Herbal and Similar Substances to Prevent or Treat Dementia

Melatonin and sage are my two favorite herbal supplements to prevent dementia.  I combine these with a healthy diet of whole grains, greens like spinach and collard greens, dark fruits like strawberries and blueberries, fish or fish oil, and 4 ounces of red wine daily, while avoiding beef, pork, salt, butter, sugar, and white bread or anything made with white flour including white pastas.  The carnitines do have a lot of research finding benefits to humans, including some benefit preventing dementia.  Melatonin, vinpocetine, and ginkgo get their own pages for dementia listed above.  Important vitamins, etc., are covered on other pages.

Ginkgo has been the best researched herb for dementia.  Larger scale studies are in process at this time.  However, initial results suggest that it may produce a modest amount of benefit, but nothing dramatic.  Of course, nothing else does either.  Prevention is the best plan.  Lemon balm, melatonin, sage, citicholine, phosphatidylserine, and vinpocetine (from lesser periwinkle leaves) have some initial encouraging results, but the amount of research to date is very limited.  The same applies to two Chinese medicines, huperzine and yizhi.  While some benefit may yet come from these herbs, there is nothing to get excited about.  Of course, adding more sage or lemon balm to your cooking is very inexpensive and appears harmless. Ginkgo, citicholine, phosphatidylserine, and vinpocetine are available at $15-$25 a month each.  Some of the research is very new, so there is the hope that any potential treatment or prevention benefits will become better known.  The Ayurvedic bacopa from India, although promoted by the health food industry, has not been studied in any controlled manner with dementia so far as I can find.

Some supplements have been well studied and found not to be of value. The 11 studies of acetyl-L-carnitine, when considered overall, find no cognitive benefit for dementia, although it may have preventive value.   Ibedenone has one very large, well-designed study that clearly established that it is of no value for dementia.  DHEA has one study suggesting possible benefit, but its side-effects and cancer risk should discourage its use.

The use of "cognitive enhancement" medications by the elderly and in dementia is very common.  In one study of caregivers of family members with dementia, 31% of the demented were being given CE medications (Am J Geriatr Psychiatry. 2004 May-Jun;12(3):250-7). 

Acetyl-L-Carnitine: Mild Cognitive Impairment Helped by ALCAR in Large Study: In a 5-month PC study of 236 mildly impaired elderly, 90 days of ALCAR at 1.5 g/day increased all measures of cognitive functioning, especially memory and constructive thinking, and of emotional-affective state and on some scores of the relational behavior. Effects of L-acetylcarnitine on mental deterioration in the aged: initial results. Cipolli C, Chiari G. Clin Ter. 1990 Mar 31;132(6 Suppl):479-510.

Acetyl-L-Carnitine: Mild Cognitive Impairment: L-Acetylcarnitine Helped Elderly Mental Functioning and Depression in Large Study: In a single-blind PC study of 481 elderly given 30 days of placebo, 90 days of L-acetylcarnitine (LAC) 1500 mg/day and 30 more days of placebo, the MMSE increased with LAC treatment (p < 0.0001). The Randt Memory Test also revealed that LAC the total score and the memory index increased significantly. Some benefit persisted after LAC was discontinued. The Geriatric Depression Scale and Hamilton Depression scores also improved (p < 0.0001). The Family Stress Scale showed a significant decrease after treatment (p < 0.0004). No significant adverse drug reactions occurred. L-acetylcarnitine treatment of mental decline in the elderly. Salvioli G, Neri M. University of Modena, Italy. Drugs Exp Clin Res. 1994;20(4):169-76. 

Acetyl-L-Carnitine: Alzheimer's Disease: Little Value: In a very large DB PC study of 431 patients under 65 years old, younger patients progressed a little more slowly in developing AD and ones older had dementia progress a little more rapidly. Thal, UCSD, Neurol ’96;47:705

Acetyl-L-Carnitine: Alzheimer's: No Help in AD: DB 1 yr study found no value for probable Alzheimers for 229 pt study. Neurology 2000 Sep 26;55(6):805-10

Acetyl-L-Carnitine: Review Says No Reason to Recommend ALC for Alheimer's:  In an analysis of all DB randomized trials (11) through Jan. 2003, all trials assessed the cognitive effects of ALC and in addition six considered severity of dementia, six considered functional ability and six considered clinical global impression (CGI). Treatment effects favored ALC at 12 and 24 weeks only for the CGI [OR 2.33, P<0.01] and [OR 3.91, P=0.01] but not at 52 weeks. There was no evidence of benefit for ALC in the areas of cognition, severity of dementia, functional ability or Clinical Global Impression as a continuous measure. The reviewer notes that the couple positive findings might be chance findings in view of the large number of measures in the studies. Maudsley Hospital, London. Acetyl-L-carnitine for dementia. Hudson S, Tabet N. Cochrane Database Syst Rev. 2003;(2):CD003158

Acetyl-L-Carnitine Probably No Good: LJ Thal of UCSD in Neurol 9/96 47:705-11 in 1 yr DB placebo for probable AD treated with 1 g t.i.d. for 431 patients found both declined at same rate. Tho those under 66yo declined more slowly on the med. And those over 65 yo declined more rapidly on med! Well tolerated. Pettegrew of U Pitt in Neurobiol Aging 1/95 in DB placebo of 7 probable AD pt and 5 placebo and 21 matched controls found less deterioration in yr with med. Parnetti of U Perugia in Drugs Aging 3/93 3:159-64 with 126 prob AD pt in found more improvement with l-alpha-glyceryl- phosphorylcholine, those on ALC also improved. 

Acetyl-L-Carnitine Claimed to Help Younger AD: In a DB PC study of 334 patients treated for 1 year, researchers found benefit for those under age 62 in retrospective analysis. JO Brooks, Stanford, Int Psychogeriatr 1998 Jun;10(2):193-203. Ed: Retrospective analysis is a questionable research approach.  Since there was no overall benefit, helping the younger would almost suggest it hurt the older.  Not a sensible analysis of an otherwise good study.

Bacopa Promoted, Ayurvedic Nerve Tonic: Indian Ayurvedic medicine for dementia with very little human research on PubMed 9/19/03 and only a small number of rat studies. This study finds anti-cholinergic activity. A comparative study in rodents of standardized extracts of Bacopa monniera and Ginkgo biloba: anticholinesterase and cognitive enhancing activities. Das A, Shanker G, Nath C, Pal R, Singh S, Singh H; Other rat studies report protective effect on brain mitochondria in rats or astrocytes in vitro. Bacopa is a plant extract. Chronic effects of Brahmi (Bacopa monnieri) on human memory. Roodenrys S, Booth D, Bulzomi S, Phipps A, Micallef C, Smoker J. Neuropsychopharmacology. 2002 Aug;27(2):279-81; Other Indian studies with animals promote antiulcerogenic, anti-hepatotoxicity and anticancer effects. Also said to be anti-oxidant and used for insomnia. Whereas Chinese traditional medicine has been a flourishing treatment field in China, Ayurvedic medicine had fallen into disrepute for 2 centuries except among folk medicine street vendors.

Bacopa Helped Memory Retention but Nothing Else: A DB PC study of 76 40- to 65-year-olds at Woolongong, Australia treated for 3 months. Brahmi (Bacopa) decreased the rate of forgetting of newly acquired information. Tasks assessing attention, verbal and visual short-term memory and the retrieval of pre-experimental knowledge were unaffected. Questionnaire measures of everyday memory function and anxiety levels were also unaffected.

Bacopa Helps Learning in Normals in DB: DB PC 12 week study normal adults (number unmentioned in abstract) claims B. monniera significantly improved speed of visual information processing measured by the IT task, learning rate and memory consolidation measured by the AVLT (P<0.05), and state anxiety (P<0.001) compared to placebo, with maximal effects evident after 12 weeks. Victoria, Australia. The chronic effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy human subjects. Stough C, Lloyd J, Clarke J, Downey LA, Hutchison CW, Rodgers T, Nathan PJ. Psychopharmacology (Berl). 2001 Aug;156(4):481-4

Bacopa Helps Rat Depression: Author says Bacopa is commonly used in India for mental disorders and that the standardized extract was reported earlier to have significant anti-oxidant effect, anxiolytic activity and improve memory retention in Alzheimer's disease. Says 20 and 40 mg/kg, orally once daily for 5 days was found to have significant antidepressant activity in forced swim and learned helplessness models of depression in rats and was comparable to that of imipramine. Banaras Hindu Univ, Antidepressant activity of standardized extract of Bacopa monniera in experimental models of depression in rats. Sairam K, Dorababu M, Goel RK, Bhattacharya SK. Phytomedicine. 2002 Apr;9(3):207-11. (Ed: If it is commonly used and with few side-effects, why waste the time doing a rat study when large numbers of humans are already taking it? How about a human DB PC study.)

Bacopa Protects Against Phenytoin Cognitive Impairment: New Delhi study. Abstract doesn’t mention how many subjects. Significantly reversed PHT-induced impairment when given at 40mg/kg for 7 days after subjects on phenytoin for 14 days. Both acquisition and retention of memory showed improvement without affecting its anticonvulsant activity. Protection from phenytoin-induced cognitive deficit by Bacopa monniera, a reputed Indian nootropic plant. Vohora D, Pal SN, Pillai KK. J Ethnopharmacol. 2000 Aug;71(3):383-90

Bacopa May Have Helped Memory of Some Retarded: Reference made to a study with administration of extract from Bacopa monnieri to children with mental retardation, in which was reported to significantly improve short-term and long-term memory. Author notes little research on effects of 3000yo Ayurvedic medicine system. New Delhi. Traditional Indian systems of medicine. Lodha R, Bagga A. Ann Acad Med Singapore. 2000 Jan;29(1):37-41. Some recent work in drug development relates to species of Commiphora (used as a hypolipidaemic agent), Picrorhiza (which is hepatoprotective), Bacopa (used as a brain tonic), Curcuma (antiinflammatory) and Asclepias (cardiotonic).

Citicoline or CDP Choline: A reportedly best selling herbal supplement from Jarrow costs 35 cents per 250 mg capsule, it is a naturally occurring, water soluble biological compound that is an essential intermediate for the synthesis of phosphatidylcholine, a major constituent for the grey matter of brain tissue (30%), primarily cell membranes.  It is widely used in Europe for memory conditions, especially with cerebrovascular factors are involved.  CDP choline is metabolized to yield the free nucleotide cytidine and choline.  Scientific research demonstrates that CDP choline consumption promotes brain metabolism by enhancing the synthesis of acetylcholine, restoring phospholipid content in the brain and regulation of neuronal membrane excitability and osmolarity (by its effect on the ATP-dependent sodium and potassium pumps). Seven DB studies found it of help for mild cognitive impairment, although only one of the studies was longer than 3 months (Cochrane Database Syst Rev. 2005 Apr 18;(2):CD000269). DB studies have found it of value after strokes, for Parkinson's disease, for closed head injuries, for glaucoma and amblyopia, and cognitive impairment.  

CDP Choline Didn't Help Vascular Dementia: A Brown University study of just 30 patients with vascular dementia treated in a DB PC study using citicoline 500 mg b.i.d. or placebo found no benefit over a one year period of time. Long-term citicoline (cytidine diphosphate choline) use in patients with vascular dementia: neuroimaging and neuropsychological outcomes. Cohen RA, Browndyke JN, Moser DJ, Paul RH, Gordon N, Sweet L. Cerebrovasc Dis. 2003;16(3):199-204

Citicoline May Help Cognitive Impairment Some: A meta-analysis of seven studies giving citicoline to elderly patients suffering cognitive impairment found there is no significant evidence of a beneficial effect of CDP-choline on attention, but modest beneficial effects of CDP-choline on memory function and behavior. For the outcome of clinical global impression, the odds ratio for improvement in the subjects treated with CDP-choline as opposed to the subjects treated with placebo is 8.89 [5.19 to 15.22]. The drug is well tolerated. University of Rome, Cytidinediphosphocholine (CDP choline) for cognitive and behavioural disturbances associated with chronic cerebral disorders in the elderly. Fioravanti M, Yanagi M. Cochrane Database Syst Rev. 2000;(4):CD000269; One study used 1000mg/d for 12 weeks in a DB PC study of just 30 Alzheimer's patients. Methods Find Exp Clin Pharmacol. 1999 Nov;21(9):633-44; An MIT study of 32 adults ages 50-85 with relatively inefficient memories in a DB PC crossover 2 months study using 2000 mg/d and a 3 month study of 95 elderly using 1000 mg/d found the higher dose helped delayed recall and that only people with inefficient memories benefited. Arch Neurol. 1996 May;53(5):441-8. For more, see Citicholine.

DHEA Helps: A DB PC study of 58 patients with probable Alzheimer's disorder were given DHEA 50mg b.i.d. or placebo for 6 months. Treatment restored serum DHEA levels to those seen in young adults. Improvement of ADAS-Cog ratings at 3 months and 6 months is reported. Owen Wolkowitz, UCSF, APA 5/99. Benefit appears modest. DHEA, unfortunately, probably increases the risk of cancer.

DHEA: No Benefit DHEA on Memory in Short Studies: OT Wolf, Univ. of Trier, Germany, Psychoneuroendocrin 8/98 23:617-29 DB placebo with 75 elderly 50 mg/d for 2 wk. No net benefit to memory. Second DB study by OT Wolf in J Gerontol and Biol Sci 9/98 53:M385-90 with 17 elderly men with 50 mg vs. placebo crossover for 2 wk found no memory or mood benefit. A third DB study by Wolf in J Clin Endocrinol Metab 7/97 82:2363-7 with 2 weeks 50 mg vs. placebo for 40 healthy elderly men and women again found no benefit memory or well-being. OM Wolkowitz of UCSF in Biol Psychiatry 2/97 41:311-8 gave DHEA to 6 elderly depressed in open trial of 30-90 mg for 4 wk with one showing good improvement in treatment resistant depression.

DHEA: Promoted on internet for AD with recommendations for males over 50 50-100mg/d and females 25-50mg/d. No benefit have been found above in multiple studies.

Dronabinal Said to Help Agitation in Poor Quality Study: Dronabinol (Marinol) may reduce agitation and improve appetite in patients with Alzheimer's disease, when traditional therapies are not successful. Retrospective review 48 patients (mean age = 77) dementia unit, DSM-IV Alzheimer's disease had unsatisfactory control of their agitation. Initially received 5 mg/day of dronabinol in two doses up to a maximum of 10 mg/day. In addition, all patients were treated with atypical neuroleptics and at least four medications to control behavior. The evaluation by caregivers 66 percent experienced a significant improvement in agitation. Functional improvement was observed in 69 percent. Prior to the study, all patients experienced weight loss and had been diagnosed with anorexia. After treatment with dronabinol, all patients (100 percent) had gained weight. No adverse events. Joshua Shua-Haim, Meridian Institute for Aging, New Jersey, International Psychogeriatric Association. 8/20/03

Huperzine a Cholinesterase Inhibitor: Cholinesterase inhibitors huperzine A, donepezil and rivastigmine were compared for their effects on extracellular acetylcholine concentration and acetylcholinesterase activity in the rat cortex. Huperzine A was 8- and 2-fold more potent than donepezil and rivastigmine in increasing cortical acetylcholine levels, with a longer-lasting effect. Comparative effects of huperzine A, donepezil and rivastigmine on cortical acetylcholine level and acetylcholinesterase activity in rats. Liang YQ, Tang XC, Shanghai Institute of Materia Medica, Neurosci Lett. 2004 May 6;361(1-3):56-9

Huperzine Helped in One DB Study: DB PC study 103 Alzheimer's patients for 8 weeks at 0.2 mg twice a day. 58% improved on memory, cognitive, and behavioral measures vs. 36% on placebo. SS Xu, Zhejiang Med Univ, Hangzhou, Chung Kuo Yao Li Hsueh Pao ’95;16:391. Old herbal med (shuangyiping) from club moss used for fever and inflammation. Pure reversible and selective acetylcholinesterase inhibitor stronger than tacrine in in vitro or animal studies. No GABA or glutamate effects. No other human studies. Promoted in Taste for Life 4/99 which reports an open US study by Alan Mazurek in Rockville NY of 22 pt (50-100 microgr bid with some up to 200) with no controls and presented at an Alternative Medicine Symposium. One monkey study showed improved memory performance. Causes some mild dizziness.

Idebenone No Value for Alzheimer's: Idebenone is an anti-oxidant and short chain analogue of coenzyme Q-10. In a very large, well-designed 536-patient DB PC study of patients with probable Alzheimer's disease and MMSE scores 12-25, one of three different doses of idebenone up to 360 mg t.i.d. or placebo were given. The study found no evidence of any clinically significant benefit. Univ. of Calif. San Diego. Idebenone treatment fails to slow cognitive decline in Alzheimer's disease. Thal LJ, Grundman M, Berg J, Ernstrom K, Margolin R, Pfeiffer E, Weiner MF, Zamrini E, Thomas RG. Neurology. 2003 Dec 9;61(11):1498-1502. Ed: Idebenone is an expensive supplement ($40 for 30 150 mg. tablets) available without prescription and heavily promoted for dementia, heart disease, and much else. It has been found of modest benefit in a 1-year DB PC study of cardiomyopathy in Friedreich's Ataxia but didn't slow the progression of the ataxia. Neurology. 2003 May 27;60(10):1676-9. Co Q-10, in contrast, is much less expensive and has been found of some value for heart attack victims and for high blood pressure in DB studies.

Lemon Balm Helps Agitation in Nursing Homes in DB: 7 nursing homes using either sunflower oil or lemon balm oil twice a day to face and arms for 4 weeks found a greater than 29% decrease agitation in 61% of lemon balm residents vs. 15% in placebo. Ballard, J Clin Psych 02;63:553.

Lemon Balm: Aromatherapy Didn’t Work for AD: Aromatherapy for 10 weeks using an ABCBA design for 2 weeks each (A = lavender oil, B = thyme oil, C = unscented grapeseed oil) with the oil was placed every 3 hours on an absorbent fabric sachet pinned near the collarbone of each participant's shirt had no effect on agitation in severely demented patients. Cutaneous application of essential oils may be necessary to achieve the effects reported in previous controlled studies. A controlled trial of aromatherapy for agitation in nursing home patients with dementia. Snow LA, Hovanec L, Brandt J. Houston VA. J Altern Complement Med. 2004 Jun;10(3):431-7

Lemon Balm (Melissa Officialis) Helps AD in DB: In a DB PC study using 60 drops/day on 42 patients for 4 months, those given the lemon balm showed significantly greater improvement. Melissa officinalis extract in the treatment of patients with mild to moderate Alzheimer's disease: a double blind, randomized, placebo controlled trial. Akhondzadeh S, Noroozian M, Mohammadi M, Ohadinia S, Jamshidi AH, Khani M. Tehran. J Neurol Neurosurg Psychiatry. 2003 Jul;74(7):863-6. Lemon balm leaves and extract are used for headaches, calming nerves, inducing sleep, and easing insect bites by herbal community. 

Lemon Balm: Artemis Herbs website says: Arabs were the first to extol its virtues (sic). The Romans introduced to Britain. Dioscorides and Pliny noted the plant’s healing and relaxing properties. Avicenna in his 11th Century book on herbs called ‘The Canon of Medicine’ wrote that ‘balm maketh the heart merry and joyful, and strengthens the vital spirits’. Ancient reputation for easing cardiac and nervous disorders, and above all, for counteracting melancholy. It was widely considered to promote longevity. John Evelyn (1620-1706) said; ‘Balm is sovereign for the brain, strengthening memory and powerfully chasing away melancholy’, and Paraclesus called it ’The Elixir of Life’. Thomas Coghan, a 16th Century Oxford Don, said ‘It is an hearbe greatly to be esteemed of students, for by a special property it driveth away heaviness of mind, sharpeneth the understanding and encreaseth memory’. There has been much modern research into balm herb, much of it yielding positive results. The volatile oils in the herb help to calm the central nervous system, and some of the water-soluble constituents are anti-viral - especially against the herpes (cold-sore) virus.

Lemon Balm Helped Memory & Mood: Single weekly dose varying amounts of dry leaf or placebo in capsule to 20 college students found that 1600 mg dry leaf was best. Says potential for treating AD. Northumbria Univ (sage study place). Modulation of Mood and Cognitive Performance Following Acute Administration of Single Doses of Melissa Officinalis (Lemon Balm) with Human CNS Nicotinic and Muscarinic Receptor-Binding Properties. Kennedy DO, Wake G, Savelev S, Tildesley NT, Perry EK, Wesnes KA, Scholey AB. Neuropsychopharmacology. 2003 Jul 23; Also, oregano, sage, peppermint, garden thyme, lemon balm, clove, allspice and cinnamon as well as the Chinese medicinal herbs Cinnamomi cortex and Scutellariae radix all contained very high concentrations of antioxidants (i.e., >75 mmol/100 g). Several culinary and medicinal herbs are important sources of dietary antioxidants. Dragland S, Senoo H, Wake K, Holte K, Blomhoff R. J Nutr. 2003 May;133(5):1286-90; German chamomile, lavender, hops, lemon balm and passionflower are reputed to be mild sedatives but need much more experimental examination. Valerian best herbal sedative. Univ of Illinois at Chicago, Efficacy and safety of herbal stimulants and sedatives in sleep disorders. Gyllenhaal C, Merritt SL, Peterson SD, Block KI, Gochenour T. Sleep Med Rev. 2000 Jun;4(3):229-251.

NADH Helped AD in Very Small Study: In a 6-month DB PC study of 26 Alzheimer’s patients, those given stabilized NADH 10 mg/day showed no evidence of progressive cognitive deterioration and had higher MDRS scores compared with placebo (p < 0.05). NADH is a coenzyme that plays a key role in cellular energy production and stimulates dopamine production. In previous trials NADH has been shown to improve cognitive functioning in patients with Parkinson's disease, depression and AD. Treatment of Alzheimer's disease with stabilized oral nicotinamide adenine dinucleotide: a randomized, double-blind study. Demarin V, Podobnik SS, Storga-Tomic D, Kay G. University Hospital, Zagreb, Drugs Exp Clin Res. 2004;30(1):27-33

Phosphatidylserine Helped Cognitive Problems in Elderly: In a very large DB PC Italian study of 494 elderly patients with mild to moderate cognitive impairment done at 23 geriatric units in Northern Italy, the patients on phosphatidylserine reported did better on both cognitive and behavioral measures. Cognitive decline in the elderly: a double-blind, placebo-controlled multicenter study on efficacy of phosphatidylserine administration. Cenacchi T, Bertoldin T, Farina C, Fiori MG, Crepaldi G. Aging (Milano). 1993 Apr;5(2):123-33. Ed: Phosphatidylserine is heavily promoted by the health food industry for dementia although the research on it is very limited. The cost is $22 for one month at 100 mg t.i.d. A pharmaceutical company funded and ran the above study.

Phosphatidylserine May Have Helped in Small Study: In a DB PC crossover study of just 33 patients with each on placebo or phosphatidylserine for 8 weeks with a four week washout in between, the clinical global improvement measure showed significant improvement although other measures did not. Univ Munich. Double-blind cross-over study of phosphatidylserine vs. placebo in patients with early dementia of the Alzheimer type. Engel RR, Satzger W, Gunther W, Kathmann N, Bove D, Gerke S, Munch U, Hippius H. Eur Neuropsychopharmacol. 1992 Jun;2(2):149-55

Phosphatidylserine Helped in a Small U.S. Study: In a 51 patient DB PC 12-week study, patients on phosphatidylserine 100 mg. t.i.d. improved on several measures. Patients with mild dementia were most likely to do better. Bethesda. Effects of phosphatidylserine in Alzheimer's disease. Crook T, Petrie W, Wells C, Massari DC. Psychopharmacol Bull. 1992;28(1):61-6

Phosphatidylserine May Have Helped in Small Study: In a 42-patient DB PC 12-week study, those on phosphatidylserine 100 mg t.i.d. did significantly better on one measure. Double-blind randomized controlled study of phosphatidylserine in senile demented patients. Delwaide PJ, Gyselynck-Mambourg AM, Hurlet A, Ylieff M. Acta Neurol Scand. 1986 Feb;73(2):136-40

Phosphatidylserine of Some Benefit for Dementia in 3 Old DB: DB study of 494 65-93yos with mod to severe mental decline Rx phosphatidylserine 300mg/d x 6 mo vs placebo found improvement on behav and cognitive measures and med well tolerated. Cenacchi (working for drug manufacturer), Padova, Cognitive decline in the elderly: a double-blind, placebo-controlled multicenter study on efficacy of phosphatidylserine administration. Cenacchi T, Bertoldin T, Farina C, Fiori MG, Crepaldi G, Aging (Milano) 4/93 5:123-33. RR Engel of U Munich in Eur Neuropsychopharm 6/92;2:149-55 Rx 33 pt with mild primary degenerative dementia in DB crossover with 300 mg/d for 8 wk. CGI showed med better but no psychometric improvement. T Crook of Bethesda in Psychopharm Bull ’92;28:61-6 Rx 51 with prob AD for 12 wk 100 mg TID or placebo and med with cognitive improvement esp those with less severe disease. Available from Puritan’s Pride on sale 9/03 for 25 cents per 100mg capsule. No studies in last 10 years.

Quercetin Helps Aged Mice: Chronic administration of quercetin (10, 25 and 50 mg/kg) for 30 days or its co-administration with ethanol (15% w/v, 2g/kg per orally) for 24 days significantly reversed the age-related or chronic ethanol-induced retention deficits in both the test paradigms, but was no benefit to young mice. Chronic quercetin administration for 30 days also reversed age associated increase in TBARS levels and decline in forebrain total glutathione (GSH), SOD and catalase levels. Reversal of aging and chronic ethanol-induced cognitive dysfunction by quercetin a bioflavonoid. Singh A, Naidu PS, Kulkarni SK. Panjab University, India. Free Radic Res. 2003 Nov;37(11):1245-52. Quercetin is a flavone found in many fruits.

Sage (Salvia Officialis) Helps AD in Small DB: In a 41-patient DB PC 4 month study, researchers found better cognition on ADAS-cognitive testing and less agitation with 60 drops/day of salvia. Salvia officinalis extract in the treatment of patients with mild to moderate Alzheimer's disease: a double blind, randomized and placebo-controlled trial. Akhondzadeh S, Noroozian M, Mohammadi M, Ohadinia S, Jamshidi AH, Khani M. Tehran. J Clin Pharm Ther 2003 Feb;28(1):53-9; Sage should not be used in pregnancy, while breastfeeding, or with HBP according to Artemis Herbs website. It is promoted for fatigue. Another listing claims it is good for skin troubles, gargle, sore throats, bleeding gums, quinsy and tonsillitis.  However, I could find no evidence for these claims.

Sage Helped Normals in Single Dose Study: In a DB PC crossover study of 24 normal adults, 25 mul and 50 mul of a standardised essential oil of S. lavandulaefolia resulted in a consistent improvement on the 'Speed of Memory' factor. There was also an improvement on the 'Secondary Memory' factor for the 25-mul dose. Mood was consistently enhanced, with increases in self-rated 'alertness', 'calmness' and 'contentedness' following the 50-mul dose and elevated 'calmness' following 25 mul. Positive modulation of mood and cognitive performance following administration of acute doses of Salvia lavandulaefolia essential oil to healthy young volunteers. Tildesley NT, Kennedy DO, et al. Northumbria University, Newcastle upon Tyne, UK. Physiol Behav. 2005 Jan 17;83(5):699-709

Sage May Block Cholinesterase: A time dependent increase in the inhibition of butyrylcholinesterase by the oils of S. fruticosa and S. officinalis var. purpurea was found, but apparently not with S. lavandulaefolia, or S. officinalis. Butyryl- and acetyl-cholinesterase inhibitory activities in essential oils of Salvia species and their constituents. Savelev SU, et al. University of Newcastle, UK. Phytother Res. 2004 Apr;18(4):315-24.  The same team of researchers reported that in controlled trials in normal volunteers, both sage and lemon balm extracts improved memory, and lemon balm also improved mood. Lemon balm reduced agitation and improved quality of life in people with Alzheimer's. The effects of sage on AD reportedly showed preliminary data indicating significant effects on attention and behavior. Psychiatry of Old Age annual meeting in Liverpool. Aug/04. Cholinesterase inhibitor medications have a poor track record in helping dementia, slowing progression of the disease only a few months and at great cost.  If sage is no better, it's not much relief.

Sage Might Help: S. lavandulaefolia Vahl. (Spanish sage) extracts and constituents have demonstrated anticholinesterase, antioxidant, anti-inflammatory, oestrogenic and CNS depressant (sedative) effects. The essential oil inhibits the enzyme acetylcholinesterase (AChE) from human brain tissue and bovine erythrocyte and individual monoterpenoid constituents inhibit AChE with varying degrees of potency. In vivo AChE inhibition of select brain (striatal and hippocampal over cortical) AChE was obtained following oral administration of the essential oil to rats. In a study in healthy volunteers essential oil administration produced significant effects on cognition. In a pilot open-label study involving oral administration of the essential oil to patients with AD, a significant increase in diastolic and systolic blood pressure was observed in two patients, however this may have been due primarily to preexisting hypertension and there were no abnormalities in other vital signs or blood samples during the trial period. In an open trial (prone to observer bias), significant reductions in neuropsychiatric symptoms and an improvement in attention were found. Salvia for dementia therapy: review of pharmacological activity and pilot tolerability clinical trial. Perry NS, et al. University of Otago, Dunedin, New Zealand. Pharmacol Biochem Behav. 2003 Jun;75(3):651-9.

Yizhi Helps Vascular Dementia in DB: Study in Chinese journal of 61 patients of yizhi vs. hydergine shows a decrease in depression and improved gait in 2 months of treatment using the HAM-D and MMSE in a single-blind study. Zhongguo Zhong Xi Yi Jie He Za Zhi 1997 Jul;17(7):393-7;

modern-psychiatry.com

Thomas E. Radecki, M.D., J.D.