What medication should be started for an elderly patient with a history of hypertension, presenting with symptoms of dementia, including forgetting recent events, misplacing items, and social withdrawal, with a low mini-mental state examination (MMSE) score and cortical atrophy on magnetic resonance imaging (MRI)?

Cholinesterase Inhibitor Recommended for Alzheimer's Disease

Start a cholinesterase inhibitor (donepezil, galantamine, or rivastigmine) for this elderly patient presenting with classic Alzheimer's disease symptoms, low MMSE score, and cortical atrophy on MRI. 1

Clinical Presentation Analysis

This patient demonstrates the hallmark features of Alzheimer's disease:

• Recent memory impairment with preserved remote memory - the classic temporal gradient of memory loss 1
• Anomia (forgetting names) and misplacing items - typical early AD symptoms 1
• Social withdrawal and apathy - behavioral changes consistent with dementia 1
• Low MMSE score - objective cognitive impairment 1
• Cortical atrophy on MRI - structural brain changes supporting neurodegenerative dementia 1

Why Cholinesterase Inhibitors Are Indicated

Cholinesterase inhibitors (donepezil, galantamine, rivastigmine) are specifically indicated for mild to moderate dementia, particularly Alzheimer's disease. 1 These medications work by increasing acetylcholine availability in the brain, addressing the cholinergic deficit characteristic of AD. 1, 2

The Canadian Consensus Conference on Dementia explicitly recommends cholinesterase inhibitors for vascular cognitive impairment and dementia in selected patients, which is relevant given this patient's hypertension history. 1

Why NOT the Other Options

Antipsychotics (Option A) - AVOID

Antipsychotics should be avoided in dementia patients unless there are severe behavioral disturbances that pose safety risks. 1 This patient shows apathy and social withdrawal, NOT psychosis, aggression, or dangerous behaviors requiring antipsychotic intervention.

• The FDA has issued a black box warning about increased risk of death when antipsychotics are used for dementing disorders 1
• Antipsychotics worsen cognitive function in dementia 1
• They cause sedation, falls, and motor impairment in elderly patients 1
• The Beers Criteria specifically recommend avoiding antipsychotics for behavioral control in cognitive disease 1

Antidepressants (Option B) - Not First-Line

While the presentation includes social withdrawal and lack of interest, this patient's primary problem is cognitive impairment with objective findings (low MMSE, cortical atrophy), not depression. 3, 4

Depression (pseudodementia) typically presents with:

• Prominent mood symptoms and subjective cognitive complaints disproportionate to objective testing 3, 4
• Potentially reversible cognitive impairment with antidepressant treatment 3, 4

This patient has objective cognitive decline with structural brain changes, making true neurodegenerative dementia far more likely than pseudodementia. 3 If depressive symptoms persist after initiating cholinesterase inhibitor therapy, adding an SSRI could be considered as adjunctive treatment. 3, 4

Specific Medication Recommendations

Start with one of these cholinesterase inhibitors:

• Donepezil: Most commonly used, once-daily dosing 1, 5
• Galantamine: Alternative option 1
• Rivastigmine: Another alternative, available as patch or oral formulation 1, 2

All three have demonstrated efficacy in mild to moderate Alzheimer's disease. 1

Important Monitoring Considerations

Common Adverse Effects to Monitor

Cholinesterase inhibitors can cause: 1, 2

• Gastrointestinal effects: nausea, vomiting, diarrhea (most common)
• Cardiac effects: bradyarrhythmias, syncope
• Neuropsychiatric effects: nightmares, vivid dreams
• Worsening of Parkinson's disease if present

Special Precautions in Hypertensive Patients

Continue optimizing blood pressure control alongside dementia treatment. 1 Effective antihypertensive therapy may reduce progression of cognitive impairment. 1

• Monitor for orthostatic hypotension - measure BP sitting and standing, especially in elderly patients 1
• Target BP <140/90 mmHg if tolerated 1
• Certain antihypertensive classes (ACE inhibitors, ARBs, calcium channel blockers) may provide additional neuroprotection beyond BP control 3, 4, 6

Critical Caveat About Long-Term Benefit

Cholinesterase inhibitors have limited long-term benefit, particularly in advanced dementia. 1 However, they remain the standard of care for mild to moderate Alzheimer's disease and should be initiated at diagnosis. 1 The decision to continue therapy should be reassessed periodically based on perceived benefit and tolerability. 1

Additional Consideration: Memantine

For moderate to severe dementia (MMSE typically ≤14), memantine (an NMDA receptor antagonist) can be added to cholinesterase inhibitor therapy or used as monotherapy. 5 However, based on the clinical presentation suggesting mild to moderate disease, start with a cholinesterase inhibitor first. 1