A 79-year-old man is brought to the office by his daughter. The patient has been having increasing difficulty caring for himself over the last 2 years. He is now dependent on his daughter for meal preparation, shopping, and cleaning. He will frequently go a week without bathing and often has difficulty dressing himself appropriately. The patient sometimes grows frustrated and shouts at his daughter but has never been physically violent. On direct questioning, he states that he feels fine, does not see any reason for coming to the office, and is quite suspicious of his daughter's motives. The patient has lived alone since his wife died 5 years ago. He has hypertension, osteoarthritis, and a history of remitted major depressive disorder. Medications include hydrochlorothiazide and acetaminophen as needed. Neurologic examination is nonfocal. The patient scores 20 out of 30 on the Montreal Cognitive Assessment. Neuroimaging studies reveal diffuse cortical atrophy. The laboratory workup is unremarkable. Which of the following is the most appropriate next step in pharmacotherapy?

Question

A 79-year-old man is brought to the office by his daughter.  The patient has been having increasing difficulty caring for himself over the last 2 years.  He is now dependent on his daughter for meal preparation, shopping, and cleaning.  He will frequently go a week without bathing and often has difficulty dressing himself appropriately.  The patient sometimes grows frustrated and shouts at his daughter but has never been physically violent.  On direct questioning, he states that he feels fine, does not see any reason for coming to the office, and is quite suspicious of his daughter's motives.  The patient has lived alone since his wife died 5 years ago.  He has hypertension, osteoarthritis, and a history of remitted major depressive disorder.  Medications include hydrochlorothiazide and acetaminophen as needed.  Neurologic examination is nonfocal. The patient scores 20 out of 30 on the Montreal Cognitive Assessment.  Neuroimaging studies reveal diffuse cortical atrophy.  The laboratory workup is unremarkable.  Which of the following is the most appropriate next step in pharmacotherapy?

Quizplus · Accepted Answer

Explanation: Acetylcholinesterase inhibitors (eg, donepezil, rivastigmine, galantamine) are first-line pharmacotherapy for dementia-related cognitive impairment. These medications inhibit acetylcholinesterase at the synaptic cleft, thereby increasing cholinergic transmission and resulting in modest symptomatic improvement in some patients. The NMDA receptor antagonist memantine is another medication that has been shown to be modestly beneficial for symptomatic management of moderate to severe dementia. Importantly, there is no evidence to suggest that any medication is disease-modifying; as such, pharmacotherapy for dementia should be considered symptomatic treatment. (Choice A) Bromocriptine, a dopamine agonist, may address parkinsonian symptoms in Parkinson disease dementia or dementia with Lewy bodies; however, it has no indication for treatment of non-parkinsonian dementia. (Choice B) Antipsychotics are associated with an increased risk of death in patients with dementia and should be used only as a last resort in the treatment of severe behavioral disturbance. When this class of medications is indicated, second-generation antipsychotics (eg, quetiapine) are generally preferred because of their favorable side effect profile. (Choice D) Selegiline, a monoamine oxidase inhibitor, has been studied as a treatment for dementia due to its antioxidant properties; however, results have been mixed and it is currently not considered a first-line treatment. (Choice E) There is limited evidence that selective serotonin reuptake inhibitors (eg, sertraline) are effective in the treatment of dementia-related neuropsychiatric symptoms other than depression. This patient does not currently meet criteria for a depressive disorder, and his prominent cognitive impairment would be better targeted with an acetylcholinesterase inhibitor. Educational objective: Acetylcholinesterase inhibitors are first-line pharmacotherapy for cognitive symptoms associated with dementia. Memantine, an NMDA receptor antagonist, may also be beneficial for patients with dementia. References: Donepezil and memantine for moderate-to-severe Alzheimer's disease. (http://www.ncbi.nlm.nih.gov/pubmed/22397651) Nursing home placement in the Donepezil and Memantine in Moderate to Severe Alzheimer's Disease (DOMINO-AD) trial: secondary and post-hoc analyses. (http://www.ncbi.nlm.nih.gov/pubmed/26515660)

A 79-Year-Old Man Is Brought to the Office by His