A 75-year-old woman is brought to the office by her son for evaluation of worsening forgetfulness over the past few years. She has had difficulty remembering names of the people she meets and frequently misplaces household items. Recently, the patient forgot to turn off the stove after cooking but had no major fire. She has also had disrupted sleep with frequent awakenings throughout the night. Vital signs are within normal limits. On physical examination, the patient is alert and cooperative but disoriented to time and can recall only 1 of 3 items on a short-term memory test. MRI of the head reveals diffuse cortical atrophy. A medication with which of the following effects would be most beneficial for this patient?

Question

A 75-year-old woman is brought to the office by her son for evaluation of worsening forgetfulness over the past few years.  She has had difficulty remembering names of the people she meets and frequently misplaces household items.  Recently, the patient forgot to turn off the stove after cooking but had no major fire.  She has also had disrupted sleep with frequent awakenings throughout the night.  Vital signs are within normal limits.  On physical examination, the patient is alert and cooperative but disoriented to time and can recall only 1 of 3 items on a short-term memory test.  MRI of the head reveals diffuse cortical atrophy.  A medication with which of the following effects would be most beneficial for this patient?

Quizplus · Accepted Answer

11ec160b_3c06_2672_9249_e3de531bd390_MD0001_00 This patient's progressive memory loss, functional impairments (ie, trouble with activities of daily living), and sleep disturbances are consistent with a dementia syndrome. MRI of the head reveals only diffuse cortical atrophy and no evidence of structural disease (eg, hydrocephalus, chronic subdural hematoma, vascular infarction). Therefore, she is most likely suffering from Alzheimer disease (AD), the most common form of primary dementia. The pathogenesis of AD is complex but culminates in diffuse atrophy of cortical neurons. Specifically, degeneration of cholinergic neurons in the basal forebrain contributes to memory loss and functional decline. These cholinergic neurons project throughout the neocortex to positively regulate areas involved in memory (hippocampal formations) and executive function (frontal cortex), which are impaired in AD. Cholinesterase inhibitors (eg, donepezil, galantamine) block acetylcholinesterase in the synaptic cleft to compensate for the loss of cholinergic transmission. Cholinesterase inhibitors have modest effects on memory and cognition to improve daily functioning. Cholinergic therapy should be considered in most patients with AD. Conversely, anticholinergic medications (eg, tricyclic antidepressants) should be discontinued whenever feasible because they can exacerbate cognitive dysfunction. Although they improve symptoms, procholinergic agents do not enhance neuron survival, so they have little impact on the overall trajectory of AD. In contrast, NMDA receptor antagonists (eg, memantine) inhibit glutamate NMDA signaling (Choice C) to prevent excitotoxicity (calcium overload) and subsequent neuronal apoptosis. These agents likely serve a neuroprotective role, slowing disease progression. (Choice A) Norepinephrine-dopamine reuptake inhibitors (eg, methylphenidate, atomoxetine) are central stimulants. They can promote wakefulness to treat narcolepsy or enhance concentration to treat attention deficit hyperactivity disorder. (Choice D) Dopamine precursors (eg, levodopa) can enhance dopamine availability in Parkinson disease (PD), which can be associated with dementia in later stages. They are used to improve motor rigidity but have no role in PD-related cognitive decline. (Choice E) Selective serotonin reuptake inhibitors (SSRI; eg, citalopram) are first-line medications for major depressive disorder, which may mimic dementia (ie, pseudodementia). SSRIs are also used to manage the depressive mood symptoms related to AD. They do not address the underlying cognitive impairment due to neuron cell death and loss of cholinergic signaling. Educational objective: Alzheimer disease (AD) is a progressive dementia featuring diffuse cortical atrophy involving loss of cholinergic neurons. Memory, cognitive, and functional impairments of AD are partially mediated by insufficient cholinergic output. Cholinesterase inhibitors (eg, donepezil) enhance cholinergic neurotransmission to compensate for this defect. __________ References: Alzheimer's disease: targeting the cholinergic system. (http://www.ncbi.nlm.nih.gov/pubmed/26813123) Therapies for prevention and treatment of Alzheimer's disease. (http://www.ncbi.nlm.nih.gov/pubmed/27547756)

A 75-Year-Old Woman Is Brought to the Office by Her