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P4‐318: Neuroprotective effect of Nao Yikang on central cholinergic system in rat model of Alzheimer's disease
Author(s) -
Guo-Hua Wang,
Ai-Ling Zhou,
Jin-Song Geng,
Ya-Er Hu
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.2388
Subject(s) - basal forebrain , choline acetyltransferase , cholinergic neuron , nucleus basalis , cholinergic , acetylcholinesterase , hippocampus , neuroscience , neuroprotection , acetylcholine , medicine , endocrinology , forebrain , biology , central nervous system , biochemistry , enzyme
the behavioural symptoms of Alzheimer’s disease (AD), as measured by the Neuropsychiatric Inventory (NPI). However, the total NPI score can be difficult to interpret, due to the heterogeneity of the symptoms gathered. Therefore, it is relevant to perform additional analyses focusing on a symptom cluster of major impact in terms of resource use, i.e., symptoms such as agitation/ aggression and irritability, as well as psychotic symptoms such as hallucinations and delusions that often require the use of atypical neuroleptics. Methods: A meta-analysis was performed on the population of patients with moderate to severe AD (MMSE 20) from six Phase III, randomised, doubleblind, placebo-controlled, 6-month clinical studies of memantine. Assessments were based upon the NPI cluster score, defined as the sum of the NPI scores for the four domains agitation/aggression, hallucination, delusion, and irritability. The two outcome measures were change from baseline in NPI cluster score, and emergence of at least one of the cluster symptoms in patients who had no cluster symptoms at baseline. Both OC and LOCF analyses were performed. Results: Memantine significantly decreased the NPI cluster compared to placebo (p 0.006), with a weighted mean difference of -0.78 (95% CI: -1.33, -0.23; OC analysis). The corresponding LOCF analysis supported this outcome (p 0.002). Memantine also significantly prevented the emergence of the NPI cluster symptoms compared to placebo (p 0.009), with an odds ratio of 1.60 (95% CI: 1.13, 2.28). Again, this result was supported by the corresponding LOCF analysis (p 0.03). Conclusions: Memantine is effective at reducing the NPI cluster (agitation/ hallucinations/delusion/irritability) of symptoms of AD, as well as preventing their emergence in patients without the symptoms at baseline. These symptoms, which can be present in early AD, are stressful for carers, disrupt family life, and often determine a patient’s progression to institutional care. Therefore, treatment with memantine may be able to reduce caregiver distress and delay institutionalisation. In addition, the emergence of behavioural symptoms is often an indicator of an overall rapid decline, which memantine may help to address. A reduction in use of atypical neuroleptics and other psychotropic drugs may also be possible.