X-Message-Number: 32232
Date: Thu, 17 Dec 2009 21:17:39 -0800 (PST)
From: 
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 saffron 
    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 protein 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=.50), 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 
    older, 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 
    difference= 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 that 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 psychiatric 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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