Diet & Nutrition Findings from ICAD

Vienna, July 14, 2009 A Plant Based diet can reduce risk for dementia, DHA from fish may also help-if taken soon enough. However, other fats may increase the risk for AD, and a new zinc formula appears to be of added value, as well as a little wine for prevention.

Dietary Approaches to Stop Hypertension (DASH) Eating Pattern May Reduce Age-Related Cognitive Decline

The Dietary Approaches to Stop Hypertension (DASH) diet is often recommended by physicians to people with high blood pressure or pre-hypertension. The DASH diet eating plan has been proven to lower blood pressure in studies sponsored by the National Institutes of Health. High blood pressure is considered a risk factor for Alzheimer’s and dementia.

Heidi Wengreen, RD, PhD, Assistant Professor of Nutrition at Utah State University, and colleagues examined associations between how closely people adhered to the DASH diet and risk of cognitive decline and dementia among older participants in the Cache County Study on Memory, Health and Aging.

In 1995, 3,831 study participants 65 years of age or older completed a survey that included a food frequency questionnaire and cognitive assessment. Cognitive function was checked again during four assessments over 11 years using the Modified Mini-Mental State examination (3MS), which is graded on a 100 point scale. A DASH diet adherence score was created based on consumption levels of nine food-group/nutrient components — fruit, vegetables, nut/legumes, whole grains, low-fat dairy, sodium, sweets, non-fish meat, and fish. Participants were ranked by DASH score into five groups, or quintiles.

The researchers found that higher DASH scores were associated with higher scores for cognitive functioning at the beginning of the study and over time. Those in the highest quintile scored 1.42 points higher at baseline and 1.81 points higher after 11 years on the 3MS than did those in the lowest quintile of the DASH score (p-values <0.001).

They also found that four of the nine food-group/nutrient components used to create the DASH score were independently associated with 3MS scores — vegetables, whole grains, low-fat dairy, nut/legumes. The scientists created a diet adherence score based on just these four components which they then tested for association with changes in cognitive abilities on the 3MS. Those in the highest quintile scored 1.72 points higher at baseline and 3.73 points higher after 11 years than did those in the lowest quintile of the four-component score (p-values <0.001).

“Our results suggest that including whole grains, vegetables, low-fat dairy foods, and nuts in one’s diet may offer benefits for cognition in late life,” Wengreen said. “However, we need more research before we can confidently say how much of these foods to include in your diet to experience some benefit.”

Can DHA as found in fish oil and algae protect the brain from Alzheimer’s? One of the major news stories on brain health and prevention coming out of Sunday’s oral presentations at the International Conference on Alzheimer’s Disease (ICAD) in Vienna, were the reports on the effectiveness of DHA, an Omega-3 fatty acid, present in fish oil and algae. Last year a major study looking at fish oil’s affect in arresting Alzheimer’s was disappointing. I reported yesterday on a minor study investigating the value of DHA for prevention in an animal study. But on Sunday, the 2nd day into the conference, long awaited results (I’ve personally been looking for this since March) were finally presented on two major well designed multi-center studies of DHA – one conducted in part here in Salt Lake City.

In the first MIDAS (Memory Improvement with DHA Study) researchers looked at the Effects of DHA on Physiological and Safety Parameters in Age-Related Cognitive Decline. This was a randomized, double-blind, placebo-controlled, multi-center, six month study to determine the effects of 900mg/d DHA on improving cognitive functions in healthy elderly with ARCD (Age Related Cognitive Decline). Safety and tolerability were also assessed. 485 subjects, some from Utah, were involved in this study.

Results showed significantly fewer errors made on a visuospatial memory test with DHA versus placebo at six months compared to baseline (diff. score -1.63±0.76, p<0.03). A significant decrease in heart rate (DHA change from baseline of -3.2 vs. -1BPM, p<0.03) occurred and highly correlated with week 24 plasma levels (p<0.01).

Conclusions:

Six month supplementation with DHA (900mg/d) improves memory function and decreases heart rate in healthy older adults with ARCD. DHA also exhibited an excellent safety profile in this older population.

Those results were good, but expected (see my article on Omega-3 and DHA under the diet and nutrition section of this website). The second study was or greater interest for those concerned about AD (Alzheimer’s Disease). It was a clinical trial of DHA (docosahexanoic acid) for the treatment of Alzheimer’s disease. This study was also a double blind, randomized, placebo-controlled clinical trial comparing DHA and placebo in AD patients. It was conducted by the National Institute on Aging Alzheimer’s Disease Cooperative Study Unit. Fifty one sites in the United States enrolled 402 subjects between February and November 2007. Subjects had a diagnosis of probable AD with Mini-mental state exam score (MMSE) 14-26, and dietary DHA intake of ≤ 200 mg per day.

Subjects in this study were treated with DHA or placebo at a dose of 2 grams per day for 18 months, [that’s a lot of DHA] with the final subjects completing clinical activity in May 2009. Co-primary outcomes were rate of change on Alzheimer’s disease assessment scale-cognitive (ADAS-cog) and rate of change on Clinical Dementia Scale-sum of the boxes (CDR-SOB).

Results: The study population was 52.2% female with a mean age of 76 ± 8.7 years, mean education of 14.3± 2.8 years, and mean MMSE=20.7 ± 3.6, with 59% ApoE4 positive and 41% ApoE4 negative. Mean plasma DHA at baseline was 3.15±1.12 weight percent.

Conclusions: Unfortunately they found no significant difference over the 18 month period in thinking or memory abilities, nor on subjects abilities to perform activities of daily living. Although there was some difference in behavioral symptoms, like sleep, anxiety etc, favoring those on the DHA. However, they did find that in those who did not have the APOe4 Alzheimer’s gene, DHA supplementation did appear to have some protective value.

[What is the take-home from these two studies? While DHA was not shown to significantly impact the course of Alzheimer’s in later stages, it may help to prevent the development of dementia symptoms if sufficient amounts are taken early enough. And it may be of some value in reducing anxiety and sleep related problems for some with dementia.]

The prolonged high-fat dietary impairs functional neuronal insulin sensitivity in hippocampus Siriporn Chattipakorn, DDS, PhD1,2, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand, 2Cardiac Electrophysiology Research and Training Center, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand. Abstract:

Background:
The development of abdominal obesity following long-term consumption of high-fat diet has been shown to contribute to peripheral insulin resistance. Although the correlation between insulin resistance and cognitive impairment has been demonstrated, the relationship between high-fat consumption and functional neuronal insulin sensitivity in CA1 hippocampus has never been investigated. In the present study, we tested the hypothesis that high-fat diet consumption causing peripheral insulin resistance can lead to impair neuronal responses to insulin (or neuronal insulin resistance).

Methods:
Extracellular recording in acutely prepared rats’ hippocampal slices was performed to determine functional neuronal insulin sensitivity from normal dietary fed rats and at different time courses of high-fat dietary fed rats. Immunoblotting technique was used to investigate the alteration of the functional phosphorylation of neuronal insulin receptor obtained from both dietary fed groups.

Results:
Peripheral insulin resistance was demonstrated in all rats fed with high-fat diet for 8 weeks. The depression of field excitatory postsynaptic potentials (fEPSPs) induced by 500-nM insulin (or insulin-induced long-term depression (LTD)) in CA1 hippocampus was reduced in rats fed with high-fat diet for 12 weeks (Figure). This reduction of insulin-induced LTD in hippocampus was significantly correlated with increased body weight, visceral fat, plasma insulin and liver triglyceride (p<0.05). Furthermore, levels of tyrosine phosphorylation of insulin receptor (IR) and insulin receptor substrate 1 (IRS-1) in the brain in response to insulin were significantly decreased in 12-week high-fat fed rats.

Conclusions:
Functional insulin resistance can develop in the central nervous system as well as in the peripheral tissues in rats fed with high-fat diet for 12 weeks. These findings indicate that high-fat diet not only causes endocrine abnormalities, but also induces the neuronal insulin resistance. Since impairment of neuronal insulin response is linked to neurodegenerative disease, neuronal insulin resistance caused by long-term high-fat consumption may lead to cognitive deficits.

Effects of zinc plus cyclo(his-pro) on pathology, learning and memory in a transgenic mouse model of Alzheimer’s disease 1Western University of Health Sciences, Pomona, CA, USA, 2Veterans Affairs Greater Los Angeles Healthcare System and David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. Abstract:

Background:
Memory loss is a major clinical hallmark of Alzheimer’s disease (AD), which currently affects over 26 million individuals worldwide. While the causes of AD are unknown, recent epidemiological studies show an increased risk of AD in both type 1 and type 2 diabetic patients. This may explain why mice given a high fat diet present with increased insulin resistance, enhanced amyloidosis and decreased levels of the zinc containing, Aβ metabolizing, insulin degrading enzyme (IDE). Previous work from our group shows that treatment with a novel patented formulation of zinc plus cyclo(his-pro), named ZC, significantly improves insulin sensitivity in several diabetic animals models. As AD may be linked to diabetes, we recently tested ZC’s ability to alter Aβ levels, IDE activity, as well as learning and memory in a transgenic mouse model of AD.

Methods:
Nine to twelve month old huAPP-YAC transgenic mice (R1.40 strain) were treated with 10 mg/L Zn plus 1.0 mg/L cyclo(his-pro) in water ad libitum, with controls receiving access to water alone ad libitum. At the end of five weeks of treatment, Aβ levels and IDE activity were measured. Nine month old R1.40 mice, treated as previously described, were tested on a Barne’s Maze for learning and memory at baseline and at monthly intervals.

Results:
In this study we show that ZC decreases both cytosolic and membrane forms of Aβ1-42 and Aβ1-40, while enhancing IDE activity. Mice treated with ZC also show an increased ability to learn and remember the location of an escape hole.

Conclusions:
Here we demonstrate for the first time that a novel patented formulation decreases Aβ levels, increases IDE activity, and enhances learning and memory in an AD transgenic mouse model.

What is The Effect of Alcohol Consumption on AD A Wake Forest, NC study also looked at modifiable risk factors for dementia. In this 6 year study researchers found those who consumed a moderate amount of alcohol (8-14 drinks per week/ 1-2 per day) appeared to have a somewhat lower risk of developing dementia than abstainers. In cognitively normal individuals the moderate drinkers has 37% less risk of developing dementia than those who abstained. Mild consumption also had a protective effect. However, in older adults with mild cognitive impairment alcohol was not protective, in fact in this population drinking increased the risk, and the more they drank the faster their dementia progressed.

So while moderate drinking appears to have some protective effect, for those without memory problems, once dementia gets started continued alcohol consumption only appears to accelerates that decline.