1. Curtin University is a trademark of Curtin University of Technology CRICOS Provider Code 00301J Curtin University is a trademark of Curtin University of Technology CRICOS Provider Code 00301J Dr Kreshnik Hoti BPharm, MPS, AACPA, PhD Best Practice Pharmacy Dementia care

2. Curtin University is a trademark of Curtin University of Technology CRICOS Provider Code 00301J 2 Learning outcomes  Develop and understanding on medications used in dementia  Identify medications that can worsen cognition  Develop an understanding on medication related monitoring needs and outcomes in patients with dementia  Develop an understanding on pharmacists’ role in Dementia care

3. Curtin University is a trademark of Curtin University of Technology CRICOS Provider Code 00301J What is dementia?  Latin word ‘demens’  Broad term  Symptoms descriptive of a range of conditions Brain function impairment Language, memory, perception, personality and cognitive skills  >65 years of age, likelihood doubles in 5 year intervals

4. Curtin University is a trademark of Curtin University of Technology CRICOS Provider Code 00301J Definition (WHO) “a syndrome due to disease of the brain, usually of a chronic or progressive nature, in which there is disturbance of multiple higher cortical functions, including memory, thinking, orientation, comprehension, calculation, learning capacity, language, and judgement. Consciousness is not clouded. The impairments of cognitive function are commonly accompanied, and occasionally preceded, by deterioration in emotional control, social behaviour, or motivation. This syndrome occurs in Alzheimer’s disease, in cerebrovascular disease, and in other conditions primarily or secondarily affecting the brain”

5. Curtin University is a trademark of Curtin University of Technology CRICOS Provider Code 00301J Early signs  Ability to learn and remember new information  Difficulties with tasks which are familiar Progression  More basic activities affected  Higher mental function impairment progress over months to years

6. Curtin University is a trademark of Curtin University of Technology CRICOS Provider Code 00301J Cognitive, psychiatric and behavioural symptoms  memory problems  communication difficulties  confusion, wandering, getting lost  personality changes and behaviour changes such as agitation, repetition, following  depression, delusions, apathy and withdrawal

7. Curtin University is a trademark of Curtin University of Technology CRICOS Provider Code 00301J Dementia – national figures Source: Alzheimer’s Australia 280.000 Australians 1600 new cases weekly 3 rd leading cause of death Worldwide cost: US$604 billion in 2010

8. Curtin University is a trademark of Curtin University of Technology CRICOS Provider Code 00301J Source: Alzheimer’s disease international; World Alzheimer’s report 2010. The global economic impact of dementia

9. Curtin University is a trademark of Curtin University of Technology CRICOS Provider Code 00301J Dementia major contributor to disability Source: World Health Organization. World Health Report 2003— Shaping the future. Geneva: WHO, 2003.

10. Curtin University is a trademark of Curtin University of Technology CRICOS Provider Code 00301J Dementia predictions  35.6 million worldwide  4.6 million cases every year  People affected double every 20 years  81.1 million people affected by 2040

11. Curtin University is a trademark of Curtin University of Technology CRICOS Provider Code 00301J Dementia predictions cont’d Ferri et al. Global prevalence of dementia: a Delphi consensus study. Lancet 2005; 366: 2112–17

12. Curtin University is a trademark of Curtin University of Technology CRICOS Provider Code 00301J Dementia – causes 62% (Alzheimer’s disease) 17% (vascular dementia) 10% (mixed dementia) 3% (other) 2% (fronto- temporal) 4% (lewy bodies)

13. Curtin University is a trademark of Curtin University of Technology CRICOS Provider Code 00301J Dementia – causes Alzheimer’s disease causes: Biological Genetics Inflammation

14. Curtin University is a trademark of Curtin University of Technology CRICOS Provider Code 00301J Risk factors  Modifiable: Obesity Smoking Physical activity and exercise Alcohol Cognitive reserve *head injury

15. Curtin University is a trademark of Curtin University of Technology CRICOS Provider Code 00301J Risk factors  Treatable medical conditions: stroke diabetes midlife hypertension midlife hypercholesterolemia hyperhomocysteinaemia depression (?)

16. Curtin University is a trademark of Curtin University of Technology CRICOS Provider Code 00301J Risk factors  Non-Modifiable: age family history small head size male gender

17. Curtin University is a trademark of Curtin University of Technology CRICOS Provider Code 00301J Treatment  Patients and family involvement as soon as diagnosis is made  Support for daily activities  Address co-existing medical conditions  Avoid medications exacerbating cognitive function  Treat Vitamin B12 or folate deficiency if present

18. Curtin University is a trademark of Curtin University of Technology CRICOS Provider Code 00301J Treatment  No cure  None of the available drugs prevent Alzheimer’s or modifies its pathology  Symptoms such as memory loss and confusion may be reduced (for a limited time)  Acetylcholinesterase inhibitors& memantine  Combination

19. Curtin University is a trademark of Curtin University of Technology CRICOS Provider Code 00301J Treatment - Acetylcholinesterase inhibitors Donepezil Galantamine Rivastigmine  Decrease the breakdown of acetylcholine and therefore reduce the deficiency of cholinergic neurotransmitter activity  First line agents

20. Curtin University is a trademark of Curtin University of Technology CRICOS Provider Code 00301J Treatment - Acetylcholinesterase inhibitors  25-50% of patients experience delayed deterioration of cognition by 6 months  12-20% of patients by 1 year  Benefits in cognition, function and global outcomes (MMSE gain 1.5-2 points)  Benefits assessed after 3 months

21. Curtin University is a trademark of Curtin University of Technology CRICOS Provider Code 00301J Acetylcholinesterase inhibitors-ADVERSE EFFECTS  Incidence related to dose  Use in some patients is limited by adverse effects, especially gastrointestinal  Common: nausea, vomiting, loss of appetite, diarrhoea  Commonly increase bladder and bowel urgency and contribute to incontinence

22. Curtin University is a trademark of Curtin University of Technology CRICOS Provider Code 00301J Treatment - memantine  AD associated with excess glutamate, therefore memantine reduces glutamate-induced neuronal degradation  Specialist initiated  Moderate to severe AD  Benefits in cognition, function, global outcome  Common adverse effects: Headache, constipation, confusion and dizziness

23. Curtin University is a trademark of Curtin University of Technology CRICOS Provider Code 00301J Treatment summary GenericDosage formDoseApproved forContraindicated Donepezil (Aricept) tablet5mg up to 10mg evening All stagesGI/ureteric obstruction; Active PU Galantamine (Reminyl, Galantyl) CR capsule8mg daily up to 16mg morning with food Mild to moderateSevere hepatic impairment; CrCl <10 mL/minute; GI/ureteric obstruction; Active PU Rivastigmine (Exelon) Capsule, oral liquid, patch Oral: 1.5mg BD up to 6mg BD CC Patch: 4.5mg up to 9.5mg daily Mild to moderateSevere hepatic impairment; GI/ureteric obstruction; Active PU Memantine (Ebixa) Tablet5 mg up to 20mg daily Moderate to severe History of seizures

24. Curtin University is a trademark of Curtin University of Technology CRICOS Provider Code 00301J Pharmaceutical Benefits Scheme implications  Acetylcholinesterase inhibitors and memantine require authority approval  Donepezil example: INITIAL APPLICATION FOR THE TREATMENT OF MILD TO MODERATELY SEVERE ALZHEIMER'S DISEASE - Patients with an (S)MMSE of 10 or more Confirmation of diagnosis must be made by or in consultation with a specialist/consultant physician (including a psychiatrist). To continue treatment: patient demonstrated improvement in cognitive function

25. Curtin University is a trademark of Curtin University of Technology CRICOS Provider Code 00301J Vitamins and supplements Do they help?  B vitamins  Omega 3  Mediterranean diet  Vitamin E  Ginkgo Biloba  Aspirin  Brahmi

26. Curtin University is a trademark of Curtin University of Technology CRICOS Provider Code 00301J Other agents  Statins  Testosterone  Oestrogen  Anti-inflammatory agents  Selegiline  Future therapies

27. Curtin University is a trademark of Curtin University of Technology CRICOS Provider Code 00301J Medications negatively affecting dementia Drugs with anticholinergic effects (Australian Medicines Handbook 2012) amantadine, amitriptyline, atropine belladonna alkaloids, benzhexol, benztropine, biperiden, brompheniramine chlorpheniramine, chlorpromazine, clomipramine, clozapine, cyclizine, cyclopentolate, cyproheptadine darifenacin, dexchlorpheniramine, dimenhydrinate, diphenhydramine, disopyramide, dothiepin, doxepin glycopyrrolate homatropine, hyoscine (butylbromide or hydrobromide) imipramine, ipratropium (nebulised) mianserin nortriptyline olanzapine, orphenadrine, oxybutynin pericyazine, pheniramine, pizotifen, prochlorperazine, promethazine, propantheline solifenacin tiotropium, tolterodine, trimeprazine, trimipramine, triprolidine, tropicamide

28. Curtin University is a trademark of Curtin University of Technology CRICOS Provider Code 00301J Medications negatively affecting dementia  Anticholinergic Cognitive Burden (ACB) Score 1-3 Definite anticholinergics score 2&3 Every definite anticholinergic increases the risk of cognitive impairment by 46% over 6 years 1 point increase in ACB score = 0.33 decline in MMSE over 2 yrs  Antipsychotics  Sedatives  Tricyclic antidepressants

29. Curtin University is a trademark of Curtin University of Technology CRICOS Provider Code 00301J Behavioural and psychological symptoms in dementia (BPSD)  Challenging & distressing  Causes: Brain cells progressively deteriorate Environmental Medications

30. Curtin University is a trademark of Curtin University of Technology CRICOS Provider Code 00301J BPSD  Early stages: irritability anxiety depression  Later stages: aggression agitation emotional distress hallucinations outbursts delusion sleep disturbances restlessness

31. Curtin University is a trademark of Curtin University of Technology CRICOS Provider Code 00301J BPSD Review/Treat potential underlying causes:  Possible physical causes of distress or delirium Pain, dehydration, LUTS, infection…  Medications which impair cognition  Environmental factors  Depression

32. Curtin University is a trademark of Curtin University of Technology CRICOS Provider Code 00301J BPSD treatment  Non-drug options – first line  Antipsychotics (hallucinations, delusions or seriously disturbed behaviour)  Mood stabilizers such as carbamazepine or valproate  Antidepressants  Acetylcholinesterase inhibitors or memantine  Anxiety and agitation (oxazepam for no longer than 2 weeks)

33. Curtin University is a trademark of Curtin University of Technology CRICOS Provider Code 00301J Antipsychotics – considerations:  Risperidone approved for BPSD  Recommended for use when symptoms cause severe distress or immediate risk of harm  Monitor if behaviour improved and adverse effects tolerated  Therapy reviewed every three months  Many troublesome symptoms do not respond  BPSD often resolves spontaneously within 12 weeks  Antipsychotics increase the risk of death in BPSD patients

34. Curtin University is a trademark of Curtin University of Technology CRICOS Provider Code 00301J Pharmacists’ role  Refer patients with suspected cognitive impairment  Early diagnosis  Patient & family counselling and education  Promotion of risk reduction strategies

35. Curtin University is a trademark of Curtin University of Technology CRICOS Provider Code 00301J Pharmacists’ role  Source of information Patient, Family, Health professionals  Monitoring drug interactions  Monitoring drug contraindications  Monitor medication compliance

36. Curtin University is a trademark of Curtin University of Technology CRICOS Provider Code 00301J Pharmacists’ role  Dose administration aids  Medication reviews Medication usage reviews Home medication reviews  Identifying medications contributing/exacerbating cognitive decline  Quality use of medicines

37. Curtin University is a trademark of Curtin University of Technology CRICOS Provider Code 00301J References  Australian Medicines Handbook 2012  eTherapeutic Guidelines, Neurology  Alzheimer’s Australia; http://www.fightdementia.org.au Alzheimer’s Australia; http://www.fightdementia.org.au  Alzheimer’s Association; www.alz.org Alzheimer’s Association; www.alz.org  Ballard et al. Alzheimer’s disease. Lancet 2011; 377: 1019–31  Ferri et al. Global prevalence of dementia: a Delphi consensus study. Lancet 2005; 366: 2112–17  Alzheimer’s disease international; World Alzheimer’s report 2010. The global economic impact of dementia  World Health Organization. World Health Report 2003—Shaping the future. Geneva: WHO, 2003.  McCullagh CD et al. Risk factors for dementia. Advances in Psychiatric Treatment 2001; 7:24–31  Australian Institute of Health and Welfare 2007. Dementia in Australia. National data analysis and development  Archer et al. The effects of commonly prescribed drugs in patients with Alzheimer’s disease on the rate of deterioration. J Neurol Neurosurg Psychiatry 2007;78:233–239.  The Aging Brain Program at the IU Center for Aging Research. Anticholinergic Cognitive Burden List (ACB). 4/4/12  Campbell N, Boustani M, Limbil T, Ott C, et al. The cognitive impact of anticholinergics: a clinical review. Clinical Interventions in Aging. 2009;4(1):225-33