Do patients at high risk of Alzheimer's disease benefit from early treatment?

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Abstract

Evidence-based answer

Yes, but the extent of the benefit is unclear. Treating patients with early-stage Alzheimer's disease yields statistically significant, though perhaps not clinically significant, improvement in cognition and global function (strength of recommendation [SOR]: A, consistent evidence from multiple randomized controlled trials [RCTs]). In a few cases, it may delay loss of function and need for long-term care.

Evidence-based answer

Treating patients with mild cognitive impairment (MCI)—the most likely precursor to Alzheimer's disease—with cholinesterase inhibitors seems to have an initial, but perhaps unsustained, benefit over no treatment (SOR: B, inconsistent results from few trials). Withdrawing anticholinergic drugs from patients taking them promises to reduce symptoms of MCI, but is unlikely to reduce rates of Alzheimer's (SOR: C, well-designed observational study).

Clinical commentary

Remember nondrug interventions

Clinical commentary

Clinicians often forget the many nonpharmacologic treatments for dementia, including exercise, cognitive stimulation, increased socialization, addressing polypharmacy, and optimizing nutrition. Diagnosing and managing comorbidities such as depression and cardiovascular disease are also important. Primary care physicians who care for the frail elderly should advocate these interventions. In the very elderly, who are all at high risk of developing Alzheimer's disease, these measures may help prevent functional decline and reduce clinically apparent disease.

Clinical commentary

All patients diagnosed with early-stage Alzheimer's disease, and possibly patients with MCI, should be offered a trial of pharmacotherapy. However—given the high cost of drug therapy, the modest improvement it produces in patients with Alzheimer's dementia, and the lack of definitive evidence that it benefits patients with MCI—I wouldn't advocate medication for asymptomatic patients at high risk of developing dementia.

Clinical commentary

Jaqueline Raetz, MD

Clinical commentary

Departments of Family Medicine and

Clinical commentary

Long-Term Care, University of Washington

Clinical commentary

School of Medicine, Seattle

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