IDND Consultancy ACHEI and Late Stage Dementia

1. IDND ConsultancyACHEI and Late Stage Dementia Feb. 5, 2007 Patrick J. Healey, MD

2. Questions • In late stage dementia, are there indicators that continued ACHEI treatment is no longer beneficial? • Are there pitfalls to avoid in stopping ACHEI? • Is there a point at which there is agreement that ACHEI is no longer beneficial?

3. Case One • 84yo retired Army Colonel living in a locked ECF at FAST level 6e related to probable mixed dementia. Chronic underlying behavioral issues of intermittent, unpredictable physical aggression. Fairly stable medically and behaviorally. Daughters request withdrawal of ACHEI pursuant to his expressed wishes not to prolong his illness unnecessarily.

4. Case One • Chronic illnesses include, widespread ASVD, HTN, falls, AMD, presbycusis severe OA. Code C, DNH. On multiple psychotropics for BPSD and depression. • Daughters have POA, Living will signed, Code C

5. Case Two • 85yof who lives in a locked unit in an ECF who has SDAT and FAST 6d. Family requests that all medications be stopped since she has a terminal disease and would not wish to live this way. No major BPSD problems. Chronic diseases include only hypothyroidism, osteoporosis, HTN, OA. Family has POA.

6. FAST Stages 6a Difficulty putting clothing on properly w/o assistance 6b Will usually require assistance adjusting bathwater temp. 6c Inability to handle mechanics of toileting 6d Urinary incontinence, occasional or more frequent 6e Fecal incontinence, occasional or more frequent 7a Ability to speak limited to about half a dozen words/ day 7b. Intelligible vocabulary limited to a single word/day 7c. Non-ambulatory(unable to walk w/o assistance) 7d. Unable to sit up independently 7e Unable to smile 7f Unable to hold head up Reisberg B 1984

7. Global Deterioration Scale(GDS) • 1. No subjective complaints of memory • 2. Subjective c/o memory deficit • 3. Earliest clear-cut deficits • 4. Clear cut deficits on clinical interview • 5. Patient can no longer survive w/o assist. • 6. Poor STM, assist w/ ADL, personality and emotional changes • 7. All verbal and motor deficits decline/lost

8. Late Stages of Dementia • Severe • Resistiveness, incontinence, eating difficulties, motor impairment • Terminal • Bedfast, mute, dysphagia, intercurrent infections Volicer L, Hurley AC eds. Hospice Care for Patients with Advanced Prog. Dementia. 1998

9. Clinical Implications • No single definition for late stage AD • Little evidence exists curently for the efficacy of ACHEI treatments in late stage dementia • Donepezil now FDA indicated for severe SDAT

10. Donepezil in Later Stages? In the U.K., the National Institute for Health and Clinical Excellence(NICE), the drug watchdog for the NHS, has ruled that ACHEI is indicated only for moderate SDAT(and memantine should only be used for clinical studies)

11. Severe Dementia • Cognitive and functional status indicators limited by floor effects • Value of MMSE 1-10? • Life expectancy is generally low • Late stages lasting approximately 2-3 years • Clinical markers are imprecise in late stage • What can we measure as clinicians?

12. Case One Continued • Behaviors abruptly and severely deteriorated over next 3-4 weeks. Aricept and Namenda restarted w/o improvement and he required inpatient treatment for his physical aggression. He returned functionally and cognitively significantly worse and lived another 6 months before succumbing to aspiration pneumonia that was not treated with antibiotics per family wishes.

13. Case Two Continued • Stopped everything except prn analgesics per family directions. These maneuvers made no change in her slowly progressive course. Approx. 8 mos. later, she was observed to be gaining weight, edema, BP rose and alertness declined…..TSH=152! Promptly responded to thyroid repletion and returned to her usual state of health. 6 mos later, doing fine, family moved her to another facility as she ran out of money.

14. Questions • In late stage dementia, are there indicators that continued ACHEI treatment is no longer beneficial? • Are there pitfalls to avoid in stopping ACHEI? • Is there a point at which there is agreement that ACHEI is no longer beneficial?

15. Donepezil in Later Stages • 343 pts MMSE 1-12, Hachinski <6 , FAST >6 in randomized double blinded, placebo controlled trial • SIB, CIBIC-+ results at 24 weeks showed statistically significant differences • “Pts with severe AD showed greater improvement in cognition and global function with donepezil treatment.” CNS Senior Care Fall 2006. p 7

16. Donepezil in Later Stages • “Taken together with other study results, it can be said, therefore, that treatment with donepezil provides benefits to patients throughout the disease continuum.” Sandra Black MD, PhD University of Toronto CNS Senior Care Fall 2006. p 7

17. Questions • Is there sufficient evidence that late stage SDAT patients benefit from ACHEI? • Do end-points exist that indicate that further treatment with ACHEI is ineffective or harmful or not in the patients best interests? • Any pharmaco-economic data? • Could we be prolonging the dying process? • Will we obligated to attempt weaning of ACHEI at some point?

18. Questions • Do end-points exist that indicate that further treatment with ACHEI is ineffective or harmful or not in the patients best interests? • Are we obligated to attempt weaning of ACHEI at some point? • Could we be prolonging the dying process? • Does the magnitude of the initial response to ACHEI matter late in the course?

19. Questions • Do end-points exist that indicate that further treatment with ACHEI is ineffective or harmful or not in the patients best interests? • Could we be prolonging the dying process? • Will we obligated to attempt weaning of ACHEI at some point?

20. Questions • Is there sufficient evidence that late stage SDAT patients benefit from ACHEI? • Do end-points exist that indicate that further treatment with ACHEI is ineffective or harmful or not in the patients best interests? • Any pharmaco-economic data? • Could we be prolonging the dying process? • Will we obligated to attempt weaning of ACHEI at some point?