What is the appropriate evaluation and first‑line pharmacologic and non‑pharmacologic management for a patient over 65 years old presenting with progressive memory loss, executive dysfunction, and behavioral changes suggestive of Alzheimer disease?

Evaluation and Management of Alzheimer Disease in Patients Over 65

Initial Evaluation

For any patient over 65 presenting with progressive memory loss, executive dysfunction, and behavioral changes, initiate a comprehensive multi-tiered evaluation immediately—do not attribute symptoms to "normal aging" without proper assessment. 1

Essential History Components

• Obtain detailed history from both the patient AND a reliable informant (spouse, family member, or close contact who knows the patient well), as patients may lack awareness of their deficits (anosognosia) 1
• Document the specific types, trajectory, and functional impact of cognitive and behavioral changes, particularly:
  • Memory impairment (difficulty learning and remembering new information) 1
  • Executive dysfunction (impaired judgment, problem-solving, reasoning) 1
  • Behavioral changes (personality shifts, apathy, social withdrawal) 1
  • Interference with independence in daily activities, minimally requiring assistance with complex instrumental activities like paying bills or managing medications 1

Cognitive Assessment

• Administer standardized cognitive screening using MMSE or Montreal Cognitive Assessment (MoCA), recognizing limitations in patients with language barriers, low education, sensory impairments, or psychiatric comorbidities 1
• For atypical presentations or confounding factors, refer for formal neuropsychological testing, which provides comprehensive assessment across cognitive domains, assists with differential diagnosis, and offers tailored recommendations for management 1
• Establish baseline testing when subjective concerns exist, even before overt symptoms, to enable future comparison and early detection 1

Physical and Neurological Examination

• Assess for sensory deficits (hearing loss/presbycusis, vision loss/presbyopia) that are common, potentially reversible dementia risk factors 1
• Evaluate gait and balance carefully, as impairments increase fall risk when combined with cognitive deficits and may indicate Lewy body disease, vascular dementia, or frontotemporal lobar degeneration 1
• Screen for extrapyramidal motor features (rigidity, bradykinesia) and visual hallucinations suggesting dementia with Lewy bodies 1

Laboratory and Imaging Workup

• Obtain brain MRI without contrast (when available and not contraindicated) to:
  • Exclude non-neurodegenerative causes (tumors, infections, inflammatory conditions) 1
  • Identify atrophy patterns suggestive of specific neurodegenerative diseases (medial temporal and lateral temporal-parietal atrophy with ventricular enlargement supports AD) 1
• Screen for reversible/contributing conditions: vitamin B12 deficiency, thyroid dysfunction, metabolic disorders, medication effects 1, 2

Differential Diagnosis Considerations

• Progressive amnesic syndrome (single or multi-domain with prominent memory impairment) most commonly indicates AD, often with co-pathologies 1
• Depression must be actively considered, as it commonly presents with cognitive symptoms in older adults and may be an early manifestation of AD rather than a separate entity 1
• Mixed etiology dementia is common in patients over 80, with multiple pathologies (AD + vascular disease, AD + Lewy bodies) contributing to symptoms 1

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First-Line Pharmacological Management

For Mild to Moderate Alzheimer Disease

Initiate a cholinesterase inhibitor (donepezil, rivastigmine, or galantamine) as first-line pharmacological treatment—all three are equivalent options. 2

Donepezil Dosing

• Start 5 mg once daily, increase to 10 mg after 4-6 weeks 2, 3
• Can be taken any time of day; take with food to reduce gastrointestinal side effects 2

Rivastigmine Dosing

• Start 1.5 mg twice daily with food, increase by 1.5 mg twice daily every 4 weeks as tolerated to maximum 6 mg twice daily 2, 3
• Taking with food reduces gastrointestinal adverse effects 2

Galantamine Dosing

• Start 4 mg twice daily with meals, increase to 8 mg twice daily after 4 weeks, consider up to 12 mg twice daily based on tolerance 2, 3
• Contraindicated in hepatic or renal insufficiency 2, 4

Expected outcomes: Approximately 20-35% of patients show meaningful response, with symptomatic (not disease-modifying) benefits that are dose-dependent. 2

For Moderate to Severe Alzheimer Disease

Use memantine alone OR in combination with a cholinesterase inhibitor—combination therapy provides cumulative, additive benefits over monotherapy. 2, 5

Dosage Adjustments

• In moderate hepatic impairment: reduce galantamine dose 4
• In renal impairment (CrCl 9-59 mL/min): reduce galantamine dose 4
• Avoid galantamine if CrCl <9 mL/min or severe hepatic impairment 4

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First-Line Non-Pharmacological Management

Implement structured non-pharmacological interventions as the foundation of comprehensive care—these should be initiated before resorting to medications for behavioral symptoms. 2, 5

Establish Predictable Daily Routine

• Create consistent schedules for wake times, meals, exercise, and bedtime to reinforce circadian rhythms and reduce confusion 2, 3
• Simplify daily tasks and provide meaningful activities tailored to the patient's current abilities 5

Environmental Modifications

• Eliminate hazards: remove trip hazards, install grab bars in bathroom, ensure adequate lighting 2, 5
• Install safety measures: safety locks on doors/windows, consider GPS tracking devices for wandering risk 2, 5
• Use orientation aids: calendars, clocks, color-coded labels, written reminders 3, 5
• Enroll in Alzheimer's Association Safe Return program to address wandering risks 3, 5

Structured Exercise Program

• Implement regular physical activity including walking, aerobic exercise, resistance training, and balance exercises 2, 3
• Maximize bright light exposure during morning hours, reduce evening light exposure to improve sleep-wake cycles 3

Cognitive Engagement

• Encourage cognitive training activities: reading, games, music therapy 2
• Promote brain-healthy diet: Mediterranean diet, nuts, berries, leafy greens, fish 2

Behavioral Symptom Management

Use the "three R's" approach: Repeat, Reassure, and Redirect when managing behavioral disturbances 2, 5

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Management of Comorbid Conditions

Optimally treat all comorbid conditions to reduce excess disability and maximize function—this is critical for slowing disease progression. 2, 5

Priority Conditions to Address

• Treat depression aggressively with SSRIs (citalopram or sertraline with minimal anticholinergic effects), as depression is common and often untreated in older adults with AD 2, 5
• Optimize cardiovascular risk factors: hypertension, diabetes (target HbA1c 8-9% in elderly with limited life expectancy, avoid tight control) 2, 5
• Correct sensory deficits: hearing aids, vision correction 2, 5
• Address sleep disorders, pain syndromes, metabolic disorders 2, 5

Medications to Avoid

Discontinue or avoid anticholinergic medications (diphenhydramine, hydroxyzine, oxybutynin), benzodiazepines, sedative-hypnotics, and narcotics—these worsen cognitive impairment. 2, 5

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Caregiver Support and Safety Planning

Link families to community resources and support services immediately upon diagnosis—caregiver burden significantly impacts patient outcomes. 2, 5

• Connect with Alzheimer's Association for education and support programs 2, 5
• Establish alliance with primary caregiver to ensure follow-up and minimize distress 2
• Discuss advance care planning early, including realistic expectations, future care preferences, and end-of-life decisions 2, 5

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Monitoring and Reassessment

• Reassess every 6 months as new symptoms emerge and care plans need modification 2
• If abnormalities raise concern for future decline, re-evaluate in 1 year; if normal with subjective concerns, re-evaluate in 2 years 1
• Average decline is 3-4 points per year on MMSE; more marked deterioration should trigger search for complicating comorbid illness 2
• Patients with rapid cognitive decline (≥3 points/year on MMSE) may benefit more from rivastigmine and galantamine 2

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Critical Caveats

• All symptomatic therapies do not alter underlying disease progression—patients continue to decline despite treatment 3
• Antipsychotics should be avoided due to increased mortality risk and only used when patients pose imminent danger to self or others, then discontinued after 3 months if used 5
• Never assume "normality" or attribute symptoms to "normal aging" without proper evaluation—this constitutes suboptimal care 1
• Emerging disease-modifying therapies (lecanemab, donanemab) targeting amyloid are now available for early-stage AD and require biomarker confirmation of amyloid pathology 6