What medication should be started for an elderly patient with dementia symptoms, including memory loss and social withdrawal?

Start a Cholinesterase Inhibitor

For this elderly patient with clinical features consistent with Alzheimer's disease (recent memory loss, preserved remote memory, cortical atrophy on MRI, low MMSE), the correct medication to initiate is C - a cholinesterase inhibitor. 1

Rationale for Cholinesterase Inhibitor Selection

Cholinesterase inhibitors (ChEIs) are the first-line pharmacological treatment for mild to moderate Alzheimer's disease dementia. 1 International guidelines from the UK (NICE), US, China, and Japan consistently recommend ChEIs as the standard of care for this population. 1

• The patient's presentation—recent memory impairment with preserved remote memory, misplacing items, social withdrawal, low MMSE, and cortical atrophy—is classic for Alzheimer's disease. 1
• ChEIs delay clinical decline, benefit cognitive function, and help reduce symptoms such as memory loss and confusion. 1
• These medications improve outcomes across multiple domains: cognition (measured by ADAS-cog), global clinical function (CIBIC-plus), activities of daily living, and behavioral symptoms. 1

Specific Medication Recommendation

Start with donepezil 5 mg once daily in the evening, just prior to retiring. 2

• Donepezil is FDA-approved for mild, moderate, and severe Alzheimer's disease. 2
• The starting dose is 5 mg/day for 4-6 weeks before considering escalation to 10 mg/day. 2
• Donepezil can be taken with or without food. 2
• This agent has a simple once-daily dosing schedule, improving adherence compared to other ChEIs that require multiple daily doses. 3, 4

Expected Benefits

• Cognitive improvement: At 24 weeks, donepezil 5 mg/day shows a statistically significant improvement of -2.02 points on the ADAS-Cog scale compared to placebo. 5
• Global clinical state: Independent clinicians rate global clinical state more positively in treated patients at 12 and 24 weeks. 5
• Activities of daily living: Donepezil 10 mg/day significantly delays deterioration in ADL by up to 55 weeks. 3
• Behavioral symptoms: Improvements in behavior and reduced caregiver burden are documented. 5

Why NOT Antipsychotics or Antidepressants

Antipsychotics (Option A) are contraindicated as first-line treatment:

• They are used off-label for neuropsychiatric symptoms in dementia without FDA approval. 1
• They carry an FDA black box warning for increased risk of death when used for dementing disorders. 1
• Associated with deleterious side effects including falls, stroke, and death. 1
• Should only be considered when patients pose serious risk of harm to themselves or others—not present in this case. 1

Antidepressants (Option B) are not indicated:

• While social withdrawal is present, this patient's primary presentation is cognitive decline, not a primary depressive disorder. 1
• Depression should be ruled out as a comorbidity, but the clinical picture (cortical atrophy, memory pattern, low MMSE) points to Alzheimer's disease as the primary diagnosis. 1
• If depression coexists, it can be addressed after initiating ChEI therapy. 1

Monitoring and Follow-up

• Reassess cognitive, functional, neuropsychiatric, and behavioral symptoms periodically to monitor disease progression and adjust treatment. 1
• After 4-6 weeks on donepezil 5 mg/day, consider increasing to 10 mg/day if tolerated and additional benefit is needed. 2
• For moderate to severe disease progression, doses up to 23 mg/day may be considered after at least 3 months on 10 mg/day. 2

Common Pitfalls to Avoid

• Do not delay ChEI initiation while pursuing extensive workup for reversible causes if the clinical picture clearly suggests Alzheimer's disease. 1
• Avoid rapid dose escalation: The 7-day increase schedule used in some early trials led to higher cholinergic side effects; a 4-6 week interval minimizes adverse events. 3, 4
• Monitor for cholinergic side effects: nausea, vomiting, diarrhea (more common with 10 mg than 5 mg dose). 2, 5
• Do not use ChEIs as behavioral control agents: Their primary benefit is cognitive and functional, not behavioral management. 1