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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