The purpose of this study was to learn the effect of omental transposition to the brain of patients who exhibited the most serious effects of long-standing Alzheimer's disease. Ten patients who had extremely low Mini Mental-State Examination scores of 2-14 underwent placement of their elongated pedicled omentum onto their left parietal-temporal cerebral cortex. Patients underwent pre- and post-operative MRI and SPECT scans in addition to long-term neurological and neuropsychological testing. All were followed up to one year. In spite of the patients' severe cognitive and functional disability, several of the patients demonstrated subjective and objective improvement, especially in terms of their functional status. [Neurol Res 2003; 25: 625-634]
Keywords:: Alzheimer's disease; omentum transposition; cerebral hypoperfusion; cerebral blood flow
Alzheimer's disease (AD) is the leading cause of dementia in the United States with the incidence of the disorder increasing in the late middle age and elderly population. With a population that is continuing to increase and grow older, it is inevitable that the number of AD patients and the cost for their treatment will continue to rise.
Alzheimer in 1907 first showed at autopsy the presence of abnormal nerve cells within the cerebral cortex which contained intraneural collections of fibers that were classified as neurofibrillary tangles (NFT) and extracellular collections of amyloid and neuronal process which were classified as senile plaques (SP)1. Controversy still remains as to whether these NFTs and SPs, which are the neuropathological markers for AD, are responsible for the dementia associated with AD or are simply a by-product of the disease. Some believe there is a direct relationship between the cognitive performance of AD patients and the number of senile plaques found in their brain2. Other investigators believe there is no such connection3,4.
The neurodegenerative characteristics of AD are known neurologically and neuropathologically, but the underlying cause of the disease still remains unknown. What seems reasonable to believe is that there are three groups of neurons which exist in the brain of an AD patient: 1. surviving neurons; 2. dead neurons; 3. neurons that are slowly shrinking and deteriorating over an extended period of time. The question arises as to what is the cause of neuronal deterioration and what if anything can be done to improve the situation. There is increasing belief and evidence that the cause of the decline in neuronal activity in AD may be the result of decreasing cerebral blood flow (CBF) with its associated decline in glucose and other nutrients that are necessary for continued function and survival of individual neurons.
Evidence has accumulated which strongly suggests that a unifying concept to explain AD can be postulated on the basis of cerebral hypoperfusion which is known to be present in the disease. The question to be asked and hopefully eventually answered is whether directly improving the ischemic condition present in AD could lead to an associated improvement of the cognitive and neurological condition of an AD patient?
It is known that placing the intact pedicled omentum directly on the brain of animals and humans significantly increases cerebral blood flow to both cerebral hemispheres5. In addition to the increase in CBF, the omentum incorporates in its tissues various neurotransmitters6,7, growth and angiogenic factors8, and additional biological substances. Based on the evidence that the omentum can supply these biological ingredients, the omentum has been placed on the brain of AD patients with preliminary studies showing that in half the patients there was demonstrable neurological and cognitive improvement9. The purpose of the study being presented was to gain further information as to the effect of omentum transposition on long-term AD patients who exhibited the most severe sequelae of their neurodegenerative disease.
The idea of omental transposition (OT) onto the human brain began in the surgical research laboratory where it was first learned that placing the omentum on the brain of dogs10 and monkeys11 led to an increase in CBF which originated from the omentum. Studies showed the blood flow from the omentum drained into the brain through numerous blood vessels that grew through the omental-cerebral interface after which these vessels penetrated vertically and deeply into the underlying brain12.
After it had become apparent that blood could be brought to an animal's brain by way of an intact pedicled omentum, operations using the technique began on humans. The initial patients who underwent omental transposition to their brain were those who had had a cerebral infarct and/or transient ischemia attacks. It was subsequently learned that omental transposition to these patients was effective in a number of cases13-16. It was believed that the reason for the success was due to the overall increase in CBF to patients with TIAs and the specific increase in CBF to penumbral cells surrounding the cerebral infarct in the post-stroke patients.
It was at this time that consideration was given to the idea that omental transposition might benefit AD patients by having the biologic agents within omental tissue exert their effects on deteriorating neurons located in the AD brain. It was further postulated that the slow decline of neuronal activity in AD was due to decreased CBF which gradually lowers neuronal energy (adenosine triphosphate-ATP) production to the point where neuronal death eventually occurs. The test of the benefit of omental transposition for patients with AD was to observe if the operation would stabilize neurological and cognitive decline and even more hopefully, reverse symptoms of AD.
The surgical technique for omental transposition has been previously reported17 but will be briefly described. The operation requires a laparotomy and a craniotomy thus requiring a general surgeon and a neurosurgeon. The initial maneuver is to make an upper midline incision followed by the removal of the omentum from its attachments to the entire length of the transverse colon. After this has been accomplished, the omentum is then separated from its proximal and central attachments to the stomach. When removing the omentum from the stomach, the separation is done directly on the greater curvature of the stomach leaving the gastroepiploic arteries and veins within the omental apron.
The final step for separating the omentum from the proximal position of the stomach requires the division of the left gastroepiploic vessels. This division of blood vessels at the high proximal level of the stomach eventually involves short gastric vessels. The arterial and venous connections between the stomach and the omental apron are supplied at this point solely from the right gastric and right gastroepiploic vessels. The omental pedicle is now elongated at this time, and to allow the intact pedicle to reach the brain without tension, further surgical tailoring of the omentum must be carried out. This involves dividing blood vessels in the omental apron with care being taken to ensure the preservation of at least one major artery and vein.
After the omental pedicle has been lengthened so that it can reach the top of the patient's head, several small (3-4 inch) transverse incisions are made along the chest wall just lateral to the midline with the side chosen for the transverse incisions depending on the side of the brain upon which the omentum is to be placed. The transverse incisions are connected subcutaneously which creates a long tunnel that extends from the upper pole of the midline abdominal incision, up the chest wall and neck to behind the ear.
One of the most difficult problems in the operation is developing the subcutaneous tunnel directly behind the ear where the tissue is extremely dense. It is essential that the tunnel at this location be at least 2-3 finger breadths in width so that there is no constriction on the omentum in this particular area within the tunnel. After the omentum has passed through the tunnel behind the ear, it is brought beneath the base of the scalp flap that had been previously dissected in making the initial craniotomy incision.
While the omental lengthening process is being developed, the neurosurgical portion of the operation is simultaneously being carried out. This aspect of the operation involves the removal of a piece of bone over the temporal-parietal area, which is later replaced. The dura mater is opened and small patches of arachnoid membrane are removed with great care being taken to avoid blood vessels on the surface of the brain.
At this point in the operation, the omentum is laid directly on the brain overlying the temporal-parietal area in addition to the frontal area if there is sufficient omental tissue. The dura is then sutured to the omentum. It is not necessary that the edges of the omentum be sutured to the cut edges of the dura since the omentum can be tucked under the edges of the dura for greater coverage of the brain. The edges of the dura are then sewn to the top surface of the omentum using absorbable sutures. It is important that the dura be sutured to the omentum in a fairly loose manner because if the dura is approximated too firmly, there is pressure placed on the underlying omentum which then causes direct pressure on the underlying brain. If this pressure is too excessive, there can be adverse neurological consequences affecting the contralateral side of the body.
If a lengthened pedicled omentum cannot reach the brain because of anatomical and technical reasons (the author has never experienced this), it is possible to bring a large and free piece of omentum up to the brain. The problem with this technique is that it requires vascular anastomoses between the gastroepiploic artery and vein in the omental segment and the superficial temporal artery and vein located in the scalp. This technique markedly increases operative time and the difficulty in performing the operation. Another drawback in this alternative method for placing the omentum on the brain is that a totally free piece of omentum ensures that all lymphatic channels connected to the free piece have been divided, which results in a marked and possibly even total loss of edema fluid absorption by the omentum. This is unfortunate since edema absorption is a major characteristic of the omentum and loss of this function can be critical if edema and cerebrospinal fluid accumulates around the free piece of omentum.
PATIENTS AND METHODS
Ten patients who ranged in age from 58 to 81 were selected for this study. The operations were performed at the 2nd Shanghai Medical University at the Xin Hua Hospital. Five men and five women were chosen who showed signs of what was diagnosed as being caused by Alzheimer's disease. Post-operative brain tissue examination later showed, however, that one patient had no pathological evidence of the disease in the very small piece that was examined (absence of senile plaques and neurofibrillary tangles), and another two patients showed histologic evidence of Lewy body dementia.
All patients were followed up post-operatively for a period of not less than one year. Pre- and post-operative magnetic resonance imaging (MRI) and single photon evolved computer tomography (SPECT) were performed on all the subjects in the study.
Neurological and neuropsychological testing was done by a neurologist. The later studies included pre- and post-operative Mini-Mental State Examinations (MMSE) and a modified Activities of Daily Living (ADL) score. MMSE scores range from 30 (normal) to 1 (most severe dementia). A score below 20 indicates moderate AD, and a score under 10 indicates severe dementia. An ADL level of 40 was the worst a patient could be and a 10 was the optimal. ADL scores indicating complete dependency on others would be 40 (10 categories at level 4 = 40). A patient demonstrating complete independence would be 10 (10 categories at level 1 = 10).
Activities of daily living
1. Gets in and out of tub by self if tub is usual means of bathing
2. Receives assistance in bathing only one part of body, such as the back or a leg
3. Receives assistance in bathing more than one part of body
4. Bathed in the bed
1. Controls urination and bowel movement completely by self
2. Has occasional 'accidents'
3. Needs supervision to keep urine or bowel control
4. Uses catheter, or is incontinent
1. Gets clothes (underwear and outer garments) from closets and drawers; dresses self completely
2. Gets clothes and dresses without assistance except in tying shoes
3. Gets dressed with partial assistance
4. Gets dressed or undressed with complete assistance
1. Feeds self using chopsticks and chooses the dish he/she likes
2. Feeds self except for assistance under particular circumstances such as removing fish bones
3. Receives assistance in feeding completely
4. Feeds by gastric tubes or intravenous fluids
1. Goes to 'toilet', cleans self, and rearranges clothes without assistance
2. Receives assistance in going to 'toilet' and arranging clothes after elimination, but cleans self
3. Receives assistance in cleaning self and arranging clothes after elimination or receives assistance in using night bedpan or commode
4. Is incontinent
1. Goes upstairs and downstairs without assistance
2. Moves in and out of bed or chair without assistance (may use object for support such as cane or walker)
3. Moves in and out of bed or chair with assistance
4. Does not get out of bed
1. Looks up numbers, dials, receives, and makes calls without help
2. Answers phone, but needs help in getting numbers or dialing
3. Does not dial, but answers the phone when it rings
4. Does not use telephone
1. Does heavy housework such as washing, cooking meals
2. Does light housework such as fixing the table
3. Does some housework under supervision
4. Does not do any housework
1. Manages buying needs; pays bills
2. Manages daily buying needs, but needs help managing payment of bills
3. Distinguishes money
4. Does not manage money
1. Washes face, brushes teeth, combs and trims nails on one's own
2. Washes face and combs hair, but needs partial help to brush teeth and is unable to trim nails
3. Receives assistance in washing face and brushing teeth
4. Does not wash face or brush teeth without assistance
BRIEF CLINICAL SUMMARIES
This was a 66-year-old male chemical engineer who had suffered memory loss for six years. Over this period he had become fully dependent on others and at the end of this time was unable to recognize any of his family. He had become violent and was known to strike others. Particularly disturbing was his pre-operative incontinence of urine and feces.
Following omental transposition (OT), his aggressive tendencies had disappeared by the third month. By the fifth post-operative month he showed further functional improvement and became cordial to neighbors. Over the next several months he started to watch television and reacted appropriately to the programs. His family claimed he began to joke. Of significance, he became continent of urine and feces.
His pre-operative Mini Mental-State Examination (MMSE) went from 11 to 17 at the end of one year. Also significantly, his ADL level which pre-operatively was 27, dropped to 15 (Figure 1). Pathology report of the patient's brain biopsy taken at the time of OT demonstrated histological evidence of Alzheimer's disease.
This was a 75-year-old male worker who had a five-year history of memory loss and marked decline in cognitive function associated with a diagnosis of Alzheimer's disease. Prior to OT he was violent to his wife. By three months after surgery he had become less belligerent to his wife, but over the next nine months showed no obvious improvement. At one year following surgery he exhibited neurologic and cognitive decline as evidenced by increased memory loss and decreased function of both hands. He had been incontinent of urine and feces pre-operatively and this condition remained unchanged post-operatively. His MMSE had dropped from 13 pre-op to 11 at one year. His ADL was 23 pre-op and was 24 at one year (Figure 1). The pathology report of his brain biopsy taken at surgery showed what was described as histologic evidence of Lewy body dementia with positive staining for alpha synuclein.
Patient is a 58-year-old female college instructor who had what was diagnosed as Alzheimer's disease over a six-year period. Prior to surgery the patient had become aphasic. By her third post-operative month she appeared to be more responsive and responded to questions directed at her by her facial expressions, but she still remained aphasic. During the year following her surgery her husband claimed she required less care. She had been incontinent of urine and feces before surgery and remained so post-operatively.
Mini-mental state examination rose very slightly from a pre-operative level of 2 to a level of 5 one year after surgery. ADL levels went from 31 pre-operatively to 26 at the end of the year (Figure 1). Brain biopsy at surgery was diagnosed as showing Alzheimer's disease.
Patient is a 65-year-old female who was a former school teacher. She had what was diagnosed as Alzheimer's disease for five years during which time she became demented and frequently became lost after leaving her home. By the time of her OT, she was not speaking and did not respond to her surroundings.
By the third post-operative month she was smiling and humming songs. She had more dexterity in her hands. By the sixth month her husband stated that there was definite improvement and her communication was constantly improving. Her husband was greatly appreciative over what had transpired concerning her condition. By one year after surgery her speech had definitely improved. Also of importance was she was no longer incontinent of urine and feces, a condition that was present before surgery.
Her MMSE went from 8 to 15 in twelve months. Her ADL went from 30 to 17 in twelve months (Figure 1). The pathology report of her brain biopsy taken at surgery showed Alzheimer's disease.
Patient is a 72-year-old former office director. His deteriorating cognitive condition began six years earlier when changes began to be noticed at home and at work. Eventually the patient was unable to find the bathroom and had to be fed. By the time he underwent OT he was unable to recognize anyone except his wife.
By three months after surgery, the patient's speech became clearer and his vocabulary increased. He began to choose his meals and learned the location of his bathroom. By six months after OT he could count his money, and over the next months the patient continued to improve. This included progression in his ability to speak and walk. His urinary and bowel functions which were stable pre-operatively remained the same during the post-operative period. His MMSE went from 15 to 19 after one year, and during this period his ADL went from 27 to 21 (Figure 1). Pathology report of brain biopsy taken at surgery was Lewy Body dementia with positive staining for alpha synuclein..
The patient is a 70-year-old male college instructor who was described as an intellectual. Pre-operatively he did not recognize his family and was unable to care for himself. He showed little if any post-operative improvement although his wife said at three months after surgery that it was easier to look after him than before the operation and he would let her know when he wanted to use the toilet.
He had an episode of epilepsy at four months and at twelve months after surgery. Pathology report of his brain biopsy taken at surgery was classified as Alzheimer's disease. Patient's MMSE pre-operatively was 9 and at one year post-operatively it remained at 9 (Figure 2). His ADL level was 33 pre-operatively and at one year was 30.
This patient is a 60-year-old housewife who had a five-year history of dementia. Prior to OT she did not know any member of her family and had lost all long- and short-term memory. She was considered by her family to be totally uncooperative. She was continent of urine and feces.
At three months after surgery, it was felt she had become somewhat more cooperative and had become interested in her grandchildren. At six months post-operative she remained stable, showing no change. At nine months she had become incontinent of urine and feces, and by twelve months after surgery had once again become more difficult to care for. Her MMSE before surgery was 10 and at twelve months was 8. Her ADL before surgery was 33 and at twelve months was 30 (Figure 2). Her brain biopsy taken at surgery confirmed the diagnosis of AD.
This was an 81-year old male who was very restless and difficult for his family to control. He had been diagnosed as having Alzheimer's disease. His pre-operative MRI showed extensive brain atrophy (Figure 3). This radiological finding was more vividly observed at the time of operation with his extensive brain atrophy exhibiting large empty spaces in the cranial cavity.
The patient's early post-operative course was very difficult. He developed respiratory failure which led to apnea and a tracheotomy with assisted ventilatory support. Associated with these complications was the development of auricular fibrillation and an abdominal incision separation.
By one month after surgery the patient had greatly improved and became very alert. By three months after surgery the patient was responding to television programs and laughing at appropriate times. He was once again conversing with his wife and was choosing his own meals. He was incontinent of urine and feces before surgery, but by three months had become continent. His clinical improvement was obvious, with such functional changes being considered surprising at his advanced age. Pre- and post-operative SPECT scans showed significant increase in CBF (Figure 4a,b).
His MMSE score was 5 pre-operatively and 7 at three months. His ADL level was 28 pre-operatively and 23 at three months (Figure 2). The pathology report of his brain biopsy taken at surgery confirmed the diagnosis of Alzheimer's disease. Tragically, the patient died suddenly four months after surgery from an acute myocardial infarction.
The patient is a 69-year-old retired teacher who was diagnosed over a six-year period as having Alzheimer's disease. Her cognitive symptoms had deteriorated rapidly during the last two years of her dementia. By the end of this time she no longer knew people except for her husband who became afraid to leave her alone at home since she frequently left her house and became lost. When she talked, it was without any continuity or logic.
In the days following OT, she failed to speak. Both these problems improved gradually over the next two weeks. By her third post-operative month, she could write her name when asked, but after this period her cognitive function began to deteriorate. At ten months after surgery the patient became incontinent of urine and feces; she was continent pre-operatively. During her eighth and fourteenth post-operative month she had a seizure.
Her MMSE level pre-operatively was 12 and one year later had dropped to 10. Her ADL pre-operatively went from 17 to 20 at one year post-operatively (Figure 2). Pathology report of her brain biopsy taken at surgery confirmed histologic evidence of Alzheimer's disease.
The patient is a 60-year-old female nurse who experienced five years of forgetting things and stumbling over words. At the end of this period she didn't know any of her family and had lost both long- and short-term memory. She was diagnosed as having Alzheimer's disease.
At time of OT she had become completely dependent on others since she was unable to brush her teeth, eat, and go to the toilet without help. She continuously drooled and was constantly moaning. She was incontinent of urine and stool and this condition remained post-operatively.
Little if anything occurred of benefit to the patient post-operatively.
Her MMSE level pre-operatively was 2, and at one year after surgery was still 2. Her ADL pre-operatively was 33 and at one year post-operatively was 34 (Figure 2).
This study showed that it is possible in some AD patients with severe dementia to show improvement following OT to their brain. The patients who were involved in this study were severely impaired (two patients with an MMSE of 2) and showed that there is potential for a surgical procedure (OT) to have some effect on their cognitive and neurological problem. It would be expected that patients who might undergo this operation in the future would be in earlier stages of their disease and would have a better opportunity to show subjective and objective improvement. This is based on the idea that the earlier in the progression of AD, the greater the number of deteriorating but still viable neurons that could be enhanced in metabolic activity due to the support offered to these failing neurons by the omentum.
There is increasing evidence being frequently presented that the underlying development of AD is based on decreased vascular perfusion to the brain18. Up to the present time the main focus in attempts to treat AD has been the use of cholinesterase inhibitors. The basis for using these agents is that they impede the enzyme cholinesterase from breaking down acetylcholine (ACh) which is the neurotransmitter that is believed essential, but considered deficient in amount in supplying critical areas of the brain involved with cognition and memory. This concept is under intense scrutiny, and recent papers by de la Torre19 and Aliev20 strongly discredit this belief and they present evidence that cerebral hypoperfusion leads to decreased metabolic activity in critical cerebral neurons that are at risk in AD. They both discuss cholinesterase inhibitors and agree that in the short term they can lead to moderate and short term improvement, but that the improvement is secondary to an effect known to all cholinesterase inhibitors: they all increase CBF21.
In view of the popular view that ACh deficiency is the cause of AD, let us look at evidence that attempts to diminish to a major degree this consideration. A long held belief has been that a lowered ACh level in AD could well be the cause of AD, and if ACh could be elevated in the brain, the AD patient would benefit. The argument that can question this concept is based on studies of choline acetyltransferase (ChAT) which is the marker for ACh. One would surmise that if a lower level of ACh is truly the cause of AD, it would be reasonable to expect its marker (ChAT) to have low concentrations in AD as compared to normal controls. Surprisingly this has not been found to be the case since patients with mild cognitive impairment (MCI) and moderate AD have been found to have ChAT levels that were comparable to levels found in nondemented, aging patients22. Even more surprising were ChAT levels that were found to be elevated in the frontal cortex and hippocampus of individuals with MCI23. These findings must begin to raise questions pertaining to the long-held belief that cholinergic hypoperfunction is the major course of AD. Evidence continues to surface which shows that the progression of AD is not due to the lack of the neurotransmitter, ACh, but that cerebral hypoperfusion is very likely the major factor in the etiology of the disease.
As one ages, there is a significant decrease in CBF that is simply a reflection of a normal aging phenomenon. Compounded with the expected loss of CBF associated with aging are unfavorable factors that are associated with daily living that further reduces CBF. These would include atherosclerosis, smoking, elevated cholesterol levels, diabetes, hypertension, and a host of other conditions.
Coupled with this decreasing CBF that goes along with routine aging and harmful living conditions is an associated decrease in CBF caused by capillary degeneration that occurs in practically all patients with AD24. These particular capillaries in AD patients have been found to be severely deformed, which results in disturbed microcirculation that causes the blood flow through these twisted and coiled blood vessels to revert from normal linear flow to abnormal disturbed flow - conditions which result in reduced CBF. The multiple factors that cause a lowering of the CBF across the blood-brain barrier lead to decreased levels of glucose and oxygen being delivered to the brain that are essential for the production of adenosine triphosphate (ATP) which is the energy source for neurons. Additionally, along with this detrimental decrease in CBF seen in AD is an associated limit of egress of catabolic products from the brain. All of these activities are harmful to the large numbers of deteriorating neurons that are present in AD.
It is now known that an intact pedicled omentum when placed on the surface of the brain can be helpful in patients with AD12. The question this raises is why should this occur? Probably the most important reason is that the omentum can deliver a large volume of blood into the brain, with this new volume of blood increasing on a yearly basis5.
Since decreasing CBF is one of the earliest signs of AD (if not the earliest sign)25, even a small increase in CBF originating from the omentum would be beneficial, especially if this new source of blood could be offered early in AD. This increase in CBF would be expected to increase glucose and oxygen levels presented to the brain. Being able to accomplish this would be of extreme importance since the areas of the AD brain that have been found to be the most seriously affected by suboptimal utilization of glucose and oxygen are the same areas that are present in AD26,27.
When there are decreased levels of glucose and oxygen in the brain, less metabolic support is offered to neurons that must produce adequate ATP levels as their energy source. The ATP levels within the neurons rely on adequate amounts of oxygen and glucose, glucose being the main substrate for glycolysis and oxygen required for oxidative phosphorylation. A progressive decline in levels of CBF eventually results in decreased ATP (energy) production within a neuron. When there is a critical reduction in CBF and ATP, a parallel drop in the activity of ischemic-sensitive cells such as CAI hippocampal neurons would be expected to occur. If CBF and ATP levels continue to decrease, eventually a decrease in cognitive and memory levels will result. The pathophysiological activity within a neuron caused by a lowered CBF leading to depressed metabolic activity should strongly highlight to pharmaceutical companies the importance of directing efforts toward developing methods for increasing CBF.
Even though increasing evidence appears to show that the principal driving force in the development of AD is cerebral hypoperfusion leading to decreased metabolic activity, there are other biological substances in the omentum that also may play a role in the benefit that has been observed following OT to the AD brain. There is the possibility, although small, that the omentum might have some effect on ACh levels in the brain since ChAT, the marker for ACh, is present in omental tissue28. Small amounts of ACh originating from the omentum might theoretically be transported through vascular connections at the omental-cerebral interface, which could have some effect on introducing or maintaining brain levels of ACh within the brain. That maintenance of ACh levels might occur is based on the finding that in the presence of middle cerebral artery (MCA) occlusion, various neurotransmitter levels drop within the brain and abnormal neuroelectrical (SEP) patterns develop. However, when MCA occlusion is done in association with OT to the brain, cerebral neurotransmitters did not decrease and no abnormal SEP patterns develop29. Additional studies have also shown that in the presence of MCA occlusion, OT to the brain continues to maintain cerebral protein synthesis, and prevents brain edema and Na-K flux30. When the omentum had not been placed on the brain, these protective cerebral events did not occur.
Other biological substances are present in omentum tissue which might benefit AD patients. These would include acidic31 and basic32 fibroblastic growth factors, a glycolipid which has been found to be angiogenic33, as well as another powerful angiogenic factor that has been reported to be the most angiogenic factor in the human body; namely, vascular endothelial growth factor (VEGF)34. Nerve growth factor is also present in omentum tissue8 which might have a stimulating effect in increasing neuritic growth into neurologically deficient areas of the brain that are present in the AD brain. All these biological agents known to be present in the omentum could have implications in treating AD, but the omentum's ability to increase CBF would seem to be the major cause of improvement that has been observed following OT to the AD brain.
An increase in CBF appears important in maintaining cognitive and neurological stability in the development of AD. Such an increase is especially critical if AD is eventually found to be a vascular disease that leads to neurodegeneration rather than a neurodegenerative process that leads to vascular changes. This increase in CBF would be very important, especially in the early stages of AD. The earlier CBF increases could be produced, the better would be the expected prognosis. The type of AD patient who might be best suited for OT to the brain would be those with mild cognitive impairment (MCI) or early AD. Only until future clinical trials are instituted to evaluate these suggestions will the place of OT for AD be established. If cerebral hypoperfusion eventually turns out to be a - if not the - major cause of AD, methods for combating cerebral hypoperfusion should increase in clinical and pharmaceutical interest.
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Harry S. Goldsmith*, Weilie Wu[dagger], Jun Zhong[dagger] and Mark Edgar[double dagger]
*Department of Surgery, University of Nevada School of Medicine, Reno, NV, USA
[dagger]Department of Neurosurgery, Shanghai 2nd Medical University, Shanghai, People's Republic of China
[double dagger]Department of Neuropathology, New York Presbyterian - Cornell Medical Center, New York, NY, USA
Correspondence and reprint requests to: Harry S. Goldsmith, PO Box 493, Glenbrook, NV 89413, USA. [firstname.lastname@example.org] Accepted for publication April 2003.
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