CHICAGO—A recent postmortem study has added a perplexing new twist to the tangled relationship between Alzheimer's disease and dementia with Lewy bodies (DLB). While the presence of Lewy bodies in brainstem and cortical neurons is the pathologic hallmark of DLB—patients with "pure" Alzheimer's lack the structures—researchers at Mount Sinai School of Medicine, in New York, have found that patients with both diseases have far more cortical Lewy bodies than do patients with DLB alone.

"Something about the co-occurrence leads to greater proliferation of Lewy body pathology," said lead author Michael Serby, MD, in an interview. "It seems that whatever the process of Lewy body formation is, it is somehow enhanced by the presence of Alzheimer's."

The study, presented at the annual meeting of the American Psychiatric Association, was an effort to shed light on the pathophysiology and cognitive impact of the dual diagnosis, often referred to as the Lewy body variant (LBV) of Alzheimer's disease. The researchers analyzed postmortem cortical samples collected from a series of patients who met the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria for either Alzheimer's disease (n = 49), Lewy body dementia (n = 10), or LBV (n = 16). Neuropathologic and clinical measures were then compared among the three groups.

As the researchers expected, the Alzheimer's disease and LBV groups were largely similar in their degree of typical Alzheimer's pathology. There was no difference between the groups in the prevalence of senile plaques in numerous CERAD-defined brain regions; tangle severity differed in only one area, the midfrontal cortex.

However, when the DLB and LBV groups were compared, the difference was far more striking. Assessing Lewy body counts in five cortical regions, Dr. Serby and colleagues observed an average of 108.6 Lewy bodies in LBV patients but only 17.0 in DLB patients. This disparity—a more than sixfold difference—supports the view that LBV is more than merely the co-occurrence of two distinct diseases. "The number of Lewy bodies is so much greater than in plain Lewy body dementia, it implies that there may be some interaction of these [pathologic] processes," said Dr. Serby, who is Associate Professor of Psychiatry at Mount Sinai.

THE CLINICAL PICTURE

A review of patients' clinical status reinforced this interpretation. The three groups did not differ in age at death or nursing home admission, nor in time spent in nursing homes. However, Clinical Dementia Ratings (CDRs) measured in the six months before death revealed that LBV patients were far more severely demented (mean CDR score, 4.25) than were patients with Alzheimer's disease (3.2) or DLB (3.0). Surprisingly, no previous studies have examined the relative severity of dementia in the three diagnoses.

While the new findings have little immediate clinical utility, they may shed light on the pathogenesis of LBV, Dr. Serby noted. However, "the most important clinical thing that we can do at this point is to perfect the diagnostic criteria for DLB, which I think are out of line."

—Peter Doskoch

Suggested Reading
1. Heyman A, Fillenbaum GG, Gearing M, et al. Comparison of Lewy body variant of Alzheimer's disease with pure Alzheimer's disease: Consortium to Establish a Registry for Alzheimer's Disease, Part XIX. Neurology.1999;52:1839-1844.

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