X-Message-Number: 32229
Date: Thu, 17 Dec 2009 21:21:21 -0800 (PST)
From: 
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 patients 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) and 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. After 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 officinalis 
    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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