1. Dementia and Pharmacy Intervention
Melissa R. Lewis, Pharm.D.
September 17, 2010

2. Objectives
Define dementia and understand the requirements for diagnosis
Recognize the neuropathology and neurotransmitters involved in dementia
Discuss the pharmacokinetics and pharmacodynamics in the geriatric population
Be able to assess a patient with or suspected to have dementia and make recommendations to optimize therapy

3. A Brief History First coined by a French physician in 1801
Dr. Philippe Pinel
Alzheimer’s disease first described in 1906
Dr. Alois Alzheimer
Dr. Philippe Pinel worked with a 34 year-old women who lost her memory, speech, ability to walk and use of common house hold items in over a period of just a few years- Autopsy noted brain full of fluid and significantly decreased size
Alois Alzheimer worked with a 51 year-old women with memory failure, paranoia, and decrease executive functioning
Autopsy of brain noted fluid, shrunk and neurofibrillary tangles and amyloid plaques. - 4 hallmark features of AD;
Reference: Tam Cummings, MS, Gerontologist; (central Texas area website for geriatric information)

4. Types of Dementia Mild Cognitive Impairment (MCI)
Alzheimer’s Disease (AD)
Vascular Dementia
Lewy Body Dementia
Frontal Lobe dementia
Mixed Dementia
Short definition of all types: MCI may be a transition or progress to AD; Vascular dementia is the second most common form of dementia after Alzheimer disease (AD). The condition is not a single disease; it is a group of syndromes relating to different vascular mechanisms. Lewy type, is a type of dementia closely allied to both Alzheimers and Parkinson's Diseases. It is characterized by the presence of Lewy bodies, clumps of alpha-synuclein and ubiquitin protein in neurons,; FLD- changes in personality/usually effect younger population; mixed when patients have contributing factors that could be characterized as more than one type of dementia.

5. Definition
According to the Diagnostic and Statistical Manual of Mental Disorders-IV-TR
Multiple cognitive deficits
Memory impairment plus one or more:
Aphasia
Apraxia
Agnosia
Dysfunction is executive functioning
Deficits must be severe enough to cause impairment in occupational and/or social functioning
Aphasia- unable to understand or speak language; apraxia- inability to make purposeful movements; agnosia- inability to recognized objects; must represent a decline from a previously higher level of functioning

6. Epidemiology Dementia Prevalence Alzheimer’s Disease
Higher in women than men
Static's vary depending on the source
3.0% with MCI in adult population
% for ages to 16-25% over age 85
Alzheimer’s Disease
5.3 million people have AD
7th leading cause of death
$172 billion dollars in annual costs
10.9 million unpaid caregivers
DMS-IV; per Alzheimers Association 2010 facts and figures
DSM-IV; Alzheimer’s Association 2010 facts and figures

7. Risk Factors for Dementia
Alzheimer’s Disease (AD)
Age
Family History
ApoE E4 genetic allele
History of psychiatric illness
VaD- both increased age; sex; HTN, diabetes, CAD, HLP, Stroke/CVE
Vascular Dementia (VaD)
Age
Conditions altering vasculature
Smoking

8. Neuropathology in BriefAD
B-amyloid plaques
Leads to neuronal death
Neurofibrillary tangles
Abnormal neurons die and form tangles
Inflammation processes lead to neuronal death and plaque formations
VaD
Disruptions of blood flow to different structures in the brain responsible for cognition, executive functioning and behavior
Neuropathology was initially discovered by autopsy; PET and CT used for 2 hallmark signs of fluid and decreased brain mass; but tangles and plaques are still questionable in scans and usually found in later stages. Lewy body dementia similar to AD with inclusion of lewy bodies

9. Neurochemical Disruptions
Cholinergic Systems
Plaque formations damage cholinergic neurons and result in decrease in cognition and memory
Glutamatergic System
Plaque aggregation disrupts transmission of glutamate which results in stimulation of NMDA
This can lead to excitotoxicity and neuronal death
By binding to the NMDA receptor with a higher affinity than Mg2+ ions, memantine is able to inhibit the prolonged influx of Ca2+ ions, which forms the basis of neuronal excitotoxicity. The low affinity and rapid off-rate kinetics of memantine at the level of the NMDA receptor-channel, however, preserves the physiological function of the receptor, as it can still be activated by the relatively high concentrations of glutamate released following depolarization of the presynaptic neuron

10. Morbidity and Mortality
Cognitive and behavioral symptoms are seen in earlier stages
High rates of depression in patients and caregivers
Late stages require extensive care with ADL
Death occurs due to complications
Aspiration
Infection
Falls and other injuries
7th leading cause of death

11. Differential Diagnosis
Delirium
Sudden alterations in cognition
Fluctuations throughout the day
Impaired attention span
Disturbances in sleep-wake cycle and psychomotor activity
Maybe due to medical condition or medications
Other psychiatric disorder
Mood disorder
Substance abuse and or withdrawal
Per DSM-IV; with any psychiatric diagnosis, differential diagnoses must be addressed; delirium is commonly misdiagnosed as dementia (especially in elderly and acute hospital setting); depression and alcohol w/d can also mimic symptoms of dementia (more like a delirium)

12. Pharmacology in Geriatrics
Medication use in geriatrics
35% of all prescriptions dispensed
50% of all OTC medications
Polypharmacy
4-5 medications
At least 2 OTC medications regularly
In 2000, estimates
106,000 deaths from medication errors
Annual cost of $85 billion
Fick DM, Arch Intern Med 2003.
Fick et al. Arch Intern Med 2003; 163:

13. Geriatric Pharmacokinetics
Absorption
Generally unaffected
Distribution
Decreased total body water
Increased body fat
Decreased serum albumin
Metabolism
Decreased hepatic blood flow and metabolizing enzymes
Excretion
Decreased renal function
Absorption- Decreased bioavailability Decreased intestinal blood flow Decreased gastric emptying/motility Increased gastric pH Increase bioavailability Decreased first-pass effect = higher plasma concentrations
Distribution- Decrease Vd for water soluble and increased Vd for fat soluble Increased free-fraction of protein bound medications
Metabolism- usually decreased doses and increase frequency of administration
Elimination- Decreased GFR Decreased renal blood flow and mass Decreased creatinine production can lead to inaccurate assumption of renal function

14. Geriatric Pharmacodynamics
Dopaminergic
Decreased D2 receptors in striatum
Serotonergic
Decreased nerve terminals and transporters
Cholinergic system
Decreased choline acetyltransferase and cholinergic cells
Gaba-ergic system
Potential increase in response to potentiation at GABA receptors
Adrenergic system
Impaired baroreceptor function may result in orthostasis
Receptor changes alter sensitivity, amount, binding and cellular response; Catterson ML et al Zubenko et al Harvard Rev Psychiatry 2000
Zubenko et al. Harvard Rev Psychiatry 2000

15. Prescribing in Geriatrics
Complete and thorough medication reconciliation
Reduce polypharmacy
Appropriate dosing and drug selection
Utilizing pharmacists for consultation and effective communication/education
Medication education focused on compliance and adherence
Geriatric Medicine: An Evidence Based Approach - 4th Ed. (2003) Copyright© 2003 Spring-Verlag New York, Inc. All rights reserved.
Geriatric Medicine: An Evidence Based Approach - 4th Ed. (2003)

16. Pharmacist Intervention
Screen for medication interactions
Screen for medications that impair cognition or have anticholinergic side effects
Prepared with alternate medication recommendations

17. Approach to Dementia Consult
Always look at the overall picture of your patient
Environment
Busy or loud unit
New people with each shift change
Medical conditions
HPI and PMH
Order/Assess pertinent labs
Life-style changes
Recent move to care facility
Recent loss of loved one(s)
Address differential diagnosis
Delirium
Medical condition
Psychiatric disorder
Substance induced
Address medications known to alter cognition
Beers Criteria
Medications with anticholinergic properties
Opioids might contribute to confusion but uncontrolled pain can also lead to delirium;
Vascular disease and HIV are also possible causes of dementia
Depression can display symptoms of irritability and confusion- note if pt has history of depression or current situation could also precipitate depression

18. Drug Interactions
Occur when the effectiveness or toxicity of a drug is altered by the concomitant administration of another drug
3 classifications of drug interactions
Pharmaceutic
Physical or chemical incompatibility
Pharmacodynamic
Addition, synergism or antagonism of each drug’s effect
Pharmacokinetic
Changes in blood levels of the object drug
pharmaceutic- syringe or y-site incompatibility; PD- Watch for duplicate therapies that can compound effects Sedation Disorientation or confusion Stimulant effects Orthostasis Hypoglycemia; PK- induction or inhibition of CYP450; alterations in renal clearance; protein binding interaction

19. Medications in Delirium
Many drugs are suspect in delirium or cognitive impairment cases
Psychoactive meds suspect in 15-75% of cases
Identified as definite cause in only 2-14%
There are not many well designed studies examining drug-induced delirium
The studies have conflicting results, vary in design and analysis
Benzodiazepines and antipsychotics noted significant results in few studies
Anticholinergics, anticonvulsants, antidepressants, antiemetics, antiparkinsonians, corticosteroids, H-2 antagonists, and NSAIDs were not significantly associated with delirium
Critical review conclusions: the current evidence of an association of specific medications and delirium is rather weak.
Gaudreau JD, et al. Psychosomatics 2005; 46(6):
Gaudreau JD, et al. Psychosomatics 2005; 46(6):

20. Medications in Delirium
Borovick and Fuller. Drug-Induced Diseases: Prevention, Detection, and Management: 2nd ed. ASHP 2010; Chapter 15: Delirium.
Borovick and Fuller. Drug-Induced Diseases: Prevention, Detection, and Management: 2nd ed. ASHP 2010; Chapter 15: Delirium.

21. Beers Criteria Based on expert consensus
Extensive literature reviews
Utilization of the medications on the list
Increase provider/facility cost
Increase inpatient, outpatient and emergency visits
Centers for Medicare and Medicaid (CMS) utilized in nursing home regulation
Last updated in 2002
o The Beers criteria are based on expert consensus developed through extensive literature reviews identifying medications that may potentially inappropriate in older adults
o Centers for Medicare and Medicaid (CMS) adopted the Beers Criteria in July 1999 for nursing home regulation.
o Studies examining the use of medications found on the list indicate increased provider/facility costs and increased inpatient, outpatient and emergency visits.
o The Beers Criteria was last update via an expert panel examining current literature and professional surveys in 2002
Fick DM, et al. Arch Intern Med 2003; 163:

22. Abbreviated Beers Criteria
Fick DM, et al. Arch Intern Med 2003; 163:
PA-PSRS Patient Safety Advisory 2005; Vol 2(4)

23. Abbreviated Beers Criteria
Fick DM, et al. Arch Intern Med 2003; 163:
PA-PSRS Patient Safety Advisory 2005; Vol 2(4)

24. Abbreviated Beers Criteria
Fick DM, et al. Arch Intern Med 2003; 163:
PA-PSRS Patient Safety Advisory 2005; Vol 2(4)

25. Tips for Recommendations
Always include non-medication factors in consults if pertinent
Environment - Pain control
Medical condition - Daily routine
Approach medication changes, discontinuations and/or additions one at a time
Multiple changes that occur rapidly could exacerbate cognitive or behavioral changes
Just because a medication might be found on the Beers Criteria or associated with delirium it might still be necessary
Assess the current medical illness and past medical conditions prior to changing a therapy and weight the risk vs. benefit

26. Questions???