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The Management of Alzheimer’s Disease

The Management of Alzheimer’s Disease. Laurel Coleman, MD Maine Medical Center Portland, Maine. Management of Alzheimer’s Disease. Manage cognitive symptoms. Increased quality of life for patient and family. Manage BPSD. Support patient/family. Pharmacologic Options for AD.

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The Management of Alzheimer’s Disease

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  1. The Management of Alzheimer’s Disease Laurel Coleman, MD Maine Medical Center Portland, Maine

  2. Management of Alzheimer’s Disease Managecognitive symptoms Increased quality of life for patient and family Manage BPSD Support patient/family

  3. Pharmacologic Options for AD • Cognitive enhancers • 2 classes • Cholinesterase inhibitors (ChEIs) • NMDA-receptor antagonist • Do not cure the disease or reverse cognitive impairment • Can improve cognition and functional ability • Reduce the rate of decline 9-12 months (ChEIs) • Delay in nursing home placement was 17-21 months (ChEIs)

  4. Management of Alzheimer’s Disease: Cognitive Enhancers *Available in generic Aricept® package insert. Razadyne® package insert. Exelon® package insert.

  5. Pharmacologic Options for ADCommon Side Effects Aricept® package insert. Razadyne® package insert. Exelon® package insert.

  6. Switching ChEIs Lack or loss of therapeutic benefit Immediate switchNo washout needed Washout period of 1-2 weeks before starting another agent Tolerability issues Try an alternate dosage form before switching Noncompliance

  7. Discontinuation of Therapy • Data for optimal duration of treatment as disease progresses is limited • Modest cognitive and functional benefits associated with continued therapy with (donepezil) in moderate to severe AD1 • Discontinuation associated with adverse behavioral changes and reduced participation in activites2 • Consider discontinuation in the following situations: • Inability to tolerate multiple ChEIs • No improvement or greater than expected decline after one or more therapeutic trials • End-stage dementia • Howard et al. New Engl J Med. 2012;366:893-903. • Daiello et al. Am J Geriatr Pharmacother. 2009;7:74-83.

  8. Impact of Coexisting Medical Conditions 2.4 conditions/pt HTN 82% DM 39% CAD 21% CHF 14% Stroke 10% Cognitive Impairment Prevalence of coexisting conditions in PWD Schubert CC, et al. J Am Geriatr Soc. 2006;54(1):104–109.

  9. Impact of Coexisting Medical Conditions • PWD in primary care average 5.1 medications/pt1 • 50% take ≥1 anticholinergic medications • Medications with anticholinergic activity • Impairs cognition acutely (delerium) and chronically2 • Anticholinergic burden • Interfere with the therapeutic effect of ChEIs3 1. Schubert CC, et al. J Am Geriatr Soc. 2006;54(1):104–109. 2. Campbell N, et al. Clin Interv Aging. 2009;4:225–233. 3. Lu C, Tune LE. Am J Geriatr Psychiatry. 2003;11(4):458–461.

  10. Disinhibition Euphoria Loss of appetite Sleep disturbances Stereotyped behaviors (eg, pacing, wandering, rummaging, picking Behavioral and Psychological Symptoms of Dementia (BPSD) • Apathy • Depressive symptoms • Anxiety • Agitation/irritability/aggression • Psychotic symptoms • Delusions • Hallucinations Tampi et al. Clinical Geriatrics. 2011;19:41-46.

  11. Managing BPSD • Identify triggers • Observe symptom timing and frequency • Look for environmental triggers, eg noise, lighting • Investigate potentially treatable causes, eg pain • Make adjustments • Address medical causes • Adapt environment • Adapt caregiving • Modify as needed

  12. Managing BPSDNonpharmacological Interventions • Use the “3 Rs”—repeat, reassure, redirect • Simplify the environment, task, routine • Anticipate unmet needs • Allow adequate rest between stimulating events • Use cues • Encourage physical activity • Other interventions

  13. Managing BPSD:Pharmacologic Interventions *2nd-generation antipsychotics Adapted from Tampi et al. Clin Geriatr. 2011;19:31-32.

  14. Alzheimer’s Disease Education of Patientand Family

  15. Education of Patient and Family • Safety issues: • Home environment • Driving • Medication adherence • Financial exploitation • Elder abuse • Address future needs: financial planning, advanced directives, power of attorney

  16. Education of Patient and FamilyMedications • Define treatment success • Symptomatic benefit in • Cognition • Physical function and ADLs • Behavior • Increases time to nursing home placement • Discuss length of therapy • Adequate trial is 6 months Cummings JL. Am J Geriatr Psychiatry. 2003;11(2):131–145. Doody RS, et al. Arch Neurol. 2001;58(3):427–433.

  17. Impact on CaregiversTasks Change Over Time • Late stage • Help with all personal care • Cope with unresponsiveness and end-of-life issues • Early stage • Help with IADLS, eg, paying bills and preparing meals • Cope with mood swings and reluctance to engage • Mid stage • Help with ADLS, eg, dressing and toileting • Cope with increased memory loss, sleep disturbances, wandering, loss of driving

  18. Education of Patient and FamilyAlzheimer’s Association • 24/7 Nationwide Helpline • 800.272.3900 • Information and referral in 170 languages • www.alz.org • Current reliable information for healthcare professionals, people with dementia, family members and caregivers • 300 local offices • Information and referral • Support groups • Care consultation • Safety services • Education, local conferences

  19. Clinical Trials • >120 clinical studies in the US are recruiting participants • Slow recruitment is a barrier to discovering new treatments • Alzheimer’s Association TrialMatch™ • Connect potential participants with appropriate clinical studies • Access via phone or online • Confidential • Free

  20. Understanding prevention research • Much evidence comes from large epidemiological studies that show associations, not proof • Study results apply to populations, not individuals • Large randomized studies for many prevention strategies unlikely • Cost prohibitive

  21. PreventionFactors with a consistent association • Heart-head connection • Preventative drug treatments • Physical exercise • Diet • Social connections • Intellectual activity • Head trauma prevention

  22. PreventionFactors with a consistent association Increased risk of AD Decreased risk of AD Physical activity Mediterranean diet Cognitive engagement • Conjugated equine estrogen with progesterone* • Diabetes • Depression • Smoking *Moderate evidence, all other factors had low evidence

  23. The Future of Alzheimer’s Disease • Earlier recognition • Dependent on reliable biomarkers • New medications • Current medications only address symptoms • New medications in development • Disease-modifying therapy • Combination disease-modifying and symptomatic therapy • Prevention

  24. Alzheimer's Disease Progression Beta-amyloid and neurofibrillary tangle formation begins in pre-clinical phase Cell death Pre-Clinical MCI Probable AD TIME Asymptomatic Clear cognitive deficits Aβ=Beta-amyloid AD=Alzheimer’s diseaseMCI=Mild cognitive impairment Mild cognitive deficits Adapted from Shaw et al. Nature Reviews Drug Discovery. 2007;6:295-303.

  25. Targets for Future Therapies • A • -secretase inhibitors • -secretase inhibitors • Monoclonal antibodies • Tau protein • Inflammation • Insulin resistance

  26. Emerging Treatments for AD  A production  A  aggregation  A  clearance  tau aggregation or phosphorylation Cholinergic drugs Other

  27. Clinical Trials

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