Dementia with Lewy bodies: Reliability and validity of clinical and pathologic criteria z Michael S. Mega, MD; Donna L. Masterman, MD; D. Frank Benson, MD; Harry V. Vinters, MD; Uwamie Tomiyasu, MD; Ann H. Craig, MD; Dean J. Foti, MD; Daniel Kaufer, MD; Douglas W. Scharre, MD; Lynn Fairbanks, PhD; and Jeffrey L. Cummings, MD Article abstract-Clinical criteria for dementia with Lewy bodies (DLB) have been proposed, but their formulation, reliability, and validity require further study. Pathologic criteria for DLB are also undergoing evolution. Two studies were conducted with the goal of identifying the components of these evolving criteria that may benefit from further refinement; one study evaluated the components of the clinical criteria and another study operationalized the pathologic criteria for DLB. Twenty-four patients with a premorbid diagnosis of probable or possible Alzheimer’s disease (AD) (n zy = 18), Parkinson’s disease (PD) (n = 51, or progressive supranuclear palsy (PSP) (n = 1) were studied. Inter-rater reliability and validity of the clinical criteria were determined by a retrospective chart review, done by five neurologists, and a blinded pathologic evaluation. The Consortium on dementia with Lewy bodies (CDLB) pathologic criteria were operationalized to compare past criteria and test the validity of the evolving clinical criteria on the dementia patients. Three or more cortical fields (at 250X magnification) with many (four or more) Lewy bodies (LBs) on ubiquitin immunoreactive sections were required to meet the CDLB neocortical score of >6. Fifteen of the AD patients had at least one LB in a cortical section, four had many LBs, while three had no LBs; all patients with movement disorder had at least one LB in a cortical section. The sensitivityhpecificity ratio of the CDLB probable DLB clinical criteria based upon many LBs being present was 75%/79%. Reformulated clinical criteria that require the presence of extrapyramidal signs significantly predicted those patients with many LBs versus those with few or no LBs zyxwv (x2 = 5.48, zyxwv p = 0.02) and increased clinical specificity to 100%. This preliminary study identifies components of the evolving clinical and pathologic criteria for DLB that require further refinement. NEUROLOGY 1996;47:1403-1409 The brains from patients with Alzheimer’s disease (AD)-type cortical changes reveal the presence of Lewy bodies (LBs) in 10 to 55% of Al- though most dementia patients with LBs also have AD pathology, some patients have multiple cortical LBs and no AD These patients support the claim that LBs alone may produce dementia. Unlike AD pathology, which occurs to some extent in many cognitively intact elderly individuals,I2 LBs have been found in only 2.3% of 131 nondemented elderly.’” In 273 cognitively intact individuals be- tween 10 and 109 years old, the prevalence of LBs was 5.1%, with a peak in the ninth decade of 12.8%.‘* Although this low reported frequency may increase with exhaustive searches for LBs and the use of more sensitive immunohistochemical techniques in wider populations, the current data suggest that LBs are uncommon in the normal aging brain. The pres- ence of a few LBs in the cortex does not appear to produce dementia; a pathologic review of 100 pa- tients with Parkinson’s disease (PDY revealed at least a few cortical LBs in every patient but a de- mentia syndrome in only zyx 44% of patients (one-third of these patients met pathologic criteria for AD). Chart review of patients with LBs has provided a clinical profile that may differentiate these patients from others with AD.B3J6-27 Interpretation of these studies is difficult because the evolving clinical pro- file associated with cortical LBs has not been tested against a common pathologic criterion. Pathologic validation of a clinical diagnosis helps refine the clin- ical criteria of a disease and thereby improves the specificity of antemortem diagnosis. Clinicopatho- logic correlations require an unequivocal pathologic marker that serves as the gold standard against which clinical criteria are compared. Due to this lack of agreement on both the clinical and pathologic cri- teria for the disorder, or group of disorders, associ- ated with cortical LBs, a Consortium on dementia with Lewy bodies (CDLB) established guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLBLZ8 Prior to the CDLB guide- lines DLB had at least three different pathologic cri- teria and two alternate sets of clinical criteria. Pro- From the Departmcmts of Neurology (Drs. Mega, Masterman, Benson, Craig, Foti, and Cummings) UCLA School of Medicine, Pathology and Laboratory Medicine, Section of Neuropathology (Drs. Vinters and Tomiyasu); West Los Angeles Veteran’s Affairs Medical Center Department of Laboratory Service (Dr. Tomiyasu); the Department of Neurology tDr. Kaufer), University of Pittsburgh, Pittsburgh, PA the Department of Neurology (Dr. Scharre), Ohio State University, (!olumbus, OH; and Psychiatry and Biobehavioral Sciences (Drs. Fairbanks and Cummings), UCLA School of Medicine, Los Angeles, CA. Supported by a VA Neuroscience Fellowship and an NIA Alzheimer’s Disease Center grant (P30, AG10123). Received April 24, 1996. Accepted in final form May 16, 1996. Address correspondence and reprint requests to Dr. Michael S. Mega, Department of Neurology, UCLA School of Medicine, 710 Westwood Plaza, Los Angeles, CA 90025. Copyright zyxwv 0 1996 by the American Academy of Neurology 1403