"Diet can have a very significant impact on some of the pathological markers of Alzheimer's disease. I think we're starting to see in epidemiologic studies a connection between diet and brain aging, but I think our study is the first that has really shown, in an experimental fashion, that by creating a very carefully controlled diet you could show these very significant effects."
-Suzanne Craft, PhD, associate director of the Geriatric Research and Clinical Center at the Veterans Affairs Puget Sound Health Care System in Seattle, "Diet Intervention and Cerebrospinal Fluid Biomarkers in Amnestic Mild Cognitive Impairment," Archives of Neurology 68(6):743-52, 2011-
"One in 3 of us will have a stroke, dementia, or both, unless we improve prevention.
Although cerebrovascular disorders and Alzheimer disease tend to occur together, they are studied apart and [too] late in their evolutions, when less or little can be done.
The commonest forms of stroke are silent, and Alzheimer disease begins decades before any symptoms appear. Moreover, epidemiological studies show that strokes and Alzheimer disease occur together and pose risks for each other, and clinical, pathological, and experimental studies suggest that they may also interact."
-Vladimir Hachinski, MD, DSc, Dept. of Clinical Neurological Sciences, University of Western Ontario, London, Ontario, "Stroke and Alzheimer Disease. Fellow Travelers or Partners in Crime? Archives of Neurology 68(6):797-98, 2011-
"*Dr. Megan C. Leary of UCLA examined over 5,500 MRIs of the brains of 50 year olds & found many had tiny white spots that indicated that they had unknowingly experienced tiny, imperceptible strokes. These "brain attacks" have the same history and cause as heart attacks. *(correction made 6/25/11) See "Annual Incidence of First Silent Stroke in the U.S" Cerebrovasc Dis 2003;16(3):280-5.
According to Leary, "'Silent strokes' are epidemic in this country. While they occur in parts of the brain where they don't cause symptoms right away, the word 'silent' should be put in quotes, because their effects accumulate over the years.''
While a single silent stroke may have no impact, repeated ones lead to memory lapses, mood problems and difficulty walking. They are also a sign that people are especially prone to full-blown strokes.
Keep on eating the same way at age 60, 70, & 80 and there's a good chance that those tiny strokes will add up to increasing memory lapses, and progress on to dementia--depending upon what part of the brain has been affected. What's good for the blood vessels of the heart, is good for the blood vessels of the brain."
Dr. Caldwell Esselstyn, Jr., Prevent & Reverse Heart Disease lecture 6/18/2010. see also: The Rotterdam Scan Study; "Silent Brain Infarcts and the Risk of Dementia and Cognitive Decline," New England Journal of Medicine 2003 Mar 27;348(13):1215-2; "Silent Brain Infarcts: a systematic review," Lancet Neurology 2007 Jul;6(7):611-9.
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The VA Puget Sound Study on Diet & Alzheimers/Dementia
Frankly, I worry more about the health of my brain than that of my heart. The VA Puget Sound study is one of the most exciting stories that I've read this month. But, I'm a sucker for any study that points to ways to prevent Alzheimer's or dementia.
This is the first randomized controlled trial that shows how a low fat diet that's also high in the kinds of low-glycemic foods that can keep our blood sugar steady (think oats & beans & greens), just might turn the Alzheimer's/Dementia ship around--provided that the dementia tipping point hasn't yet been reached. "Diet Intervention and Cerebrospinal Fluid Biomarkers in Amnestic Mild Cognitive Impairment," just appeared in the June 2011 issue of the Archives of Neurology.
Want to learn more about the Glycemic Index? What's high? What's low? Go to the official website, here.
Bottom Line, Here's What The Study Found:
A diet that's low in fat, especially saturated fat, with lots of low-glycemic foods, like whole grains and vegetables that keep blood sugar & insulin levels steady, can literally change the levels of the specific substances found in the cerebrospinal fluid that are associated with the development of Alzheimer's.
This diet not only improved many of the biomarkers for Alzheimer's, but it also improved scores on the delayed visual memory test--and did so in only 4 weeks. Makes me wish the study lasted much longer.
On the other hand, the diet that was high in fat & high glycemic foods increased the markers that would put one on the road to Alzheimer's--especially for healthy people. It also raised insulin levels, cholesterol/lipid levels, and saw performance declines on the delayed visual memory recall test in healthy subjects. No contest.
For years now we've heard that being overweight, having high cholesterol, type-2 diabetes, a big belly, insulin resistance, metabolic syndrome, and eating a high-fat-refined-carbohydrate diet upped the risks for dementia &/or Alzheimers as we got older. No news flash here.
Plenty of studies have already pointed the finger squarely in the direction of saturated fat, sugar, & refined carbs as the culprits in dementia--but up until now, no one has conducted a randomized controlled trial to carefully compare how high fat/high-glycemic versus low fat/low-glycemic diets affect a whole list of biomarkers for Alzheimers.
What's Unique about This Study?
It looked at the whole-diet--not just individual nutrients or individual foods
Instead of focusing on one single food or nutrient--like fish, olive oil, blueberries, omega-3s, or sugar--the VA Puget Sound researchers decided it was time to look at a "whole diet approach"---how people really eat. Previous studies of specific foods haven't found anything conclusive when it comes to influencing Alzheimer's risk.
This study compared how the So-Called Good Reputation Foods (low fat & low-glycemic foods) stack up against the So-Called Bad Reputation Foods (high fat & high-glycemic foods, which are the simple carbs like sugar & white flour). Kind of like a food fight face-off between steak, butter, french fries, Coke, white bread & cookies, matched up against fish, beans, salad, oatmeal, blueberries and whole wheat bread.
Home delivery of meals
The VA researchers weren't taking any chances with their study. They didn't depend on people remembering what they ate--they actually delivered the precise meals to their research subjects twice a week--so they could make sure everyone was eating the same foods.
A Complete Physical! Pre- and Post-Study Comparisons of Alzheimer's Markers in the Cerebrospinal Fluid, Lipid Levels, Blood Glucose & Insulin Levels, and Memory/Cognition Tests
They compared participants who were healthy with those who already had pre-Alzheimer's Amestic Mild Cognitive Impairment (aMCI)--analyzing their results after 4 weeks of following either a High-Fat-High- Glycemic Diet or a Low-Fat-Low-Glycemic Diet.
They did pre- and post-study measurements of everyone's insulin, glucose & lipid levels because these are all Alzheimer risk factors. They also ran pre- and post-study cognitive & memory tests.
The Importance of Measuring the Cerebrospinal Fluid Markers of Alzheimers
But the most important part of the study was the pre- and post- comparisons of the effects of the two different diets on the cerebrospinal fluid markers of Alzheimer's disease. The researchers used spinal taps to analyze participants' cerebrospinal fluid--the clear liquid that bathes the brain and can give a snapshot of brain health. Here's what they looked at:
- Beta-amyloid (beta-amyloid 42) in the cerebrospinal fluid--this rises as we age--that is, until amyloid plaque starts to deposit in the brain--at which point the levels counterintuitively start to decline. This is a complicated concept, that can best be explained by the drawing below. If you're healthy, and you improve your diet, a decrease in cerebrospinal fluid (CSF) levels of beta-amyloid would means you're on the right track towards avoiding Alzheimer's. But, if you've already reached that tipping point of pre-dementia, where plaque has started to deposit, a decrease in CSF beta-amyloid levels means you're heading towards full-blown Alzheimer's. However, even at this point, if you manage to improve your diet, as some aMCI participants did in this study, an increase in CSF beta-amyloid 42 levels could mean you're actually moving back towards the tipping point--and to a healthier state. Very confusing stuff!
Model of hypothetical trajectory of brain & cerebrospinal fluid (CSF) beta-amyloid 42 accumulation with increasing Alzheimer disease symptoms and pathologic features. Figure 3, Arch Neurol 68(6):749, June 2011.
- Cerebrospinal fluid levels of insulin. This plays an important part in many brain functions that are relevant to Alzheimers--like forming & maintaining synapses. Reduced central nervous system insulin is a marker for Alzheimer's--and brain insulin is compromised by persistent high insulin states, a high fat diet, & a high-fructose diet.
- Apolipoprotein E. This is a protein that helps clear out beta-amyloid--the culprit in beta-amyloid plaque formation, the hallmark of Alzheimer's. When it comes to APOE, increased levels are beneficial--decreased levels point towards Alzheimer's.
- CSF-F2-isoprostanes. This is a marker for oxidative damage to the central nervous system (yes, the brain) caused by free radicals. The CSF-F2-isoprostane levels increase in both Alzheimer's and pre-dementia-and dietary fat can adversely affect their levels. Decreased levels are a good sign.
And the Envelope Please! The Contestants & the Results.
Who was in the study?
49 adults participated, including 20 healthy individuals (the control group), with an average age of 69.
29 participants had aMCI (amnestic mild cognitive impairment--a precursor to Alzheimer's), with an average age of 68. aMCI was determined through a comprehensive neuropsychological battery.
All of the study participants were free of neurologic and psychiatric disorders, unstable cardiac disease, alcoholism, diabetes, liver or kidney or pulmonary disease.
No one was taking cholesterol-lowering medications.
What are the details of the diets in the study?
The participants followed their assigned diets for 4 weeks.
The diets were carefully measured, analyzed, & delivered twice a week to the participants. These were designed to maintain each person's weight--which took out any effect that the weight loss variable might have on the Alzheimer's markers.
The LOW Diet: This was a low-fat, low-glycemic diet. Specifically, 25% fat, less than 7% saturated fat, 55-60% carbohydrates, with a glycemic index of less than 55, and 15-20% protein. Not exactly low-fat--but lower than average.
The HIGH Diet: This was a high-fat, high-glycemic diet. Specifically, 45% fat, with 25% saturated fat, 35-40% carbohydrates with a glycemic index of greater than 70, and 15-20% protein.
Unfortunately, we don't know the specific foods used in this study, nor their micronutrients--something I would be very interested in knowing.
Diet adherence was high.
Study participants were randomized with 24 individuals following the HIGH Diet; and 25 individuals following the LOW Diet.
What measurements were taken pre- and post-study?
- Tests of immediate & delayed memory, executive function, verbal fluency, and motor speed. The only memory test that was affected after 4 weeks was the delayed visual memory.
- Oral glucose tolerance test
- Tests of blood insulin (AUC), blood glucose levels, & lipid/cholesterol levels
- The Alzheimer biomarkers found in the cerebrospinal fluid: CSF AB42, AB40, tau protein, CSF-insulin, F2-isoprostanes, & apolipoprotein E.
- NOTE: No effects were seen in the AB40, tau protein, or p-tau levels in any of the groups.
For the Healthy Adults
The HIGH fat/High GI Index
"In healthy adults, the HIGH fat/high-glycemic diet increased levels of beta-amyloid and other markers of inflammation and free radical damage in the spinal fluid, suggesting that the high amounts of unhealthy fats and wide swings in blood sugar from the high-glycemic diet may be moving the brain toward changes associated with Alzheimer's."
Cholesterol/lipids & blood insulin levels all increased. HDL levels, however, increased as fat increased.
The results on the delayed visual memory tests declined.
The LOW fat/low GI Index
The LOW fat/low-glycemic diet, however, decreased those levels of beta-amyloid, insulin, and F2-isoprostanes, and increased levels of apolipoprotein E, suggesting a protective effect.
Cholesterol/lipids, glucose, & insulin levels all decreased--and improved over baseline. HDL decreased because the fat decreased. Results on the delayed visual memory tests improved over baseline.
All excellent news, as far as I'm concerned.
Can't help but wonder what improvements might be seen on the low-fat/low glycemic diet over time.
The AMCI Pre-Alzheimer's Group
In those participants who were diagnosed with aMCI, who had already begun to have some memory or brain impairments, the results were more complex.
The HIGH fat/High GI Index
Those on the HIGH fat/high glycemic diet, saw little changes in the Alzheimer's biomarkers.
Dr. Suzanne Craft, the study author says, "That's possibly because they've already got a very pathological process going on, and such a short study wasn't going to to make things much worse.
However, their cholesterol/lipid levels increased far more than those of the healthy subjects who were on the HIGH Diet--especially their LDLs and total cholesterol.
The LOW fat/low GI Index
Those who were on the low-fat diet saw increases in the levels of beta-amyloid in their spinal fluid.
Researchers say other studies that have looked at changes in beta-amyloid as Alzheimer’s disease progresses have observed a tipping point, where levels rise until a critical level is reached and plaques begin to form. When that happens, the disease accelerates, more plaques form in the brain, and levels of beta-amyloid in spinal fluid drop.
They say the rise in beta-amyloid seen in adults with cognitive impairment on the low-fat diet may indicate that the brain is moving away from the tipping point of plaque formation and back toward a healthier, more normal state.
People with early memory loss saw other markers of oxidative damage drop on the low-fat diet, and their scores on some measures of memory improved after the study, though the changes were subtle.
They also saw small improvements in their blood insulin & glucose levels, and substantial improvements (decreases) in their cholesterol/lipids--especially in their LDLs & total cholesterol.
Taken together, researchers say their results show that high-fat, high-sugar diets can have consequences for the brain.
“Exposing your body and your brain to this type of diet over a very long period of time is going to put you on the path to Alzheimer’s disease,” Craft says. (WebMD)
The Secret of This Diet's Success? Does a Low-Glycemic Diet Have the Added Benefit of Boosting Nitric Oxide?
After reading this study I'm even more convinced of the benefits of eating a no-added fat low-glycemic plant-based diet.
If you think that the prevention of Alzheimers/Dementia is beyond your control--this study just might change your mind! Combine this study with what we learned from the Mayo Clinic's recent research on how a steady supply of nitric oxide can protect the brain from plaque formation & Alzheimer's--and we just might have a prescription for a "NO (nitric oxide) Dementia Diet".
What keeps our nitric oxide supply kicking? Plenty of oats, leafy greens like kale, chard, & collards--and plenty of exercise, too! And what foods also happen to be low-glycemic? That's right. The same ones that also help boost our nitric oxide supply.
Could this help explain why the VA Pugent Sound researchers found that their low-fat low-glycemic diet had such a positive effect on the Alzheimer's biomarkers? To learn more about the nitric oxide Alzheimer's connection read: Mayo Clinic Researchers Discover the Nitric Oxide Connection to Brain Health, Alzheimer's, and Cognitive Impairment. Better Keep Your Endothelial Cells Healthy with Diet & Exercise!
How do the low-glycemic nitric oxide-boosting foods benefit our brains?
- They keep insulin levels steady--preventing the "up & down" blood sugar spikes that damage the "dentate gyrus", which is within the hippocampus--that's the part of the brain responsible for forming memories. Small, SA et al, "The brain in the age of old; the hippocampal formation is targeted differenially by diseases of late life," Annals of Neurology 2008 Dec;64(6):698-706
- Even slight elevations of blood sugar--less than those seen in type-2 diabetes can cause memory decline. Because blood sugar tends to rise as we age--even in healthy people, it makes Small's study a wake-up call to take steps to keep the blood sugar stable.
- Even if you don't have type-2 diabetes, blood glucose levels tend to rise as we grow older. Small recommends physical exercise, diet or drugs to improve glucose metabolism and help avert the cognitive slide that occurs in many of us as we age.
- The nitric oxide boost from low-glycemic foods keeps blood vessel walls healthy (even in the brain), resists atherosclerotic plaque formation, prevents amyloid plaque formation in the brain, lowers blood pressure, relaxes blood vessels, and helps to reduce cerebrovascular risk factors. According to Dr. Randolph Schiffer, the head of the Cleveland Clinic's Ruvo Center for Brain Health, cardiovascular diseases & Alzheimer's share similar blood vessel pathologies. Read more here.
How a low-fat diet benefits our brains
- Low intake of saturated fats is associated with a reduced risk of Alzheimer's and its precursor, amnestic mild cognitive impairment (aMCI).
- "Elevations in LDL cholesterol and total cholesterol concentrations have been demonstrated in early Alzheimer's--with cholesterol increases occurring in conjunction with greater Beta-amyloid disease."
- "Diets high in saturated fat impair blood-brain barrier function; in a rodent model, evidence suggested that high-saturated fat diets may allow delivery of cholesterol and Beta-amyloid [combined] with lipoproteins from the periphery into the central nervous system."
- A low-fat diet reduces the free radical injury to the blood vessels--and reduces the oxidative damage to the central nervous system. Cerebrospinal fluid markers for oxidative stress naturally increase as we age, reflecting accumulated oxidative stress--but in the VA Puget Sound study, the low-fat low-glycemic diet was able to reduce the biomarkers of oxidative stress in the brain.
1. The study was designed to keep the participant's weight stable, not reduce it. The researchers speculate that weight change might have produced different results. There are multiple studies linking belly fat & obesity with a higher risk of dementia. One study of middle-age people (44-66 year old) found "that the obese tended to have smaller, more atrophied brains than thinner people." I'm betting that a healthy diet that also promotes weight loss would have shown even greater improvements in the Alzheimer biomarkers.
2. The study only lasted for four weeks. Because of safety precautions, the length of time that the researchers would allow the participants to stay on a high fat/high glycemic diet had to be kept short. Longer exposure to such a diet might be needed to observe changes in cognition & other end points.
3. This trial did not include participants with high cholesterol, or those on statins, which likely increased the difficulty in detecting diet-related effects.
4. The study size was small
5. There may be nutrition & diet factors that when combined together would show even more profound effects on the Alzheimer's/Dementia biomarkers. Consider lower fat, different ratios of macronutrients, and a diet combined with foods that are high in certain nutrients known for brain health.
6. The study's counter viewpoint: “We are getting closer to the day where we might give someone an anti-Alzhimer's diet prescription, but we are not there yet,” says P. Murali Doraiswamy, MD, professor of psychiatry and head of the division of biological psychiatry at the Duke University Medical Center in Durham, NC--who wasn't involved in the study.
“There are many unknowns here, such as how a person’s genetic makeup influences how their diet affects the brain, so it’s entirely possible that a low-fat diet may just help people with a certain genetic makeup," Doraiswamy says.
Me: Sure, additional studies are needed--ones that are larger and last longer, so we can tease out a number of variables. And this is just one small study--that's certainly not "prescription-ready". It's a step in a hopeful direction.
But, let's face it--Alzheimer's takes years to develop, and often we don't know we're at risk until it's too late.
If you're already in or past middle age--why delay in making such simple risk-free diet modifications that have a long history in also preventing type-2 diabetes, strokes, and heart disease? What could be the possible harm?
And wouldn't it be fascinating to see a study like this one done with a nutrient-dense plant-based diet, that's high in leafy greens, with at least 6 servings of vegetables, high in berries & anthocyanins, high in omega-3s, less than 15% fat, very low levels of saturated fats, no-added oils, and plenty of exercise? Guess I'll just have to run that experiment on myself!
Any other takers out there?
Anything you would add to an Alzheimer's Prevention Diet?