Mediterraneam Diet in preventing Alzheimer's Disease.

I agree with R Kale ⁽¹⁾ who wrote that "tackling the problems posed by the neurodegenerative disorders is difficult”. We could draw inspiration from the former US president (R. Reagan) who survived falls from horses, cancer of the skin and colon, and a bullet in the chest and is now quietly battling Alzheimer's".

However, even in such neurodegenerative disorder, in my opinion, we must aim early "clinical" diagnosis, possibly soon after the disease on-set, or better in the so-called "pre-pathological" phase (i.e. at the disease "real" risk). The diagnosis must be necessarily "clinical", and GPs (whom these patients visit first) have to recognize the initial or "pre-pathological" stages. These stages are characterized functionally by modification of Neuronal and Cerebral Evoked Potentials, and nowadays can be assessed at the bed-side by means of Biophysical Semeiotics (see Cerebral Tumour application of the method at semeioticabiofisica.it) .

As i presented in BMJ rapid response (16 June 2001) entitled "Early clinical biophysical-semeiotic Diagnosis of Alzheimer's Disease", the early development of the above method ^{(2, 3)}, yielded interesting data, based on the fact that there is notorious association between high serum cholesterol, raised blood pressure and, finally, insulin-resistance. In healthy individuals, from the microcirculatory point of view, during stress test both vasomotility (chaotic-deterministic oscillations of arterioles) and vasomotion (chaotic-deterministic fluctuations of nutritional capillaries and post-capillary venules) particularly in hippocampus, pre-frontal and parietal cerebral regions are maximally activated ^(2,3,4,5). On the contrary, individuals with a family history positive for Alzheimer's disease (and, of course, in patients in the first stages of the disease) under identical conditions have a particular form of microcirculatory activation, characterized by increased vasomotility and decreased vasomotion. I termed this condition "dissociated type". In brief, the flow- and flux-motion in the cerebral microcirculatory bed appears to be clearly decreased, possible due to the dangerous phenomenon of the so-called "microcirculatory blood-flow centralization".

Sadly, it is generally admitted that diagnosis of Alzheimer's disease (particularly in initial stages) is very difficult. In my 45-year-long clinical experience the test of acute pick of insulin secretion ^{(2, 3)} proved to be reliable in bed-side recognition of this devastating disorder at its initial stages. Although insulin is not necessarily involved in the glucose utilizations of cerebral neurons, there is a large number of insulin receptors in both cerebral cortex and hippocampus ⁽⁶⁾. Initial stages of Alzheimer's disease has been characterised by abnormal glucose metabolism in cerebral tissue, particularly the decrease in venous glucose level ⁽⁶⁾.
However, it was demonstrated that O₂ consumption is not affected, possibly due to the fact of neuronal utilization of the other "endocellular" substances rather then glucose, capable of causing neuronal impairment and death ⁽⁷⁾.

Alzheimer's disease is characterised by faulty response of cerebral insulin receptors, while the hormon may act as a growth factor. Clinically i observed that acute pick of insulin secretion ^{(2, 3, 4)} in healthy individuals activates the microcirculation in all biological systems, while in patients at risk for Alzheimer's disease and in Alzheimer's patients (even in early stage) microcirculatory activation is totally absent. It is importan, as well as interesting, that in no other cerebral disorders (including cerebral arteriosclerosis) i did observe the absence of insulin-receptor response, i.e. the absense of associated with the receptor microcirculatory activation, type I.

From the above remarks, I consider that Dr. Koudinov et al. theory (that I learned after my clinical research) according to which cholesterol is implicated in Alzheimer's disease (AD) ⁽⁸⁾. In fact, their own recent studies show that accurate neuronal cholesterol dynamics is critical for the synaptic plasticity and neural degeneration. These data also imply the link between neuronal lipid metabolism and tau and amyloid beta neurochemistry and propose that the classical AD brain lesions are functional consequences of the neuronal cholesterol and possibly phospholipid biological misregulation. In addition, i think that also insulin-receptors are less responsiv to insulin under such circumstances, as i demonstrated in my research. In my opinion, we have to pay attention to this intriguing theory, that finally enlightens the physiopathology of the biophysical-semeiotic manoeuvre, specific in diagnosing AD, even in early pre-clinical stage.

Author: Stagnaro Sergio M.D, Founder of Biophysical Semeiotics (Genova) Italy

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Credit and References:
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⁽¹⁾ Kale R. Neurodegenerative disorders. BMJ 323: 879-880 ( 20 October 2001) [ Full Text ]
⁽²⁾ Stagnaro S., Valutazione percusso-ascoltatoria della microcircolazione cerebrale globale e regionale. Atti, XII Congr. Naz. Soc. It. Di Microangiologia e Microcircolazione. 13-15 Ottobre, Salerno, e Acta Med.Medit. 145, 163 1986.
⁽³⁾ Stagnaro-Neri M., Stagnaro S., Semeiotica Biofisica: la manovra di Ferrero- Marigo nella diagnosi clinica della iperinsulinemia- insulinoresistenza. Acta Med. Medit. 13, 125 1997.
⁽⁴⁾ Stagnaro S., Stagnaro-Neri M., Valutazione percusso- ascoltatoria degli attacchi ischemici transitori e della insufficienza cerebrovascolare cronica in pazienti trattati con mesoglicano. Atti, IX Congr. Naz. It. Patologia Vascolare. Copanello, 6-9 Gennaio 1987. A cura di R. Del Guercio, G. Leonardo e G. Zanini. Pg. 765, Monduzzi Ed. Bologna 1987.
⁽⁵⁾ Stagnaro S., Stagnaro-Neri M., Il Test dell'Apnea nella Valutazione della Microcircolazione cerebrale in Cefalalgici. Atti, Congr. Naz. Soc. Ita. Microangiologia e Microcircolazione. A cura di C. Allegra. Pg. 457, Roma 10-13 Settembre 1987. Monduzzi Ed. Bologna 1987
⁽⁶⁾ Hoyer S. Models of Alzheimer's disease: cellular and molecular aspects. Journal of Neurotrasmission.(Suppl.) 49, 11, 1997.
⁽⁷⁾ Barinaga M. Is Apoptosis Key in Alzheimer's Disease? Science.281, 1303-4, 28August 1998 [ Full Text ].
⁽⁸⁾ Koudinov A.R., Koudinova N.V. Brain cholesterol pathology is the cause of alzheimer's disease. Clin. Med. & Health Research, November 27, 2001 Full Text ].