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39 Cards in this Set
- Front
- Back
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1. Prevalence of dementia?
2. More common in males or females? 3. Shortened life span 4. Alzheimer’s disease is ____ leading cause of death? 5. First degree relatives have _____times higher likelihood of developing AD? |
1. 5-8% > 65 y/o, 15-20% > 75 y/o, 25-50% >85 y/o
2. females 3. 8 years is mean survival time from diagnosis 4. 6th leading cause 5. 2-4x higher |
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Types of Dementia
(10) |
Alzheimer’s dementia (most common form)
Vascular dementia (second most common form) Mixed dementia Lewy Body dementia Parkinson’s disease dementia Frontotemporal dementia/ Pick’s disease HIV-related Substance-induced Creutzfeldt-Jacob disease Huntington’s disease |
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Risk factors for Vascular Dementia (11)
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Age
Male sex African American Hypertension MI CHD Diabetes Atherosclerosis Smoking Hyperlipidemia Stroke |
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Lewy body dementia (LBD)
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~20% of dementia cases
Symptoms Fluctuating cognition, spontaneous motor features of parkinsonism, recurrent visual hallucinations Rigidity, tremor, bradykinesia helpful in distinguishing from AD ~50% of patients with LBD very sensitive to antipsychotics |
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Mixed dementia
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Alzheimer’s dementia + another dementia
Frontotemporal dementia Rare, ~10-15% of dementias Usually earlier onset (~40-70 y/o) Symptoms Personality changes and disorderly social conduct Disinhibition, impulsivity, hyperorality, sexual disinhibition |
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RISK FACTORS FOR ALZHEIMER’S DISEASE (9)
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Age
Female African-American, Hispanic (1.5x more likely than white) Reduced brain size Fewer years of education Reduced mental and physical activity later in life Head injury Risk factors for vascular disease -Hypercholestermia -Hypertension -Atherosclerosis -Coronary heart disease -Smoking -Obesity -Diabetes Genetic factors -Chromosome variation - APOE4 - Trisomy 21 |
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DSM-IV TR® CRITERIA: ALZHEIMER’S/VASCULAR DEMENTIA
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Development of multiple cognitive deficits manifested by both:
Memory impairment AND ≥ 1 of the following: Aphasia (language disturbance) Apraxia (impaired ability to carry out motor activities ex: buttoning shirt, eating) Agnosia (failure to recognize or identify objects Ex: childrens faces, objects) Disturbances in executive functioning (planning, organizing, sequencing, abstracting) |
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TOP 10 WARNING SIGNS OF ALZHEIMER’S DISEASE
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Memory loss that affects job skills
Difficulty performing familiar tasks Problems with language Disorientation to time and place Poor or decreased judgment Problems with abstract thinking Misplacing things Changes in mood or behavior Changes in personality Loss of initiative |
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ALZHEIMER’S DEMENTIA SYMPTOMS
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Early symptoms
Difficulty remembering names and recent events Apathy, depression Late symptoms Impaired judgment Disorientation Confusion Behavioral changes Difficulty speaking, swallowing, and walking |
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How do you differentiate diagnosis of dementia from other diseases?
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CNS conditions
Cerebrovascular disease Parkinson’s disease Huntington’s disease Subdural hematoma Normal-pressure hydrocephalus Brain tumor Medications Benzodiazepines Sedative hypnotics Anticholinergics Opioid analgesics Antipsychotics Anticonvulsants Systemic conditions Hypothyroidism Vitamin B12 or folic acid deficiency Niacin deficiency Hypercalcemia Neurosyphillis HIV infection |
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SCREENING FOR SUSPECTED DEMENTIA (6)
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CT or MRI
Blood cell counts Rule out UTI Serum electrolytes Can cause confusion Liver function tests Thyroid function tests Vitamin B12 level |
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Mini Mental Status Exam (MMSE)
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Assess cognitive impairment
Brief, structured mental status exam 10-15 minutes to administer Assesses Orientation Registration Attention/calculation Recall Language Praxis Scoring: maximum of 30 points Untreated patient has average decline of 2-4 points/year (in patients untreated) |
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ALZHEIMER’S DISEASE STAGES based on MMSE score
-Mild -Moderate -Severe |
Mild: <26
Moderate: 10-19 Severe: <10 |
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OTHER COGNITIVE RATING SCALES (3)
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Blessed Information Memory Concentration Test (BIMC)
Assesses orientation and memory 27 items (0- no impairment; 33- severe impairment) Clock Drawing Test (CDT) Assesses orientation, conceptualization of time, visual spatial organization Alzheimer’s Disease Assessment Scale (ADAS-cog) Most widely used dementia assessment in clinical trials |
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Goals of treatment for Alzheimers disease (4)
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Temporarily slow worsening of symptoms for 6- 24 months
Delay time to nursing home placement Primary goal: Treat cognitive difficulties and preserve daily functioning Secondary goal: Treat behavioral and psychological symptoms of dementia (BPSD) No treatment available to slow or stop progression of dementia |
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Treatments of AD (2 categories)
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Cognitive symptoms
Cholinesterase inhibitors (ChEIs) -Tacrine (Cognex® ) -Donepezil (Aricept®): gold standard -Rivastigmine (Exelon®) -Galantamine (Razadyne®) NMDA antagonist -Memantine (Namenda®) Glutamate antagonist: excitation of neurons lead to cell death, so it preserves the neurons. |
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Cholinesterase inhibitors:
Overview |
No good head-to-head trials comparing ChEIs
Indications -Mild to moderate dementia -Donepezil also approved for severe dementia -Also used for Parkinson’s dementia and Lewy Body dementia -Uncertain efficacy and safety in vascular dementia Some data says it works, other says it increases mortality Demonstrate modest improvement Differ in dosing and side effect profile Side effects results from cholinergic excess (nausea, diarrhea, vomiting) Discontinuation of ChEIs may lead to deterioration (going to baseline cognitive function) |
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Cholinesterse Inhibitors: Use with CAUTION in these 6 patients
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GI disorders (gastritis, ulcerative disease)
Sick sinus syndrome or conduction defects Cerebrovascular disease Seizures Asthma COPD |
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DONEPEZIL (ARICEPT®)
-MOA -indication -dosing -administration -AE -PK |
Selective, reversible AChEI
Indication Mild to severe Alzheimer’s dementia Dosing Mild to moderate Initial dose: 5 mg/day Can titrate to 10 mg/day after 4-6 weeks Moderate to severe Initial dose:5 mg/day Can titrate to 10 mg/day after 4-6 weeks Can titrate to 23 mg/day after 12 weeks (3 months) Has a lot more GI side effects due to double peak. Might not be able to tolerate this dose Administration PI: before bedtime (but may cause nightmares so am dose ok with meal Common adverse effects Nausea, diarrhea, vomiting, muscle cramps, fatigue, anorexia Less common: increase dreaming, disturbed sleep May cause bradycardia or syncopal episodes in patients with and without underlying cardiac abnormalities Clinically significant weight loss reported in 8.4% and 4.9% of patients receiving 23 mg and 10 mg of donepezil, respectively Pharmacokinetics Tmax 10 mg: 3 hours 23 mg: 8 hours Metabolism: CYP2D6, 3A4 Half-life: 70 hours |
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RIVASTIGMINE (EXELON®)
-MOA -indication -dosing -administration -AE -PK |
Non-selective butyrylcholinesterase (BuChEI) and acetylcholinesterase (AChEI) pseudo-irreversible inhibitor
Indications Treatment of mild to moderate dementia associated with Alzheimer’s or Parkinson’s disease Dosing Transdermal system Initial: 4.6 mg/24 hour patch Can titrate to 9.5 mg/24 hour patch after 4 weeks If nausea, diarrhea, vomiting, or loss of appetite occur, discontinue treatment for 3 days and start at same or lower dose If > 3 days off treatment, reinitiate with lowest daily dose and titrate Oral Initial: 1.5 mg PO BID Can increase by 3 mg/day every 2 weeks Max: 6 mg PO BID Administration Upper or lower back preferred If not accessible, apply to upper arm or chest Rotate site daily Adverse effects Higher doses associated with higher risk of nausea, vomiting, anorexia, weight loss Pharmacokinetics Tmax: 8-16 hours Metabolism: minimal CYP activity Half-life: 3 hours Converting from oral to transdermal Apply first patch on day following last oral dose Can increase after 4 weeks |
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GALANTAMINE (RAZADYNE®, RAZADYNE ER)
-MOA -indication -dosing -administration -AE -PK |
Dual MOA
Selective, reversible, competitive AChEI Enhances actions of acetylcholine on nicotinic receptors Indications Mild to moderate Alzheimer’s dementia Dosing IR (dose range: 16-24 mg/day) Administer at breakfast and dinner Initial: 4 mg PO BID Titrate to 8 mg PO BID after 4 weeks Titrate to 12 mg PO BID after 4 weeks ER (dose range: 16-24 mg/day) Administer in the morning with food Initial: 8 mg/day Titrate to 16 mg/day after 4 weeks Titrate to 24 mg/day after 4 weeks Common adverse effects Nausea, vomiting, diarrhea, anorexia, weight loss Pharmacokinetics Tmax: 1 hour Metabolism: CYP 2D6, 3A4 Half-life: 7 hours ***If therapy interrupted for ≥ 3 days, must restart at lowest dose and increase to current dose*** |
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MEMANTINE (NAMENDA®, NAMENDA XR®)
-MOA -indication -dosing -administration -AE -PK |
Non-competitive NMDA antagonist
Indications Moderate to severe Alzheimer’s dementia monotherapy or in combination with donepezil or other AchI Combination therapy more likely to delay symptom progression vs. monotherapy with cholinesterase inhibitor Dosing Immediate release Initial: 5 mg PO Q Day x 1 week Increase to 5 mg PO BID x 1 week Increase to 10 mg PO Q Day x 1 week Increase to 10 mg PO BID Extended release Initial: 7 mg PO Q Day Increase by 7 mg weekly to target dose of 28 mg/day Can be administered with or without food Common adverse effects Constipation, confusion, dizziness, headache, sedation, agitation, falls Pharmacokinetics Tmax IR: 3-7 hours XR:9-12 hours Metabolism: minimal CYP450 involvement Half-life: 60-80 hours |
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Other potential treatment options for AD (5)
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Estrogen replacement
NSAIDs Statins Vitamin E Increased mortality associated with higher dose Ginkgo Biloba |
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Consequences of BPSD (6)
(behavioral and psychological symptoms of dementia) |
Caregiver “burnout”
Patient institutionalization Impaired ADLs (activities of daily living) More rapid cognitive decline Decrease in patient quality of life Increase in medical costs May require hospitalization |
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Progression of BPSD
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Up to 90% of patients with AD may have at least one symptom
Intensity increases with severity of dementia Depression more common in earlier stages, delusions and hallucinations more common in later stages Most frequent symptoms Apathy (72%) Delusions (70%) Aggression/Agitation (60%) Anxiety (48%) Treat underlying cause, try non-pharmacologic management |
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Non pharmacological approaches for BPSD (5)
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Behavioral interventions
Antecedent, behavior, consequence (A,B,C model) Staff training antipsychotic use without worsening behavior Behavioral activation Ex: music or bingo Social interaction Sensory interventions Lavender oil, melissa oil |
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Pharmacological Treatment for BPSD (7)
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Antipsychotics
Psychosis Agitation Mood Stabilizers Agitation Antidepressants Depression Agitation Benzodiazepines (avoid if possible) Anxiety PRN agitation Topiramate BPSD Propranolol Agitation/aggression Memantine Agitation/aggression |
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4 main causes for increased Risk of Death with APs (antipsychotics): black box warning on FGAs and SGAs
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Cerebrovascular events
Cognitive impairment demonstrated to be strong, independent predictor of ischemic stroke Increased incidence of stroke Orthostatic hypotension Thromboembolic events Excessive sedation/stiffness Hyperprolactinemia and enhanced platelet activity Cardiac events QT prolongation Peripheral vasodilation-> cardiovascular collapse Acute myocarditis Cardiomyopathy Pneumonia High aspiration risk at baseline H1 receptor blockade and anticholinergic side effects (impaired swallowing) Excessive sedation and swallowing problems |
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Risk of Death with Antipsychotics?
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Increased risk of death with FGAs and SGAs
Higher doses associated with higher risk of death Higher risk of death in first 90 days of therapy Higher risk of CVE (stroke) with FGA use in non-AD dementia |
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Benefits (4) and Risks (3) of antipsychotics
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Benefits:
Hostility Suspiciousness Psychosis Agitation Risks: -Increased risk of death -Increased risk of tardive dyskinesia (involuntary movement in face or body) -No benefit Functioning Care needs Quality of life |
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Mood Stabilizers in BPSD
-indication - 2 drugs |
Often used to control agitation in dementia
-Valproate (Depakote) Most studies show ineffective for agitation in dementia and increased adverse effects Effective in clinical practice Starting dose: 125-250 mg/day Adverse effects Sedation, GI effects, confusion, ataxia, falls -Carbamazepine (Tegretol) Modest benefit for agitation High risk of drug-drug interactions Starting dose: 50-100 mg/day Adverse effects Ataxia, falls, sedation, confusion |
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Antidepressants in BPSD
-indication -drugs used -drugs avoided |
Up to 50% of patients with AD have depression
Assess for suicidal ideation Increased risk in elderly, especially elderly men Highest risk in white males older than 85 ***SSRIs preferred (due to lower se and interactions) -Avoid paroxetine due to anticholinergic side effects -Avoid TCAs due to anticholinergic activity -Can also use venlafaxine, bupropion, mirtazapine |
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BENZODIAZEPINES IN BPSD
-indication -drugs used -AEs |
May be used for anxiety or episodes of agitation
Lorazepam and oxazepam preferred -No active metabolites -No CYP-mediated metabolism -Shorter half-life than diazepam, clonazepam Adverse effects -Sedation, ataxia, anterograde amnesia, confusion, paradoxical activation (might make some patients even more agitation) -Increased risk of falls |
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General Treatment Guidelines for BPSD (4)
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Use lowest dose possible
Monitor closely Titrate slowly Document |
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Mild dementia treatment option for AD
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Cholinesterase inhibitor
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Moderate to Severe treatment for dementia
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Cholinesterase inhibitor + memantine
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AFTER BEING STABILIZED ON RIVASTIGMINE 6 MG PO BID FOR 1 YEAR, GM IS ADMINISTERED ANOTHER MMSE TO MONITOR FOR FURTHER CHANGES IN COGNITION. SHE RECEIVES A 16/30 ON HER MMSE. WHAT MODIFICATIONS WOULD YOU LIKE TO MAKE TO HER CURRENT MEDICATION REGIMEN?
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Discontinue rivastigmine, switch to galantamine, and add memantine
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AT A FOLLOW-UP APPOINTMENT 3 MONTHS AFTER STARTING DONEPEZIL, GM’S BP IS 130/76 AND HER HR IS 50 BPM. SHE COMPLAINS OF FEELING DIZZY AND WEAK LATELY. HER CURRENT REGIMEN IS DONEPEZIL 10 MG PO Q DAY. HOW WOULD YOU LIKE TO MANAGE HER MEDIATION REGIMEN, ASSUMING HER SYMPTOMS ARE NOT DUE TO ANOTHER MEDICAL COMORBIDITY?
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Discontinue donepezil and switch to rivastigmine without a washout period
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TWO YEARS LATER, GM PRESENTS TO HER GERIATRICIAN ACCOMPANIED BY HER DAUGHTER, WHO STATES THAT HER MOTHER HAS BEEN ACTING “OUT OF CHARACTER” LATELY. SHE MENTIONS THAT HER MOTHER HAS LOST ALL PATIENCE AND HAS STARTED CUSSING AT FAMILY MEMBERS. SHE EVEN HIT A FEW FAMILY MEMBERS DURING HEATED ARGUMENTS WITH THEM. HOW WOULD YOU LIKE TO TREAT GM’S SYMPTOMS?
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Initiate divalproex 125 mg PO QHS
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