From the Camarillo Brain Study Project decades ago, this is the result of 5 hour glucose tolerance tests administered to mental hospital patiens with advanced Alzheimer’s disease. In the age group 75-84, the blood glucose values reached a peak of 215 mg% only after 2 hours and did not return to fasting levels even at 5 hours. This seems likely to reflect impaired capacity of the entire body for glucose utilization.

After decades of conflicting research on the development of this metabolic defect prior to dementia, a recent study has made major progress in filling the gap.Glucose Tolerance Status and Risk of Dementia in the Community: T.Ohara et al. , Neurology, 2011, Sept. 20.

This is a 15 year study of glucose tolerance tests in 1017 persons who were initially free of dementia. It was found that most, if not all, persons who developed Alzheimer’s disease had elevated 2 hour blood glucose levels while fasting levels were not elevated. This supports the writer’s view that Alzheimer’s disease is a generalized impairment in glucose utilization . A progressive elevation of the 2 hour blood glucose with normal fasting levels may be the first clinical manifestation of the disease and  this may be identified many years prior to dementia.

For more information visit www.saynotodementia.com

Peri-tangle neurites (Green arrows) are essential in the process of neuritic plaque formation. They are seen only in the neural tissue adjacent to post-necrotic neurofibrillary tangles and only in Alzheimer’s disease and in normal aging. Neuritic plaques and peri-tangle neurites are mutually interdependent (one does not occur without the other). It appears that a toxic material (presumably beta amyloid or a precursor) emanates from the dead nerve cell into the  neural tissue causing degeneration in adjacent nerve fibers which either terminate on the dead cell or are passing by. This is one way, if  not the only way, that beta amyloid (or its precusors) gain entrance into the neural tissue and this is likely a source of the extracellular deposit of insoluble beta amyloid in the neuritic plaques.

For more information: view e-book

In Alzheimer’s disease there are two distinct forms of neurofibrillary tangles. These are not different stages of the same pathologic process. The above image is a pre-necrotic form of tangle. The neurofibrils are compactly contained in large bundles and they stain very darkly with the silver stain. The nucleus is intact and of fairly normal appearance. These cells do not die unless they also show granulovacuolar degeneration. In the hippocampus the nerve cells with these tangles tend to be spared the lethal granulovacuolar degeneration suggesting a protective role.

The above image is a post-necrotic neurofibrillary tange. The neurofibrils are not as darkly stained and they appear like bars and the cell looks like an empty cage.These structures appear only after death of the cell. There is never a viable cell nucleus or other sign of cell  viability. The structure may be infiltrated by scavenger cells.

The concept that mental stress in mid-life may contribute to Parkinson’s diseas in later life is not a new idea. Shiba et al. in 2000* used the medical records linkage of the Rochester Epidemiology Project to identify 196 subjects who developed Parkinson’s disease in Olmstead County, Minnesota,during the years 1976- 1995. Each case was matched by sex and age to a general population control. For a period of 5 years prior to the motor symptoms, the frequency of documented anxiety and depression was more than double that of the controls.

In the Camarillo Brain Study Project autopsy series of 1200 cases admitted to an adult mental hospital, the incidence of classical Lewy bodies in cases, without Alzheimer’s disease, was almost restricted to those cases admitted over age 50 with long standing mental illness but without dementia. In this group the incidence of classical Lewy body formation was 28% compared to 1% in the controls. The incidence of Parkinson’s disease (11 cases) in the series was also restricted to this subgroup. www.saynotodementia.com

This relationship between Lewy body formation and stress may relate to the frequent development of Parkinson’s disease in persons recognized for their achievement whether for good or evil as in the cases of Pope John II and Adolf Hitler. More likely than not Lewy body formation may have been a factor in President Reagan’s Alzheimer disease. Recent studies have revealed a reduced risk of Parkinson’s diease in cigarette smokers. It is well known that cigarette smoking relieves anxiety and when persons quit cigarettes they often seek other anxiety relieving behaviors such as over-eating.

*Shiba M et al.  Anxiety disorders and depressive disorders preceeding Parkinson’s disease: A cases-controlled study  Mov Disord 2000 July 15 (4) 669-77

The Camarillo 1200 series included 45 similar cases in whch classical Lewy bodies were encountered as an isolated entity and without clear-cut clinical or pathologic features of dementia ( Woodard, 2007). That series included 135 cases of mental illness admitted at age 55 or older without clear-cut clinical dementia or pathologic criteria of dementia. In this subgroup 28% had classical brain stem Lewy bodies compared to 1% in the control material. This leaves no doubt that the association between classical Lewy bodies and mental illness is real and very significant. Most of these patients had incapacitating mental symptoms for many years prior to the Camarillo State Hospital admission but they presented a wide range of clinical diagnoses. Confusion in the literature results from inapropriately attributing dementia to “diffuse Lewy bodies” and from the inadequate pathologic criteria for the diagnosis of Alzheimer’s disease.

For more information and case studies: view e-book

LEWY  BODY  DEMENTIA.  DOES  IT  EXIST?

Some researchers have recently suggested that Lewy body dementia is secondary only to Alzheimer’s disease in the total problem of dementia. In the Camarillo Brain Study Project (Camarillo 1200 series) classical Lewy bodies were found as an isolated brain abnormality in 25% of patients admitted with a long standing history of mental disorder compared to 1% in the controls. However, These Camarillo State Hospital patients were not demented. These inclusions are easily and reliably identified using routine histologic stains.

In recent decades the Lewy body literature has been clouded by the emergence of the concept of “diffuse Lewy bodies”. These are poorly formed aggregations of material with chemical constituents similar to that of the classical Lewy body. Special stains for these chemical substances are used for identification. Counts of  “diffuse Lewy bodies” for pathologic diagnosis have been abandoned because the experts cannot aggree on the morphologic criteria. The more they look, the more they find. In a recent study of surgical specimens it was found the 27% of men have “diffuse Lewy bodies”  in the nerve cells of their prostatic tissue without evident clinical significance. These “diffuse Lewy bodies” may be assumed to be precursors of true Lewy bodies but as yet there is no definitive evidence that they cause dementia. Do they contribute to chronic mental illness without dementia?  That is a very interesting possibility.  

In the present state of knowledge, The real significance of real Lewy bodies is their association with enormous increase in risk for Alzheimer’s disease and Parkinson’s disease. The great majority of persons with classical Lewy bodies will have Alzheimer’s disease by age 80.

An autopsy study of 36 subjects over age 80, presenting all of the currently used criteria of Alzheimer’s disease (no assessment of granulovacuolar neuronal degeneration in the hippocampus). Twelve cases (33%) had no dementia. This suggests that 33% of cases with the pathologic diagnosis over age 80 do not have the disease. The error may be even grreater because some cases with Alzheimer dementia may not meet the inadequate criteria. This error in pathologic diagnosis has contributed to much confusion in the dementia literature of recent decades including that of “Lewy body dementia”.Probably most, if not all, cases of severe dementia associated with Lewy bodies are actually Alzheimer’s disease.The correct diagnosis depends upon assessment of granulovacuolar degeneration in hippocampal nerve cells.wwwsaynotodementia.com                                                                                                                

 Erton-Lyons et al.   2009   Neurology 72(4):354-60

var sc_project=3499702;
var sc_invisible=1;
var sc_partition=33;
var sc_security=”cd69c643″;

In a recent population study of 959 randomly selected subjects including 45 with Alzheimer’s disease (ages 69-78), the 2 hour blood glucose level was 27% higher and the fasting level 12% higher in the Alzheimer cases as compared to the nonalzheimer cases. (Vanhanen et al. 2006, Neurology 66:821-27)

This apathy of glucose metabolism is most likely related to the basic disease process leading to death of nerve cells in Alzheimer’s disease. Annual monitoring of the 2 hour blood glucose may prove to be an important part of any dementia prevention program with the goal of minimizing the incremental elevation wich probably appears many years prior to the dementia. Such monitoring would also detect diabetes mellitus in the earliest stages and thereby reduce risk for multi-infarct dementia.

For more information: view ebook