Early Treatment With Cholinesterase Inhibitors And Memantine

Treatment With Cholinesterase Inhibitors and Memantine of Patients in the Alzheimer's Disease Neuroimaging Initiative

Currently, cholinesterase inhibitors (ChEI’s) are approved for individuals with Alzheimer’s, while memantine is approved for those with moderate to severe AD. Nonetheless, physicians frequently prescribe ChEI’s and memantine earlier than indicated by the US Food and Drug Administration. Previously, clinical trials have failed to show efficacy for ChEI’s in Mild Cognitive Impairment (MCI) or for memantine in mild to moderate AD. The target study therefore sought to further our understanding of the effect this early treatment has on the clinical characteristics of those with MCI and AD. 

Of the 402 MCI patients, 44% were treated with ChEI’s and 11.4% were treated with memantine upon entry into the study. Of the 188 participants with mild-AD, 84.6% were treated with ChEI’s and 45.7% were treated with memantine at entry. The MCI patients who received ChEI’s with or without memantine were more impaired and showed greater decline in scores on the ADAS-cog (AD Assessment Scale-cognitive subscale), CDR (Clinical Dementia Rating scale), and FAQ (Functional Activities Questionnaire) than those not receiving treatment. Participants taking both ChEI’s and memantine performed the worst, with a decline over 2-fold greater than those treated with ChEI’s only. For instance, decline on the MMSE was .87 points greater/year in those treated with ChEI’s only, and 1.89 points greater/year in those treated with both ChEI’s and memantine, compared to those receiving neither treatment. A total of 128 MCI patients progressed to having dementia, including 22.3% of those in the non-treated group, 42.6% in the ChEI treated group, and 55.6% of those in the ChEI and memantine treated group. Duration of exposure to ChEI treatment at baseline was associated with a greater decline on the CDR, MMSE, and FAQ, compared with no treatment.

The AD participants who received ChEI’s and memantine were more functionally impaired, showed greater decline on the MMSE and CDR (but not on the ADAS-cog or FAQ) by .93 and .50 points/year, respectively, compared to those who received ChEI’s only. Duration of use was not associated with a greater decline on scores among the patients treated only with a ChEI vs. treatment with both types of medication. APOE e4 carriers were more prevalent in both the MCI and AD treated groups.

While these results are somewhat alarming, it is important to keep in mind the possibility that the MCI participants receiving ChEI’s with or without memantine may have been prescribed the medications after already showing signs of progressing more rapidly towards cognitive impairment. The same can be said for the AD participants receiving ChEI’s and memantine. Furthermore, it is unclear as to whether or not the physicians’ made their treatment decisions based on biomarkers such as APOE e4 genotype.