**8. The "train body and brain" protocol for a primary intervention on AD in the city of Volterra (Tuscany, Italy)**

In view of the continuing increase in the prevalence of dementia to a magnitude growing to emergency [54, 55], a free of charge program to train people at higher risk of disease has been started in the Italian city of Volterra. Since AD is an agingassociated multifaceted disease that is hard to treat by single-modal treatment, a corresponding multifaceted preventive approach was included in a teaching program on how to counteract in practice the effects of biological and pathological aging on human body and brain.

Program includes activation of the global antioxidant defense system in order to attenuate the AD-causative oxidative stress, improvement of the function of the free radical conducting mechanism responsible for membrane resistance to oxidative stress, reinforcement of cell repair mechanisms at the molecular and subcellular level by dietary and physical intervention, and targeted high-intensity training of cognitive brain functions to boost the induction of neurotrophic factors by the physiological mechanism. Here, a few details on protocol are given.


#### **Figure 1.**

*Model of the membrane antioxidant machinery based on the proposed locations of dolichol (disc, green), ubiquinone (hexagon, red), and vitamin E (rhomb, pink) (see Cathcart et al. [69]; Sharma et al. [70]).*

**27**

*Primary Prevention of Alzheimer's Disease (AD) DOI: http://dx.doi.org/10.5772/intechopen.85418*

oxidative status over time [68].

app are included in the protocol.

**9. Conclusion**

of disease appearance.

**Acknowledgements**

c.Promoting cell cleaning and rejuvenation. It is done by teaching participants in practice how to eat a healthy calorie-restricted diet and to make aerobic physical exercise during fasting. It is known indeed that calorie restriction is the most robust antiaging intervention known so far [64], and that benefit comes from the alternation of a long time of fasting and good meal (twice a week, participants spend a great part of their time in a state of fasting) [65] in order to get cells free of altered ROS-hypergenerating organelles in older cells [66, 67]. Good maintenance will be finalized later, thanks to a good meal. If needed, benefit might be magnified by taking a pill of an antilipolytic drug on the time of fasting [41]. Benefits of protocol might be monitored noninvasively by the assay of the urinary excretion of 8-hydroxy-2′-deoxyguanosine, a recently recommended biomarker for monitoring

d.A targeted high-intensity training of cognitive brain functions. In addition to the previously described interventions on diet and physical activity, the mental and the social activity protocols tested by Paillard-Borg et al. [38] are being practiced. In view of the results obtained by Dahlgren et al. [51], high intensity interval training (HIIT) and memory training using the PEAK brain training

A dynamic antiaging nutritional and physical intervention protocol including enriched living conditions is described useful to prevent the appearance of agingassociated AD. Treatment is already granted for free to the citizens of the city of Volterra known to be at higher risk of AD (relatives of AD patients and persons with mild cognitive impairment, likely to progress to clinically probable AD at a considerably accelerated rate compared with healthy age-matched individuals) to teach them how to counteract and retard the disease. Treatment was designed to delay biological aging and empower adult brain plasticity in order to retard the progress of brain aging and associated diseases. It includes a daily assumption of antioxidants (red wine polyphenols enriched with resveratrol), a reinforcement of membrane antioxidant defenses by the timed assumption of polyunsaturated fatty acids, and an enhancement of cell repair function at the molecular and subcellular level by an intermittent feeding regimen and physical exercise, whose efficiency is empowered by the pharmacological intensification of autophagy by an antilipolytic drug (Acipimox) taken at a very low dosage while fasting. The beneficial effects on neurodegeneration are magnified by living an enriched environment. The effectiveness of the treatment will be detected by comparison with the expected frequencies

Research is a part in the "train body and brain" project organized and supported by Volterra Research Foundation, Rotary District 2071, and Alberto Sordi Association, Rome, under the patronage of the city of Volterra. The project was born to give school-age citizens the most modern information on how to achieve an effective primary prevention of all chronic age-associated diseases, including neurodegenerative diseases, and to offer adult people at higher risk of Alzheimer's *Primary Prevention of Alzheimer's Disease (AD) DOI: http://dx.doi.org/10.5772/intechopen.85418*

*Geriatric Medicine and Gerontology*

protection throughout the day.

phospholipids are paramount [63].

level by dietary and physical intervention, and targeted high-intensity training of cognitive brain functions to boost the induction of neurotrophic factors by the

a.Strengthening antioxidant defenses by nutritional intervention. It is said that the efficiency of antioxidant defenses may be boosted by eating the colors in the peel of fruits and vegetables that are known to contain complex mixtures of polyphenols and other phytochemicals. (e.g., polyphenols in blueberries and red grapes and wine [56]; epigallocatechin-3-gallate in green tea [57]; total phenolic, flavonoids, and flavonols in pomegranate [58, 59]). Red wine is particularly rich in specific polyphenolic compounds that appear to affect the biological processes of AD and Parkinson's disease, such as quercetin, myricetin, catechins, tannins, anthocyanidins, resveratrol, and ferulic acid. Indeed, there is now a consistent body of in vitro and in vivo data on the neuroprotective activity of red wine polyphenols [60], and it is known that effects may be boosted by adding more resveratrol [61]. Obviously, to enjoy optimum benefits, participants are taught to assume phytochemicals in a way to ensure

b.Increasing the resistance of cell membranes to oxidative stress. In order to get a better resistance to ROS-induced damage to brain and prevent from neurodegeneration and neuronal apoptosis, participants are instructed to a timed assumption of omega-3-rich fish oil. PUFAs are essential to control oxidative damage to neurons [62] when they are incorporated in the phospholipid molecules as a part in the proposed antioxidant machinery that protects membrane proteins from peroxidation (**Figure 1**) (On the contrary, free PUFAs are very sensitive to a free radical attack and ready to peroxidation.) To get full benefit from supplement, participants are requested to take pills at the first good meal after the long time of fasting, when chances to be incorporated in membrane

*Model of the membrane antioxidant machinery based on the proposed locations of dolichol (disc, green), ubiquinone (hexagon, red), and vitamin E (rhomb, pink) (see Cathcart et al. [69]; Sharma et al. [70]).*

physiological mechanism. Here, a few details on protocol are given.

**26**

**Figure 1.**


### **9. Conclusion**

A dynamic antiaging nutritional and physical intervention protocol including enriched living conditions is described useful to prevent the appearance of agingassociated AD. Treatment is already granted for free to the citizens of the city of Volterra known to be at higher risk of AD (relatives of AD patients and persons with mild cognitive impairment, likely to progress to clinically probable AD at a considerably accelerated rate compared with healthy age-matched individuals) to teach them how to counteract and retard the disease. Treatment was designed to delay biological aging and empower adult brain plasticity in order to retard the progress of brain aging and associated diseases. It includes a daily assumption of antioxidants (red wine polyphenols enriched with resveratrol), a reinforcement of membrane antioxidant defenses by the timed assumption of polyunsaturated fatty acids, and an enhancement of cell repair function at the molecular and subcellular level by an intermittent feeding regimen and physical exercise, whose efficiency is empowered by the pharmacological intensification of autophagy by an antilipolytic drug (Acipimox) taken at a very low dosage while fasting. The beneficial effects on neurodegeneration are magnified by living an enriched environment. The effectiveness of the treatment will be detected by comparison with the expected frequencies of disease appearance.

#### **Acknowledgements**

Research is a part in the "train body and brain" project organized and supported by Volterra Research Foundation, Rotary District 2071, and Alberto Sordi Association, Rome, under the patronage of the city of Volterra. The project was born to give school-age citizens the most modern information on how to achieve an effective primary prevention of all chronic age-associated diseases, including neurodegenerative diseases, and to offer adult people at higher risk of Alzheimer's disease (relatives of patients and patients with MCI) a free service of practical education on how to prevent and slow down the progression of the disease. The first goal is achieved by donating to high school students a pdf entitled "How to keep in shape, preventing diseases and defending good health" (available on the site www. fondazionevolterraricerche.org). The "train body and brain" project was approved by the Istituto Superiore di Sanità and has patronage of the Italian Ministry of Education.
