tai chijogactionmouseresveratrolbbb brain capilliariesDEMENTIANVU

Recent studies report that diet can mediate the vasculoplastic reserve of the hippocampus. For example, consuming high levels of cocoa flavanols increased capillary density and enhanced dentate gyrus-associated cognitive function in cognitively normal healthy subjects. This suggests an interaction between vasculoplasticity and neuronal plasticity during normal aging and dementia, but how this relationship is affected by lifestyle and vascular risk factors is currently unclear and should be investigated in future studies.

Growing evidence supports the benefits of a Mediterranean diet in protecting against dementia and prolonging one’s cognitive reserve during aging. Age-related cognitive decline was attenuated in individuals consuming a Mediterranean diet, as found in a recent study of the Mediterranean-Dietary Approach to Systolic Hypertension (DASH)

Diet intervention for neurodegenerative delay. In comparing Mediterranean and Western diets, the primary difference is the source and proportion of dietary fats, with olive oil specifically being the main fat consumed in the Mediterranean diet and high levels of saturated fatty acids and simple carbohydrates being consumed in Western diets. Microvascular dysfunction is evident in rodent models fed unhealthy diets, namely, those fed diets of Western culture [219], high fat [220], and high cholesterol [221]. An intact BBB is needed for proper cholesterol metabolism. In CSF, decreased cholesterol levels correlate with decreased Aβ42 and increased CSF APPα and APPβ (products of APP processing) levels, supporting an association between disrupted cholesterol metabolism and increased amyloidogenesis.

Resveratrol is a biologically active plant-derived phytoalexin. Resveratrol has been shown to cross BBB and regulate expression of MMPs, reduce pericyte loss, maintain integrity of BBB, and promote Aβ clearance. Treatment with resveratrol completely reversed diabetes-induced vascular dysfunction by reducing capillary leakage, pericyte degeneration, and VEGF protein expression in the murine retina. An earlier study has shown that resveratrol inhibits RAGE expression in vascular cells , which is implicated in Aβ transport into the brain and accelerated Aβ pathology in a mousemodel].

Furthermore, long-term consumption of resveratrol reduced oxidative stress and prevented behavioral deficits in a rat model with disrupted NVU.

Olive oil is high in essential omega-3 fatty acids, the major component of which is docosahexaenoic acid (DHA), and has long been reported to benefit cognition and overall brain health.

DHA cannot be synthesized by the body and thus must be consumed, and the primary transporter of DHA from blood-to-brain is the major facilitator superfamily domain containing 2A (MFSD2A) at the BBB. Individuals with AD have lower CSF DHA lipid levels, and those with mild dementia have lower CSF α-liolenic acid levels. Interestingly, reduced MFSD2A expression at the BBB can lead to a loss of its important functions, including maintenance of BBB integrity and omega-3 fatty acid transport into the brain.

Transgenic APOE4 mice also exhibit reduced uptake of DHA into the brain compared with transgenic APOE2 mice, but whether this is related to reduced Mfsd2a expression is currently unknown. Additional studies are needed elucidate the underlying mechanisms of MFSD2A and fatty acids in relation to dementia and AD.

Exercise and environmental enrichment

Regular exercise and physical activity, particularly during midlife, are associated with improved cerebrovascular function and reduced rates of dementia and AD [236]. Individuals that exercised regularly for 28 days exhibited reduced plasma homocysteine levels and increased endothelial progenitor cells in peripheral blood, factors that protect against vascular damage and cognitive impairment .

Experimental studies in diabetic rats have shown that treadmill exercise maintains claudin-5 expression at the BBB compared to rats not receiving exercise.

Physical activity and cognitive stimulation in the form of enriched environment (e.g., tunnels, balls, ladders, and running wheel) accelerated Aβ enzymatic degradation and enhanced transvascular Aβ clearance, reducing Aβ accumulation in brains of AD transgenic mouse models.

Additionally, physical activity promoted Aβ clearance from brain to blood via upregulation of LRP1 and downregulation of RAGE at the BBB. Mice without access to a running wheel had decreased occludin tight junction levels and disrupted BBB integrity.

Sources of resveratrol

Resveratrol is a stilbenoid, a type of natural phenol, and a phytoalexin produced naturally by several plants in response to injury or when the plant is under attack by pathogens such as bacteria or fungi. Food sources of resveratrol include the skin of grapes, blueberries, raspberries, mulberries, and senna.

Here are 5 foods that are great sources of resveratrol:

Red Grapes

Grapes don’t have to be fermented to contain this antioxidant. It’s actually found in the skin of red grapes along with other nutrients, such as minerals manganese and potassium and vitamins K, C and B1.

Peanut Butter

Peanut butter is great for dressing up apples and celery, but it also contains some resveratrol (up to .13 mg per cup). Peanut butter is a great source of niacin and manganese.

Dark Chocolate

In dark chocolate, resveratrol blends nicely with other antioxidants and also minerals, such as iron, copper and manganese. Who doesn’t like chocolate?

Itadori Tea

Used in Japan and China as a traditional herbal remedy for the prevention of heart disease and strokes, itadori tea: contains resveratrol, consequently, The Journal of Agricultural Food Chemistry studies state that, ”For people who do not consume alcohol, Itadori tea may be a suitable substitute for red wine.”


Blueberries don’t have quite as much resveratrol as grapes, but they are also a great source of other antioxidants, dietary fiber, vitamins C and K and manganese.

For all of the above, it would be wise to choose organic sources to reduce pesticides, especially for red grapes, peanut butter and chocolate.

 Low doses of resveratrol improve cell survival as a component of cardio- and neuro-protection, while high doses increase cell death, so this is always something to keep in mind before purchasing supplements with the next greatest dose.

 “Reports on the benefits of red wine are almost two centuries old,” said Lindsay Brown, associate professor in the School of Biomedical Sciences at The University of Queensland

 * Resveratrol exhibits therapeutic potential for cancer chemoprevention as well as cardioprotection.

 “It sounds contradictory that a single compound can benefit the heart by preventing damage to cells, yet prevent cancer by causing cell death, said Brown. “The most likely explanation for this, still to be rigorously proved in many organs, is that low concentrations activate survival mechanisms of cells while high concentrations turn on the in-built death signals in these cells.”

 * Resveratrol may aid in the prevention of age-related disorders, such as neurodegenerative diseases, inflammation, diabetes, and cardiovascular disease.

 “The simplest explanation is that resveratrol turns on the cell’s own survival pathways, preventing damage to individual cells,” said Brown. “Further mechanisms help, including removing very reactive oxidants in the body and improving blood supply to cells.”

 * Low doses of resveratrol improve cell survival as a mechanism of cardio- and neuro-protection, while high doses increase cell death.

 “The key difference is probably the result of activation of the sirtuins in the nucleus,” said Brown. “Low activation reverses age-associated changes, while high activation increases the process of apoptosis or programmed cell death to remove cellular debris. Similar changes are seen with low-dose versus high-dose resveratrol: low-dose resveratrol produces cellular protection and reduces damage, while high-dose resveratrol prevents cancers.”


Neurovascular dysfunction and neurodegeneration in Dementia/Alzheimer’s disease

Amy R. Nelson, Melanie D. Sweeney, Abhay P. Sagare, Berislav V. Zlokovic

Department of Physiology and Biophysics and the Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90089, USA