Alternative Medicine Review 1999

A Review of Nutrients and Botanicals in the Integrative Management of Cognitive Dysfunction Parris M. Kidd, PhD Abstract Dementias and other severe cognitive dysfunction states pose a daunting chal- lenge to existing medical management strategies. An integrative, early intervention approach seems warranted. Whereas, allopathic treatment options are highly limited, nutritional and botanical therapies are available which have proven degrees of efficacy and generally favorable benefit-to-risk profiles. This review covers five such therapies: phosphatidylserine (PS), acetyl-l-carnitine (ALC), vinpocetine, Ginkgo biloba extract (GbE), and Bacopa monniera (Bacopa). PS is a phospholipid enriched in the brain, validated through double-blind trials for improving memory, learning, concentration, word recall, and mood in middle-aged and elderly subjects with dementia or age-related cognitive decline. PS has an excellent benefit-to-risk profile. ALC is an energizer and metabolic cofactor which also benefits various cognitive functions in the middle- aged and elderly, but with a slightly less favorable benefit-to-risk profile. Vinpocetine, found in the lesser periwinkle Vinca minor, is an excellent vasodilator and cerebral metabolic enhancer with proven benefits for vascular-based cognitive dysfunction. Two meta-analyses of GbE demonstrate the best preparations offer limited benefits for vascular insufficiencies and even more limited benefits for Alzheimer’s, while “commodity” GbE products offer little benefit, if any at all. GbE (and probably also vinpocetine) is incompatible with blood-thinning drugs. Bacopa is an Ayurvedic botanical with appar- ent anti-anxiety, anti-fatigue, and memory-strengthening effects. These five substances offer interesting contributions to a personalized approach for restoring cognitive function, perhaps eventually in conjunction with the judicious application of growth factors. (Altern Med Rev 1999;4(3):144-161) Introduction Progressive memory loss, dementia, and related cognitive dysfunction states have become a catastrophic medical and social problem in Western societies. According to the U.S. National Institute on Aging, in the United States alone there are as many as four million cases of the most extreme form of cognitive breakdown, namely the dementia of Alzheimer’s Disease.1 Parris M. Kidd, PhD - Biomedical consultant, nutrition educator, Contributing Editor, Alternative Medicine Review. Correspondence address: 847 Elm St., El Cerrito, CA 94530, USA. Fax: 510-526-6114. Page 144 Alternative Medicine Review ◆ Volume 4, Number 3 ◆ 1999 Copyright©1999 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission Cognitive Function Other types of dementia add to the burden Nature and Scope of The Cognitive imposed on society by this tragic human af- Dysfunction Problem fliction. For every case of diagnosed demen- The term “dementia” connotes cogni- tia there are probably several additional cases tive deterioration so severe that social and oc- of individuals with Mild Cognitive Impairment cupational functioning is markedly impaired, (MCI)2 or ARCD (Age-Related Cognitive to the extent the afflicted individual can no Decline).3 longer be a fully independent and productive Cognitive dysfunction often is taken citizen.5 As the disease progresses, personal- for granted, both by health-care practitioners ity changes emerge, and subsequently mood and by the public at large. A pattern of pro- lability and social withdrawal take hold. Ad- gressive cognitive decline which usually be- vanced dementia is characterized by progres- comes noticeable in middle age has tradition- sive loss of the personality and increasing in- ally been dismissed as part of “getting old.” ability to perform even the simplest tasks. Mild This assumed causal link between aging and Cognitive Impairment (MCI) features abnor- cognitive dysfunction is not scientifically sup- mal memory loss relative to one’s age, but portable, as many individuals age into their without the other changes which characterize 90s with only modest loss of mental skills.4 dementia.2 Age-Related Cognitive Decline But for subjects who show measurable cogni- (ARCD) is a diagnosis reserved for abnormal tive decline, failure to positively intervene can cognitive function less severe than dementia prove disastrous, as abnormally lowered cog- in persons older than 50.3 nitive performance during the sixth decade has Currently, the majority of diagnosed been linked to increased risk of dementia in dementias are thought to be Alzheimer’s Dis- later life.1 The dementias, as with other de- ease, and “Alzheimer’s” has now become a generative diseases, necessitate an integrative- popular icon used to stigmatize memory prob- wholistic approach which stresses early inter- lems of any degree. Sadly, this societal preoc- vention. cupation with Alzheimer’s is not without fac- Despite intensive clinical testing over tual basis; within the general U.S. population the past two decades, the allopathic manage- one in 10 of those aged 75-85 could progress ment of dementia and other cognitive dysfunc- to Alzheimer’s, and as many as one in three of tion states is still not much better than pallia- those 85 and over.1 Such widespread occur- tive. On the other hand, numerous controlled rence of severe cognitive dysfunction, featur- clinical trials have demonstrated improved ce- ing uncoupling from one’s personal history, rebral performance from dietary supplemen- detachment from one’s surroundings, and fi- tation with specific nutrients and botanicals, nally the loss of one’s very personality, is with- generally with a minimum degree of risk. Any out historical precedent. nutrient can benefit brain function when a sys- A workable approach to curbing this temic deficiency state exists, but a handful of virtual epidemic of dementia hinges on the de- nutrients and botanicals offer clinically-signifi- velopment of a strategy for halting (or at least cant benefits to memory and the allied cogni- slowing) cognitive decline before it crosses the tive functions. Included in this unique group threshold to dementia. Research is progress- are phosphatidylserine, acetyl-L-carnitine, ing towards the definition of a “window of vinpocetine, Ginkgo biloba extract, and opportunity” for effective intervention to halt Bacopa monniera. This review examines the the progression to dementia. From the point proven cognition-enhancing effects of each of of birth forward, the old adage, “Use it or lose these five nutritional supplements. it,” applies to the brain. The brain’s situation Alternative Medicine Review ◆ Volume 4, Number 3 ◆ 1999 Page 145 Copyright©1999 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission Figure 1. The matrix of interactive risk factors for dementia.10-18 By quantitatively imaging the baseline Dementia Risk Factor Matrix metabolic activities of the brain and the capacities of the various zones to “turn Very Likely Advanced age, family history (Alzheimer's, on” in response to stimulation, it should Parkinson's), apolipoprotein E-4, Down's become possible to define a “pre-clini- syndrome, head trauma (10x risk w/ApoE4) depression, reduced blood flow, stroke, cal” stage of accelerated nerve network estrogen imbalance, poor word fluency. loss, which for many subjects is possible as early as the fourth decade of life. Likely emotional stress, toxic damage, alcohol The window of opportunity for salvag- abuse, nutrient deficiencies, transmitter ing brain function probably is closed deficits, metabolic deficits, underactivity, lower educational level, occupational when so many circuits have been lost that electromagnetic exposure. the remaining circuits cannot sufficiently adapt to maintain an acceptable level of Possible Aluminum exposure, latent viruses, sugar learning, recollection, or concentration. consumption, olfactory deficit, coronary artery Past this point, the individual will be disease. hard-pressed to remain productive and live independently. Patients with mod- erate-to-severe dementia are likely to ex- is somewhat analogous to skeletal mass, in that perience only symptomatic improvement from the more dense the brain circuitry is earlier in therapeutic intervention, since so little brain life, the more that can be lost later in life be- circuitry remains from which to attempt to re- fore function becomes seriously compro- build. Whatever the diagnostic advances, early 6 mised. intervention in cognitive dysfunction states With the tragic exception of those in- will remain crucial to their management. dividuals who suffer early-onset forms of cognitive breakdown, the window of opportunity The Matrix of Risk Factors for for positive intervention against dementia can extend at least into the sixth decade of life. Dementia For many subjects this is the stage during As with other degenerative disease, which cognitive losses become measurable, dementia progression is associated with vari- sometimes with the diagnosis of Age Related ous risk factors. The reduction or elimination Cognitive Decline. ARCD signifies a symp- of known risk factors is one manageable step tom cluster of accelerated mental decline docu- toward the prevention or slowing of demen- mented after the age of 50. By definition tia, and of course can be set into motion prior ARCD is an age-linked condition, not a dis- to the onset of noticeable signs and symptoms. ease. Although ARCD is not as severe as de- A matrix of risk factors for dementia is pre- mentia, the worst

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