What medication should be started for an elderly patient with a history of hypertension (HTN), presenting with recent memory loss, misplacement of items, and social withdrawal, with a low Mini-Mental State Examination (MMSE) score and cortical atrophy on MRI?

Recommended Medication for Dementia with Cortical Atrophy

Start a cholinesterase inhibitor (Option C) as first-line pharmacological treatment for this patient presenting with probable Alzheimer's disease, characterized by recent memory loss, impaired object placement, social withdrawal, low MMSE score, and cortical atrophy on MRI. 1, 2

Clinical Presentation Analysis

This patient demonstrates the classic pattern of Alzheimer's disease:

• Recent memory impairment with preserved remote memory (hallmark of early-to-moderate AD) 1, 2
• Executive dysfunction (misplacing items and inability to locate them) 1
• Social withdrawal (apathy/behavioral changes common in AD) 1
• Low MMSE score (objective cognitive impairment) 1, 2
• Cortical atrophy on MRI (structural changes consistent with neurodegenerative disease) 1, 2

The absence of acute confusion, psychotic symptoms, or prominent mood symptoms makes antipsychotics and antidepressants inappropriate as first-line therapy.

Cholinesterase Inhibitor Selection and Dosing

Donepezil is the preferred cholinesterase inhibitor due to:

• Once-daily dosing improving adherence 1
• Extensive evidence in mild-to-moderate AD (MMSE 10-26) 1, 2
• Superior tolerability profile compared to rivastigmine 2
• No food requirements for administration 1

Specific Dosing Algorithm:

• Start donepezil 5 mg once daily for 4-6 weeks 1, 3
• Titrate to 10 mg once daily if the 5 mg dose is well tolerated 1, 3
• Administer at a convenient time of day to establish habitual medication-taking patterns 4
• The 10 mg dose provides additional cognitive and functional benefits over 5 mg 3

Expected Outcomes with Cholinesterase Inhibitors

Cognitive benefits:

• Improvement or stabilization on ADAS-cog scores (cognitive assessment) 1, 2
• Slowing of cognitive decline compared to natural disease progression 1, 2
• Patients with mild-to-moderate AD typically decline 6-12 ADAS-cog units annually without treatment; cholinesterase inhibitors reduce this rate 2

Functional benefits:

• Improvement in activities of daily living (ADL) scores 1
• Better maintenance of day-to-day function 1
• Reduced care dependency 1

Why Not Antipsychotics or Antidepressants?

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

• FDA black box warning for increased mortality risk in elderly patients with dementia 4
• Worsen cognitive function in dementia patients 4
• Should only be used for severe behavioral disturbances (agitation, aggression, psychosis) that pose safety risks and have failed non-pharmacological interventions 4
• This patient shows social withdrawal, not agitation or psychosis 4

Antidepressants (Option B) are not indicated as first-line:

• No evidence of major depressive disorder described in this case
• Social withdrawal in AD is typically due to apathy (frontal lobe dysfunction) rather than depression
• Antidepressants do not address the underlying cholinergic deficit in AD
• May be considered as adjunctive therapy if comorbid depression is diagnosed after cholinesterase inhibitor initiation

Monitoring and Follow-up Considerations

Initial monitoring (first 4-6 weeks):

• Assess tolerability for gastrointestinal side effects (nausea, vomiting, diarrhea) 1, 2, 3
• Monitor for bradycardia, particularly given the patient's hypertension history 1
• Evaluate for insomnia (may require morning dosing adjustment) 5

Ongoing assessment:

• Repeat MMSE every 3-6 months to track cognitive trajectory 1, 2
• Assess functional status and ADL performance 1
• Monitor for emergence of behavioral symptoms requiring additional intervention 1

Critical Pitfalls to Avoid

• Do not delay cholinesterase inhibitor initiation while pursuing extensive workup; start treatment promptly once probable AD is diagnosed 1, 2
• Do not use antipsychotics for apathy or social withdrawal; these are cognitive/frontal symptoms, not psychotic symptoms 4
• Do not stop at 5 mg donepezil if well tolerated; the 10 mg dose provides superior efficacy 3, 6
• Do not combine cholinesterase inhibitors with anticholinergic medications (including certain antidepressants, antihistamines, or overactive bladder medications), as they directly counteract therapeutic effects 4
• Monitor standing blood pressure in this elderly patient with hypertension to assess for orthostatic hypotension, which increases fall risk 4

Hypertension Management Considerations

Continue evidence-based antihypertensive therapy:

• First-line agents (ACE inhibitors, ARBs, dihydropyridine CCBs, or thiazides) should be continued for cardiovascular protection 4, 7
• Target BP <140/90 mmHg, or <130/80 mmHg if well tolerated 4
• Measure BP in both sitting and standing positions due to increased orthostatic hypotension risk in elderly patients 4
• Cholinesterase inhibitors do not interact with standard antihypertensive medications 2