Huperzine A for Alzheimer’s Disease: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

<div><p>Background</p><p>Huperzine A is a Chinese herb extract used for Alzheimer’s disease. We conducted this review to evaluate the beneficial and harmful effect of Huperzine A for treatment of Alzheimer’s disease.</p><p>Methods</p><p>We searched for randomized clinical trials (RCTs) of Huperzine A for Alzheimer’s disease in PubMed, Cochrane Library, and four major Chinese electronic databases from their inception to June 2013. We performed meta-analyses using RevMan 5.1 software. (Protocol ID: CRD42012003249)</p><p>Results</p><p>20 RCTs including 1823 participants were included. The methodological quality of most included trials had a high risk of bias. Compared with placebo, Huperzine A showed a significant beneficial effect on the improvement of cognitive function as measured by Mini-Mental State Examination (MMSE) at 8 weeks, 12 weeks and 16 weeks, and by Hastgawa Dementia Scale (HDS) and Wechsler Memory Scale (WMS) at 8 weeks and 12 weeks. Activities of daily living favored Huperzine A as measured by Activities of Daily Living Scale (ADL) at 6 weeks, 12 weeks and 16 weeks. One trial found Huperzine A improved global clinical assessment as measured by Clinical Dementia Rating Scale (CDR). One trial demonstrated no significant change in cognitive function as measured by Alzheimer’s disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and activity of daily living as measured by Alzheimer’s disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) in Huperzine A group. Trials comparing Huperzine A with no treatment, psychotherapy and conventional medicine demonstrated similar findings. No trial evaluated quality of life. No trial reported severe adverse events of Huperzine A.</p><p>Conclusions</p><p>Huperzine A appears to have beneficial effects on improvement of cognitive function, daily living activity, and global clinical assessment in participants with Alzheimer’s disease. However, the findings should be interpreted with caution due to the poor methodological quality of the included trials.</p></div

Summary of finding table of Huperzine A versus placebo for Alzheimer's disease.

<p>Presentation of the summary of findings on Huperzine A versus placebo for Alzheimer’s disease in trials reporting the original score after treatment, including information about the review, GRADE of the quality of evidence, and summary of the statistical results information.</p><p>Notes: *The basis for the <b>assumed risk</b> (e.g. the median control group risk across studies) is provided in footnotes. The <b>corresponding risk</b> (and its 95% confidence interval) is based on the assumed risk in the comparison group. †: Two of the three trials did not report the method of randomization and allocation concealment. ‡: One trial just mentioned "randomized" but did not report the method of randomization and blinding. §: The two trials just mentioned "randomized" but did not report the method of randomization. ¶: One trial could not allow to judge inconsistency of results, indirectness of evidence, imprecision and publication bias. <b>CI:</b> Confidence interval; <b>MMSE</b>: Mini-Mental State Examination; <b>ADAS-Cog:</b> Alzheimer’s Disease Assessment Scale-Cognitive Subscale; <b>HDS:</b> Hastgawa’s Dementia Scale; <b>WMS:</b> Wechsler Memory Scale; <b>ADCS-ADL:</b> Alzheimer’s disease Cooperative Study Activities of Daily Living Inventory; <b>ADL:</b> Activities of Daily Living Scale; <b>CDR:</b> Clinical Dementia Rating Scale.</p><p>(GRADE Working Group grades of evidence: we rate study design and specific factors that can downgrade one or two levels of the quality of the evidence including limitations in study design or risk of bias, inconsistency of results, indirectness of evidence, imprecision and publication bias, and factors that can upgrade one or two levels of the quality of the evidence including large magnitude of effect, all plausible confounding would reduce the demonstrated effect or increase the effect if no effect was observed, and dose-response gradient. <b>High quality:</b> Further research is very unlikely to change our confidence in the estimate of effect. <b>Moderate quality:</b> Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. <b>Low quality:</b> Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. <b>Very low quality:</b> We are very uncertain about the estimate.)</p

PRISMA flow diagram.

<p>Presentation of the procedure of literature searching and selection with numbers of articles at each stage.</p

Risk of bias summary.

<p>Presentation of the risk of bias summary of the review author’s judgments about each risk of bias item for each included study.</p

Risk of bias graph.

<p>Presentation of the risk of bias graph of the review author’s judgments about each risk of bias item presented as percentages across all included study.</p

Additional file 2: of Pathological tau deposition in Motor Neurone Disease and frontotemporal lobar degeneration associated with TDP-43 proteinopathy

File S1. Clinical histories and neuropathological findings in patients #35 and 41. (DOCX 21 kb

Additional file 1: Figure S1. of Pathological tau deposition in Motor Neurone Disease and frontotemporal lobar degeneration associated with TDP-43 proteinopathy

α-synuclein (a-c) pathology in cingulate gyrus (a), CA2 region of hippocampus (b) and substantia nigra (c) and TDP-43 pathology in anterior horn cells of the spinal cord (d-f), with fine, particulate accumulations of TDP-43 (d,e) or skein-like structures (e,f) being present in affected cells in which the nucleus has been ‘cleared’ of its normal immunoreactivity. Immunoperoxidase, x400 microscope magnification. (DOCX 6504 kb