Lewy body dementia?

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.

Major diagnostic defect

MORE FACTS ON THE FAILURE OF CURRENTLY USED PATHOLOGIC CRITERIA OF ALZHEIMER’S DISEASE IN LATE ONSET CASES

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

Traumatic Encephalopathy Without Dementia

A case from the Camarillo Brain Study Project control series. This was a 27 year old man who had left spastic hemiplegia since sustaining severe head injury during infancy. The entire right cerebral hemisphere is reduced to a collapsible membrane of glial tissue, while the left crebral heisphere is essentially normal. In spite of the left hemiparesis, intellectual function was considered to be normal and he led a productive life. The case illustrates how severe brain damage can be without dementia if the damage is unilateral.

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Glucose Metabolism in Alzheimer’s Disease

The five hour glucose tolerance test results in Camarillo State Hospital patients with advanced Alzheimer’s disease are presented. In the older group (age 75-84), the mean 2 hour blood glucose level was 30% higher than normal according to the “normogram” of Andres. The elevation is prolonged, not returning to the base line in the entire five hours. The fasting level is not elevated.

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.
www.saynotodementia.com

Post-necrotic Neurofibrillary Tangle

This is the post-necrotic form of neurofibrillary tangle. These appear only after cell death and there is usually no stainable cell nucleus or other residual of the dead nerve cell. These may appear in any cerebral cortex and they are the only form of neurofibrillary tangle encountered in the brain stem. The pre-necrotic form of neurofibrillary tangle (refer to the 9-20-07 post) occurs only in cerebral cortex and these are most likely neuroprotective.

Alzheimer’s Disease Prevention

The Camarillo Brain Study Project is probably the largest controlled clinicopathologic study of mental hospital material, of its kind, ever undertaken. (refer to Nov. 20, 2007 post) The data suggests that the basic defect in Alzheimer’s disease is a generalized incapacity of cells to utilize glucose (sugar), leading to elevation of the blood sugar level. This process differs from diabetes mellitus in that it causes death of those cells most dependent on normal glucose utilization such as the hippocampal nerve cells, which are essential to memory. For many decades an age-related elevation in the blood sugar level has been recognized but this is not seen in all aging persons. It now seems likely that this insiduous elevation of blood sugar may be the earliest clinical manifestation of Alzheimer’s disease appearing many years prior to the dementia. Annual monitoring of the 2 hour blood glucose level (2 hours after a meal or test dose) after age 50 may prove to be an essential component in an Alzheimer’s disease prevention program with the goal of minimizing blood sugar elevation by controlling known Alzheimer’s disease risk factors. www.saynotodementia.com

Lewy Bodies in Mental Disease

In recent years some researchers have claimed that Lewy body dementia is the most prevalent dementia next to Alzheimer’s disease. Classical Lewy bodies are intraneuronal inclusions found only in certain brain stem nuclei and may be associated with nerve cell death in those nuclei (nerve cell clusters). Classical Lewy bodies are associated with nerve cell death in one specific nucleus (substantia nigra) in nearly all cases of Parkinson’s disease. Analysis of the material of the Camarillo Brain Study Project reveals that in the mental hospital population, classical Lewy bodies co-exist with Alzheimer’s disease in the majority of cases and with Parkinson’s disease in 27 percent of cases. Classical Lewy bodies do co-exist within a segment of the mental hospital population without Alzheimer’s disease but these cases are generally not demented and they are usually admitted to the hospital over age 50 after a long history of mental disorder or other mental stresses.

In recent decades much attention has focused on “diffuse Lewy bodies” which contain chemical constituents of classical Lewy bodies (alpha synuclein) as poorly formed protein aggregations. These diffuse Lewy bodies are found at all levels of the brain stem and in the cerebral cortex and they are not associated with nerve cell death. In the opinion of the writer they are not in themselves  a direct cause of dementia. In one recent pathologic study of surgical specimens, diffuse Lewy bodies were found in the prostatic tissue of 27 percent of men over age 40 without known clinical significance. www.saynotodementia.com

Liver Atrophy in Alzheimer’s Disease

In performing the many autopsies in the Camarillo Series it became evident that all organs of the body in Alzheimer’s disease were small as compared to the non-Alzheimer cases. The difference was often conspicuous with respect to the liver and the heart. A small pilot study was undertaken comparing a group of Alzheimer cases to a group of non-Alzheimer cases matched for age and sex in the age ranges of 60-69, 70-79 and 80-89 years. The difference in mean liver weghts was 19%, 15% and 12% respectively.In terms of mean gross organ weights the liver atrophy was actually greater than the brain atrophy. Just as in the case of the brain, the liver atrophy was greatest in the youngest group of cases. Recent research has demonstrated that loss of total body weight is a constant feature of Alzheimer’s disease. These observations are important because they support the growing view that Alzheimer’s disease adversely impacts all cells of the body even though those cells most dependent on normal glucose metabolism are the most vulnerable. www.saynotodementia.com

Alcoholic Mammillary Body Atrophy

The mammillary bodies are a tiny pair of spheroid structures protruding from the bottom of the brain.They are called mammillary bodies because, viewed externally, they simulate female human breasts. They are essential to memory function because they receive nerve impulses from hippocampal nerve cells and relay them to many other brain strutures. In some cases of chronic alcoholism there occurs severe nerve cell loss with gross atrophy and pigmentation of these structures (green arrows). Alcoholic memory blackouts are very common in heavy drinkers to the extent of not remembering how one got home from the party even after driving home. These recover after a night’s sleep and they are benign. However when the blackout extends into the next day, the risk becomes very great. Incapacity is immediate and severe due to memory impairment for recall and recognition of past experience. The Camarillo series yielded 40 of these cases. Even after admission to the mental hospital for several weeks many of these cases had complete remissions and then went on home leave. They all resumed drinking requiring re-admission within one month. There was never a second remission. Knowledge of this entity would no doubt have had preventive value. www.saynotodementia.com

The Camarillo Brain Study Project

This was probably the largest controlled study of brain morphology in mental disorders ever undertaken. The study was based on 2700 unselected autopsies with uniform gross and histologic evaluations. The autopsy sources in southern California included Camarillo State Hospital for acquired Mental disorders (1200 cases), Pacific State Hospital and Fairview State Hospital for mental retardation (600 cases) and controll cases from The Los Angeles County Coroner and Medical Examiner and from several regional general medical centers (900 cases). Camarillo State Hospital provided space for a Neuropathology Research Laboratory. The project was affiliated with the University of Southern California and with the University of California, Irvine, and funded by the California Dept. of Mental Hygiene Grants-in-Aid and by the National Institute of Mental Health. The Camarillo series (1200 cases) included 306 cases of Alzheimer’s disease, 42 cases of “classical” Lewy body disease, 16 cases of Pick’s disease, 119 cases of multi-infarct dementia, 40 cases of alcoholic mammillary body atrophy and 64 cases of syphilitic meningoencephalitis.

One of the most important findings in the study is the importance of granulovacuolar degeneration in hippocampal nerve cells for the pathologic diagnosis of Alzheimer’s disease. The failure to use this diagnostic criterion has led to gross errors in clinico-pathologic research. The entire concept of “Lewy body dementia” is flawed by the failure to identify all cases of Alzheimer’s disease in the pathologic laboratory. There is a major association between “classical” Lewy bodies and incapacitating mental disorders but these cases are not generally demented. www.saynotodementia.com