Huperzine A shows promise in Alzheimer’s disease according to stringent review

     Alzheimer's disease (AD) has become a major public health problem around the world due to its increasing prevalence, long duration, caregiver burden, and high financial cost of care. Acetyl-choline is a neurotransmitter that plays a crucial part in learning and memory. The degeneration of acetylcholine-containing neurons in the forebrain has been implicated in the symptoms of AD. Cholinesterase inhibitors block the degradation of acetylcholine, thus increasing the effectiveness of the remaining cholinergic neurons. Huperzine A is a reversible inhibitor of acetyl cholinesterase. Inhibiting this enzyme allows acetylcholine-brain levels to increase.  Huperzine A is related to both central and peripheral activity with the ability to protect cells against hydrogen peroxide, beta-amyloid protein (or peptide – the destructive protein laid down in AD), glutamate (a neurotoxin), ischemia (or lack of blood flow), cytotoxicity and apoptosis (cell death). These properties might qualify Huperzine A as a promising agent for treating dementia including AD.
     The Specialized Register of the Cochrane Dementia and Cognitive Improvement Group was searched on 1 February 2006 using the search term: huperzin*. The CDCIG Specialized register contains records from all major health care databases (MEDLINE, EMBASE, PsycINFO, CINAHL, SIGLE, ISTP, INSIDE, LILACS) as well as from many trials databases and grey literature sources. In addition, the CBM and AMED databases and relevant websites were searched and some journals were hand-searched. Specialists in the field were approached for unpublished material and any publications found were searched for additional references. SELECTION CRITERIA: All relevant randomized controlled trials (RCTs) studying the efficacy and safety of Huperzine A for AD were included (if found of course).
     Data were extracted independently by two reviewers using a self-developed data extraction form and entered into RevMan 4.2.10 software. Meta-analyses were performed when more than one trial provided data on a comparable outcome on sufficiently similar patients. Standardized differences in mean outcome measures were used due to the use of different scales and periods of treatment.
     Six trials including a total of 454 patients met the inclusion criteria. It was shown that compared to placebo, Huperzine A had beneficial effects on the improvement of general cognitive function measured by MMSE and ADAS-Cog scales at six weeks and further improved at 12 weeks, global clinical assessment measured by CDR and CIBIC-plus, behavioral disturbance measured by ADAS-non-Cog at six weeks demonstrated improvement and at 12 weeks improved further, and functional performance measured by ADL showed improvement. However, Huperzine A did not improve general cognitive function measured by Hasegawa Dementia Scale and specific cognitive function measured by Weshler Memory Scale.
     The adverse events of Huperzine A were mild and there were no significant differences of adverse events between Huperzine A groups and control-placebo groups. AUTHORS' CONCLUSIONS: From the available evidence, Huperzine A seems to have some beneficial effects on improvement of general cognitive function, global clinical status, behavioral disturbance and functional performance, with no obvious serious adverse events for patients with AD. However, more research is needed in the field of AD to recommend Huperzine A for these patients. The research review appears in the April 16th, 2008 issue of the Cochrane Database of Systematic Reviews.