Effectiveness of Antidementia Drugs in Delaying Alzheimer Disease Progression

Susan D. Rountree, Department of Neurology, Alzheimer’s Disease and Memory Disorders Center, Baylor College of Medicine, Houston, TX, USA, Alireza Atri, Department of Neurology, Massachusetts General Hospital and Neurology Memory Disorders Unit, Boston, MA, USA, Oscar L. Lopez, Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA,  Rachelle S. Doody, Department of Neurology, Alzheimer’s Disease and Memory Disorders Center, Baylor College of Medicine, Houston, TX, USA

PII: S1552-5260(12)00016-7 doi:10.1016/j.jalz.2012.01.002

Abstract

Background

Randomized controlled trials (RCTs) provide safety and efficacy data for regulatory approval of antidementia drugs, but offer limited data regarding real-world effectiveness. Long-term observational controlled studies (LTOCs) extend our understanding by providing longitudinal data across multiple stages of Alzheimer’s disease (AD).

Methods

Comparisons of strengths, limitations, evidence level, and results for monotherapy (cholinesterase inhibitors) and combination therapy (cholinesterase inhibitors + memantine) in RCTs versus LTOCs were made.

Results

Similar to RCTs, LTOCs have shown that both monotherapy and combination therapy are associated with slower cognitive and functional decline. Combination therapy is associated with better cognitive outcomes and greater delays in time to nursing home admission versus monotherapy or no treatment. Persistent antidementia drug treatment is associated with slower decline in cognition, daily function, and global severity, even in patients with advanced disease.

Conclusions

LTOCs provide complementary evidence regarding effectiveness of antidementia therapy over many years, a time course relevant to AD management. These findings also provide compelling arguments in favor of using LTOCs to estimate effectiveness, risk–benefit, and costs of AD treatments.

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