Download Dementia: Diagnosis and Treatment

Dementia: Clinical
Challenges
Outline
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Background
Dementia medications
Nutrition
Agitation
Background
Dementia is frequently overlooked
• Early symptoms attributed to normal aging
• Physicians don’t detect early changes
• Physicians do detect changes but don’t
document them because
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Not confident in dementia care?
Don’t consider it a true medical problem?
Not enough time to deal with it?
Want to avoid stigmatizing patients?
Sternberg SA et al. JAGS, 2000; Boustani M. et al. JGIM, 2005
Dementia Defined
• Decline in cognitive function from baseline
Epidemiology
• In the US population
Over 65:
Over 85:
5-10%
30-50%
Gauthier S et al. Lancet 2006. 376: 1262-1270.
Kennedy, GJ. Geriatric Medicine, 4th Ed. Cassel et al, Eds. 2003, p.1079
Screening
• Mini Mental State Examination
• St. Louis University Mental State
Examination
• Montreal Cognitive Assessment tool
• MiniCog
Diagnostic criteria
Decline in 2 of the following 5 domains:
1. Memory
2. Language
3. Visuospatial skills
4. Handling complex tasks
5. Judgment/reasoning
Rule out delirium, psychiatric disorders
Symptoms represent a decline from baseline
Symptoms result in a decline in function
Knopman DS. Mayo Clin Proc. Feb 2006; 81(2):223-230.
Workup
• History & physical examination with a
complete neurologic exam
• Comprehensive Metabolic Panel, Complete
Blood Count, Vitamin B12, Thyroid Function
Tests, possibly also Vitamin D, Rapid Plasma
Reagin and HIV
• Brain imaging if appropriate
• Neuropsychological testing if appropriate
Dementia types
5%
5-10%
5-10%
15-20%
60%
Other
DLB
Vascular
Mixed
Alzheimer
Disease
Mild Cognitive Impairment (MCI)
• Subjective change in cognition
• Objective findings of impairment in one or
more cognitive domains
• Minimal interference with function
• In the US population over 65:
3-19%
Albert MS et al. Alzheimer’s & Dementia 2011; Gauthier S et al. Lancet 2006
Alzheimer Disease
• New diagnostic criteria published in 2011
– Clinical criteria
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Insidious onset of months to years
Progression of cognitive decline
Amnestic or nonamnestic cognitive impairment
No obvious symptoms/signs of alternative type of
dementia
– Biomarkers
• Accumulation of amyloid beta (CSF amyloid beta 42, PET
amyloid imaging)
• Neuronal injury (CSF tau, FDG PET, Functional MRI)
McKhann GM et al. Alzheimer Dement 2011
Mixed dementia
AD
Mixed
Knopman DS. Mayo Clin Proc. Feb 2006; 81(2):223-230.
VaD
Vascular Dementia
• Diagnosis
– Currently no consensus on what location or size
infarct correlates with pathologic diagnosis
of vascular dementia
– Look for a suggestive history, physical exam with 23 focal signs, and brain imaging that shows
ischemic disease
Knopman DS. Dementia and Cerebrovascular disease. Mayo Clin Proc. Feb 2006; 81(2):223-230.
Dementia with Lewy Bodies
• Characteristics
– Prominent visual hallucinations
– Parkinsonism (gait, balance, rigidity,
bradykinesia- rest tremor less common)
– Falls or gait difficulties
– Fluctuations in cognition
– Sensitivity to antipsychotics (extrapyramidal side
effects)
• Also
– REM sleep behavior disorder
Knopman DS. Mayo Clin Proc, 2006; Blass DM, Rabins PV. Annals Int Med, 2008
Understand prognosis
• Life expectancy from the time of diagnosis:
– Alzheimer Disease
5-10 years
– Vascular Dementia
4 years
– Dementia with Lewy Bodies
4 years
Is my patient on the
right dementia drugs?
Dementia Drugs: Dos, Don’ts, and
Don’t knows
Acetylcholinesterase Inhibitors
• Donepezil (Aricept)
• Galantamine (Razadyne)
• Rivastigmine (Exelon)
Cummings JL, NEJM,
2004
Efficacy
Rogers: Neurology, 1998.136-145
NMDA antagonist
Memantine (Namenda)
Reisberg B et al. NEJM 2003
Drug candidates that to date have
no proven efficacy
• Anti-inflammatories
• Cholesterol reducing
agents
• Estrogen
• Antioxidants
• Gingko biloba
• Fish oil, omega-3 fatty
acids
• Vitamin E
• Lowering
homocysteine
• Alcohol, especially
wine
• Huperzine
• Curcumin
• Nicotine
• Insulin & insulin
sensitizers, ketones
How to handle
nutrition in patients
with dementia?
Anorexia and Weight Loss
• Common in patients with dementia
• Especially Alzheimer disease
• Possible causes
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Forgetting to eat
Inability to prepare and eat foods
Impaired olfaction and taste
Behavior problems (restlessness, etc)
Depression
Comorbid medical illness
Medications (esp cholinesterase inhibitors)
Inflammatory abnormalities
(causing anorexia, procatabolic state)
Wang et al, J Neurol 2004, 251:314-320; Aziz NA et al, J Neurol 2008
• Controlled study of 51 AD subjects and 27 non-demented
controls
– AD subjects were thinner and less active
– AD subjects actually ate the same or MORE than
controls
– Presence of AD was a risk factor for weight loss even if
other factors were controlled
• So maybe it’s poor absorption or metabolic changes
Wang et al, J Neurol 2004, 251:314-320
• AD pts have increased serum levels of:
– Glucagon
– Ammonia
– Lactate
– Cortisol
– Interleukins 1 and 6
– TNF alpha
• AD pts have greater insulin resistance
• All of above is similar to cancer patients
Knittweis J, Medical Hypotheses, 1999
Strategies
Diet- liberalize it! No special diets!
Environment
– Pleasant, quiet setting
– Music may help
Eating Schedule
– AD pts ate more at breakfast than other meals
– Frequent, small meals
– Eat with others
Tamura BK et al. Nutrition and the Institutionalized Elderly. 2007
Strategies
Food Modifications
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Single items, presented one at a time
Contrast color of food with the dish
Make food and setting look attractive
Make food portable for those who are restless
Sweet, hot/cold, juicy
Tamura BK et al. Nutrition and the Institutionalized Elderly. 2007
Limited Data on
Pharmacologic Strategies
• Nutritional supplements between meals
• Micronutrients (MVI) probably not needed
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Megestrol acetate (Megace)
Dronabinol (Marinol)
Methylphenidate (Ritalin)
Mirtazepine (Remeron)
Tamura BK et al. Nutrition and the Institutionalized Elderly. 2007
Feeding tubes
When are they
appropriate?
Improved Survival?
• Observational studies:
– Study of 99 hospitalized patients with advanced
dementia
• survival without PEG 189 days, with PEG 195 days
(P=0.9)
• Mortality is high after G-tube placement
– 6-28% in first 30 days
– 60% mortality at 6 months, perhaps 90% at one
year
Murphy LM. Arch Int Med, 2003; Gillick MR. N Engl J Med. 2000; Meier
DE et al, Arch Int Med 2001
Patient Comfort?
• Studies of dying cancer or ALS patients with
anorexia:
– Little hunger or thirst
• Any thirst can be treated with mouth swabs and ice
chips
– Sense of euphoria (endorphins)
• Goes away if fed
– Patients were left alone more
Gillick MR. NEJM, 2000
Comfort?
• Eating is pleasant!
– depriving a person (who wants to eat) of the
pleasure of eating does not increase comfort
• Pulling out the tube
– Return trips to GI or IR
– Restraints
• More stool and urine
– Caregiver burdens high
Finucane T et al. JAMA 1999
Aspiration
• Aspiration of oral secretions is not reduced
by feeding tubes
• Aspiration of refluxed stomach contents is
still also possible… and perhaps more likely
given tendency towards gastric distension,
low LES tone in tube-fed patients
Mitchell SL. JAMA 2007
Slow hand feeding
• Survival can be substantial despite
emaciation and poor po intake
• Human, nurturing, time for closeness with
loved ones
Finucane TE, JAMA, 1999
Dementia Taboo
• Feeding tube- what is it, risks/benefits?
– PEG, insert, endoscopy, interventional radiology,
gastric, nutrition
• Lack of efficacy of artificial nutrition
– PEG, nutrient, mortality, euphoria, restraints,
aspiration, palliative
• Prognosis of advanced dementia
– Mortality, terminal, PEG, limited life expectancy,
palliative, cachexia, anorexia
How can I help my
patient who is
agitated?
Workup of agitation
• Differential diagnosis for NEW agitation:
– Delirium- drugs, infection, CNS process, etc
– Psychiatric condition
– Dementia
Ballard CG et al. Nature Reviews Neurology, 2009
If no other cause is found…
• Then it could be the dementia itself
• Potential triggers:
– PHYSICAL
• Pain, constipation, hunger, thirst
– EMOTIONAL
• Anxiety, boredom, grief
– ENVIRONMENTAL
• Disruption in routine, new caregiver, life
stressor, overstimulation, understimulation
Lyketsos CG et al. Am J. Geriatric Psychiatry, 2006
Behavioral and Psychiatric
Symptoms (BPSD)
• Affects 60-98% of dementia patients
• Aggression, agitation, delusions, hallucinations,
repetitive vocalizations, wandering
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increased caregiver stress
unemployment
loss of income
NH placement
increased costs of hospitalization
• 30% of cost of caring for pts with dementia due
to BPSD
Sink KM et al, JAMA, 2005
BPSD Management
• First line always nonpharmacologic
• Try to analyze the behavior using A-B-C
– A- antecedent
– B- behavior
– C- consequence
• Also:
– Correct sensory deficits
– Create daily routine with activities
– Create a structured environment
– Ensure adequate sleep and eating
– Provide respite and support to caregivers
– Redirection and distraction
Salzman C et al. J Clin Psychiatry 2008
Pharmacologic Management
Pharmacologic treatment is a last resort
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Antipsychotics
Acetyl cholinesterase inhibitors
NMDA antagonists
Antidepressants
Anticonvulsants/mood stabilizers
Sink et al, JAMA, 2005
Antipsychotics
• Haloperidol can be used if IV/IM route
necessary
– Mechanism: dopamine antagonist
– Dosing: start at 0.5mg
– Cost: $10/month
• Atypical Antipsychotics are preferable due to
lower rates of EPS, primarily po
– Mechanism: dopamine/serotonin antagonists
– Dosing: start risperidone at 0.5mg qhs, seroquel
25mg qhs
– Cost: $95-300/mo
Risks of Antipsychotics
Extrapyramidal symptoms
Sedation
Prolonged QT
Hyperglycemia, obesity (atypicals only)
CVA
– Post-hoc analyses (4% vs 2% for risperidone)
• Infection (pneumonia)
• Increased risk of mortality (RR 1.54)
– Post-hoc analyses (2.3% vs 3.6%)
– FDA black box warning
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Schneider LS et al, JAMA 2005; 294:1934-43; Wang PS et al, NEJM 2005; 353:2335-41
Antipsychotics Summary
• Discuss risks with patients/family prior to initiating
these medications
• Never use for insomnia
• Doses should be low
• Attempts to discontinue pharmacologic treatment
should be performed early and often
Dementia Summary
• Dementia is common and commonly overlooked
• Alzheimer disease is by far the most common
type
• Current medications for dementia have modest
benefits but should be offered if appropriate
• Feeding issues in advanced dementia are not
usually solved with feeding tubes
• Antipsychotics should be avoided in dementia
patients with agitation
Useful References
• Blass EM and Rabins PV. In the clinic:
Dementia. Annals of Internal Medicine 2008
• Mitchell SL. A 93 year old man with advanced
dementia and eating problems. JAMA
2007;298(21):2527-2536
• Salzman C et al. Elderly patients with
dementia-related symptoms of severe
agitation and aggression: Consensus
statement on treatment options, clinical
trials methodology, and policy. Journal of
Clinical Psychiatry 2008;69:889-898