X-Message-Number: 29312
Date: Thu, 15 Mar 2007 10:42:11 -0800 (PST)
From: 
Subject: reversing Alzheimer's

[Combination therapy may be able to partially reverse dementia now.]

Am J Alzheimers Dis Other Demen. 2005 Jan-Feb;20(1):21-6.
Integrated treatment approach improves cognitive function in demented and
clinically depressed patients.
Bragin V, Chemodanova M, Dzhafarova N, Bragin I, Czerniawski JL, Aliev
G. Stress Relief and Memory Training Center, Brooklyn, New York, USA.
    The purpose of this study was to evaluate the efficacy of an
integrative treatment approach on cognitive performance. The study sample
comprised 35 medically ill patients (20 male, 15 female) with an average
age of 71.05, who were diagnosed with mild dementia and depression. These
patients were evaluated at baseline and at six, 12, and 24 months of
treatment, which included antidepressants (sertraline, citalopram, or
venlafaxine XR, alone or in combination with bupropion XR),
cholinesterase inhibitors (donepezil, rivastigmine or galantamine), as
well as vitamins and supplements (multivitamins, vitamin E, alpha-lipoic
acid, omega-3 and coenzyme Q-10). Patients were encouraged to modify
their diet and lifestyle and perform mild physical exercises. Results
show that the integrative treatment not only protracted cognitive decline
for 24 months but even improved cognition, especially memory and frontal
lobe functions.
PMID: 15751450

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

Arch Neurol. 2006 Oct;63(10):1402-8.
Omega-3 fatty acid treatment in 174 patients with mild to moderate
Alzheimer disease: OmegAD study: a randomized double-blind trial.
Freund-Levi Y, Eriksdotter-Jonhagen M, Cederholm T, Basun H, Faxen-Irving
G, Garlind A, Vedin I, Vessby B, Wahlund LO, Palmblad J. Department of
Neurobiology, Caring Sciences and Society, Section of Clinical
Geriatrics, Karolinska University Hospital Huddinge, Stockholm.
    BACKGROUND: Epidemiologic and animal studies have suggested that
dietary fish or fish oil rich in omega-3 fatty acids, for example,
docosahexaenoic acid and eicosapentaenoic acid, may prevent Alzheimer
disease (AD). OBJECTIVE: To determine effects of dietary omega-3 fatty
acid supplementation on cognitive functions in patients with mild to
moderate AD. DESIGN: Randomized, double-blind, placebo-controlled
clinical trial. PARTICIPANTS: Two hundred four patients with AD (age
range [mean +/- SD], 74 +/- 9 years) whose conditions were stable while
receiving acetylcholine esterase inhibitor treatment and who had a
Mini-Mental State Examination (MMSE) score of 15 points or more were
randomized to daily intake of 1.7 g of docosahexaenoic acid and 0.6 g of
eicosapentaenoic acid (omega-3 fatty acid-treated group) or placebo for 6
months, after which all received omega-3 fatty acid supplementation for 6
months more. MAIN OUTCOME MEASURES: The primary outcome was cognition
measured with the MMSE and the cognitive portion of the Alzheimer Disease
Assessment Scale. The secondary outcome was global function as assessed
with the Clinical Dementia Rating Scale; safety and tolerability of
omega-3 fatty acid supplementation; and blood pressure
determinations. RESULTS: One hundred seventy-four patients fulfilled the
trial. At baseline, mean values for the Clinical Dementia Rating Scale,
MMSE, and cognitive portion of the Alzheimer Disease Assessment Scale in
the 2 randomized groups were similar. At 6 months, the decline in
cognitive functions as assessed by the latter 2 scales did not differ
between the groups. However, in a subgroup (n = 32) with very mild
cognitive dysfunction (MMSE >27 points), a significant (P<.05) reduction
in MMSE decline rate was observed in the omega-3 fatty acid-treated group
compared with the placebo group. A similar arrest in decline rate was
observed between 6 and 12 months in this placebo subgroup when receiving
omega-3 fatty acid supplementation. The omega-3 fatty acid treatment was
safe and well tolerated. CONCLUSIONS: Administration of omega-3 fatty acid
in patients with mild to moderate AD did not delay the rate of cognitive
decline according to the MMSE or the cognitive portion of the Alzheimer
Disease Assessment Scale. However, positive effects were observed in a
small group of patients with very mild AD (MMSE >27 points).
PMID: 17030655

Nutr Neurosci. 2003 Jun;6(3):153-62.
Blueberry supplementation enhances signaling and prevents behavioral
deficits in an Alzheimer disease model.
Joseph JA, Denisova NA, Arendash G, Gordon M, Diamond D, Shukitt-Hale B,
Morgan D. USDA-HNRCA at Tufts University, 711 Washington Street, Boston,
MA 02111, USA.
    Previously, we showed that blueberry (BB) supplementation reversed
the deleterious effects of aging on motor behavior and neuronal signaling
in senescent rodents. We now report that BB-fed (from 4 months of
age) APP + PS1 transgenic mice showed no deficits in Y-maze performance
(at 12 months of age) with no alterations in amyloid beta burden. It
appeared that the protective mechanisms are derived from BB-induced
enhancement of memory-associated neuronal signaling (e.g. extracellular
signal-regulated kinase) and alterations in neutral
sphingomyelin-specific phospholipase C activity. Thus, our data indicate
for the first time that it may be possible to overcome genetic
predispositions to Alzheimer disease through diet.
PMID: 12793519

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 Alzheimer's disease.
PMID: 16945610

Neurobiol Aging. 2005 Dec;26 Suppl 1:133-6. Epub 2005 Nov 2.
Prevention of Alzheimer's disease: Omega-3 fatty acid and phenolic
anti-oxidant interventions.
Cole GM, Lim GP, Yang F, Teter B, Begum A, Ma Q, Harris-White ME,
Frautschy SA. Greater Los Angeles Veterans Affairs Healthcare System,
Geriatric Research, Education and Clinical Center, Sepulveda, CA 91343,
USA.
    Alzheimer's disease (AD) and cardiovascular disease (CVD) are
syndromes of aging that share analogous lesions and risk factors,
involving lipoproteins, oxidative damage and inflammation. Unlike in CVD,
in AD, sensitive biomarkers are unknown, and high-risk groups are
understudied. To identify potential prevention strategies in AD, we have
focused on pre-clinical models (transgenic and amyloid infusion models),
testing dietary/lifestyle factors strongly implicated in reducing risk in
epidemiological studies. Initially, we reported the impact of
non-steroidal anti-inflammatory drugs (NSAIDs), notably ibuprofen, which
reduced amyloid accumulation, but suppressed few inflammatory markers and
without reducing oxidative damage. Safety concerns with chronic NSAIDs
led to a screen of alternative NSAIDs and identification of the phenolic
anti-inflammatory/anti-oxidant compound curcumin, the yellow pigment in
turmeric that we found targeted multiple AD pathogenic cascades. The
dietary omega-3 fatty acid, docosahexaenoic acid (DHA), also limited
amyloid, oxidative damage and synaptic and cognitive deficits in a
transgenic mouse model. Both DHA and curcumin have favorable
safety profiles, epidemiology and efficacy, and may exert general
anti-aging benefits (anti-cancer and cardioprotective.).
PMID: 16266772

J Neurosci. 2001 Nov 1;21(21):8370-7.
The curry spice curcumin reduces oxidative damage and amyloid pathology
in an Alzheimer transgenic mouse.
Lim GP, Chu T, Yang F, Beech W, Frautschy SA, Cole GM. Departments of
Medicine and Neurology, University of California, Los Angeles, Los
Angeles, California 90095, USA.
    Inflammation in Alzheimer's disease (AD) patients is characterized by
increased cytokines and activated microglia. Epidemiological studies
suggest reduced AD risk associates with long-term use of nonsteroidal
anti-inflammatory drugs (NSAIDs). Whereas chronic ibuprofen suppressed
inflammation and plaque-related pathology in an Alzheimer transgenic APPSw
mouse model (Tg2576), excessive use of NSAIDs targeting cyclooxygenase I
can cause gastrointestinal, liver, and renal toxicity. One alternative
NSAID is curcumin, derived from the curry spice turmeric. Curcumin has an
extensive history as a food additive and herbal medicine in India and is
also a potent polyphenolic antioxidant. To evaluate whether it could
affect Alzheimer-like pathology in the APPSw mice, we tested a low (160
ppm) and a high dose of dietary curcumin (5000 ppm) on inflammation,
oxidative damage, and plaque pathology. Low and high doses of curcumin
significantly lowered oxidized proteins and interleukin-1beta, a
proinflammatory cytokine elevated in the brains of these mice. With
low-dose but not high-dose curcumin treatment, the astrocytic marker GFAP
was reduced, and insoluble beta-amyloid (Abeta), soluble
Abeta, and plaque burden were significantly decreased by 43-50%. However,
levels of amyloid precursor (APP) in the membrane fraction were not
reduced. Microgliosis was also suppressed in neuronal layers but not
adjacent to plaques. In view of its efficacy and apparent low toxicity,
this Indian spice component shows promise for the prevention of
Alzheimer's disease.
PMID: 11606625

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