neurologic disorders
Alzheimer Disease
Treatment of Alzheimer Disease
Safety and support measures Possibly cholinesterase inhibitors andmemantine Treatment for Alzheimer disease are the same as those for all dementias. For example, the environment should be bright, cheerful, and familiar, and it should be designed to reinforce orientation (eg, placement of large clocks and calendars in the room). Measures to ensure patient safety (eg, signal monitoring systems for patients who wander) should be implemented. Providing Caregiver assistance , who may experience substantial stress, is also important. Nurses and social workers can teach caregivers how to best meet the patient’s needs. Health care practitioners should watch for early symptoms of caregiver stress and burnout and, when needed, suggest support services. Cholinesterase inhibitorsmodestly improve cognitive function and memory in some patients. Four are available. Generally,donepezil,rivastigmine, andgalantamineare equally effective, but tacrine is rarely used because of its hepatotoxicity. Donepezilis a first-line medication because it has once-a-day dosing and is well-tolerated. The recommended dose is 5 mg orally once a day for 4 to 6 weeks, then increased to 10 mg once a day.Donepezil23 mg once a day may be more effective than the traditional 10 mg once-a-day dose for moderate to severe Alzheimer disease. Treatment should be continued if functional improvement is apparent after several months, but otherwise it should be stopped. The most common adverse effects are gastrointestinal (eg, nausea, diarrhea). Rarely, dizziness and cardiac arrhythmias occur. Adverse effects can be minimized by increasing the dose gradually (see table). Memantine,anN-methyl-d-aspartate (NMDA) receptor antagonist, appears to improve cognition and functional capacity of patients with moderate to severe Alzheimer disease. The dose is 5 mg orally once a day, which is increased to 10 mg orally twice a day over about 4 weeks. For patients with renal insufficiency, the dose should be reduced or the medication should be avoided.Memantinecan be used with a cholinesterase inhibitor. Aducanumab,a human IgG1 anti-amyloid monoclonal antibody specific for beta-amyloid oligomers implicated in the pathophysiology of Alzheimer disease, is available as a monthly infusion to treat Alzheimer disease. Although some experts consideraducanumabto be the first efficacious disease-modifying treatment for Alzheimer disease, its approval by the US Food and Drug Administration (FDA) was controversial. The medication’s accelerated approval was based mainly on its ability to reduce brain beta-amyloid plaques in patients in clinical trials. But evidence of clinical benefit (slowing progression of the disease) in these trials was inconsistent; thus, additional trials are needed to confirm clinical benefit. in phase 3 clinical trials; ARIA-E usually occurred early in treatment and caused no symptoms. However, up to 0.9% of patients with ARIA had severe symptoms, including confusion, disorientation, gait disturbance, ataxia, visual disturbance, headache, nausea, and falls ( Treatment reference ). Other medicationsare being studied. Efficacy of high-dosevitamin E(1000 IU orally once or twice a day),selegiline, nonsteroidal anti-inflammatory drugs (NSAIDs),Ginkgobilobaextracts, and statins is unclear. Estrogen therapy does not appear useful in prevention or treatment and may be harmful. 1.Alexander GC, Emerson S, Kesselheim AS: Evaluation ofaducanumabfor Alzheimer disease: scientific evidence and regulatory review involving efficacy, safety, and futility.JAMA325(17):1717-1718, 2021. PMID: 33783469. doi: 10.1001/jama.2021.3854 