Limitations of mainstream treatments of Alzheimer’s disease
Available prescription medications used to treat Alzheimer’s disease (AD) may temporarily lessen the severity of memory loss and other cognitive and behavioral symptoms associated with AD, but they do not correct its root causes nor do they reverse the steady cognitive decline typical of dementia (Dou et al 2018). The cholinesterase inhibitors (tacrine, donepezil, rivastigmine, and galantamine) often cause vomiting, nausea, appetite loss and diarrhea. Early promising results of studies on tacrine, the first commercially marketed acetylcholinesterase inhibitor, were offset by findings of significant hepatotoxicity. Second-generation acetylcholinesterase inhibitors (donepezil, rivastigmine, and galantamine) are no more effective than tacrine but require less frequent dosing and have fewer associated safety issues. These concerns led to the discontinuation of tacrine in 2013. In contrast to the cholinesterase inhibitors, Memantine acts by antagonizing glutamate neurotransmitter receptors. A combined regimen of donepezil and memantine is sometimes used to treat severe symptoms of AD (Dou et al 2018).
Huperzine A: what it is and how it works
Huperzine A is an alkaloid derivative of the herb Huperzia serrata and is an important ingredient of many compound herbal formulas used in Chinese medicine to treat cognitive impairment related to normal aging. Huperzine A reversibly inhibits acetylcholinesterase, the enzyme that breaks down the neurotransmitter acetylcholine which plays a critical role in the formation of new memories. Huperzine may also slow the production of nitric oxide in the brain, reducing age-related neurotoxicity (Zhao & Li, 2002).
Research review
Findings on Huperzine A for AD are inconsistent. An early human trial reported that Huperzine A may be more effective than piracetam for age-related memory loss (Wang et al., 1994). Several early placebo-controlled trials reported consistent beneficial effects in both age-related memory loss (i.e., benign senescent forgetfulness) and Alzheimer’s disease at doses between 0.2 and 0.8 milligrams per day (Wang et al. 1994). However, findings of recent systematic reviews remain inconclusive.
Two systematic reviews of placebo-controlled randomized trials on Huperzine A in patients diagnosed with Alzheimer’s disease (AD) found inconclusive evidence that Huperzine A ameliorates symptoms of memory loss and other cognitive problems. Methodological problems and small study size were cited as issues in both reviews (Li et al 2008; Li-Min and Ju-Tzu 2011). A 2013 systematic review (Yang et al 2013) included 10 randomized controlled trials found evidence for improved cognitive function as measured by the MMSE and other standardized rating scales but reported inconclusive evidence for Huperzine A in AD based on heterogeneity in study designs (different durations, different dosing protocols, different measures of cognitive performance), poor methodological quality of many studies (e.g., unclear blinding, unreported dropout rates during trial, randomization protocols not reported), short study duration (most studies were 8 or 12 weeks long) and small study size. Because most studies on Huperzine A are of short duration, it is possible that observed beneficial effects might reflect temporary symptomatic improvement (Tian et al 2010). However, as most studies do not report adverse effects thus the reviewers could not comment on its safety profile.
Few safety issues
Huperzine A is generally well tolerated (Rafii et al 2011). Huperzine A is generally safe when used at dosages indicated for AD and other cognitive problems. As the molecule functions in the same way that pharmaceuticals work to improve memory, individuals who take it report similar adverse effects such as nausea, and diarrhea. However, they are less frequent and milder than reported with pharmaceutical cholinesterase inhibitors.
Bottom line
In the face of limitations of available pharmacologic treatments of Alzheimer’s disease Huperzine A, a component of a traditionally used herbal in Chinese medicine, is a promising alternative approach. Methodological problems in many studies make it difficult to draw definitive conclusions about its effectiveness, and findings should be viewed as preliminary pending confirmation by large well-designed studies.
To learn more about complementary and alternative treatments of dementia read my book Dementia and Mild Cognitive Impairment: The Integrative Mental Health Solution.