Memantine Treatment of Cognitive Symptoms in Mild to Moderate Alzheimer Disease: Secondary Analyses From a Placebo-controlled Randomized Trial

Abstract

Memantine, an N-methyl-D-aspartate receptor antagonist, is approved in the United States and Europe for the treatment of moderate to severe Alzheimer disease (AD) and has also been investigated in patients with mild to moderate AD. To characterize the specific cognitive benefits of memantine in patients with mild to moderate AD, a post hoc analysis was conducted of a 24-week randomized, double-blind, placebo-controlled, clinical trial comparing memantine (10 mg twice daily) to placebo. Cognition was assessed using the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) total score, individual items, and aggregated subscales, using a mixed model repeated measures analysis. As assessed by the ADAS-cog total score, participants in the placebo group demonstrated significantly more cognitive decline from baseline than participants treated with memantine at all visits beginning at week 8. Subjects treated with placebo also declined significantly more than individuals in the memantine group on 5 of 11 ADAS-cog individual items: orientation, language, comprehension, word finding, and recall of test instructions. Out of 3 ADAS-cog aggregated item subscales (language, memory, and praxis), outcomes in 2 (language and memory) favored memantine. Consistent with findings from trials conducted in moderate to severe AD patients, this post hoc analysis of a randomized clinical trial suggests that memantine benefits core aspects of language and some aspects of memory in patients with mild to moderate AD.

Changes in cerebral glucose metabolism in patients with posttraumatic cognitive impairment after memantine therapy: a preliminary study

“…However, memantine is under investigation as a potential treatment for other diseases as well, including traumatic and hypoxic brain injuries [23,24]. In AD, memantine monotherapy or combined with cholinesterase inhibitors improved attention, memory, and language functions [19,25]. Based on the current findings, increased cerebral glucose metabolism in the frontal lobe, including the dorsolateral prefrontal cortex, and in the parietal lobe, including the precuneus, the angular gyrus, and the inferior parietal lobule, may be associated with the previously reported cognitive enhancing effects of memantine.…”

“…Recently, positive effects of memantine treatment for neurodegenerative diseases [19], stroke [20], neuropathic pain [21], and schizophrenia [22] have been reported. However, memantine is under investigation as a potential treatment for other diseases as well, including traumatic and hypoxic brain injuries [23,24].…”

The Effect of Memantine on Cognitive Function and Behavioral and Psychological Symptoms in Mild-to-Moderate Alzheimer's Disease Patients

“…However, an earlier clinical trial (MD-10) demonstrated that memantine treatment produced significant improvements in cognition, global status, and behavior compared with placebo [6]. Afterwards, a post hoc analysis of this trial found that, compared to the control group, the memantine group exhibited significantly smaller declines on the spoken language, comprehension, word finding, orientation, and recall of test instructions items of the ADAS-cog and demonstrated significant advantages on the language and memory subscales, but not the praxis subscale, of the ADAS-cog at week 24 [19]. Our study and the MD-10 study included a higher percentage of moderate AD patients (73.7% in our study, 67.4% in the MD-10 study) than the 99679 study (51.6%).…”

“…The CIBIC-Plus and the MMSE were assessed at baseline and at week 24. For the secondary analysis, the 12 items of the ADAS-cog were aggregated into 4 subscales according to a previously published factor analysis [19]; the subscales included memory (word recall, naming objects and fingers, orientation, word recognition, and remembering test instructions), language (commands, spoken language, word finding, and comprehension), praxis (construction and ideational praxis), and attention. Each item of the NPI was compared between the two treatment groups.…”

Antidementiva – wem nützen sie wirklich?

“…Neue Ergebnisse sprechen auch für eine Wirksamkeit der Cholinesterasehemmer im Stadium der schweren AD [4] und von Memantin bei leichter AD [23].…”