CryoNet #32226 - #32233

CryoNet - Fri 18 Dec 2009

    #32226: Re: Grim story on cryonics [David Stodolsky]
    #32227: Cryonics' paleo-futuristic reputation? [Mark Plus]
    #32229: evidence based OTC treatment of Alzheimer's disease IV [oberon]
    #32230: evidence based OTC treatment of Alzheimer's disease V [oberon]
    #32231: evidence based OTC treatment of Alzheimer's disease III [oberon]
    #32232: evidence based OTC treatment of Alzheimer's disease II [oberon]
    #32233: evidence based OTC treatment of Alzheimer's disease I [oberon]

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Message #32226
From: David Stodolsky <[email protected]>
Subject: Re: Grim story on cryonics
Date: Thu, 17 Dec 2009 12:50:48 +0100
References: <[email protected]>

On 17 Dec 2009, at 11:00 AM, CryoNet wrote:
>
> With regards to
>
>>>>
> The Chronic Dependence of Popular Religiosity upon Dysfunctional
> Psychosociological Conditions
>
>
> The nonuniversality of strong religious devotion, and the ease with
> which large populations abandon serious theism when conditions are
> sufficiently benign, refute hypotheses that religious belief and
> practice are the normal, deeply set human mental state, whether they
> are superficial or natural in nature. Instead popular religion is
> usually a superficial and flexible psychological mechanism for coping
> with the high levels of stress and anxiety produced by sufficiently
> dysfunctional social and especially economic environments. Popular
> nontheism is a similarly casual response to superior conditions.
> <<<
>
> I suspect it means this:
>
> <begin>
> Distressed people's dependence on religion
>
> When good conditions prevail, a majority of people lose interest in  
> going to religious ceremonies. This suggests that performing  
> religious ceremonies are not normal deeply set behaviour. Instead,  
> these ceremonies are a superficial and flexible psychological  
> mechanism for dealing with threatening situations. In good times,  
> atheism is more prevalent.
> <end>

This misses the point of the article. The question being addressed is  
whether religion is a neurological built-in or a function of social  
conditions. If it is the second, then it is a psychological process,  
not an evolved brain function.

The lesson here is that much theorizing in the social sciences sounds  
like something that anyone can come up with, since it uses everyday  
language. However, there are precise, usually mathematical models  
behind the words. You find this out by reading the entire article.

This confusion doesn't come up with the hard sciences, such as  
physics, chemistry, genetics, etc., since they have special words for  
what they study, like boson, fermion, tensor, etc.


dss


David Stodolsky
[email protected]  Skype: davidstodolsky

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Message #32227
From: Mark Plus <[email protected]>
Subject: Cryonics' paleo-futuristic reputation?
Date: Thu, 17 Dec 2009 07:46:55 -0800

This book apparently has a section on cryonics as bad futurology:

Your Flying Car Awaits: Robot Butlers, Lunar Vacations, and Other Dead-Wrong Predictions of the Twentieth Century, by Paul Milo 

http://www.amazon.com/Your-Flying-Car-Awaits-Predictions/dp/0061724602/

Mark Plus


 		 	   		  
_________________________________________________________________
Hotmail: Trusted email with Microsoft's powerful SPAM protection.
http://clk.atdmt.com/GBL/go/177141664/direct/01/

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Message #32229
Date: Thu, 17 Dec 2009 21:21:21 -0800 (PST)
From: [email protected]
Subject: evidence based OTC treatment of Alzheimer's disease IV

[A combination of pyridoxine (B6) 5 mg, folic acid 1 mg, and other vitamins and iron s a dud.]

Clin Ther. 2007 Oct;29(10):2204-14.
Efficacy of multivitamin supplementation containing vitamins B6 and B12 and folic acid as adjunctive treatment with a cholinesterase inhibitor in Alzheimer's disease: a 26-week, randomized, double-blind, placebo-controlled study in Taiwanese patients.
Sun Y, Lu CJ, Chien KL, Chen ST, Chen RC. Department of Neurology, En Chu Kong Hospital, San-shia, Taipei, Taiwan.
    BACKGROUND: Elevated serum homocysteine levels have been associated with the development of Alzheimer's dementia (AD). The combined use of a mecobalamin capsule preparation, which contains vitamin B12 0.5 mg with an active methyl base, and an over-the-counter nutritional supplement that contains folic acid 1 mg and pyridoxine hyperchloride 5 mg may be effective as a homocysteine-lowering vitamin regimen. OBJECTIVE: The aim of this study was to determine whether oral multivitamin supplementation containing vitamins B6 and B12 and folic acid would improve cognitive function and reduce serum homocysteine levels in patients with mild to moderate AD. METHODS: This randomized, double-blind, placebocontrolled trial was conducted at En Chu Kong Hospital, Taipei, Taiwan. Male and female patient
 s aged >50 years with mild to moderate AD and normal folic acid and vitamin B12 concentrations were enrolled. All patients received treatment with an acetylcholinesterase inhibitor and were randomized to receive add-on mecobalamin (B12) 500 mg + multivitamin supplement, or placebos, PO QD for 26 weeks. The multivitamin contained pyridoxine (B6) 5 mg, folic acid 1 mg, and other vitamins and iron. Serum homocysteine level was measured and cognitive tests were conducted at baseline and after 26 weeks. The primary efficacy outcome was change in cognition, measured as the change in score from baseline to week 26 on the Alzheimer's Disease Assessment Scale 11-item Cognition subscale. Secondary efficacy outcomes included changes in function in performance of activities of daily living (ADLs) an
 d concentrations of homocysteine, B12, and folic acid. Tolerability was assessed by comparing the 2 study groups with respect to physical examination findings, including changes in vital signs, laboratory test abnormalities, concomitant medication use, and compliance of study medication was assessed using an interview with the patient's caregiver, as well as the monitoring of adverse events (AEs) throughout the study. RESULTS: Eighty-nine patients (45 men, 44 women; all Taiwanese; mean [SD] age, 75 [7.3] years) were enrolled and randomized. Overall, there were no significant differences in cognition or ADL function scores between the 2 groups. At week 26, the mean (SD) between-group difference in serum homocysteine concentration versus placebo was -2.25 (2.85) micromol/L (P = 0.008), and
  the mean serum concentrations of vitamin B12 and folic acid were significantly higher (but within normal range) in the multivitamin group compared with placebo (., +536.9 [694.4] pg/mL [P < 0.001] and +13.84 ng/mL [11.17] [P = 0.012] at 26 weeks, respectively). The 2 most common AEs were muscle pain (11.1% and 6.8%) and insomnia (8.9% and 9.1%) in the multivitamin and placebo groups, respectively. CONCLUSIONS: In this population of patients with mild to moderate AD in Taiwan, a multivitamin supplement containing vitamins B(6) and B(12) and folic acid for 26 weeks decreased homocysteine concentrations. No statistically significant beneficial effects on cognition or ADL function were found between multivitamin and placebo at 26 weeks.
PMID: 18042476

[Lipoic acid may be slightly beneficial.]

J Neural Transm Suppl. 2007;(72):189-93.
Alpha-lipoic acid as a new treatment option for Alzheimer's disease--a 48 months follow-up analysis.
Hager K, Kenklies M, McAfoose J, Engel J, Munch G. Department of Medical Rehabilitation and Geriatrics, Henriettenstiftung, Hannover, Germany.
    Oxidative stress and neuronal energy depletion are characteristic biochemical hallmarks of Alzheimer's disease (AD). It is therefore conceivable that pro-energetic and antioxidant drugs such as alpha-lipoic acid might delay the onset or slow down the progression of the disease. In a previous study, 600mg alpha-lipoic acid was given daily to nine patients with AD (receiving a standard treatment with choline-esterase inhibitors) in an open-label study over an observation period of 12 months. The treatment led to a stabilization of cognitive functions in the study group, demonstrated by constant scores in two neuropsychological tests (the mini mental state exam, MMSE and the Alzheimer's disease assessment score cognitive subscale, ADAScog). In this report, we have extended the analysis to
  43 patients over an observation period of up to 48 months. In patients with mild dementia (ADAScog < 15), the disease progressed extremely slowly (ADAScog: +1.2 points/year, MMSE: -0.6 points/year), in patients with moderate dementia at approximately twice the rate. However, the progression appears dramatically lower than data reported for untreated patients or patients on choline-esterase inhibitors in the second year of long-term studies. Despite the fact that this study was not double-blinded, placebo-controlled and randomized, our data suggest that treatment with alpha-lipoic acid might be a successful 'neuroprotective' therapy option for AD. However, a state-of-the-art phase II trial is needed urgently.
PMID: 17982894

[Conflicting results with NADH. Only stabilizated NADH was effective.]

Drugs Exp Clin Res. 2004;30(1):27-33.
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. Department of Neurology, Sestre Milosrdnice University Hospital, Zagreb, Croatia.
    This study was designed to evaluate the effect of stabilized oral reduced nicotinamide adenine dinucleotide (NADH) on cognitive functioning in patients with Alzheimer's disease (AD). 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. The present trial was a randomized, placebo-controlled, matched-pairs, double-blind, 6-month clinical study. Patients with probable AD (n = 26) were randomized to receive either stabilized oral NADH (10 mg/day) or placebo. Twelve pairs of subjects were matched for age and baseline total score on the Mattis Dementia Rating Scale (MDRS) and the Mini Mental State Examination. A
 fter 6 months of treatment, subjects treated with NADH showed no evidence of progressive cognitive deterioration and had significantly higher total scores on the MDRS compared with subjects treated with placebo (p < 0.05). Analysis of MDRS subscales revealed significantly better performance by NADH subjects on measures of verbal fluency (p = 0.019), visual-constructional ability (p = 0.038) and a trend (p = 0.08) to better performance on a measure of abstract verbal reasoning. There were no differences between groups in measures of attention, memory, or in clinician ratings of dementia severity (Clinical Dementia Rating). Consistent with earlier studies, the present findings support NADH as a treatment for AD.
PMID: 15134388

J Neural Transm. 2000;107(12):1475-81.
No evidence for cognitive improvement from oral nicotinamide adenine dinucleotide (NADH) in dementia.
Rainer M, Kraxberger E, Haushofer M, Mucke HA, Jellinger KA. Memory-Clinic and Psychiatric Department, Donauspital, Sozialmedizinisches Zentrum Ost, Wein, Austria.
    Reduced nicotinamide adenine dinucleotide (NADH) is advertised as an over-the-counter product or dietary supplement to treat Alzheimer's disease. We performed a 3-month open-label study with oral 10 mg/day NADH with 25 patients with mild to moderate dementia of the Alzheimer, vascular, and fronto-temporal types in addition to their current cholinomimetic drug medication. In 19 patients who completed the study, we found no evidence for any cognitive effect as defined by established psychometric tests. We conclude that NADH is unlikely to achieve cognitive improvements in an extent reported earlier, and present theoretical arguments against an effectiveness of this compound in dementia disorders.
PMID: 11459000

[An extract of lemon balm (melissa officinalis) extract was highly beneficial in a small trial in Iran. While the placebo patients continued to deteriorate, the lemon balm patients continuously improved throughout the trial. The results of this trial have been largely ignored in the USA, which may be significant error since the results exceed those of prescription drugs, which typically only slow the decline, or help to temporarity stabilize patients.]

J Neurol Neurosurg Psychiatry. 2003 Jul;74(7):863-6.
Melissa officinalis extract in the treatment of patients with mild to moderate Alzheimer's disease: a double blind, randomised, placebo controlled trial.
Akhondzadeh S, Noroozian M, Mohammadi M, Ohadinia S, Jamshidi AH, Khani M. Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences, Tehran, Iran.
    OBJECTIVE: To assess the efficacy and safety of Melissa officinalis extract using a fixed dose (60 drops/day) in patients with mild to moderate Alzheimer's disease. DESIGN: A four month, parallel group, placebo controlled trial undertaken in three centres in Tehran, Iran. METHODS: Patients with mild to moderate Alzheimer's disease aged between 65 and 80 years (n = 42; 18 women, 24 men) with a score of >or= 12 on the cognitive subscale of Alzheimer's disease assessment scale (ADAS-cog) and <or= 2 on the clinical dementia rating (CDR) were randomised to placebo or fixed dose of Melissa officinalis extract. The main efficacy measures were the change in the ADAS-cog and CDR-SB scores compared with baseline. Side effects were systematically recorded. RESULTS: At four months, Melissa officin
 alis extract produced a significantly better outcome on cognitive function than placebo (ADAS-cog: df = 1, F = 6.93, p = 0.01; CDR: df = 1, F = 16.87, p < 0.0001). There were no significant differences in the two groups in terms of observed side effects except agitation, which was more common in the placebo group (p = 0.03). CONCLUSIONS: Melissa officinalis extract is of value in the management of mild to moderate Alzheimer's disease and has a positive effect on agitation in such patients.
PMID: 12810768
Fre text: >
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1738567/?tool=pubmed

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Message #32230
Date: Thu, 17 Dec 2009 21:23:56 -0800 (PST)
From: [email protected]
Subject: evidence based OTC treatment of Alzheimer's disease V

[Rosmarinic acid is an effective peroxynitrite scavenger, and is found in a number of spices, including lemon balm, marjorum, oregano, peppermint, rosemary, sage, and thyme. In addition to the lemon balm trial, two different varieties of sage (spanish:salvia lavandulaefolia & common:salvia officinalis) have been successful at reversing symptoms of Alzheimer's disease in two human clinical trials conducted in New Zealand, and Iran respectively . Rosmarinic acid also extended lifespan in an animal model of ALS in Japan.]

[Spanish sage appears to be beneficial.]

Pharmacol Biochem Behav. 2003 Jun;75(3):651-9.
Salvia for dementia therapy: review of pharmacological activity and pilot tolerability clinical trial.
Perry NS, Bollen C, Perry EK, Ballard C. Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand.
    S. lavandulaefolia Vahl. (Spanish sage) extracts and constituents have demonstrated anticholinesterase, antioxidant, anti-inflammatory, oestrogenic and CNS depressant (sedative) effects all of which are currently relevant to the treatment of Alzheimer's disease (AD). 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 th
 e 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. Although an open label trial is not free from practice effects or rater-caregiver expectations, statistically significant differences between baseline and 6 weeks treatment were a reduction in neuropsychiatric symptoms and an improvement in attention.
PMID: 12895683

[An extract of common sage was successful at reversing Alzheimer's disease to an extent similar to that of lemon balm.]

J Clin Pharm Ther. 2003 Feb;28(1):53-9.
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. Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences and Institute of Medicinal Plants, Iranian Academic Centre for Education, Culture and Research, Tehran, Iran.
    BACKGROUND: Alzheimer's disease is characterized by a slow, progressive decline in cognitive function and behaviour. Acetylcholine esterase inhibitors are the only agents approved by the Food and Drug Administration for the treatment of Alzheimer's disease. All other agents prescribed for the treatment of Alzheimer's disease are used on an off-label basis. Current research into new drugs is focused on agents that will prevent, slow down and/or halt the progress of the disease process. Salvia officinalis has been used in herbal medicine for many centuries. It has been suggested, on the basis of traditional medicine, its in vitro cholinergic binding properties and modulation of mood and cognitive performance in humans, that Salvia officinalis might potentially provide a novel natural tre
 atment for Alzheimer's disease. The objective of this study was to assess the efficacy and safety of Salvia officinalis extract using a fixed dose (60 drops/day), in patients with mild to moderate Alzheimer's disease, over a 4-month period. METHODS: This was a 4-month, parallel group, placebo-controlled trial undertaken in three centres in Tehran, Iran. Patients with mild to moderate Alzheimer's disease aged between 65 and 80 years (n = 42, 18 women) with a score of > or = 12 on the cognitive subscale of Alzheimer's Disease Assessment Scale (ADAS-cog) and < or = 2 on the Clinical Dementia Rating (CDR) were randomized to placebo or fixed dose of S. officinalis extract. Over the 16 weeks, the main efficacy measures were the change in the ADAS-cog and CDR-Sum of Boxes scores compared with b
 aseline. In addition, side-effects were systematically recorded throughout the study using a checklist. RESULTS: At 4 months, S. officinalis extract produced a significant better outcome on cognitive functions than placebo (ADAS-cog: F = 4.77, d.f. = 1, P = 0.03) (CDR-SB: F = 10.84, d.f. = 1, P < 0.003). There were no significant differences in the two groups in terms of observed side-effects except agitation that appears to be more frequent in the placebo group (P = 0.09). CONCLUSIONS: The results of this study indicate the efficacy of S. officinalis extract in the management of mild to moderate Alzheimer's disease. Moreover, S. officinalis may well reduce agitation of patients but this needs to be confirmed.
PMID: 12605619

[Rosmarinic acid extends lifespan in an animal model of amyotrophic lateral sclerosis.]

J Neurosci Res. 2009 Oct 1. [Epub ahead of print]
Effect of rosmarinic acid in motor dysfunction and life span in a mouse model of familial amyotrophic lateral sclerosis.
Shimojo Y, Kosaka K, Noda Y, Shimizu T, Shirasawa T. Beauty Care Product Developing Team, Research and Development Center, Nagase & Co., Ltd.,Hyogo, Japan.
    Amyotrophic lateral sclerosis (ALS) is a late-onset progressive neurodegenerative disease affecting motor neurons. About 2% of patients with the disease are associated with mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1). The purpose of this study is to assess the effect of rosemary extract and its major constituents, rosmarinic acid (RA) and carnosic acid (CA), in human SOD1 G93A transgenic mice, which are well-established mouse models for ALS. The present study demonstrates that intraperitoneal administration of rosemary extract or RA from the presymptomatic stage significantly delayed motor dysfunction in paw grip endurance tests, attenuated the degeneration of motor neurons, and extended the life span of ALS model mice. In addition, RA administration significantly 
 improved the clinical score and suppressed body weight loss compared with a vehicle-treated group. In conclusion, this study provides the first report that rosemary extract and, especially, RA have preventive effects in the mouse model of ALS. (c) 2009 Wiley-Liss, Inc.
PMID: 19798750

[Colostrum extract was slightly beneficial.]

Med Sci Monit. 2002 Oct;8(10):PI93-6.
Colostrinin proline-rich polypeptide complex from ovine colostrum--a long-term study of its efficacy in Alzheimer's disease.
Leszek J, Inglot AD, Janusz M, Byczkiewicz F, Kiejna A, Georgiades J, Lisowski J. Department of Psychiatry, Medical University of Wroclaw, Wroclaw, Poland.
    BACKGROUND: Colostrinin, a proline-rich polypeptide complex (PRP) isolated from ovine colostrum, with immunoregulatory and procognitive properties, has shown positive effects in the treatment of Alzheimer's disease (AD). The aim of the present study was to evaluate the effects of long-term Colostrinin treatment of AD patients. MATERIAL/METHODS: The patients were taking Colostrinin tablets (containing 100 mg of PRP complex) every other day for three weeks, followed by a 2-week hiatus to avoid the development of hyporeactivity. This mode of application, '3+2 weeks,' was used consistently throughout the trial. The efficacy of treatment was assessed by the MMSE scale, and each patient was evaluated at 4-month intervals. 33 patients were treated for 16 months. However, 13 patients from this
  group had already been treated with Colostrinin for 12 months during placebo-controlled studies, and thus participated in the trial for a total of 28 months. RESULTS: The results we obtained showed that Colostrinin induced slight but statistically significant improvement or stabilization of the health status of the patients in the trial. The adverse reactions observed, if any, were remarkably mild, including anxiety, logorrhea, and insomnia, and subsided spontaneously within a short period of time (3-4 days). CONCLUSIONS: Colostrinin is a very promising preparation which can be used to retard the development of AD.
PMID: 12388930

Arch Immunol Ther Exp (Warsz). 1999;47(6):377-85.
Colostrinin: a proline-rich polypeptide (PRP) complex isolated from ovine colostrum for treatment of Alzheimer's disease. A double-blind, placebo-controlled study.
Leszek J, Inglot AD, Janusz M, Lisowski J, Krukowska K, Georgiades JA. The Psychiatric Unit, University Medical School, Wroclaw, Poland.
    A proline-rich polypeptide (PRP) complex, subsequently called Colostrinin, was isolated from ovine colostrum. The complex showed immunomodulatory properties in mice, rats, and chickens, inducing maturation and differentiation of thymocytes. It was recently found that Colostrinin is a cytokine-like factor that acts as an inducer of interferon gamma (IFN-gamma) and other cytokines in human peripheral blood and cord blood leukocyte cultures and has psycho-immuno-enhancing activity in volunteers. These observations prompted us to study the effect of Colostrinin on patients with Alzheimer's disease (AD). Forty six AD patients were divided into 3 groups and randomly assigned to receive orally either Colostrinin (100 microg per tablet, every second day), commercially available bioorganic sele
 nium (100 microg selenium per tablet, every second day) or placebo tablets. One cycle of the treatment lasted 3 weeks and was separated from the next cycle by a 2 week hiatus. Each patient received 10 cycles of treatment during the year of the clinical trial. Outcomes were assessed by psychiatrists blinded to the treatment assignment. Eight of the 15 AD patients treated with Colostrinin improved and in the 7 others the disease had stabilized. In contrast, none of the 31 patients from the selenium or placebo groups with similar mild or moderate AD improved. The administration of selenium promoted stabilization in 13 of the 15 patients, whereas in the placebo group only 8 of the 16 patients were stabilized at the 12 month trials end-evaluation. Colostrinin was found to be a remarkably safe
  drug. Mild and transient effects were anxiety, stimulation, insomnia, and tiredness. The results obtained showed that oral administration of Colostrinin improves the outcome of AD patients with mild to moderate dementia. The results are very encouraging and deserve further research.
PMID: 10608295

[Thiamin is slightly beneficial.]

J Geriatr Psychiatry Neurol. 1993 Oct-Dec;6(4):222-9.
Preliminary findings of high-dose thiamine in dementia of Alzheimer's type.
Meador K, Loring D, Nichols M, Zamrini E, Rivner M, Posas H, Thompson E, Moore E. Department of Neurology, Medical College of Georgia, Augusta 30912-3200.
    Thiamine is important not only in the metabolism of acetylcholine but also in its release from the presynaptic neuron. Pathologic, clinical, and biochemical data suggest that thiamine deficiency is detrimental to the cholinergic system and that thiamine-dependent enzymes may be altered in Alzheimer's disease. Two previous studies reported contradictory results in patients with dementia of Alzheimer's type treated with 3 g/day of thiamine. In the present study, we examined the effects of 3 to 8 g/day thiamine administered orally. Our results suggest that thiamine at these pharmacologic dosages may have a mild beneficial effect in dementia of Alzheimer's type. The mechanism of the observed effect is unknown, but the findings warrant further investigation, not only for their therapeutic i
 mplications but for their possible etiologic clues. In addition, the results suggest long-term carry-over effects that should be considered in the design of future studies.
PMID: 8251051

Arch Neurol. 1991 Jan;48(1):81-3.
A trial of thiamine in Alzheimer's disease.
Nolan KA, Black RS, Sheu KF, Langberg J, Blass JP. Altschul Laboratory for Dementia Research, Cornell University Medical College, Burke Rehabilitation Center, White Plains, NY 10605.
    Because a previous short-term study demonstrated a statistically significant, but not clinically important, improvement in cognitive test scores during thiamine treatment in patients with dementia of the Alzheimer's type, a 12-month, double-blind, parallel-group study was conducted to examine whether long-term administration of thiamine at 3 g/d might slow the progression of dementia of the Alzheimer's type. Fifteen subjects were enrolled and 10 completed the 1-year study. Data are available for two additional subjects through the first 9 months of study. No significant differences were found between the placebo and thiamine groups at any point during the study. In both groups, overall means for the Mini-Mental State Examination, verbal learning, and naming scores decreased significant
 ly over the 12-month study period. These results do not support the hypothesis that long-term administration of thiamine at 3 g/d might slow the progression of dementia of the Alzheimer's type.
PMID: 1986730

Arch Neurol. 1988 Aug;45(8):833-5.
Thiamine and Alzheimer's disease. A pilot study.
Blass JP, Gleason P, Brush D, DiPonte P, Thaler H. Will Rogers Institute, White Plains, NY.
    As a test of the significance of previously described biochemical abnormalities in thiamine-dependent enzymes in brains and other tissues in patients with Alzheimer's disease, a double-blind, placebo-controlled, crossover, outpatient pilot study compared the effects of 3 g/d of oral thiamine hydrochloride for three months with those of a niacinamide placebo. Eleven moderately impaired patients with "probable Alzheimer's disease" by the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria completed the study. All patients were well nourished and had no stigmata of dietary thiamine deficiency. Their initial mean +/- SEM Mini-Mental State Examination score was 14.2 +/- 1.4, and the mean age was 72 years. G
 lobal cognitive rating by the Mini-Mental State Examination was higher during three months with 3 g/d of oral thiamine hydrochloride than with niacinamide placebo. Behavioral ratings, however, did not differ significantly, nor did clinical state when it was judged subjectively.
PMID: 2969232

[Guess the number of human clinical trials using fruit and vegetable juices. The answer is appended at the end of this file.]

Am J Med. 2006 Sep;119(9):751-9.
Fruit and vegetable juices and Alzheimer's disease: the Kame Project.
Dai Q, Borenstein AR, Wu Y, Jackson JC, Larson EB. Department of Medicine, Division of General Internal Medicine and Public Health, Vanderbilt Center for Health Services Research, Vanderbilt-Ingram Cancer Center, Vanderbilt School of Medicine, Nashville, Tenn, USA.
    BACKGROUND: Growing evidence suggests that oxidative damage caused by the beta-amyloid peptide in the pathogenesis of Alzheimer's disease may be hydrogen peroxide mediated. Many polyphenols, the most abundant dietary antioxidants, possess stronger neuroprotection against hydrogen peroxide than antioxidant vitamins. METHODS: We tested whether consumption of fruit and vegetable juices, containing a high concentration of polyphenols, decreases the risk of incident probable Alzheimer's disease in the Kame Project cohort, a population-based prospective study of 1836 Japanese Americans in King County, Washington, who were dementia-free at baseline (1992-1994) and were followed through 2001. RESULTS: After adjustment for potential confounders, the hazard ratio for probable Alzheimer's disease
  was 0.24 (95% confidence interval [CI], 0.09-0.61) comparing subjects who drank juices at least 3 times per week with those who drank less often than once per week with a hazard ratio of 0.84 (95% CI, 0.31-2.29) for those drinking juices 1 to 2 times per week (P for trend < .01). This inverse association tended to be more pronounced among those with an apolipoprotein Eepsilon-4 allele and those who were not physically active. Conversely, no association was observed for dietary intake of vitamins E, C, or beta-carotene or tea consumption. CONCLUSIONS: Fruit and vegetable juices may play an important role in delaying the onset of Alzheimer's disease, particularly among those who are at high risk for the disease. These results may lead to a new avenue of inquiry in the prevention of Alzhei
 mer's disease.
PMID: 16945610
Free text>
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2266591/pdf/nihms37963.pdf

[Guess what contains peroxynitrite scavengers?]

J Neurosci. 2008 Jun 18;28(25):6388-92.
Grape-derived polyphenolics prevent Abeta oligomerization and attenuate cognitive deterioration in a mouse model of Alzheimer's disease.
Wang J, Ho L, Zhao W, Ono K, Rosensweig C, Chen L, Humala N, Teplow DB, Pasinetti GM. Department of Psychiatry, Mount Sinai School of Medicine, New York, New York 10029, USA.
    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive impairments in memory and cognition. Extracellular accumulation of soluble high-molecular-weight (HMW) Abeta oligomers has been proposed to be largely responsible for AD dementia and memory deficits in the Tg2576 mice, a model of AD. In this study, we found that a naturally derived grape seed polyphenolic extract can significantly inhibit amyloid beta-protein aggregation into high-molecular-weight oligomers in vitro. When orally administered to Tg2576 mice, this polyphenolic preparation significantly attenuates AD-type cognitive deterioration coincidentally with reduced HMW soluble oligomeric Abeta in the brain. Our study suggests that grape seed-derived polyphenolics may be useful agents to prevent o
 r treat AD.
PMID: 18562609
Free text>
http://www.jneurosci.org/cgi/reprint/28/25/6388




ZERO.

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Message #32231
Date: Thu, 17 Dec 2009 21:19:38 -0800 (PST)
From: [email protected]
Subject: evidence based OTC treatment of Alzheimer's disease III

[Conflicting results, but ginkgo biloba is likely a dud.]

JAMA. 2008 Nov 19;300(19):2253-62.
Ginkgo biloba for prevention of dementia: a randomized controlled trial.
DeKosky ST, Williamson JD, Fitzpatrick AL, Kronmal RA, Ives DG, Saxton JA, Lopez OL, Burke G, Carlson MC, Fried LP, Kuller LH, Robbins JA, Tracy RP, Woolard NF, Dunn L, Snitz BE, Nahin RL, Furberg CD; Ginkgo Evaluation of Memory (GEM) Study Investigators. Collaborators (53)  Nahin R, Sorkin B, Carlson MC, Fried LP, Crowley P, Kawas C, Chaves P, Yasar S, Smith P, Chabot J, Robbins JA, Gundling K, Theroux S, Kwong L, Pastore L, Kuller L, Moyer R, Albig C, Burke G, Rapp S, Posey D, Lamb M, Horr R, Schmeller T, Herrmann J, Kronmal RA, Fitzpatrick AL, Lin F, Solomon C, Arnold A, DeKosky ST, Saxton JA, Lopez OL, Ives DG, Dunn L, Williamson JD, Furberg CD, Woolard N, Bender K, Margitic S, Tracy RP, Cornell E, Meltzer C, Grimm R, Berman J, Bradford H, Calabrese C, Chappell R, Connor K, Geller G, I
 glewicz B, Panush RS, Shader R. University of Pittsburgh, Pittsburgh, Pennsylvania, USA. [email protected]
Erratum in:  JAMA. 2008 Dec 17;300(23):2730.
    CONTEXT: Ginkgo biloba is widely used for its potential effects on memory and cognition. To date, adequately powered clinical trials testing the effect of G. biloba on dementia incidence are lacking. OBJECTIVE: To determine effectiveness of G. biloba vs placebo in reducing the incidence of all-cause dementia and Alzheimer disease (AD) in elderly individuals with normal cognition and those with mild cognitive impairment (MCI). DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled clinical trial conducted in 5 academic medical centers in the United States between 2000 and 2008 with a median follow-up of 6.1 years. Three thousand sixty-nine community volunteers aged 75 years or older with normal cognition (n = 2587) or MCI (n = 482) at study entry were assessed e
 very 6 months for incident dementia. INTERVENTION: Twice-daily dose of 120-mg extract of G. biloba (n = 1545) or placebo (n = 1524). MAIN OUTCOME MEASURES: Incident dementia and AD determined by expert panel consensus. RESULTS: Five hundred twenty-three individuals developed dementia (246 receiving placebo and 277 receiving G. biloba) with 92% of the dementia cases classified as possible or probable AD, or AD with evidence of vascular disease of the brain. Rates of dropout and loss to follow-up were low (6.3%), and the adverse effect profiles were similar for both groups. The overall dementia rate was 3.3 per 100 person-years in participants assigned to G. biloba and 2.9 per 100 person-years in the placebo group. The hazard ratio (HR) for G. biloba compared with placebo for all-cause dem
 entia was 1.12 (95% confidence interval [CI], 0.94-1.33; P = .21) and for AD, 1.16 (95% CI, 0.97-1.39; P = .11). G. biloba also had no effect on the rate of progression to dementia in participants with MCI (HR, 1.13; 95% CI, 0.85-1.50; P = .39). CONCLUSIONS: In this study, G. biloba at 120 mg twice a day was not effective in reducing either the overall incidence rate of dementia or AD incidence in elderly individuals with normal cognition or those with MCI. Trial Registration clinicaltrials.gov Identifier: NCT00010803.
PMID: 19017911

[Success here with ginkgo biloba, if you define success as no change.]

Eur J Neurol. 2006 Sep;13(9):981-5.
Ginkgo biloba and donepezil: a comparison in the treatment of Alzheimer's dementia in a randomized placebo-controlled double-blind study.
Mazza M, Capuano A, Bria P, Mazza S. Department of Psychiatry, Catholic University of Sacred Heart, Rome, Italy.
    The Ginkgo biloba special extract EGb 761 seems to produce neuroprotective effects in neurodegenerative diseases of multifactorial origin. There is still debate about the efficacy of Ginkgo biloba special extract EGb 761 compared with second-generation cholinesterase inhibitors in the treatment of mild to moderate Alzheimer's dementia. Our aim is to assess the efficacy of the Ginkgo biloba special extract E.S. in patients with dementia of the Alzheimer type in slowing down the disease's degenerative progression and the patients' cognitive impairment compared with donepezil and placebo. The trial was designed as a 24-week randomized, placebo-controlled, double-blind study. Patients aged 50-80 years, suffering from mild to moderate dementia, were allocated into one of the three treatment
 s: Ginkgo biloba (160 mg daily dose), donepezil (5 mg daily dose), or placebo group. The degree of severity of dementia was assessed by the Syndrom Kurz test and the Mini-Mental State Examination. Clinical Global Impression score was recorded to assess the change in the patients' conditions and the therapeutic efficacy of tested medications. Our results confirm the clinical efficacy of Ginkgo biloba E.S. (Flavogin) in the dementia of the Alzheimer type, comparable with donepezil clinical efficacy. There are few published trials that have directly compared a cholinesterase inhibitor with Ginkgo for dementia. This study directly compares a cholinesterase inhibitor with Ginkgo biloba for dementia of the Alzheimer type and could be a valid contribution in this debate. Our study suggests that
  there is no evidence of relevant differences in the efficacy of EGb 761 and donepezil in the treatment of mild to moderate Alzheimer's dementia, so the use of both substances can be justified. In addition, this study contributes to establish the efficacy and tolerability of the Ginkgo biloba special extract E.S. in the dementia of the Alzheimer type with special respect to moderately severe stages.
PMID: 16930364

[A combination of high-dose folate, vitamin B(6), and vitamin B(12) is a dud.]

JAMA. 2008 Oct 15;300(15):1774-83.
High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial.
Aisen PS, Schneider LS, Sano M, Diaz-Arrastia R, van Dyck CH, Weiner MF, Bottiglieri T, Jin S, Stokes KT, Thomas RG, Thal LJ; Alzheimer Disease Cooperative Study.
Collaborators (126)  Vicari S, Ala T, Luster K, Quinn J, Lear J, Clay T, Schneider LS, Pawluczyk S, Dagerman K, Sian S, Fleisher A, Pay MM, Barbas N, Lord J, Peskind E, Raskind MA, Mandelco L, Doody RS, Sims J, Roundtree S, Bell K, Tejeda R, Dominguez-Rivera E, Harrell L, Marson D, Zamrini E, Grossman H, Marzloff G, Nandipait S, Aggarwal N, Shah R, Bach J, Pfeiffer E, Luhn B, Hunter J, Ferris SH, Monteiro I, Maya E, Clark C, Han M, Pham C, Watson M, DeKosky ST, Simpson D, Ismail SM, Goldstein B, McCallum C, Mulnard RA, McAdams-Ortiz C, Yanez B, Weiner M, Koch K, Moore C, Levey A, Cellar J, Kippels A, Ringman J, Bardens J, Yau A, Graff-Radford NR, Parfitt F, Farlow MR, Hake A, Numberger P, van Dyck C, MacAvoy M, Black N, Hoffman P, DeCarli C, Seavey W, Conover C, Ahern G, Baldwin M, Malek-A
 hmadi M, Bernick C, Munic D, Vranesh G, Marek-Mesulam M, Johnson N, Epstein-Fields S, Mintzer JE, Davis FA, Kent J, Roffman M, Sadowdky C, Villena T, Martinez WC, Johnson K, Reynolds B, Ward C, Salisbury S, Yesavage JA, Ashford WJ, Pechonkina A, Kinoshita L, Sabbagh M, Connor D, Obradov S, Green RC, Stern RA, Nair A, Brickley M, Caselli R, Lawrence J, Obisesan T, Obisesan OA, Ahaghotu E, Ogrocki P, Sanders M, Ziol E, Ott BR, Grace J, Erbozkurt T, Kieburtz K, Miller B, Kryscio R, Alexopoulos G, Croot K, Messick V, Pamoleras A, Ryan-Jones R, Garcia-Camilo G, Schittini M, Brugger KG, Saunders PA, Kastelan J.
Department of Neurosciences, University of California, San Diego, 9500 Gilman Dr, M/C 0949, La Jolla, CA 92093, USA.
    CONTEXT: Blood levels of homocysteine may be increased in Alzheimer disease (AD) and hyperhomocysteinemia may contribute to disease pathophysiology by vascular and direct neurotoxic mechanisms. Even in the absence of vitamin deficiency, homocysteine levels can be reduced by administration of high-dose supplements of folic acid and vitamins B(6) and B(12). Prior studies of B vitamins to reduce homocysteine in AD have not had sufficient size or duration to assess their effect on cognitive decline. OBJECTIVE: To determine the efficacy and safety of B vitamin supplementation in the treatment of AD. DESIGN, SETTING, AND PATIENTS: A multicenter, randomized, double-blind controlled clinical trial of high-dose folate, vitamin B(6), and vitamin B(12) supplementation in 409 (of 601 screened) ind
 ividuals with mild to moderate AD (Mini-Mental State Examination scores between 14 and 26, inclusive) and normal folic acid, vitamin B(12), and homocysteine levels. The study was conducted between February 20, 2003, and December 15, 2006, at clinical research sites of the Alzheimer Disease Cooperative Study located throughout the United States. INTERVENTION: Participants were randomly assigned to 2 groups of unequal size to increase enrollment (60% treated with high-dose supplements [5 mg/d of folate, 25 mg/d of vitamin B(6), 1 mg/d of vitamin B(12)] and 40% treated with identical placebo); duration of treatment was 18 months. MAIN OUTCOME MEASURE: Change in the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-cog). RESULTS: A total of 340 participants (202 in active tr
 eatment group and 138 in placebo group) completed the trial while taking study medication. Although the vitamin supplement regimen was effective in reducing homocysteine levels (mean [SD], -2.42 [3.35] in active treatment group vs -0.86 [2.59] in placebo group; P < .001), it had no beneficial effect on the primary cognitive measure, rate of change in ADAS-cog score during 18 months (0.372 points per month for placebo group vs 0.401 points per month for active treatment group, P = .52; 95% confidence interval of rate difference, -0.06 to 0.12; based on the intention-to-treat generalized estimating equations model), or on any secondary measures. A higher quantity of adverse events involving depression was observed in the group treated with vitamin supplements. CONCLUSION: This regimen of h
 igh-dose B vitamin supplements does not slow cognitive decline in individuals with mild to moderate AD. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00056225.
PMID: 18854539

[Curcumin is a dud. Curcumin continues to be actively researched, and the poor results of this clinical trial were buried in a letter to the editor.]

J Clin Psychopharmacol. 2008 Feb;28(1):110-3.
Six-month randomized, placebo-controlled, double-blind, pilot clinical trial of curcumin in patients with Alzheimer disease.
Baum L, Lam CW, Cheung SK, Kwok T, Lui V, Tsoh J, Lam L, Leung V, Hui E, Ng C, Woo J, Chiu HF, Goggins WB, Zee BC, Cheng KF, Fong CY, Wong A, Mok H, Chow MS, Ho PC, Ip SP, Ho CS, Yu XW, Lai CY, Chan MH, Szeto S, Chan IH, Mok V.
PMID: 18204357

[Rosmarinic acid is highly effective while curcumin is a dud in an animal model of Alzheimer's disease. We'll be taking a further look at rosmarinic acid later.]

Am J Pathol. 2009 Nov 5. [Epub ahead of print]
Phenolic Compounds Prevent Alzheimer's Pathology through Different Effects on the Amyloid-{beta} Aggregation Pathway.
Hamaguchi T, Ono K, Murase A, Yamada M. From the Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
    Inhibition of amyloid-beta (Abeta) aggregation is an attractive therapeutic strategy for Alzheimer's disease (AD). Certain phenolic compounds have been reported to have anti-Abeta aggregation effects in vitro. This study systematically investigated the effects of phenolic compounds on AD model transgenic mice (Tg2576). Mice were fed five phenolic compounds (curcumin, ferulic acid, myricetin, nordihydroguaiaretic acid (NDGA), and rosmarinic acid (RA)) for 10 months from the age of 5 months. Immunohistochemically, in both the NDGA- and RA-treated groups, Abeta deposition was significantly decreased in the brain (P < 0.05). In the RA-treated group, the level of Tris-buffered saline (TBS)-soluble Abeta monomers was increased (P < 0.01), whereas that of oligomers, as probed with the A11 ant
 ibody (A11-positive oligomers), was decreased (P < 0.001). However, in the NDGA-treated group, the abundance of A11-positive oligomers was increased (P < 0.05) without any change in the levels of TBS-soluble or TBS-insoluble Abeta. In the curcumin- and myricetin-treated groups, changes in the Abeta profile were similar to those in the RA-treated group, but Abeta plaque deposition was not significantly decreased. In the ferulic acid-treated group, there was no significant difference in the Abeta profile. These results showed that oral administration of phenolic compounds prevented the development of AD pathology by affecting different Abeta aggregation pathways in vivo. Clinical trials with these compounds are necessary to confirm the anti-AD effects and safety in humans.
PMID: 19893028

[Aspirin is a dud.]

Lancet Neurol. 2008 Jan;7(1):41-9.
Aspirin in Alzheimer's disease (AD2000): a randomised open-label trial.
AD2000 Collaborative Group, Bentham P, Gray R, Sellwood E, Hills R, Crome P, Raftery J.
Comment in:  Lancet Neurol. 2008 Jan;7(1):20-1.
    BACKGROUND: Cardiovascular risk factors and a history of vascular disease can increase the risk of Alzheimer's disease (AD). AD is less common in aspirin users than non-users, and there are plausible biological mechanisms whereby aspirin might slow the progression of either vascular or Alzheimer-type pathology. We assessed the benefits of aspirin in patients with AD. METHODS: 310 community-resident patients who had AD and who had no potential indication or definite contraindication for aspirin were randomly assigned to receive open-label aspirin (n=156; one 75-mg enteric-coated tablet per day, to continue indefinitely) or to avoid aspirin (n=154). Primary outcome measures were cognition (assessed with the mini-mental state examination [MMSE]) and functional ability (assessed with the B
 ristol activities of daily living scale [BADLS]). Secondary outcomes were time to formal domiciliary or institutional care, progress of disability, behavioural symptoms, caregiver wellbeing, and care time. Patients were assessed at 12-week intervals in the first year and once each year thereafter. Analysis of the primary outcome measures was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN96337233. FINDINGS: Patients had a median age of 75 years; 156 patients had mild AD, 154 had moderate AD, and 18 had concomitant vascular dementia. Over the 3 years after randomisation, in patients who took aspirin, mean MMSE score was 0.10 points higher (95% CI -0.37 to 0.57; p=0.7) and mean BADLS score was 0.62 points lower (-1.37 
 to 0.13; p=0.11) than in patients assigned to aspirin avoidance. There were no obvious differences between the groups in any other outcome measurements. 13 (8%) patients on aspirin and two (1%) patients in the control group had bleeds that led to admission to hospital (relative risk=4.4, 95% CI 1.5-12.8; p=0.007); three (2%) patients in the aspirin group had fatal cerebral bleeds. INTERPRETATION: Although aspirin is commonly used in dementia, in patients with typical AD 2 years of treatment with low-dose aspirin has no worthwhile benefit and increases the risk of serious bleeds.
PMID: 18068522

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Message #32232
Date: Thu, 17 Dec 2009 21:17:39 -0800 (PST)
From: [email protected]
Subject: evidence based OTC treatment of Alzheimer's disease II

[The following lists mostly human intervention studies using items which I believe are available without a prescription in the USA. Spices which contain the peroxynitrite scavenger rosmarinic acid were found to be consistently and highly successful in the treatment of Alzheimer's disease.]

[An extract from saffron, the world's most expensive spice was slightly beneficial.]

Psychopharmacology (Berl). 2009 Oct 20. [Epub ahead of print]
A 22-week, multicenter, randomized, double-blind controlled trial of Crocus sativus in the treatment of mild-to-moderate Alzheimer's disease.
Akhondzadeh S, Shafiee Sabet M, Harirchian MH, Togha M, Cheraghmakani H, Razeghi S, Hejazi SS, Yousefi MH, Alimardani R, Jamshidi A, Rezazadeh SA, Yousefi A, Zare F, Moradi A, Vossoughi A. Psychiatric Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences, South Kargar Street, Tehran, 13337, Iran,
    RATIONALE: There is increasing evidence to suggest the possible efficacy of Crocus sativus (saffron) in the management of Alzheimer's disease (AD). OBJECTIVE: The purpose of the present investigation was to assess the efficacy of C. sativus in the treatment of patients with mild-to-moderate AD. METHODS: Fifty-four Persian-speaking adults 55 years of age or older who were living in the community were eligible to participate in a 22-week, double-blind study of parallel groups of patients with AD. The main efficacy measures were the change in the Alzheimer's Disease Assessment Scale-cognitive subscale and Clinical Dementia Rating Scale-Sums of Boxes scores compared with baseline. Adverse events (AEs) were systematically recorded. Participants were randomly assigned to receive a capsule sa
 ffron 30 mg/day (15 mg twice per day) or donepezil 10 mg/day (5 mg twice per day). RESULTS: Saffron at this dose was found to be effective similar to donepezil in the treatment of mild-to-moderate AD after 22 weeks. The frequency of AEs was similar between saffron extract and donepezil groups with the exception of vomiting, which occurred significantly more frequently in the donepezil group. CONCLUSION: This phase II study provides preliminary evidence of a possible therapeutic effect of saffron extract in the treatment of patients with mild-to-moderate Alzheimer's disease. This trial is registered with the Iranian Clinical Trials Registry (IRCT138711051556N1).
PMID: 19838862

[Omega-3 fatty acids are duds.]

Dement Geriatr Cogn Disord. 2009;27(5):481-90. Epub 2009 May 12.
Effects of omega-3 fatty acids on inflammatory markers in cerebrospinal fluid and plasma in Alzheimer's disease: the OmegAD study.
Freund-Levi Y, Hjorth E, Lindberg C, Cederholm T, Faxen-Irving G, Vedin I, Palmblad J, Wahlund LO, Schultzberg M, Basun H, Eriksdotter Jonhagen M. Department NVS, Division of Clinical Geriatrics, Karolinska University Hospital, Stockholm, Sweden.
    BACKGROUND: omega-3 fatty acids (omega-3 FAs) found in dietary fish or fish oils are anti-inflammatory agents that may influence Alzheimer's disease (AD). OBJECTIVE: To study the effects of dietary omega-3 FA supplementation on inflammatory markers in cerebrospinal fluid (CSF) and plasma from patients with mild to moderate AD. METHODS: Thirty-five patients (70.3 +/- 8.2 years) were randomized to a daily intake of 2.3 g omega-3 FAs or placebo for 6 months. The inflammatory markers interleukin (IL)-6, tumour necrosis factor-alpha and soluble interleukin-1 receptor type II (sIL-1RII) were analysed in CSF and plasma at baseline and at 6 months. The AD markers tau-protein, hyperphosphorylated tau-protein and beta-amyloid (Abeta(1-42)) were assessed in CSF. High-sensitivity C-reactive protei
 n was assessed in plasma. A possible relation to the APOE genotype was investigated. RESULTS: There was no significant treatment effect of omega-3 FAs on inflammatory and AD biomarkers in CSF or on inflammatory markers in plasma, nor was there any relation with APOE. A significant correlation was observed at baseline between sIL-1RII and Abeta(1-42) levels in CSF. CONCLUSIONS: Treatment of AD patients with omega-3 FAs for 6 months did not influence inflammatory or biomarkers in CSF or plasma. The correlation between sIL-1RII and Abeta(1-42) may reflect the reciprocal interactions between IL-1 and Abeta peptides.
PMID: 19439966

[A combination including acetylsalicylic acid, folic acid, and pyridoxine is a  dud.]

J Am Geriatr Soc. 2009 May;57(5):797-805.
Vascular care in patients with Alzheimer's disease with cerebrovascular lesions-a randomized clinical trial.
Richard E, Kuiper R, Dijkgraaf MG, Van Gool WA; Evaluation of Vascular care in Alzheimer's disease.
Collaborators (11)  Walstra GJ, Weinstein H, Scheltens P, Kwa VI, Claus J, Peetoom JJ, Kalisvaart K, Groen SP, Hafkamp GJ, de Bruijn SF, Eekhof JL. Academic Medical Centre, University of Amsterdam, Postbus 22660, Amsterdam 1100DD, The Netherlands.
    OBJECTIVES: To investigate whether vascular care slows dementia progression in patients with Alzheimer's disease with cerebrovascular lesions on neuroimaging. DESIGN: Multicenter randomized controlled clinical trial with 2-year follow-up. SETTING: Neurological and geriatric outpatient clinics in 10 Dutch hospitals: three academic, five teaching, and two midsize community hospitals. PARTICIPANTS: One hundred thirty community-dwelling patients with mild dementia fulfilling clinical criteria for Alzheimer's disease with cerebrovascular lesions on neuroimaging. INTERVENTION: Patients randomized to vascular care were treated according to strict guidelines for hypercholesterolemia and hypertension. Acetylsalicylic acid, folic acid, and pyridoxine were prescribed. During visits every 3 months
  special attention was paid to smoking cessation, losing weight, and stimulating physical exercise. MEASUREMENTS: Primary outcome was disability, measured according to the Interview for Deterioration in Daily activities in Dementia (IDDD). Secondary outcomes were changes on the Mini-Mental State Examination (MMSE), the Revised Memory and Behavioural Problems Checklist (RMBPC), a composite measure of "poor outcome" (death, institutionalization, or severe clinical decline), and costs. RESULTS: Patients in the vascular and standard care condition declined equally on the IDDD (13.7 vs 11.0 points; difference 2.7, 95% confidence interval = -3.1-8.6). There was no treatment effect on the MMSE or RMBPC. There were no differences in institutionalization rate, "poor outcome" (41.4% vs 35.4%, P=.5
 0), or costs. In the intervention group, there were three intracerebral hemorrhages and one gastrointestinal hemorrhage, versus none in the control group. CONCLUSION: Multicomponent vascular care, combining pharmacological and nonpharmacological interventions, does not slow decline in patients with Alzheimer's disease with cerebrovascular lesions.
PMID: 19484836

[Conflicting results with vitamin E.]

J Alzheimers Dis. 2009 May;17(1):143-9.
Vitamin E paradox in Alzheimer's disease: it does not prevent loss of cognition and may even be detrimental.
Lloret A, Badia MC, Mora NJ, Pallardo FV, Alonso MD, Vina J. Departamento de Fisiologia, Facultad de Medicina, University of Valencia, Valencia, Spain.
    There is controversy as to whether vitamin E is beneficial in Alzheimer's disease (AD). In this study, we tested if vitamin E prevents oxidative stress and loss of cognition in AD. Fifty-seven AD patients were recruited and divided in two groups: placebo or treated with 800 IU of vitamin E per day for six months. Of these 57 patients, only 33 finished the study. We measured blood oxidized glutathione (GSSG) and used the following cognitive tests: Mini-Mental State Examination, Blessed-Dementia Scale, and Clock Drawing Test. Of those patients treated with vitamin E, we found two groups. In the first group, "respondents" to vitamin E, GSSG levels were lower after the treatment and scores on the cognitive tests were maintained. The second group, "non-respondents", consisted of patients in
  which vitamin E was not effective in preventing oxidative stress. In these patients, cognition decreased sharply, to levels even lower than those of patients taking placebo. Based on our findings, it appears that vitamin E lowers oxidative stress in some AD patients and maintains cognitive status, however, in those in which vitamin E does not prevent oxidative stress, it is detrimental in terms of cognition. Therefore, supplementation of AD patients with vitamin E cannot be recommended without determination of its antioxidant effect in each patient.
PMID: 19494439

Alzheimers Dement. 2008 May;4(3):223-7. Epub 2008 Apr 21.
Better cognitive performance in elderly taking antioxidant vitamins E and C supplements in combination with nonsteroidal anti-inflammatory drugs: the Cache County Study.
Fotuhi M, Zandi PP, Hayden KM, Khachaturian AS, Szekely CA, Wengreen H, Munger RG, Norton MC, Tschanz JT, Lyketsos CG, Breitner JC, Welsh-Bohmer K. Department of Neurology, Johns Hopkins University School of Medicine, and Center for Memory and Brain Health, LifeBridge Health Brain & Spine Institute, Baltimore, MD, USA.
    Studies have shown less cognitive decline and lower risk of Alzheimer's disease in elderly individuals consuming either antioxidant vitamins or nonsteroidal anti-inflammatory drugs (NSAIDs). The potential of added benefit from their combined use has not been studied. We therefore analyzed data from 3,376 elderly participants of the Cache County Study who were given the Modified Mini-Mental State examination up to three times during a period of 8 years. Those who used a combination of vitamins E and C supplements and NSAIDs at baseline declined by an average 0.96 fewer points every 3 years than nonusers (P < .05). This apparent effect was attributable entirely to participants with the APOE epsilon4 allele, whose users declined by 2.25 fewer points than nonusers every 3 years (P < .05). 
 These results suggest that among elderly individuals with an APOE epsilon4 allele, there is an association between using antioxidant supplements in combination with NSAIDs and less cognitive decline over time.
PMID: 18631971
Free text: >
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2684982/?tool=pubmed

[Ibuprofen is a dud.]

Aging Clin Exp Res. 2009 Apr;21(2):102-10.
A randomized controlled study on effects of ibuprofen on cognitive progression of Alzheimer's disease.
Pasqualetti P, Bonomini C, Dal Forno G, Paulon L, Sinforiani E, Marra C, Zanetti O, Rossini PM. Medical Statistics & Information Technology, Fatebenefratelli Association for Research, Isola Tiberina, Rome, Italy.
    BACKGROUND AND AIMS: Epidemiological studies have examined the association between the use of non-steroidal anti-inflammatory drugs (NSAIDs) and the risk of Alzheimer's disease (AD). Recently, a variety of experimental studies indicates that a subset of NSAIDs, such as ibuprofen or flurbiprofen, also have Abeta-lowering properties in both AD transgenic mice and cell cultures of peripheral, glial and neuronal origin. In this trial, we evaluated whether the non-selective NSAID ibuprofen slows disease progression in patients with mild to moderate AD. METHODS: This was a 12-month multicenter, randomized, double-blind, placebo-controlled, parallel group trial. Participants with mild-moderate AD (Mini-Mental State Examination score >15, <26; Clinical Dementia Rating= 0.5-1), 65 years or olde
 r, with reliable caregivers, were recruited between April 2003 and September 2004. Seven AD Outpatient Treatment Centers screened 530 patients, 132 of whom were enrolled. Intervention consisted of 400 mg ibuprofen twice a day or placebo, together with 20 mg once a day of esomeprazol, or placebo. The primary measure was any one-year change in the Alzheimer Disease Assessment Scale- Cognitive (ADAS-Cog) subscale score. Secondary measures included changes in MMSE, CDR, Basic and Instrumental Activities of Daily Living scales, and Neuropsychiatric Inventory (NPI). RESULTS: Fifty-one patients (77%) in the ibuprofen vs 46 (70%) in the placebo group completed the protocol (p>0.20). In intention-to- treat analysis, ADAS-Cog score worsening was similar in the two groups (p=0.951, treatment differ
 ence= 0.1, CI -2.7; 2.9). No differences were found for any secondary outcomes. In a subsample of genotyped patients, ApoE epsilon4 carriers treated with ibuprofen (n=27) were the only group without significant cognitive decline. CONCLUSIONS: Ibuprofen, if used for relatively short periods of time and although well tolerated thanks to gastroprotection, does not seem to be effective in tertiary prevention of mild-moderate AD. Our results suggest the need to examine whether differences in the response to NSAIDs exist, based on ApoE epsilon4 carrier status.
PMID: 19448381

[A combination of folate, vitamin B12, alpha-tocopherol, S-adenosyl methionine, N-acetyl cysteine, and acetyl-L-carnitine is slightly beneficial.]

Am J Alzheimers Dis Other Demen. 2009 Feb-Mar;24(1):27-33. Epub 2008 Dec 3.
Efficacy of a vitamin/nutriceutical formulation for moderate-stage to later-stage Alzheimer's disease: a placebo-controlled pilot study.
Remington R, Chan A, Paskavitz J, Shea TB. Department of Nursing, University of Massachusetts Lowell, Lowell, Massachusetts, USA.
    Recent studies demonstrated efficacy of a vitamin/ nutriceutical formulation (folate, vitamin B12, alpha-tocopherol, S-adenosyl methionine, N-acetyl cysteine, and acetyl-L-carnitine) for mild to moderate Alzheimer's disease. Herein, we tested the efficacy of this formulation in a small cohort of 12 institutionalized patients diagnosed with moderate-stage to later-stage Alzheimer's disease. Participants were randomly separated into treatment of placebo groups. Participants receiving the formulation demonstrated a clinically significant delay in decline in the Dementia Rating Scale and clock-drawing test as compared to those receiving placebo. Institutional caregivers reported approximately 30% improvement in the Neuropyschiatric Inventory and maintenance of performance in the Alzheimer'
 s Disease Cooperative Study-Activities of Daily Living for more than 9 months. This formulation holds promise for delaying the decline in cognition, mood, and daily function that accompanies the progression of Alzheimer's disease, and may be particularly useful as a supplement for pharmacological approaches during later stages of this disorder. A larger trial is warranted.
PMID: 19056706

Am J Alzheimers Dis Other Demen. 2008 Dec-2009 Jan;23(6):571-85. Epub 2008 Dec 1.
Efficacy of a vitamin/nutriceutical formulation for early-stage Alzheimer's disease: a 1-year, open-label pilot study with an 16-month caregiver extension.
Chan A, Paskavitz J, Remington R, Rasmussen S, Shea TB. Center for Cell Neurobiology and Neurodegeneration Research, University of Massachusetts Lowell, MA, USA.
    We examined the efficacy of a vitamin/nutriceutical formulation (folate, vitamin B6, alpha-tocopherol, S-adenosyl methionine, N-acetyl cysteine, and acetyl-L-carnitine) in a 12-month, open-label trial with 14 community-dwelling individuals with early-stage Alzheimer's disease. Participants improved in the Dementia Rating Scale and Clock-drawing tests (Clox 1 and 2). Family caregivers reported improvement in multiple domains of the Neuropsychiatric Inventory (NPI) and maintenance of performance in the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADL). Sustained performance was reported by caregivers for those participants who continued in an 16-month extension. Performance on the NPI was equivalent to published findings at 3 to 6 months for donepezil and exceeded th
 at of galantamine and their historical placebos. Participants demonstrated superior performance for more than 12 months in NPI and ADL versus those receiving naproxen and rofecoxib or their placebo group. This formulation holds promise for treatment of early-stage Alzheimer's disease prior to and/or as a supplement for pharmacological approaches. A larger, placebo-controlled trial is warranted.
PMID: 19047474

[Vitamin B12 is a dud.]

Int Psychogeriatr. 2009 Feb;21(1):138-47. Epub 2008 Oct 17.
Cognitive and psychiatric effects of vitamin B12 replacement in dementia with low serum B12 levels: a nursing home study.
van Dyck CH, Lyness JM, Rohrbaugh RM, Siegal AP. Azheimer's Disease Research Unit, Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06510, USA.
    BACKGROUND: The aim of this study is to determine whether B12 replacement would ameliorate cognitive and psychiatric symptoms in elderly subjects with dementia and low serum B12 levels. METHODS: A test group (n = 28) of nursing home residents with low serum B12 levels (<250 pg/mL) and a matched comparison group (n = 28) with normal serum B12 levels (>300 pg/mL) were evaluated by blinded raters while the test group received intramuscular (IM) B12 replacement therapy. All subjects were assessed at baseline, 8 weeks, and 16 weeks with the Dementia Rating Scale, Brief Psychiatric Rating Scale, and Geriatric Depression Scale. RESULTS: Although B12 replacement produced significant improvement in hematologic and metabolic parameters, it yielded no significant effect on cognitive or psychiatri
 c variables. A few subjects evidenced notable individual treatment responses; however, these were not statistically more frequent than in the normal B12 group. CONCLUSIONS: These results suggest that B12 replacement is unlikely to benefit cognitive or psychiatric symptoms in the vast majority of elderly dementia patients with low serum B12 levels.
PMID: 18925978

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Message #32233
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Subject: evidence based OTC treatment of Alzheimer's disease I

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