pharmacological interventions for the cognitively impaired geriatric patient
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Pharmacological Interventions for the Cognitively Impaired Geriatric Patient. Indiana Osteopathic Association 117 th Annual Convention May 2 – 4, 2014 French Lick Resort John J. Wernert, M.D., MHA Professional Development Associates. Faculty Disclosure John J. Wernert, M.D, MHA. - PowerPoint PPT PresentationTRANSCRIPT
Pharmacological Interventions for Pharmacological Interventions for the Cognitively Impaired the Cognitively Impaired
Geriatric PatientGeriatric Patient
Indiana Osteopathic Association
117th Annual Convention
May 2 – 4, 2014
French Lick Resort
John J. Wernert, M.D., MHA
Professional Development Associates
Faculty DisclosureFaculty DisclosureJohn J. Wernert, M.D, MHAJohn J. Wernert, M.D, MHA
Consultant:– Eskenazi Health– Franciscan Alliance– Federally Qualified Health Centers– Archdiocese of Indianapolis– Extended Care Facilities
LEARNING OBJECTIVESLEARNING OBJECTIVES Discuss new discoveries and theories about brain
deterioration and memory decline. Explore genetic and environmental risk factors
for development of cognitive disorders.
Differentiate Delirium, Depression and Dementia in Geriatric patients.
Review Behavioral manifestations of dementing illnesses.
Discuss how emerging targets and therapies may impact behavioral and medical recommendations relevant to treating cognitively impaired patients.
““The singular benefit of old age is to see life whole and know The singular benefit of old age is to see life whole and know it’s natural course”it’s natural course”
Philosopher Arthur SchopenhauerPhilosopher Arthur Schopenhauer
Most common reasons for Most common reasons for referral to Geriatric Psychiatrist:referral to Geriatric Psychiatrist:
Memory Impairment– (AACD vs MCI vs Dementia)
Affective Problems
– (Apathy vs Depression)Behavioral Problems
– (wandering vs agitation)
The Cost of Brain DisordersThe Cost of Brain Disorders
U.S. Society = $500 Billion annually19 % of the average American
income is devoted to treating Brain diseases
55 % cost is DementiasPsychiatric Illnesses = $170 BillionAD alone > $100 billion
Prevalence of Mental Prevalence of Mental Disorders Age 65+Disorders Age 65+
Mental disorders: 26.3%(including dementia)
Psychiatric disorders 19.8% based on prevalence of 30-40% of dementia complicated by depression, psychosis, or agitation.
Jeste, et al., 1999
Brain Aging is not a sudden event, but rather a continuous process.
RISK FACTORS:
Decline in 20’s
Medical illness
Genetics
Plasticity
Variability
Crowded desktop
Crowded Mental Desktop Crowded Mental Desktop
More time needed to learn new information
Working-memory capacity is limitedSlowed retrieval time Too much clutter – hard to prioritizeLong-term memory becomes less
reliable
Sensory impairments Sensory impairments
Auditory and visual acuity decline Quality of sensory input blurs the sharpness
of the memory By 40’s, more distractible By 50’s, harder to focus and stay on point. By 60’s, difficult to filter out extraneous noise By 70’s, memory lost due to “missed” input
Brain Aging:Brain Aging:
Caused by metabolic stress Cell Level = transcription errors Body Level = develop comorbidities
MCI - 15% per year convert to AD AD develops slowly over decades Adults who will get AD, already have it!
– 30% over age 65 already have amyloid plaques
Risk Factors for Brain Aging:Risk Factors for Brain Aging: Confirmed
– Age– Family History– APOE-4 gene (only 50 % of genetic variability)
Possible– Other genes– Head trauma– Lower educational achievement (use it or
loose it vs healthy lifestyle)– Chronic stress– Depression
Protective Factors for Brain Protective Factors for Brain Aging:Aging:Aerobic exerciseEstrogenAnti-inflammatory drugsAnti-oxidantsLow-fat dietWine (Germans say beer)
Wine and Reduced Incidence of Dementia?Wine and Reduced Incidence of Dementia?
Copenhagen City study 83 pt’s, 1626 controls over age
65 Studied over 15 years Grouped by intake and dx MMSE scores of 24 or up Monthly and weekly intake of
wine = decreased risk Monthly intake beer = higher
risk Total alcohol intake had no
significant effect on risk• Neurology (2002;59:1313-1319)
NeurodegenerationNeurodegeneration
Usually a NORMAL Brain going through a slow, gradual deterioration– Parkinsons Disease– Dementing Illnesses– Demyelinating Disorders (MS)– Infectious (HIV, Syphilis)– Neoplastic (brain vs paraneoplastic)
Neurodegeneration predisposes to Neurodegeneration predisposes to the “Three D’s”:the “Three D’s”:
Delirium
↓↓ ↑↑Dementia
↕↕Depression
Neurodegenerative Conditions Neurodegenerative Conditions lead to all three “D’s”lead to all three “D’s”High risk of polypharmacyDespondency of chronic illnessWeakened resistance Fragile brain = iatrogenic illnessesSensitive to drug side effects
Delirium vs DementiaDelirium vs Dementia Delirium
– Acute– Fluctuating course
Dementia– Insidious Onset– Chronic memory Disturbances– Persistent Sxs
Dementia pt’s 3x more likely to get delirious Delirious elderly patients are 4X more likely to
have dementia
Delirium; Delirium;
Under-recognized (missed 50%)Reversible (if cause correctible)Present in 30 % of hospitalized
elderlyDelays dischargeIncreases need for ECF placementHigher mortality (6 mo mortality>50%)
Worse outcomes– Hip fractures– Myocardial infarction– Cancer (Mossey 1990; Penninx et al. 2001; Evans 1999)
Increased mortality rates– Myocardial Infarction (Frasure-Smith 1993, 1995)
– Long term Care Residents (Katz 1989, Rovner 1991, Parmelee 1992; Ashby1991; Shah 1993, Samuels 1997)
Depression Associated with Depression Associated with Worse Health OutcomesWorse Health Outcomes
Depression in Older Adults and Depression in Older Adults and Health Care Costs Health Care Costs
$0
$1,000
$2,000
$3,000
$4,000
$5,000
$6,000
$7,000
0 (n=859) 1-2 (n=616) 3-5 (n=659) 6-16 (n=423)
Levels of Chronic Disease Score
An
nu
al C
ost
of H
ealt
hca
re None CES-D<8Moderate CES-D=8-15Severe CES-D>16
Unutzer, et al., 1997; JAMA
Suicide in Older AdultsSuicide in Older Adults
65+: highest suicide rate of any age group85+: 2X the national average (CDC 1999)
Peak suicide rates: – Suicide rate goes up continuously for men – Peaks at midlife for women, then declines
1/3 of older men saw their primary care physician in the week before completing suicide; 70% within the prior month
Depression Delirium Dementia
Onset Weeks to months Hours to days Months to years
Mood Low/apathetic Fluctuates Fluctuates
Course Chronic; responds to treatment.
Acute; responds to treatment
Chronic, with deterioration over time
Self-Awareness Likely to be concerned about memory impairment
May be aware of changes in cognition; fluctuates
Likely to hide or be unaware of cognitive deficits
Activities of Daily Living (ADLs)
May neglect basic self-care
May be intact or impaired
May be intact early, impaired as disease progresses
Instrumental Activities of Daily Living (IADLs)
May be intact or impaired
May be intact or impaired
May be intact early, impaired before ADLs as disease progresses
Summary of FindingsSummary of Findings
Dementia and Delirium strongly linkedDepression is common in medical
disorders among older patients All three “D’s”;
– Associated with worse health outcomes– Greater use and costs of medications– Greater incidence of iatrogenic illness– ↑ medical outpatient visits, emergency
visits, and hospitalizations
Example of Neurodegenerative Example of Neurodegenerative Condition prone to the three “D’s”:Condition prone to the three “D’s”:
Parkinson’s DiseaseParkinson’s Disease
Imbalance of ACH – Dopamine– Not enough Dop = Parkinsons– Too much Dop = psychosis
20-30 % will develop Dementia Increasing Dop doesn’t prevent dementia 50 % will become depressed sometime during
illness Drug-induced delirium and hallucinations
common cause of psychiatric symptoms
DementiaDementia
Acquired persistent decline in several realms of intellectual ability
Demence described in Paris Assylums (1820’s) Frequent alteration in behavior and mood Alzheimer’s Dz most common, but not all
dementia is AD Constitutes the greatest health challenge for the
Baby Boom generation – will be the #1 reason why you need an ECF
Course of Age-Related Changes Course of Age-Related Changes in Dementiain Dementia
Age-Associated Memory Impairment
Age 30 40 50 60 70 80
MCI
AD
Assymptomatic
C
O
G
N
I
T
I
O
N
SDATSDAT39 % go undiagnosedEarly onset of Memory DeficitsAbsense of Neurologic DeficitsNo CVA or injury on CTMakes up 70 % of Dementia Pt’s>5.5 million Americans currently DxAlready 4th leading cause of deathLive 7 – 10 years after DX
International Working Group for New International Working Group for New Research Criteria for the DX of Research Criteria for the DX of Alzheimer’s DiseaseAlzheimer’s Disease
Current dx dependent upon documenting mental decline
New Proposed Diagnostic Criteria for SDAT– MCI and evidence of AD from biomarkers
( eg, + amyloid scan, CSF markers of amyloid or tau)
– AD = Dementia + biomarkers
Three of the new guidelines Three of the new guidelines focus on three stages of focus on three stages of Alzheimer's disease: Alzheimer's disease:
(1) dementia due to Alzheimer's(2) mild cognitive impairment (MCI)
due to Alzheimer's(3) preclinical (presymptomatic)
Alzheimer's.
““Pre-clinical Alzheimer’s”Pre-clinical Alzheimer’s”
5 year study of monoclonal antibodies + screening tests
Looking for specific biomarkers30% over 65 have amyloid plaquesBrain changes caused by the disease
may begin decades before symptoms such as memory loss and confusion occur.
““Pre-clinical Alzheimer’s”Pre-clinical Alzheimer’s”
The new guidelines are not an immediate call for diagnosis of this preclinical stage and do not include specific diagnostic criteria. They rather propose a research agenda to identify biomarkers that may signal when these presymptomatic brain changes begin.
Reliable predictors don’t existReliable predictors don’t exist
There are currently no validated biomarkers for Alzheimer's disease, but researchers are investigating several promising candidates
We now know that Alzheimer's has already caused severe brain damage in individuals who meet the criteria for mental decline.
NeuroimagingNeuroimaging
Neuroimaging and DementiaNeuroimaging and DementiaAAN Guidelines = MRI / CT Medicare reimbursement – FDG-PET
to differentiate AD from FTDDeveloping PET technologies –
amyloid plaque and tau tangle imaging
Neurology 2004; www.cms.gov
Amyloid ScansAmyloid Scans
Pre-senile Alzheimer’s DiseasePre-senile Alzheimer’s Disease
RarePrior to age 60Autosomal dominant inheritance due to
mutations presenelin I (chrom 14), presenelin II (chrom 1) and APOE (chrom 19).
Earlier symptom onset (personality sx)Abnormal / high amyloid deposition
SDAT: Making the Diagnosis SDAT: Making the Diagnosis Earlier (risk factors)Earlier (risk factors) Early warning signs
– Progressive and insidious– Functional– Behavioral
“Red Flags” (Natural Brain Stress tests)– Delirium (especially recurrent)– Depression (or AD apathy)– Catastophic Rxn (too much input)
Concurrent Medical Illnesses– Why is this pt doing poorly NOW
Listen to the Family (“He’s just not right”)– See them separately– They will tell you the diagnosis
Genetic ConsiderationsGenetic Considerations Should NOT be used solely as predictive test –
helpful in research and validation Rare autosomal dominant families with early
onset (age 50 – 60) dementia– Mutations cause the disease
• Presenilin genes (chromosomes 1 and 14)• APP gene (Chromosome 21)
Apolipoprotein E (APOE)– Gene on chrom 19; 3 alleles, 5 common genotypes (3/3, 3/4, 2/3,
2/4, 4/4)– APOE-4 in 20% US population– APOE-4 increases risk, lowers age onset– APOE alone not considered useful predictive test
Genetic Risk factors;Genetic Risk factors;Early onset of mutations in chromosome 1, 14, and 21
Late onset of mutations in chromosome 19 -apolipoprotein E gen (APOE 2, 3, and 4) 4/4 greatest risk (3% of population) 3/4 next risk (20% of population) 2 may be protective
APOE 4 neither necessary nor sufficient to cause dementia
Why Diagnose AD Early?Why Diagnose AD Early?
Safety Issues (driving, compliance)Advanced Planning while Pt
competent (POA, HCR, Guardian)Family Stress and MisunderstandingEarly Education of CaregiversSpecific, stabilizing Tx Available
Approved AD/Cognitive TreatmentsApproved AD/Cognitive Treatments
Aricept (Donepezil)Exelon (Rivastigmine) AChE + BuChEReminyl (Galantamine)Namenda (Memantine)
Vitamin E (a-tocopherol) 1200 IU/d
Possibly beneficial:Possibly beneficial:
Estrogen (HRT)SelegilineGinko bilobaCholesterol lowering agentsReality TherapyMusic Therapy
……and the Pipeline is dry…and the Pipeline is dry…NMDA receptor antagonists. Limits
excitotoxicity caused by excessive pre-synaptic glutamate release. Mixed results
Alzhemed – organic molecule to prevent formation & deposition of beta amyloid fibrils in the brain. (withdrawn 2007)
Preventive Therapies – “Alzheimer’s vaccine” (Lilly's Alzheimer's drug solanezumab flunks out 2012)
Vascular DementiaVascular Dementia
20% of DementiasNot always clear findings on CT/MRIEarly Gait DisturbanceFrequent fallsEarly incontinenceUsually prominent personality and
mood changes
4 Sub-types of Vascular Dementia4 Sub-types of Vascular Dementia
Single infarct Dementia (behavior worse with frontal involvement)
MIDSmall vessel disease (must be more
than mild)Watershed injury (hypoperfusion)Males vs Female considerations
The remaining 10 %The remaining 10 %
Frontal Lobe Dementias (Picks)Lewy Body DementiaParkinson’s DzOther Neurodegenerative conditions
Bottom Line -Bottom Line -
Diagnose early,
Treat early,
So patients can
Stay Home Longer!(on average, 18 – 24 months)
Geriatric Brain injuries:Geriatric Brain injuries:
Usually associated with fallsAcute and Massive CVA’sLess favorable outcomesIncreased mortalityMore likely need ECFMore likely depressedMuch more sensitive to medications
When brain is injured, behaviors When brain is injured, behaviors are inevitableare inevitable
Challenge is to determine which behaviors are tolerable, and which require medication or behavioral
treatments.
Medications used too often?Medications used too often?
“Much of medication use is due to the lack of interest, willingness, funding, or ability to provide psychosocial or environmental interventions to patients with agitation, aggression, and psychosis who have dementia.”
“Despite the widespread awareness of adverse consequences, we can only infer that atypical antipsychotics continue to be prescribed for dementia treatment because there is a lack of alternatives and there is a perceived clinical benefit by care providers.”
– Am J Psychiatry. 2011;168:831-839, 767-769. Abstract Editorial
What behaviors will respond to What behaviors will respond to medications?medications?Agitation – acute and chronicPsychosis – especially positive
symptomsDepression – situational and majorAnxietyMood Instability - Bipolar
Choices for treating Agitated Choices for treating Agitated BehaviorsBehaviors
Antipsychotics – Typical– Atypical (really second generation)
AntidepressantsAnxiolyticsMood Stabilizers
ANTIPSYCHOTICS - ANTIPSYCHOTICS - CONVENTIONALSCONVENTIONALS
Haldol (haloperidol)Prolixin (fluphenazine)Navane (thiothixene)Loxitane (loxapine)Moban (molidone)Stelazine (trifluoperazine)Mellaril (thioridazine)Thorazine (chlorpromazine)Trilafon (perphenazine)
ANTIPSYCHOTICS - ATYPICALSANTIPSYCHOTICS - ATYPICALS
Risperdal (risperidone)Zyprexa (olanzapine)Seroquel (quetiapine)Clozaril (clozapine)Geodon (ziprasidone)Abilify (aripiprazole) - ?3rd generation
New 2New 2ndnd Generation have no role Generation have no role
Fanapt (iloperidone)Saphris (asenapine)Invega (paliperidone)Latuda (lurasidone)Solian (amisulpride)
Safety vs EffectivenessSafety vs Effectiveness
Atypicals clearly safer, but don’t always work
If they do work, can be given longerConventionals often work faster and
are more effective.Must be used with more caution, and
for shorter periods of timeMonitoring is the key
FDA Advisory for Antipsychotic Drugs FDA Advisory for Antipsychotic Drugs Used for TX of Behavioral Disorders in Used for TX of Behavioral Disorders in Elderly PT’s [Black Box] Elderly PT’s [Black Box] (April 11, 2005)(April 11, 2005)
Atypicals to treat behavioral DO showed 1.7 times higher death rate vs placebo
Absolute risks: 4.5% drug, 2.6% placebo All antipsychotics may be affected Death causes varied
– Most heart related or infections (pneumonia)
Important Change in Practice Important Change in Practice Guidelines 2007: Limit AntipsychoticsGuidelines 2007: Limit Antipsychotics
For patients who have neuropsychiatric symptoms, such as agitation, delusion, hallucinations, and aggression, there is stronger evidence that nondrug treatment should be tried first and that real efforts should be made to limit the use of antipsychotics in all settings — at home and in the long-term-care setting. "That is the most important way the guidelines will change practice.“
“Real efforts need to be made to make sure that when antipsychotics are prescribed, they are both necessary and effective; when they are not effective, they should be discontinued.“
– 2007 second addition APA Treatment Guidelines Updated Guidelines for Treating Patients With Dementia
– Supplement to American Journal of Psychiatry
AntidepressantsAntidepressants
Work best when agitation clearly related to mood
Premorbid HX of DepressionDon’t expect quick results – may take
6 – 12 weeks.Can safely give long term
If you must use atypicals:If you must use atypicals:
Be prepared to do Gradual Dose Reductions (GDR’s) – even if patient is doing well
Start lowWrite for automatic stop datesDon’t assume the patient is better
solely because of medicationContinue to trial behavioral
interventions
Anti-Anxiety medicationsAnti-Anxiety medications
Benzodiazepines – Ativan most common
Benefits:– IM / PO / IV– Relatively fast acting
Risks– Falls, Falls, Falls (hypotension)– Respiratory Depression– Dependence and Withdrawal
Other AnxiolyticsOther Anxiolytics
Buspar (Buspirone)– Not much bang for the buck– Slow onset– Good data in MR/DD
Sedative Hypnotics– Watch for cumulative effect
Neurontin (Gabapentin)– Expensive, but works
Sedative/HypnoticsSedative/Hypnotics Can be helpful for sleep regulation Low dose Trazodone
– 25 – 50 mg q 8 pm– Give at 5 pm if sundowning an issue
Remeron– 7.5 mg = increase sedation / appetite
Vistaril + Benadryl – avoid Melatonin 3 -6 mg may be helpful Minimize use of Ambien, Lunesta and BZ
hypnotics
Mood StabilizersMood Stabilizers
Lithium– Oldest– Riskiest, especially in elderly– Requires much monitoring
Depakote (Divalproex)Neurontin (Gabapentin)Newer Agents (Trileptal, et al)
My Conclusions on pharmacologic My Conclusions on pharmacologic treatments of agitationtreatments of agitation
Vascular Dementia– Depakote/Neurontin work best– Get on “plateau” – Remember Stroke prophylaxis
SDAT– Short term – anything that works– Mid to Late stages need mood stabilizers– AchI may help over the long term
Delirium– Recognize, then fix the cause– Antipsychotics work best (old>new)
Depression– Think long-term
Conclusions: Brain InjuryConclusions: Brain Injury
Acute agitation responds best to older antipsychotics, but only use short term (very sensitive EPSE)
Many are prone to seizures, so anticonvulsants may be best “first line” choice
Long Acting BZ’s (Klonopin) may raise seizure threshold and help “chronic” anxiety
Conclusions on treating“non Conclusions on treating“non complicated” dementia:complicated” dementia: Achesterase Inhibitors can help decelerate
decline– “Brain Boost” lasts 1 – 2 years– May be helpful in Vascular Dementia– Can delay ECF placement by 22 months
Can also help with Symptom ControlControl upsetting behaviorsMaintain ADL’sImprove thinking function
SummarySummary Patients with cognitive impairment commonly
become restless and agitated
Environmental triggers, medical disorders, and medication side effects need to be ruled out as contributing factors
Treatment approach must include appropriate nondrug interventions, as well as thoughtfully chosen medications
Primary caregiver requires attention, support, and respite
Unfortunately, medications have become the mainstay of treatment. Use short term
What can you do at end stages?What can you do at end stages?
Care for the Caregiver(s) and keep them functional (respite works)
Increase frequency of visitsPalliative Care / HOSPICEHome VisitsJoin the Alzheimer’s Association and
be a community resource
ConclusionsConclusionsResearch Funding has dramatically
increased - biomarkersProper Diagnosis drives treatment –
Depression v Delirim v Dementia
Early diagnosis doesn’t change the outcome, but can bend the curve
Few new treatments available since 2004– still not hopeless
Proper treatment improves Quality of Life and delays ECF placement