A 74-year-old woman is brought to the office by her daughter due to behavioral changes. Over the past month, the patient has become more withdrawn. She no longer watches her favorite television shows and seems less interested in her family. The daughter has noticed increasing forgetfulness over the past 3 years but assumed it "comes with aging." Over the past year, the patient has stopped doing the daily crossword, has had difficulty remembering to eat and clean herself, and has occasionally failed to recognize her grandchildren. Montreal Cognitive Assessment is 22/30 (normal: ≥26). Serum TSH and vitamin B₁₂ levels are normal. Which of the following is the most appropriate next step in management of this patient?

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Dementia (also known as major neurocognitive disorder) may be diagnosed in patients with progressive cognitive decline that impairs activities of daily living (eg, bathing, dressing, preparing meals). The most common subtype of dementia is Alzheimer disease (AD), which typically presents with prominent but relatively isolated impairments in memory early in the disease course. As AD progresses, apathy, social withdrawal, and loss of interest in activities frequently develop and can mimic depression. This patient's 3-year history of cognitive decline preceding the development of behavioral symptoms is most consistent with AD. Although the etiology of AD is not well understood, histopathologic examination of brain tissue in affected patients indicates a selective loss of cholinergic neurons. The first-line treatment for cognitive symptoms of AD is a cholinesterase inhibitor, which may improve quality of life and cognitive function (eg, memory, language, thought, reasoning), although drugs in this class have not been shown to alter the disease course in any type of dementia. Donepezil, galantamine, and rivastigmine are effective in patients with mild to moderate AD. Memantine, an NMDA receptor antagonist, is approved for moderate to severe dementia. (Choice A) Amantadine, thought to possess dopaminergic and NMDA receptor antagonist properties, is frequently used in the treatment of Parkinson disease. The evidence of its benefit in the treatment of AD is limited and it would not be considered as a first-line treatment in this patient. (Choice B) Fluoxetine is an antidepressant used in the treatment of depression. Depression may present with cognitive impairment that can, if severe enough, masquerade as dementia. However, this patient does not meet criteria for major depressive disorder, and she experienced cognitive deficits and related functional impairment (eg, forgetfulness, difficulty recognizing relatives) years before the onset of any depressive-like symptoms (eg, social withdrawal, decreased interest), making AD more likely. Depressive symptoms are commonly seen as AD progresses. major depressive disorder (Choice D) Selegiline is a monoamine oxidase inhibitor that is sometimes used as a second-line treatment in AD for its antioxidant properties, although current evidence is weak. (Choice E) This patient is already experiencing cognitive decline sufficient to impair functioning. As a result, reassurance and follow-up, without consideration of a trial of a cholinesterase inhibitor, are inappropriate. Educational objective: Cholinesterase inhibitors such as donepezil, rivastigmine, and galantamine may provide moderate symptomatic relief of cognitive symptoms and temporarily improve functioning in Alzheimer disease; however, these medications have not been shown to alter the disease course. References: Current pharmacotherapy and putative disease-modifying therapy for Alzheimer's disease. (http://www.ncbi.nlm.nih.gov/pubmed/27250365)

A 74-Year-Old Woman Is Brought to the Office by Her