Preventing atrophy of key brain regions related to cognitive decline and Alzheimer’s disease

In a recent study the researchers state "Our results show that B-vitamin supplementation can slow the atrophy of specific brain regions that are a key component of the [Alzheimer's Disease] process and that are associated with cognitive decline," the study authors conclude that: "Further B-vitamin supplementation trials focusing on elderly subjects with high homocysteine levels are warranted to see if progression to dementia can be prevented."

In an initial, randomized controlled study on elderly subjects with increased dementia risk (mild cognitive impairment according to 2004 Petersen criteria), researchers showed that high-dose B-vitamin treatment (folic acid 0.8 mg, vitamin B6 20 mg, vitamin B12 0.5 mg) slowed shrinkage of the whole brain volume over 2 yr. Here, they go further by demonstrating that B-vitamin treatment reduces, by as much as seven fold, the cerebral atrophy in those gray matter (GM) regions specifically vulnerable to the AD process, including the medial temporal lobe. In the placebo group, higher homocysteine levels at baseline are associated with faster GM atrophy, but this deleterious effect is largely prevented by B-vitamin treatment. They also showed that the beneficial effect of B vitamins is confined to participants with high homocysteine (above the median, 11 µM) and that, in these participants, a causal Bayesian network analysis indicates the following chain of events: B vitamins lower homocysteine, which directly leads to a decrease in GM atrophy, thereby slowing cognitive decline. Our results show that B-vitamin supplementation can slow the atrophy of specific brain regions that are a key component of the AD process and that are associated with cognitive decline. Further B-vitamin supplementation trials focusing on elderly subjets with high homocysteine levels are warranted to see if progression to dementia can be prevented.

Dr. Gwenaelle Douaud, one of the researchers states,”What we have shown is that, in these elderly people at risk for dementia and with high levels of homocysteine, you can slow the grey matter loss in the areas of the brain that matter, and therefore slow their cognitive decline. However, we would need a larger and longer trial to determine the optimal threshold of homocysteine that would warrant vitamin B supplementation and, crucially, if this could therefore slow the progression of Alzheimer's."

Douaud G, Refsum H, de Jager CA, Jacoby R, E Nichols T, Smith SM, Smith AD. Preventing Alzheimer's disease-related gray matter atrophy by B-vitamin treatment. Proc Natl Acad Sci. 2013 Jun 4;110(23):9523-8.

Phytochemical rich diet & Central Nervous System Status

Phytochemical rich diet Central Nervous System Status

A Mediterranean diet is characterized by the use of virgin olive oil as the main culinary fat; high consumption of fruits, nuts, vegetables and pulses; moderate to high consumption of fish and seafood; low consumption of dairy products and red meat; and moderate intake of red wine.

In the first long term trial to look at the impact of the Mediterranean diet on brain power, 522 men and women aged (55 – 80 all taking part in the PREDIMED trial) without cardiovascular disease, but at high vascular risk because of underlying disease/conditions such as type 2 diabetes or three of the following: high blood pressure; an unfavourable blood fat profile; overweight; a family history of early cardiovascular disease; and being a smoker.

Participants were randomized to one of 3 groups: 1) a Mediterranean diet with added olive oil or 2) a Mediterranean diet with added mixed nuts or 3) a control group receiving advice to follow the low-fat diet typically recommended to prevent heart attack and stroke.

After an average of 6.5 years, they were tested for signs of cognitive decline and higher brain functions (orientation, memory, language, visuospatial and visuoconstruction abilities and executive functions such as working memory, attention span) and abstract thinking using the Mini Mental State Exam and a clock drawing test.

Regardless of factors such as age, family history of cognitive impairment or dementia, the presence of ApoE protein (epsilon), educational attainment, exercise levels, vascular riskfactors, energy intake and depression, the average scores on both tests were significantly higher for those following either of the Mediterranean diets compared with those on the low fat option.

95 participants had developed either mild cognitive impairment or dementia: 30 on the olive oil supplemented Mediterranean diet; 25 on the Mediterranean diet with added mixed nuts; and 40 on the control group.

The average scores significantly higher for those following either of the Mediterranean diets compared with those on the low fat option.

The authors from the University of Navarra in Spain acknowledge that their sample size was relatively small, and that because the study involved a group at high vascular risk, it doesn’t necessarily follow that their findings are applicable to the general population. However these outcomes point at what I suggest in my lecture, Ecological Pharmacology. A phytochemical rich diet preserves organ reserve, or loss of function.   

A phytochemical rich diet influences chronic disease outcomes and duration of life

Researchers from Loma Linda University (California, USA), and colleagues examined death rates in a group of 73,308 men and women participating in the Adventist Health Study 2. The participants were divided into five groups: 1) non-vegetarian, 2) semi-vegetarian, 3) pesco-vegetarian (consuming seafood, but not meat), 4) lacto-ovo-vegetarian (consuming dairy and eggs), and 5) vegan (no animal products). After 6 years of following these subjects the data demonstrated  “significant associations with vegetarian diet… for reduced cardiovascular mortality, noncardiovascular noncancer mortality, renal mortality, and endocrine mortality.” Moreover, the researchers concluded "Vegetarian diets are associated with lower all-cause mortality and with some reductions in cause-specific mortality. Results appeared to be more robust in males. These favorable associations should be considered carefully by those offering dietary guidance.”

But the conclusion should not be drawn that meat is detrimental. At a recent conference, the International Congress on Vegetarian Nutrition at Loma Linda University, David Jacobs, PhD, Mayo Professor in epidemiology at the U Minnesota said “it seems the presence of more phytochemical-rich plant foods rather than the complete absence of animal foods is what makes a vegetarian diet so successful.” He went on to say “In general, plant-centered and vegetarian diets have more favorable chronic disease outcomes. This is one of the most consistent findings of nutritional epidemiology ”

Michael J. Orlich, Pramil N Singh, Joan Sabate, Karen Jaceldo-Siegl, Jing Fan, Synnove Knutsen, W. Lawrence Beeson, Gary E. Fraser. ” Vegetarian Dietary Patterns and Mortality in Adventist Health Study 2 .”  JAMA Intern Med., June 3, 2013.

Exercise may reduce the risk of breast cancer

Researchers recently showed that a lifestyle intervention (exercise) reduced the 'bad' estrogen and increased the 'good' estrogen.  Premenopausal women (391 sedentary, healthy, young) were randomly assigned to 1 of 2 age-matched, body mass index-matched groups: a control group of 179 women and an intervention group of 212 women. Women in the intervention group performed 30-minutes of moderate-to-vigorous aerobic exercise 5-times a week for 16-weeks. The amount of 3 parent estrogens – estrone, estradiol, and estriol – and 9 estrogen metabolites were measured in subjects urine collected on 3 consecutive days prior to exercise and on 3 consecutive days at the end of the study.

This is what they found:

"... in healthy premenopausal women, an exercise regimen of 150 minutes of moderate-to-vigorous aerobic exercise per week for 16 weeks resulted in significant changes in estrogen metabolism in a direction consistent with reduction of breast cancer risk."

2-OHE1/16a-OHE1 increased significantly (P = 0.043), whereas E1 decreased significantly  (P = 0.030) in control participants (n = 153). The change from baseline in 2-OHE1/16a-OHE1 was significantly different between groups (P = 0.045), even after adjustment for baseline values.

Alma J Smith, William R Phipps, William Thomas, Kathryn H Schmitz, and Mindy S Kurzer. The effects of aerobic exercise on estrogen metabolism in healthy premenopausal women. Cancer Epidemiol Biomarkers Prev. 2013;22:756-764.