Transcript IDND Consultancy ACHEI and Late Stage Dementia

IDND Consultancy
ACHEI and Late Stage Dementia
Feb. 5, 2007
Patrick J. Healey, MD
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?
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.
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
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.
FAST Stages
6a
6b
6c
6d
6e
Difficulty putting clothing on properly w/o assistance
Will usually require assistance adjusting bathwater temp.
Inability to handle mechanics of toileting
Urinary incontinence, occasional or more frequent
Fecal incontinence, occasional or more frequent
7a
7b.
7c.
7d.
7e
7f
Ability to speak limited to about half a dozen words/ day
Intelligible vocabulary limited to a single word/day
Non-ambulatory(unable to walk w/o assistance)
Unable to sit up independently
Unable to smile
Unable to hold head up
Reisberg B 1984
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
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
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
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)
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?
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.
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.
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?
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
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
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?
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?
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?
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?