More Calories More AD
Ian Goddard
Thanks to Paula Mychack for findings this new study. Below
it I've included an abstract to a related review cited in my
caloric-restriction report -> http://www.IanGoddard.net/cr.htm
Archives of Neurology, 2002 Aug;59(8):1258-63
Caloric intake and the risk of Alzheimer disease.
Luchsinger JA, Tang MX, Shea S, Mayeux R.
Gertrude H. Sergievsky Center, Columbia University, PH-19, 630 W 168th
St, New York, NY 10032. rp...@columbia.edu
BACKGROUND: Diet may play a role in Alzheimer disease (AD). OBJECTIVE:
To examine the association between caloric intake and AD. METHODS:
Elderly individuals free of dementia at baseline (N = 980) were
followed for a mean of 4 years. Daily intake of calories, carbo-
hydrates, fats, and protein were recalled using a semiquantitative
food frequency questionnaire administered between the baseline and
first follow-up visits. Proportional hazards models were used to
examine the associations of quartiles of intake and incident AD,
adjusting for confounders. RESULTS: There were 242 incident cases
of AD during 4023 years of follow-up (6 cases per 100 person-years).
Compared with individuals in the lowest quartile of caloric intake,
those in the highest quartile had an increased risk of AD (hazard
ratio, 1.5; 95% confidence interval [CI], 1.0-2.2). Among individuals
with the apolipoprotein E epsilon4 allele, the hazard ratios of AD
for the highest quartiles of calorie and fat intake were 2.3 (95% CI,
1.1-4.7) and 2.3 (95% CI, 1.1-4.9), respectively, compared with the
lowest quartiles. The hazard ratios of AD for the highest quartiles
of calorie and fat intake compared with the lowest quartiles in
individuals without the apolipoprotein E epsilon4 allele were close
to 1 and were not statistically significant (P =.83 and P =.61,
respectively). CONCLUSION: Higher intake of calories and fats may be
associated with higher risk of AD in individuals carrying the
apolipoprotein E epsilon4 allele.
PMID: 12164721 [PubMed - in process]
*********************************************************************
Annals of the New York Academy of Sciences, 2000;924:153-9
Existing data suggest that Alzheimer's disease is preventable.
Mattson MP.
Laboratory of Neurosciences, National Institute on Aging, 5600 Nathan
Shock Drive, Baltimore, Maryland 21224, USA. matt...@grc.nia.nih.gov
The ultimate goal of Alzheimer's disease (AD) research is to
prevent the onset of the neurodegenerative process and thereby allow
successful aging without cognitive decline. Herein I argue that a
simple and effective preventative approach for AD may be in hand. AD
is a disorder associated with the aging process and is, accordingly,
characterized by cellular and molecular changes that occur in
age-related diseases in other organ systems. Such changes include
increased levels of oxidative stress, perturbed energy metabolism,
and accumulation of insoluble (oxidatively modified) proteins
(prominent among which are amyloid beta-peptide and tau). The risk
of several other prominent age-related disorders, including
cardiovascular disease, cancer, and diabetes, is known to be
influenced by the level of food intake--high food intake increases
risk, and low food intake reduces risk. An overwhelming body of data
from studies of rodents and monkeys has documented the profound
beneficial effects of dietary restriction (DR) in extending life span
and reducing the incidence of age-related diseases. Reduced levels of
cellular oxidative stress and enhancement of energy homeostasis
contribute to the beneficial effects of DR. Recent findings suggest
that DR may enhance resistance of neurons in the brain to metabolic,
excitotoxic, and oxidative insults relevant to the pathogenesis of AD
and other neurodegenerative disorders. While further studies will be
required to establish the extent to which DR will reduce the incidence
of AD, it would seem prudent (based on existing data) to recommend DR
as widely applicable preventative approach for age-related disorders
including neurodegenerative disorders.
Publication Types:
Review
Review Literature
PMID: 11193791 [PubMed - indexed for MEDLINE]
"To lengthen thy life, lessen thy meals." Benjamin Franklin
Caloric Restriction: http://users.erols.com/igoddard/cr.htm
Ongoing CR-monkey-study update: "In the monkeys...those on
reduced feeding since the study started are dying at a rate
that is about half that of the monkeys receiving a full food
ration." Associated Press: Eating less may extend human life.
August 1, 2002 : http://www.msnbc.com/news/788746.asp?0si=-
Ian Goddard
Here's an AP report with more details on PMID 12164721 (also see:
http://www.washingtonpost.com/wp-dyn/articles/A18077-2002Aug14.html )
High Fats May Boost Alzheimer's Risk
By Lindsey Tanner
AP Medical Writer
Wednesday, August 14, 2002; 4:05 PM
CHICAGO A diet high in calories and fat may increase the
risk of Alzheimer's disease in people who are genetically
susceptible to the mind-robbing disorder, new research suggests.
The study found that people who consumed the most calories
and fat faced double the risk of developing Alzheimer's.
The findings, which are reported in this month's Archives
of Neurology, are the latest evidence that lifestyle factors
including diet may play a role in Alzheimer's.
Some researchers believe that restricting calories may slow
the aging process by reducing production of cell-damaging
oxygen molecules called free radicals, formed during the
body's breakdown of food. The latest study, though preliminary,
suggests that for some people, calorie restriction might lower
Alzheimer's risks by curbing nerve-cell death in the brain.
Lead author Dr. Jose Luchsinger, an Alzheimer's researcher at
Columbia University, said it would be premature to recommend
specific diets for reducing Alzheimer's risks.
Study participants whose diets increased the risk had one or
two copies of the apolipoprotein-E gene variant known as apoE
e-4. People with the e-4 variant are thought to be already
prone to the disease.
About 20 percent of the U.S. population has one copy and even
fewer have two, said William Thies, vice president of medical
and scientific affairs for the Alzheimer's Association. In the
study, 28 percent of participants had one or two copies of the
variant.
The gene is involved in transporting cholesterol in the blood.
Not everyone with the e-4 variant develops the disease, and
the study suggests that diet may influence which people with
the variant become afflicted, Thies said.
A study published in the same journal earlier this year linked
high cholesterol levels with Alzheimer's and suggested that
cholesterol-lowering drugs could reduce the risk. That research
did not examine whether a low-fat diet would achieve the same
results.
The new study involved 980 Medicare patients aged 75 on average
in New York who were asked to recall their food intake during
the first year of the four-year study. They also underwent
annual exams.
Alzheimer's was diagnosed during the study in 242 people.
Patients with the gene variant who reported the highest
consumption of fats and calories faced double the risk of
developing Alzheimer's, compared with those who reported the
lowest amounts.
Because the average reported daily amounts were quite low
about 1,300 calories and 38 grams of fat Luchsinger said the
overall trend is much more significant than the actual amounts.
The lowest reported amounts about 758 calories daily and 16
grams of fat likely would be considered unhealthful for many
people and should not be used as a blueprint for avoiding
Alzheimer's, he said.
Luchsinger said it's possible that some participants had
faulty memories and inaccurately reported their food intake,
while others may have even started developing undetected
Alzheimer's that could have influenced their memories or
food choices.
Still, he said the study "certainly points in a direction"
favoring the diet theory.
Thies said the findings suggest fats may play some sort of
role in Alzheimer's that needs more study. But he also said
the study is in line with general recommendations for a healthy
diet avoiding overeating and too many fat-rich foods.
Mary Gordon
would consequently be fatter than average - and I haven't personally
been struck by the prevelence of obese seniors with dementia, even
among those I've met in early dementia.
If instead of larger total caloric intake, it was being suggested that
the risk was related to taking in bigger proportion of calories from
fats vs. carbs I might be more inclined to think there was something
in this.
My MIL never weighed more than 130 in her whole life, and she
certainly did not consume a high calorie or high fat diet - and she
was quite sedentary, so its not like she was chowing down and burning
it off with exercise.
Clearly a whole lot more to the story than just eating too much, or
eating too much fat.
Mary G.
Ian Goddard
http://groups.google.com/groups?selm=3d5b0c65.105293614%40news.erols.com
In addition to studies cited in my caloric restriction (CR)
report ( http://iangoddard.net/cr.htm See refs 26-30 & 31-34)
finding neuroprotective effects of CR in animals, the following
abstracts present further evidence pointing to possible causal
mechanisms of CR-induced neuroprotection, and another review.
The hippocampus is a primary target of Alzheimer's disease (AD).
[1] found that caloric restriction reduced damage to hippocampal
neurons in mice bread with an AD-like mutation. "Some cases of AD
are caused by mutations in presenilin-1 (PS1) ... [CR] completely
counteracted the endangering effect of the PS1 mutation."
[2] found that CR "increases resistance of the brain to insults"
similar to those found in neurodegenerative disorders such as AD.
[3] found that CR increases the growth of new cells (neurogenesis)
in the dentate gyrus of the hippocampus, a primary target of AD.
[4] also found that CR increases neurogenesis in the hippocampus.
[5] is an abstract to a review by Mark Mattson, an NIH scientist
who concludes: "Collectively, the available data suggest the that
dietary restriction, and physical and mental activity, may reduce
both the incidence and severity of neurodegenerative disorders in
humans." Another review by Mattson was cited in my previous post:
http://groups.google.com/groups?selm=3d5b0c65.105293614%40news.erols.com
*************************************************************************
[1] Brain Res 1999 Sep 18;842(1):224-9
Dietary restriction protects hippocampal neurons against the
death-promoting action of a presenilin-1 mutation.
Zhu H, Guo Q, Mattson MP.
Department of Anatomy and Neurobiology, Sanders-Brown Research Center
on Aging, University of Kentucky, 211 Sanders-Brown Building, 800
South Limestone Street, Lexington, KY 40536, USA.
Alzheimer's disease (AD) is an age-related disorder that involves
degeneration of synapses and neurons in brain regions involved in
learning and memory processes. Some cases of AD are caused by
mutations in presenilin-1 (PS1), an integral membrane protein located
in the endoplasmic reticulum. Previous studies have shown that PS1
mutations increase neuronal vulnerability to excitotoxicity and
apoptosis. Although dietary restriction (DR) can increase lifespan and
reduce the incidence of several age-related diseases in rodents, the
possibility that DR can modify the pathogenic actions of mutations
that cause AD has not been examined. The vulnerability of hippocampal
neurons to excitotoxic injury was increased in PS1 mutant knockin
mice. PS1 mutant knockin mice and wild-type mice maintained on a DR
regimen for 3 months exhibited reduced excitotoxic damage to
hippocampal CA1 and CA3 neurons compared to mice fed ad libitum; the
DR regimen completely counteracted the endangering effect of the PS1
mutation. The magnitude of increase in levels of the lipid
peroxidation product 4-hydroxynonenal following the excitotoxic insult
was lower in DR mice compared to mice fed ad libitum, suggesting that
suppression of oxidative stress may be one mechanism underlying the
neuroprotective effect of DR. These findings indicate that the
neurodegeneration-promoting effect of an AD-linked mutation is subject
to modification by diet.
PMID: 10526115 [PubMed - indexed for MEDLINE]
*********************************************************************
[2] Ann Neurol 1999 Jan;45(1):8-15
Food restriction reduces brain damage and improves behavioral outcome
following excitotoxic and metabolic insults.
Bruce-Keller AJ, Umberger G, McFall R, Mattson MP.
Sanders-Brown Research Center on Aging, Department of Anatomy and
Neurobiology, University of Kentucky, Lexington 40536-0230, USA.
Food restriction (FR) in rodents is known to extend life span, reduce
the incidence of age-related tumors, and suppress oxidative damage to
proteins, lipids, and DNA in several organ systems. Excitotoxicity
and mitochondrial impairment are believed to play major roles in the
neuronal degeneration and death that occurs in the brains of patients
suffering from both acute brain insults such as stroke and seizures,
and chronic neurodegenerative conditions such as Alzheimer's,
Parkinson's, and Huntington's diseases. We now report that FR
(alternate-day feeding regimen for 2-4 months) in adult rats results
in resistance of hippocampal neurons to excitotoxin-induced
degeneration, and of striatal neurons to degeneration induced by the
mitochondrial toxins 3-nitropropionic acid and malonate. FR greatly
increased the resistance of rats to kainate-induced deficits in
performance in water-maze learning and memory tasks, and to
3-nitropropionic acid-induced impairment of motor function. These
findings suggest that FR not only extends life span, but increases
resistance of the brain to insults that involve metabolic compromise
and excitotoxicity.
PMID: 9894871 [PubMed - indexed for MEDLINE]
*********************************************************************
[3] J Mol Neurosci 2000 Oct;15(2):99-108
Dietary restriction increases the number of newly generated neural
cells, and induces BDNF expression, in the dentate gyrus of rats.
Lee J, Duan W, Long JM, Ingram DK, Mattson MP.
Laboratory of Neurosciences, Gerontology Research Center, National
Institute on Aging, Baltimore, MD 21224, USA.
The adult brain contains neural stem cells that are capable of
proliferating, differentiating into neurons or glia, and then either
surviving or dying. This process of neural-cell production
(neurogenesis) in the dentate gyrus of the hippocampus is responsive
to brain injury, and both mental and physical activity. We now report
that neurogenesis in the dentate gyrus can also be modified by diet.
Previous studies have shown that dietary restriction (DR) can suppress
age-related deficits in learning and memory, and can increase
resistance of neurons to degeneration in experimental models of
neurodegenerative disorders. We found that maintenance of adult rats
on a DR regimen results in a significant increase in the numbers of
newly produced neural cells in the dentate gyrus of the hippocampus,
as determined by stereologic analysis of cells labeled with the DNA
precursor analog bromodeoxyuridine. The increase in neurogenesis in
rats maintained on DR appears to result from decreased death of newly
produced cells, rather than from increased cell proliferation. We
further show that the expression of brain-derived neurotrophic factor,
a trophic factor recently associated with neurogenesis, is increased
in hippocampal cells of rats maintained on DR. Our data are the first
evidence that diet can affect the process of neurogenesis, as well as
the first evidence that diet can affect neurotrophic factor
production. These findings provide insight into the mechanisms whereby
diet impacts on brain plasticity, aging and neurodegenerative
disorders.
PMID: 11220789 [PubMed - indexed for MEDLINE]
*********************************************************************
[4] J Neurochem 2002 Feb;80(3):539-47
Dietary restriction enhances neurotrophin expression and neurogenesis
in the hippocampus of adult mice.
Lee J, Seroogy KB, Mattson MP.
Laboratory of Neurosciences, National Institute on Aging Gerontology
Research Center Baltimore, Maryland 21224, USA.
The adult brain contains small populations of neural precursor cells
(NPC) that can give rise to new neurons and glia, and may play
important roles in learning and memory, and recovery from injury.
Growth factors can influence the proliferation, differentiation and
survival of NPC, and may mediate responses of NPC to injury and
environmental stimuli such as enriched environments and physical
activity. We now report that neurotrophin expression and neurogenesis
can be modified by a change in diet. When adult mice are maintained on
a dietary restriction (DR) feeding regimen, numbers of newly generated
cells in the dentate gyrus of the hippocampus are increased,
apparently as the result of increased cell survival. The new cells
exhibit phenotypes of neurons and astrocytes. Levels of expression of
brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) are
increased by DR, while levels of expression of high-affinity receptors
for these neurotrophins (trkB and trkC) are unchanged. In addition, DR
increases the ratio of full-length trkB to truncated trkB in the
hippocampus. The ability of a change in diet to stimulate neurotrophin
expression and enhance neurogenesis has important implications for
dietary modification of neuroplasticity and responses of the brain to
injury and disease.
PMID: 11905999 [PubMed - indexed for MEDLINE]
*********************************************************************
[5] Brain Res 2000 Dec 15;886(1-2):47-53
Neuroprotective signaling and the aging brain: take away my food and
let me run.
Mattson MP.
Laboratory of Neurosciences, National Institute on Aging Gerontology
Research Center, 5600 Nathan Shock Drive, 21224-6825, Baltimore, MD,
USA. matt...@grc.nia.nih.gov
It is remarkable that neurons are able to survive and function for
a century or more in many persons that age successfully. A better
understanding of the molecular signaling mechanisms that permit such
cell survival and synaptic plasticity may therefore lead to the
development of new preventative and therapeutic strategies for
age-related neurodegenerative disorders. We all know that overeating
and lack of exercise are risk factors for many different age-related
diseases including cardiovascular disease, diabetes and cancers. Our
recent studies have shown that dietary restriction (reduced calorie
intake) can increase the resistance of neurons in the brain to
dysfunction and death in experimental models of Alzheimer's disease,
Parkinson's disease, Huntington's disease and stroke. The mechanism
underlying the beneficial effects of dietary restriction involves
stimulation of the expression of 'stress proteins' and neurotrophic
factors. The neurotrophic factors induced by dietary restriction may
protect neurons by inducing the production of proteins that suppress
oxyradical production, stabilize cellular calcium homeostasis and
inhibit apoptotic biochemical cascades. Interestingly, dietary
restriction also increases numbers of newly-generated neural cells in
the adult brain suggesting that this dietary manipulation can increase
the brain's capacity for plasticity and self-repair. Work in other
laboratories suggests that physical and intellectual activity can
similarly increase neurotrophic factor production and neurogenesis.
Collectively, the available data suggest the that dietary restriction,
and physical and mental activity, may reduce both the incidence and
severity of neurodegenerative disorders in humans. A better
understanding of the cellular and molecular mechanisms underlying
these effects of diet and behavior on the brain is also leading to
novel therapeutic agents that mimick the beneficial effects of dietary
restriction and exercise.
Publication Types:
Review
Review, Tutorial
PMID: 11119686 [PubMed - indexed for MEDLINE]
*********************************************************************
michelle
I Think this is a load of rubbish.My Mother has been dogged most of
her life into dieting.My Family has always been prone to excess
weight.This has certainly not stopped the invasion of frontal Lobe
Dementia or Alzheimers combined.
Kind Regards
Michelle
> Mary G.
Evelyn Ruut
"michelle" <kris...@hotmail.com> wrote in message
news:339475ae.02081...@posting.google.com...
Dear Michelle and Mary,
Yes, I agree with you about it being rubbish. Ida was
always slender and never really overweight. When she
became ill with AD she began to lose weight because she
forgot how to cook and to shop etc.
She gained some of that lost weight back when she came to
live with us and is still at a very good weight right now.
OTOH, my father, who is 89 (7 years older than Ida) is as
sharp and clear minded now as he ever was. He has lost not
an iota of his mental clarity, and he has battled weight for
years.....(successfully, I might add....unlike me).
Best Regards,
Evelyn
michaelprice
most effective prophylactic against AD. Numerous studies support this.
A search on PubMed for folate and alzheimers yields over 50 hits.
The cognitive-protective effect of the B-vitamins seems independent
of their homcysteine-lowering effect (see last 2 studies)
[41a] Serum folate and the severity of atrophy of the neocortex in Alzheimer
disease: findings from the Nun study. DA Snowdon, CL Tully, CD Smith, KP
Riley, WR Markesbery in Am J Clin Nutr 2000 Apr;71(4):993-8
[41b] B vitamins, homocysteine, and neurocognitive function in the elderly.
Selhub J, Bagley LC, Miller J, Rosenberg IH in Am J Clin Nutr 2000
Feb;71(2):614S-620S.
[41c] Vitamin B(12) and folate in relation to the development of Alzheimer's
disease. Wang HX, Wahlin A, Basun H, Fastbom J, Winblad B, Fratiglioni L in
Neurology 2001 May 8;56(9):1188-94
[41d] Alzheimer disease: protective factors. Nourhashemi F,
Gillette-Guyonnet S, Andrieu S, Ghisolfi A, Ousset PJ, Grandjean H, Grand A,
Pous J, Vellas B, Albarede JL in Am J Clin Nutr 2000 Feb;71(2):643S-649S
[41e] Folates and prevention of disease. Molloy AM, Scott JM in Public
Health Nutr 2001 Apr;4(2B):601-9
[41f] Alzheimer's disease: insights from epidemiology. McDowell I in Aging
(Milano) 2001 Jun;13(3):143-62
[56] Effect of vitamin and trace-element supplementation on cognitive
function in elderly subjects by Chandra RK in Nutrition 2001
Sep;17(9):709-12
"Cognitive functions improved after oral supplementation with modest amounts
of vitamins and trace elements. This has considerable clinical and public
health significance. We recommend that such a supplement be provided to all
elderly subjects because it should significantly improve cognition and thus
quality of life and the ability to perform activities of daily living. Such
a nutritional approach may delay the onset of Alzheimer's disease."
[79a] Elevated plasma homocysteine levels in centenarians are not associated
with cognitive impairment. Ravaglia G, Forti P, Maioli F, Vettori C, Grossi
G, Bargossi AM, Caldarera M, Franceschi C, Facchini A, Mariani E, Cavalli G
in Mech Ageing Dev 2000 Dec 20;121(1-3):251-61
[79b] Homocysteine, vitamin B6, and vascular disease in AD patients. Miller
JW, Green R, Mungas DM, Reed BR, Jagust WJ in Neurology 2002 May
28;58(10):1471-5
Cheers,
Michael C Price
John
amount of estrogen although I don't remember why and estrogen
mitigates against AD. I've also noticed that elderly people suffering
dementia are usually thin.
Dennis P. Harris
"michaelprice" <michae...@ntlworld.com> wrote:
> Folic acid
oh, now more single-cure nuts trolling the list. sorry, i'm
killfiling this thread. too many loonies responding. they must
have a network that alerts them when threads start touting a
"cure" so they can all pile on. next will be the iron nut.
sorry, i'm outta this one.
PLONK!
michaelprice
news:40b9e4c0.02081...@posting.google.com...
> One would think that a person with a higher calorie diet than
> average would consequently be fatter than average - and I
> haven't personally been struck by the prevelence of obese
> seniors with dementia, even among those I've met in early
> dementia.
Perhaps because obese seniors are pretty thin on the ground,
if I may put it like that....
> Mary G.
Cheers,
Michael C Price