detrol, Sanctura less effects on the CNS - anticholinergic - Ditropan – can interfere with memory

45. Treatment and help are available Alzheimer’s disease is not yet curable, but effective treatments are available, and symptoms can be managed