Alzheimer's Disease Assessment and Management

Alzheimer's Disease Module II

• Learning Objectives: Students will learn to optimize medicine use and care for patients with Alzheimer's Disease (AD). By the end of the module, students will be able to demonstrate knowledge of AD epidemiology, etiology, and pathophysiology. They will understand the roles of amyloid beta, cholinergic deficiency and glutamate excess in neuronal injury. Students will also be able to recognize AD signs, symptoms, risk factors, and criteria for diagnosis and severity assessment; explain different modes of action for medications used in treating AD. Also describe key pharmacokinetic, pharmacodynamic properties, side effects, and potential drug interactions. Furthermore, students will formulate patient-specific goals, treatment efficacy, and monitoring plans for people with AD, as well as pharmacological and non-pharmacological strategies for behavioral psychological symptoms.

Case Study: Mrs. Fatima

• Demographics: 73-year-old female
• Chief Complaint (CC): Increasing memory problems (forgetfulness with paying bills, stove on, etc.) over 2 years
• History of Present Illness (HPI): Memory problems worsening over the past two months; confusion, disorientation, agitation, refusing to pay bills when stating already paid. She also reports her mother had memory issues.
• Past Psychiatric History (PPH): Problems sleeping, depression related to cognitive decline, no changes in appetite or suicidal ideation
• Past Medical History (PMH): Diabetes (diet and metformin for controlling), history of gastric ulcers (antacid for heartburn), constipation (stool softener).
• Social History (SH): Widow for 3 years, one daughter in Jordan and the other a housewife with 3 children. Lives close to daughter; housekeeper except weekends. Never smoked or consumed alcohol.

Reflect on the Disease

• Task: Write about a patient's life with AD, and their therapy options; individual insights and aspirations on the topic
• Duration: 2 minutes of writing

AD Mind Map

• Mild to moderate AD: Use Cholinesterase Inhibitors (AChIs) based on ADRs and dose forms. Consider aducanumab.
• Moderate to severe AD: Use memantine monotherapy. Add memantine to existing AChIs. Or memantine + Donepezil.
• Goal of treatment: Maintain function/Reduce symptoms, manage psychiatric & behavioral symptoms
• Approach: Medication, supportive care, lifestyle, etc.
• Specific strategies: Use of specialized therapies for cognitive decline, behavioral/emotional problems and other medical complications of AD

Goals of Therapy

• Primary Goal: Treat symptoms associated with cognitive decline and preserve patient function
• Secondary Goals: Manage psychiatric and behavioral sequelae, modify and reduce risk factors.

AD - Management Principles

• Early Stages: Discuss with patient and family, define patient-specific treatment goals. Refer to early-stage groups or adult day services for activities.
• Intermediate Stages: Use AD-specific medications to treat cognitive decline, treat behavioral symptoms and mood disorders using non-pharma approaches.
• Late Stages: If non-pharmacological is unsuccessful, use medications for specific behaviors. Provide appropriate treatment for medical conditions and offer end-of-life care when needed.

Nonpharmacologic Therapy

• Identify causative factors: Cognitive and non-cognitive symptoms and adapt the caregiving environment to address them.
• Sleep Disturbances: Behaviours and environmental interventions
• Urinary Incontinence, Agitation and Aggression: Manage use of behavioral and environmental interventions
• Lifestyle changes: On initial diagnosis: educate patients and caregivers on the illness course, available treatments, legal decisions, quality-of-life issues.
• Primary prevention: Smoking cessation, physical activity, reduction of midlife obesity, hypertension, diabetes, adherence to the Mediterranean Diet or DASH diet may reduce the risk.

Pharmacologic Therapy of Cognitive Symptoms

• Mild to moderate: Select AChIs based on ADRs and forms. Consider aducanumab.
• Moderate to severe: Use memantine monotherapy, add memantine to existing AChIs, or memantine + Donepezil.

Cholinesterase Inhibitors

• Drugs: Donepezil, rivastigmine, and galantamine
• Use: First-line therapy for mild-moderate AD, also indicated for severe AD
• Duration: Assess efficacy, stop if ineffective or switch to Memantine. Don't switch Cholinesterase inhibitors.
• Monitoring: 6 months on target dose. Re-evaluate and taper down by 50% if no benefit.

Cholinesterase Inhibitors: Dose and Administration

• (Table of drugs, forms, initial, maintenance,dosage and comments)

Options for Patients on Enteral Feeding

• Diagram: (Illustation of nasogastric tube, nasal cavity, esophagus, and stomach) Shows how the feeding is conducted.

Cholinesterase Inhibitors: Benefit and Monitoring

• Benefit: Modest improvements in cognitive, neuropsychiatric symptoms, and daily living activities
• NNT: Over minimum of 12 weeks
• Side effects: (Nausea, vomiting, diarrhea, insomnia, vivid/abnormal dreams, etc.)
• Monitoring: Heart rate monthly during titration. Blood pressure, and weight checks every six months.

Monitoring Treatment with AChIs

• Baseline tests: Urea, electrolytes, liver function, blood pressure
• Monitoring during treatment: Heart rate, blood pressure, weight, and side effects
• Other side effects: Muscle cramps, bradycardia, increased gastrointestinal acid, appetite decrease, and weight loss

N-methyl-D-aspartate (NMDA) receptor antagonists

• Drug: Memantine
• Use: Indicated for moderate to severe AD as monotherapy
• Combination: May be combined with donepezil (Namzaric) to mitigate GI effects of cholinesterase inhibitors.
• Use in Mild AD: Not indicated for mild AD (no significant benefit)
• Other indications: Vascular or mixed dementia; older adults with Down Syndrome may not achieve benefit

Memantine Dosing

• Initial: 5 mg once daily
• Dose increase: 5 mg weekly increase up to maximum tolerated dose of 20 mg per day.
• Extended release: Available form

Monitoring Treatment - Cholinesterase Inhibitors and Memantine

• Patient reassessment: 2-4 months after reaching maintenance dose and every 6 months thereafter. Monitor cognition (MMSE score), activities of daily living (ADLs). Monitor overall clinical response, including side effects.

When to Stop Cholinesterase Inhibitors and Memantine

• ( Flowchart showing decision tree for stopping medication based on patient and clinical factors)

Disease-modifying therapies (DMTs)

• Aimed at: Modifying the course of AD rather than managing symptoms
• Drugs: Aducanumab and Lecanemab
• Mechanism: Target amyloid-ß plaques
• Initial assessment: Confirm amyloid beta pathology, ApoE ε4 status, prior to initiation
• Administration: Monthly infusion for aducanumab (initial 1 mg/kg, increasing to 10 mg/KG over 24 weeks), and IV 10mg/kg every 2 weeks for Lecanemab

Aducanumab

• Use: Mild cognitive impairment or mild dementia; evidence of amyloid buildup, as it's not indicated in earlier or later stages.
• Co-administration: Can be co-administered with other AD drugs like cholinesterase inhibitors (donepezil, rivastigmine, galantamine), memantine, and psychotropic agents.

Aducanumab - Safety Monitoring

• ARIA (Amyloid-related imaging abnormalities): Edema and microhemorrhage
• Monitoring: Clinical symptoms like headache, confusion, vision disturbances. Serial cognitive testing with family reporting. MRI scans prior to initiating therapy and at 5th, 7th and 12th doses.

Dosing protocol of Aducanumab

• (Flow chart showing Aducanumab dosing protocol showing initial dose, interval, treatment duration and criteria for stopping treatment)

Management of behavioral and psychological symptoms of dementia (BPSD)

• Categories and Medications: Depression: Escitalopram, Mirtazapine; Sleep-Wake Cycle Modulators: Melatonin; Atypical Antipsychotics: Aripiprazole, Risperidone, Olanzapine, Quetiapine; Psychotic Episodes: Pimavanserin; Carbamazepine, Levetiracetam; Lithium; Mood Stabilizer: Methylphenidate; Stimulant: Brexpiprazole; Agitation: Brexpiprazole

AD - Alternative Treatments

• Studies showing use: Selegiline, Amyloid Therapy, Estrogen Therapy, Anti-inflammatory agents (NSAIDs), Cholesterol-lowering medications
• Herbal/dietary supplements: Ginkgo biloba, Coenzyme Q, Omega-3 fatty acids, Vitamin E
• Important Note: No scientific evidence of effectiveness

This quiz explores key aspects of Alzheimer's disease, including cognitive assessment tools and treatment recommendations. It also highlights important factors that can impact patient care, such as social and comorbid conditions. Test your knowledge on effective management strategies for patients like Mrs. Fatima.