Guidelines for Dementia Syndrome

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1 Guidelines for Dementia Syndrome Dementia is the chronic acquired decline in memory and at least one other cognitive function (e.g. language, visual-spatial, executive) sufficient to offset daily life. Age APOE4 (whites) Atrial fibrillation Depression Down syndrome Family hx RISK AND PROTECTIVE FACTORS FOR DEMENTIA Definite Risks Possible Risks Delirium Head trauma Heavy smoking Hypercholesterolemia HTN Lower educational level Other genes Postmenopausal HT Possible Protections Antioxidants (e.g., vitamin E., beta carotene) PROGRESSION OF ALZHEIMER S DISEASE (AD) 2011 National Institute on Aging/ Alzheimer's Association research criteria identifies preclinical stages using PET and CSF biomarkers of Aβ or neuronal injury. MILD COGNITIVE IMPAIRMENT (PRECLINICAL) MMSE 26-30; CDR 0.5; FAST 3; MOCA <26 Report by patient or caregiver of memory loss Objective signs of memory impairment No functional impairment Mild construction language or executive dysfunction 6-15% annual conversion rate to dementia syndrome Disoriented to date Naming difficulties (anomia) Recent recall problems Mild difficulty copying figures Disoriented to date, place Comprehension difficulties (aphasia) Impaired new learning Getting lost in familiar areas Impaired calculating skills Nearly unintelligible verbal output Remote memory gone Unable to copy or write Some cases of mild cognitive impairment may not progress to AD Treating vascular risk factors (HTN,OM, high cholesterol) may reduce risk of progression to AD EARLY, MILD IMPAIRMENT (YR 1-3 FROM ONSET OF SYMPTOMS) MMSE 21-25; CDR 1; FAST 4 Decreased insight Social withdrawal Irritability, mood change Problems managing finances MIDDLE, MODERATE IMPAIRMENT (YR 2-8) MMSE 11-20;CDR 2; FAST 5-6 LATE, SEVERE IMPAIRMENT (YR 6-12) MMSE G-10; CDR 3; FAST 7 Delusions, agitation, aggression Not cooking, shopping, banking Problems with dressing, grooming No longer grooming or dressing Incontinent Motor or verbal agitation * MMSE = Mini-Mental State Examination; CDR = Clinical Dementia Rating Scale; FAST = Reisberg Functional Assessment Staging Scale; MoCA = Montreal Cognitive Assessment D. Osterweil 09/2014; D. Osterweil 09/2015

2 NONCOGNITIVE SYMPTOMS Psychotic Symptoms (e.g., delusions, hallucinations) Seen in about 20% of AD patients Delusions may be paranoid (e.g., people stealing things, spouse unfaithful) Hallucinations (~11% of patients) are more commonly visual Depressive Symptoms Seen in up to 40% of AD patients; may precede onset of AD May cause acceleration of decline if untreated Suspect if patient stops eating or withdraws Apathy High prevalence end persistence throughout course of AD Causes more impairment in ADL than expected for cognitive status High overlap with depressive symptoms but lacks depressive mood, guilt, and hopelessness Agitation or Aggression Seen in up to 80% of patients with AD A leading cause of nursing-home admission Consider superimposed delirium or pain as a trigger TREATMENT Primary goals of tx are to improve quality of life and maximize functional performance by enhancing cognition, mood, and behavior. General Treatment Principles Identify and treat comorbid physical illnesses (e.g., HTN, OM) Promote brain health by exercise, balanced diet, stress reduction Avoid anticholinergic medications, e.g., benztropine, diphenhydramine, hydroxyzine, oxybutynin, TCAs, clozapine, thioridazine Set realistic goals Limit PM psychotropic medication use Specify and quantify target behaviors Maximize and maintain functioning Establish and maintain alliance with patient and family Assess and monitor psychiatric status Intervene to decrease hazards of wandering Advise patient and family concerning driving Advise family about sources of care and support, financial and legal issues Consider referral to hospice (FAST= 7) Identify and examine context of behavior (is it harmful to patient or others) and environmental triggers (e.g., overstimulation, unfamiliar surroundings, frustrating interactions); exclude underlying physical discomfort (e.g., illnesses or medication); consider non-pharmacologic strategies. NONPHARMACOLOGIC APPROACHES FOR PROBLEM BEHAVIORS To improve function: Behavior modification, scheduled toileting, and prompted toileting) for urinary incontinence Graded assistance (as little help as possible to perform ADLs), practice, and positive reinforcement to increase independence For problem behaviors: Music during meals, bathing Walking or light exercise Simulate family presence with video or audio tapes Pet therapy D. Osterweil 09/2014; D. Osterweil 09/2015

3 Speak at patient's comprehension level Bright light, "white" noise (i.e., low-level, background noise) CAREGIVER ISSUES Over 50% develop depression Physical illness, isolation, anxiety, and burnout are common Intensive education and support of caregivers may delay institutionalization Adult day care for patients and respite services may help Alzheimer's Association offers support and education services Family Caregiver Alliance offers support, education, information for caregivers Assess and treat underlying depression PHARMACOLOGIC TREATMENT OF COGNITIVE DYSFUNCTION Patients with a diagnosis of mild or moderate AD should receive a trial of a cholinesterase inhibitor; donepezil also approved for severe AD. o Controlled data for cholinergic drugs compared with placebo for 1 yr. show statistical benefit for cognition, but with limited clinical benefit. o Only 10-25% of patients taking cholinesterase inhibitors show modest global improvement, but many more have less rapid cognitive decline. o Initial studies show benefits of cholinesterase inhibitors for patients with dementia associated with Parkinson disease and vascular dementia. o Cholinesterase inhibitors have not been demonstrated to slow progression of mild cognitive impairment to dementia, but early tx may help maintain function at higher level for longer periods. o Cholinesterase inhibitors may attenuate noncognitive symptoms and delay nursing-home placement o Adverse events increase with higher dosing. Possible adverse events include nausea, vomiting, diarrhea, o dyspepsia, anorexia, weight loss, leg cramps, bradycardia, syncope, insomnia, and agitation. To evaluate response: Elicit caregiver observations of patient's behavior (alertness, initiative) and follow functional status Follow cognitive status (e.g., improved or stabilized) by caregiver's report or serial ratings of cognition Memantine (Namenda) demonstrated modest efficacy compared with placebo in moderate to severe AD as monotherapy. Recent controlled trial did not demonstrate significant advantage for the combination of memantine and donepezil compared with donepezil alone in patients with severe dementia. D/C cognitive enhancers when FAST= 7 Vitamin E at 1000 IU Q12h found to delay functional decline in AD (caution in those with cardiovascular disease because 400 IU may increase mortality). Ginkgo biloba is not generally recommended Axona (medium-chain TG) has insufficient evidence to support its value in preventing or treating AD, and long-term effects are uncertain. D. Osterweil 09/2014; D. Osterweil 09/2015

4 Medication donepezil tabs 5mg & 10mg, donepezil odt EXELON PATCHES galantamine tabs & oral soln galantamine er Pharmacologic Agents for Dementia Dosing & Administration Cholinesterase Inhibitors Tier Level & Requirements mg to 10mg PO once daily mg/24 hours to 13.3mg/24 hours patch transdermally once daily 4mg to 12mg PO twice daily 8mg to 24mg PO once daily Adverse Drug Reactions nausea, diarrhea, insomnia, vomiting, muscle cramps, fatigue, and anorexia 3 [QL] 3 [QL] nausea, vomiting, and diarrhea 2 [QL] 2 [QL] nausea, vomiting, diarrhea, dizziness, headache, decreased appetite, and weight decreased nausea, vomiting, anorexia, dyspepsia, rivastigmine caps 1.5mg to 6mg PO twice daily 2 [QL] 2 [QL] and asthenia N-methyl-D-aspartate (NMDA) Receptor Antagonists memantine hcl immediate 5mg to 20mg PO daily in release divided doses memantine hcl 5mg-10mg titration pack 5mg to 20mg PO daily in 2 divided doses 2 2 NAMENDA ORAL SOLN 5mg to 10mg PO twice daily 3 3 NAMENDA TITRATION PAK 5mg to 20mg PO daily in 2 divided doses 3 3 NAMENDA XR 7mg to 28mg PO once daily 3 [NF] Brand-name drugs are capitalized and generic drugs are listed in the lower-case italics. [NF] = Non-formulary [QL] = Quantity Limit [ST] = Step Therapy headache, diarrhea and dizziness, vomiting a: Cholinesterase inhibitors. FDA labeling for AD is as follows: donepezil mild, moderate, severe; galantamine mild, moderate; rivastigmine mild, moderate. Continue if patient improves or stabilizes; stopping medication can lead to rapid decline. Adverse events increase with higher dosage. b: Approved by FDA for moderate to severe AD. Possible adverse events include dizziness, headache, somnolence. NMDA = N-methyl-d-aspartate. c: Increased mortality found in controlled studies of mild cognitive impairment D. Osterweil & L. Vu 09/2014; D. Osterweil & A. Phan 09/2015

5 TREATMENT OF AGITATION Consider non-pharmacologic approaches first before pharmacologic tx Consider steps to reduce non-verbalized pain Cognitive enhancers may slow deterioration, and agitation may worsen if discontinued. Low doses of antipsychotic medications have limited role but may be necessary. Note this use is off-label and increases risk of death compared with placebo in patients with AD. CATIE-AD trial (NEJM2006;355: ) showed modest tx benefit compared with placebo for olanzapine and risperidone that was mitigated by greater EPS, sedation, and confusion. In this trial, quetiapine did not appear to be efficacious compared with placebo but caused greater sedation. CATIE-AD reported second-generation antipsychotics cause weight gain, particularly in women treated with olanzapine or quetiapine; olanzapine tx was also associated with decreased HDL cholesterol Cholinesterase inhibitors may worsen behavioral variant in those with Frontotemporal Dementia (FTD): consider Memantine or SSRI s. For the treatment of apathy: assess and treat underlying depression; cholinesterase inhibitors help; methylphenidate (5-20 mg/d), very limited data, may cause agitation and psychosis. Symptom Agitation in context of psychosis Medication ABILIFY ORAL aripiprazole tabs 2mg, 5mg, 10mg, & 15mg; oral solution aripiprazole tabs 20mg & 30mg Dosing & Administration 2.5mg to 12.5mg PO daily a Tier Level & Requirements [ST] 4 [ST] 2 [ST] 2 [ST] 2 [ST] 5 [ST] olanzapine oral 2.5 to 10mg PO daily a 2 2 quetiapine 12.5mg to 100mg PO daily a 2 2 risperidone 0.25mg to 3 mg daily a 2 2 Agitation in context of depression SSRI Varies e.g., citalopram tabs Refer to Comprehensive formulary Refer to Comprehensive formulary 10 to 20mg daily 1 1 Anxiety, mild to moderate irritability buspirone 15 to 60 mg PO daily b 2 2 trazodone 50 to 100mg PO daily c 1 1 Agitation or agression unresponsive to first line treatment carbamazepine ir divalproex sodium ir 300 to 600 mg PO daily d mg PO daily e 2 2 Sexual aggression, impulse-control symptoms in men olanzapine inj 2.5 to 5 mg IM a,f 2 2 Second-generation antipsychotic or divalproex see dosages above see above see above a: Avoid: Greater mortality, cardiovascular, and cerebrovascular events than placebo; use with particular caution in patients with cerebrovascular disease, prolonged QTc interval or hypovolemia. b: Can be given Q12h; allow 2-4 wk for adequate trial. c: Small divided daytime dosage and larger bedtime dosage; watch for sedation and orthostasis. d: Monitor serum levels; periodic CBCs, platelet counts secondary to agranulocytosis risk. Beware of drug-drug interactions. e: Can monitor serum levels; usually well tolerated; check complete blood count (CBC), platelets for agranulocytosis, thrombocytopenia risk. f: For acute use only; initial dose 2.5 mg to 5 mg, second dose (2.5 mg to 5 mg) can be given after 2 hr, maximum of 3 injections in 24 hr (maximum daily dose 20mg); should not be administered for more than 3 consecutive days. D. Osterweil 09/2014; D. Osterweil & A. Phan 09/2015

6 References 1. A Guide to Dementia Diagnosis and Treatment. American Geriatrics Society. (Accessed on August 7, 2014). 2. Biennow K, et al. Lancet 2006; 368(9533): Online Lexicomp (09/2015): 1100 Terex Road, Hudson, OH Reuben, D. (2013). Dementia. In Geriatrics at your fingertips (15th ed.). New York: American Geriatrics Society. D. Osterweil 09/2014; D. Osterweil & A. Phan 09/2015

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