X-Message-Number: 25963
Date: Sat, 2 Apr 2005 20:23:44 -0800 (PST)
From: Doug Skrecky <>
Subject: tips for avoiding dementia  (long)

[Blueberry, curry, fish, niacin, and red wine good.
Tofu bad for males.
Vitamin C & E useless alone, but helpful together.
Melatonin is a dud. ]

Public Health Nutr. 2004 Oct;7(7):959-63.
Mediterranean diet and cognitive decline.
OBJECTIVE: To investigate the possible role of diet in age-related
cognitive decline (ARCD) and cognitive impairment of both
degenerative (Alzheimer's disease, AD) and vascular (vascular
dementia, VaD) origin. DESIGN: Literature review. RESULTS: In an
elderly population of southern Italy with a typical Mediterranean
diet, high energy intake of monounsaturated fatty acids (MUFA)
appeared to be associated with a high level of protection against
ARCD. In addition, dietary fat and energy in the elderly seem to be
risk factors, while fish consumption and cereals are found to
reduce the prevalence of AD in European and North American
countries. Finally, the relative risk of dementia (AD and VaD) was
lower in the subjects of a French cohort who drank three or four
glasses of red wine each day compared with total abstainers.
CONCLUSION: Essential components of the Mediterranean diet--MUFA,
cereals and wine--seem to be protective against cognitive decline.
As such, dietary antioxidants and supplements, specific
macronutrients of the Mediterranean diet, oestrogens and
anti-inflammatory drugs may act synergistically with other
protective factors, opening up new therapeutic interventions for
cognitive decline.

Arch Neurol. 2003 Jul;60(7):940-6.
Consumption of fish and n-3 fatty acids and risk of incident
Alzheimer disease.
BACKGROUND: Dietary n-3 polyunsaturated fatty acids improve
brain functioning in animal studies, but there is limited study
of whether this type of fat protects against Alzheimer disease.
OBJECTIVE: To examine whether fish consumption and intake of
different types of n-3 fatty acids protect against Alzheimer
disease. DESIGN: Prospective study conducted from 1993 through
2000, of a stratified random sample from a geographically
defined community. Participants were followed up for an average
of 3.9 years for the development of Alzheimer disease. PATIENTS:
A total of 815 residents, aged 65 to 94 years, who were
initially unaffected by Alzheimer disease and completed a
dietary questionnaire on average 2.3 years before clinical
evaluation of incident disease. MAIN OUTCOME MEASURES: Incident
Alzheimer disease diagnosed in a structured neurologic
examination by means of standardized criteria. RESULTS: A total
of 131 sample participants developed Alzheimer disease.
Participants who consumed fish once per week or more had 60%
less risk of Alzheimer disease compared with those who rarely
or never ate fish (relative risk, 0.4; 95% confidence interval,
0.2-0.9) in a model adjusted for age and other risk factors.
Total intake of n-3 polyunsaturated fatty acids was associated
with reduced risk of Alzheimer disease, as was intake of
docosahexaenoic acid (22:6n-3). Eicosapentaenoic acid (20:5n-3)
was not associated with Alzheimer disease. The associations
remained unchanged with additional adjustment for intakes of
other dietary fats and of vitamin E and for cardiovascular
conditions. CONCLUSION: Dietary intake of n-3 fatty acids and
weekly consumption of fish may reduce the risk of incident
Alzheimer disease.

J Am Geriatr Soc. 2004 Apr;52(4):540-6
Alcohol intake and risk of dementia.
OBJECTIVES: To examine the association between intake of
alcoholic beverages and risk of Alzheimer's disease (AD) and
dementia associated with stroke (DAS) in a cohort of elderly
persons from New York City. DESIGN: Cohort study. SETTING: The
Washington Heights Inwood-Columbia Aging Project. PARTICIPANTS:
Nine hundred eighty community-dwelling individuals aged 65 and
older without dementia at baseline and with data on alcohol
intake recruited between 1991 and 1996 and followed annually.
MEASUREMENTS: Intake of alcohol was measured using a
semiquantitative food frequency questionnaire at baseline.
Subjects were followed annually, and incident dementia was
diagnosed using Diagnostic and Statistical Manual of Mental
Disorders, Fourth Edition, criteria and classified as AD or
DAS. RESULTS: After 4 years of follow-up, 260 individuals
developed dementia (199 AD, 61 DAS). After adjusting for age,
sex, apolipoprotein E (APOE)-epsilon 4 status, education, and
other alcoholic beverages, only intake of up to three daily
servings of wine was associated with a lower risk of AD (hazard
ratio=0.55, 95% confidence interval=0.34-0.89). Intake of
liquor, beer, and total alcohol was not associated with a lower
risk of AD. Stratified analyses by the APOE-epsilon 4 allele
revealed that the association between wine consumption and
lower risk of AD was confined to individuals without the
APOE-epsilon 4 allele. CONCLUSIONS: Consumption of up to three
servings of wine daily is associated with a lower risk of AD
in elderly individuals without the APOE epsilon-4 allele.

J Anti Aging Med. 2003;6(4):335-6.
Soy-induced brain atrophy?
Epidemiological research has demonstrated a positive correlation
between tofu consumption and brain atrophy in men. Because
correlation does not prove causation, correlation-based
hypotheses should be tested against the availability of possible
causal mechanisms. While it has been shown that the soy
phytoestrogen genistein inhibits neuroprotective functions in
cell cultures, recent in-vivo findings strengthen the case for
a possible causal mechanism of soy-induced neurodegeneration.
The author suggests possible responses to this data regarding
soy consumption.

J Am Coll Nutr. 2000 Apr;19(2):242-55
Brain aging and midlife tofu consumption.
OBJECTIVE: To examine associations of midlife tofu consumption
with brain function and structural changes in late life.
METHODS: The design utilized surviving participants of a
longitudinal study established in 1965 for research on heart
disease, stroke, and cancer. Information on consumption of
selected foods was available from standardized interviews
conducted 1965-1967 and 1971-1974. A 4-level composite intake
index defined "low-low" consumption as fewer than two servings
of tofu per week in 1965 and no tofu in the prior week in 1971.
Men who reported two or more servings per week at both
interviews were defined as "high-high" consumers. Intermediate
or less consistent "low" and "high" consumption levels were
also defined. Cognitive functioning was tested at the 1991-1993
examination, when participants were aged 71 to 93 years
(n = 3734). Brain atrophy was assessed using neuroimage (n = 574)
and autopsy (n = 290) information. Cognitive function data were
also analyzed for wives of a sample of study participants
(n = 502) who had been living with the participants at the time
of their dietary interviews. RESULTS: Poor cognitive test
performance, enlargement of ventricles and low brain weight were
each significantly and independently associated with higher
midlife tofu consumption. A similar association of midlife tofu
intake with poor late life cognitive test scores was also
observed among wives of cohort members, using the husband's
answers to food frequency questions as proxy for the wife's
consumption. Statistically significant associations were
consistently demonstrated in linear and logistic multivariate
regression models. Odds ratios comparing endpoints among
"high-high" with "low-low" consumers were mostly in the range
of 1.6 to 2.0. CONCLUSIONS: In this population, higher midlife
tofu consumption was independently associated with indicators
of cognitive impairment and brain atrophy in late life.

J Neurol Neurosurg Psychiatry. 2004 Aug;75(8):1093-9
Dietary niacin and the risk of incident Alzheimer's disease
and of cognitive decline.
BACKGROUND: Dementia can be caused by severe niacin
insufficiency, but it is unknown whether variation in intake
of niacin in the usual diet is linked to neurodegenerative
decline. We examined whether dietary intake of niacin was
associated with incident Alzheimer's disease (AD) and cognitive
decline in a large, prospective study. METHODS: This study was
conducted in 1993-2002 in a geographically defined Chicago
community of 6158 residents aged 65 years and older. Nutrient
intake was determined by food frequency questionnaire. Four
cognitive tests were administered to all study participants at
3 year intervals in a 6 year follow up. A total of 3718
participants had dietary data and at least two cognitive
assessments for analyses of cognitive change over a median
5.5 years. Clinical evaluations were performed on a stratified
random sample of 815 participants initially unaffected by AD,
and 131 participants were diagnosed with 4 year incident AD by
standardised criteria. RESULTS: Energy adjusted niacin intake
had a protective effect on development of AD and cognitive
decline. In a logistic regression model, relative risks (95%
confidence intervals) for incident AD from lowest to highest
quintiles of total niacin intake were: 1.0 (referent) 0.3
(0.1 to 0.6), 0.3 (0.1 to 0.7), 0.6 (0.3 to 1.3), and 0.3
(0.1 to 0.7) adjusted for age, sex, race, education, and ApoE
e4 status. Niacin intake from foods was also inversely
associated with AD (p for linear trend = 0.002 in the adjusted
model). In an adjusted random effects model, higher food intake
of niacin was associated with a slower annual rate of cognitive
decline, by 0.019 standardised units (SU) per natural log
increase in intake (mg) (p = 0.05). Stronger associations were
observed in analyses that excluded participants with a history
of cardiovascular disease (beta = 0.028 SU/year; p = 0.008),
those with low baseline cognitive scores (beta = 0.023 SU/year;
p = 0.02), or those with fewer than 12 years' education
(beta = 0.035 SU/year; p = 0.002) CONCLUSION: Dietary niacin
may protect against AD and age related cognitive decline.

Arch Neurol. 2004 Jan;61(1):82-8
Reduced risk of Alzheimer disease in users of antioxidant
vitamin supplements: the Cache County Study.
BACKGROUND: Antioxidants may protect the aging brain against
oxidative damage associated with pathological changes of
Alzheimer disease (AD). OBJECTIVE: To examine the relationship
between antioxidant supplement use and risk of AD. DESIGN:
Cross-sectional and prospective study of dementia. Elderly
(65 years or older) county residents were assessed in 1995 to
1997 for prevalent dementia and AD, and again in 1998 to 2000
for incident illness. Supplement use was ascertained at the
first contact. SETTING: Cache County, Utah. PARTICIPANTS: Among
4740 respondents (93%) with data sufficient to determine
cognitive status at the initial assessment, we identified 200
prevalent cases of AD. Among 3227 survivors at risk, we
identified 104 incident AD cases at follow-up. MAIN OUTCOME
MEASURE: Diagnosis of AD by means of multistage assessment
procedures. RESULTS: Analyses of prevalent and incident AD
yielded similar results. Use of vitamin E and C (ascorbic acid)
supplements in combination was associated with reduced AD
prevalence (adjusted odds ratio, 0.22; 95% confidence interval,
0.05-0.60) and incidence (adjusted hazard ratio, 0.36; 95%
confidence interval, 0.09-0.99). A trend toward lower AD risk
was also evident in users of vitamin E and multivitamins
containing vitamin C, but we saw no evidence of a protective
effect with use of vitamin E or vitamin C supplements alone,
with multivitamins alone, or with vitamin B-complex supplements.
CONCLUSIONS: Use of vitamin E and vitamin C supplements in
combination is associated with reduced prevalence and incidence
of AD. Antioxidant supplements merit further study as agents
for the primary prevention of AD.

J Neurosci. 2001 Nov 1;21(21):8370-7
The curry spice curcumin reduces oxidative damage and amyloid
pathology in an Alzheimer transgenic mouse.
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.

Nutr Neurosci. 2003 Jun;6(3):153-62.
Blueberry supplementation enhances signaling and prevents
behavioral deficits in an Alzheimer disease model.
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 s
phingomyelin-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.

J Alzheimers Dis. 2004 Aug;6(4):403-11; discussion 443-9.
Fruit extracts antagonize Abeta- or DA-induced deficits in
Ca2+ flux in M1-transfected COS-7 cells.
Evidence suggests that there is a selective sensitivity to
oxidative stress (OSS) among muscarinic receptor (MAChR) subtypes
with M1, M2 and M4 showing > OSS than M3 or M5 subtypes in
transfected COS-7 cells. This may be important in determining the
regional specificity in neuronal aging and Alzheimer disease (AD).
We assessed the effectiveness of blueberry (BB) and other high
antioxidant (HA) fruit extracts (boysenberry, BY; cranberry, CB;
black currant, BC; strawberry, SB; dried plums, DP; and grape, GR)
on the toxic effects of Abeta 25-35 (100 microM, 24 hrs) and DA
(1 mM, 4 hrs) on calcium buffering (Recovery) following
oxotremorine (750 microM) -induced depolarization in
M1AChR-transfected COS-7 cells, and on cell viability following
DA (4 hrs) exposure. The extracts showed differential levels of
Recovery protection in comparisons to the non-supplemented
controls that was dependent upon whether DA or Abeta was used as
the pretreatment. Interestingly, assessments of DA-induced
decrements in viability revealed that all of the extracts had
some protective effects. These findings suggest that the putative
toxic effects of Abeta or DA might be reduced by HA fruit extracts.

Brain Res. 2005 Mar 10;1037(1-2):209-13
Chronic melatonin therapy fails to alter amyloid burden or
oxidative damage in old Tg2576 mice: implications for clinical
Melatonin has been proposed as a treatment for Alzheimer's
disease based on the demonstration of antioxidant and
"anti-amyloid" effects in vitro and in vivo. Chronic melatonin
therapy in old, amyloid plaque-bearing transgenic mice was
studied. Tg2576 mice started melatonin treatment at 14 months
of age. After 4 months of treatment, there were no differences
between untreated and melatonin-treated mice in cortical levels
of soluble, formic acid extracted, or histologically detectable
beta amyloid (Abeta), nor in brain levels of lipid peroxidation
product (total 8,12-isoprostane F(2alpha)-VI), despite marked
elevations in plasma melatonin. We conclude that melatonin fails
to produce anti-amyloid or antioxidant effects when initiated
after the age of amyloid plaque deposition. These findings
diminish the possibility that melatonin will be useful for the
treatment of established Alzheimer's disease.

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