Kelvin Tsoi, PhD: Combination Therapy, Monotherapy in Alzheimer Disease


After identifying and reviewing 76 randomized trials, combination therapy with memantine and AChEIs is confirmed to have no additional benefits over monotherapy.

“We find that combination therapy did not show greater benefit than monotherapy.”

At the 2018 Alzheimer’s Association International Conference in Chicago, Illinois, Kelvin Tsoi, PhD, The Chinese University of Hong Kong, sat down with NeurologyLive to discuss his study comparing the benefits of acetylcholinesterase inhibitors (AChEIs) plus memantine combination therapy to AChEIs or memantine alone in patients with mild-to-moderate Alzheimer disease.

Tsoi and his team performed literature searches in MEDLINE, EMBASE, CINAHL, and EBM Reviews from Cochrane Centre from inception to August 2017, conducting a network meta-analysis of randomized controlled trials to compare the changes of assessment scales across medications by disease severity. Researchers identified a total of 23,707 patients with Alzheimer disease in 76 randomized trials in more than 30 countries. The trials that were selected evaluated AChEIs, memantine or the combination on 3 domains: cognitive function, activities of daily living and neuropsychiatric symptoms.

The primary outcomes included the post-intervention changes of placebo, donepezil, galantamine, rivastigmine, memantine and the combination of AChEIs and memantine, as measured by the Mini-Mental State Examination (MMSE), Alzheimer’s Disease Assessment Scale-cognitive (ADAS-cog), Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL), or Neuropsychiatric Inventory (NPI).

In patients with mild-to-moderate Alzheimer disease, patients given rivastigmine demonstrated better cognitive performance than those who used combination therapy (MMSE: MD (95% CRL) = .83 (.07 to 1.58)), while donepezil or galantamine users also showed greater improvement in activities of daily living than patients with combination therapy (ADCS-ADL: MD (95% Crl) = 3.62 (1.25 to 6) and 2.87 (.96 to 4.87), respectively).

Combination therapy did not show a significant difference when compared to monotherapy with memantine or any AChEI when assessing cognitive functions, activities of daily living and neuropsychiatric symptoms in patients with moderate-to-severe Alzheimer disease.

The American guidelines, Tsoi and colleagues observed, suggest use of combination therapy for patients with Alzheimer disease, which calls for a review of current guidelines. Tsoi emphasizes that more data is necessary, because in the literature search there was insufficient data to support the evidence in patients with more severe Alzheimer disease.

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