Low sensitivity in clinical diagnoses of dementia with Lewy bodies
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The success of future neurodegenerative disease (ND) therapies depends partly on accurate antemortem diagnoses. Relatively few prior studies have been performed on large, multicenter-derived datasets to test the accuracy of final clinical ND diagnoses in relation to definitive neuropathological findings. Data were analyzed from the University of Kentucky Alzheimer’s Disease Center autopsy series and from the National Alzheimer’s Coordinating Center (NACC) registry. NACC data are derived from 31 different academic medical centers, each with strong clinical expertise and infrastructure pertaining to NDs. The final clinical diagnoses were compared systematically with subsequent neuropathology diagnoses. Among subjects meeting final inclusion criteria (N = 2,861 for NACC Registry data), the strength of the associations between clinical diagnoses and subsequent ND diagnoses was only moderate. This was particularly true in the case of dementia with Lewy bodies (DLB): the sensitivity of clinical diagnoses was quite low (32.1% for pure DLB and 12.1% for Alzheimer’s disease (AD + DLB) although specificity was over 95%. AD clinical diagnoses were more accurate (85.0% sensitivity and 51.1% specificity). The accuracy of clinical DLB diagnoses became somewhat lower over the past decade, due apparently to increased “over-calling” the diagnosis in patients with severe cognitive impairment. Furthermore, using visual hallucinations, extrapyramidal signs, and/or fluctuating cognition as part of the clinical criteria for DLB diagnosis was of minimal utility in a group (N = 237) with high prevalence of severe dementia. Our data suggest that further work is needed to refine our ability to identify specific aging-related brain disease mechanisms, especially in DLB.
KeywordsDementia With Lewy Body Visual Hallucination Severe Cognitive Impairment Extrapyramidal Sign Final Clinical Diagnosis
This study was supported by grants R01 NS061933, K08 NS050110, P30-AG028383, and U01 AG016976 from the NIH, Bethesda, MD. We are deeply grateful to all of the study participants. We thank Ela Patel, Ann Tudor, Paula Thomason, Dr. Huaichen Liu and Sonya Anderson for the technical support, Nancy Stiles, MD and Allison Caban-Holt, PhD for the clinical evaluations, and Daron Davis MD for pathological evaluations. We also thank Leslie E. Phillips, MS for help with NACC data.
- 1.(1997) Consensus recommendations for the postmortem diagnosis of Alzheimer’s disease. The National Institute on Aging, and Reagan Institute Working Group on Diagnostic Criteria for the Neuropathological Assessment of Alzheimer’s Disease. Neurobiol Aging 18:S1-2Google Scholar
- 12.Jicha GA, Schmitt FA, Abner E, Nelson PT, Cooper GE, Smith CD, Markesbery WR (2008) Prodromal clinical manifestations of neuropathologically confirmed Lewy body disease. Neurobiol AgingGoogle Scholar
- 15.Luis CA, Barker WW, Gajaraj K, Harwood D, Petersen R, Kashuba A, Waters C, Jimison P, Pearl G, Petito C, Dickson D, Duara R (1999) Sensitivity and specificity of three clinical criteria for dementia with Lewy bodies in an autopsy-verified sample. Int J Geriatr Psychiatry 14:526–533CrossRefPubMedGoogle Scholar
- 17.McKeith IG, Dickson DW, Lowe J, Emre M, O’Brien JT, Feldman H, Cummings J, Duda JE, Lippa C, Perry EK, Aarsland D, Arai H, Ballard CG, Boeve B, Burn DJ, Costa D, Del Ser T, Dubois B, Galasko D, Gauthier S, Goetz CG, Gomez-Tortosa E, Halliday G, Hansen LA, Hardy J, Iwatsubo T, Kalaria RN, Kaufer D, Kenny RA, Korczyn A, Kosaka K, Lee VM, Lees A, Litvan I, Londos E, Lopez OL, Minoshima S, Mizuno Y, Molina JA, Mukaetova-Ladinska EB, Pasquier F, Perry RH, Schulz JB, Trojanowski JQ, Yamada M (2005) Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology 65:1863–1872CrossRefPubMedGoogle Scholar
- 18.McKeith IG, Galasko D, Kosaka K, Perry EK, Dickson DW, Hansen LA, Salmon DP, Lowe J, Mirra SS, Byrne EJ, Lennox G, Quinn NP, Edwardson JA, Ince PG, Bergeron C, Burns A, Miller BL, Lovestone S, Collerton D, Jansen EN, Ballard C, de Vos RA, Wilcock GK, Jellinger KA, Perry RH (1996) Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the Consortium on DLB International Workshop. Neurology 47:1113–1124PubMedGoogle Scholar
- 22.Nelson PT, Abner EL, Schmitt FA, Kryscio RJ, Jicha GA, Smith CD, Davis D, Poduska JW, Patel E, Mendiondo MM, Markesbery WR (2008) Modeling the association between 43 different clinical and pathological variables and the severity of cognitive impairment in a large autopsy cohort of elderly persons. Brain Pathol (in press)Google Scholar
- 24.Nelson PT, Jicha GA, Schmitt FA, Liu H, Davis DG, Mendiondo MS, Abner EL, Markesbery WR (2007) Clinicopathologic correlations in a large Alzheimer disease center autopsy cohort: neuritic plaques and neurofibrillary tangles “do count” when staging disease severity. J Neuropathol Exp Neurol 66:1136–1146CrossRefPubMedGoogle Scholar
- 25.Nelson PT, Kryscio RJ, Abner EL, Schmitt FA, Jicha GA, Mendiondo MS, Cooper G, Smith CB, Markesbery WR (2009) Acetylcholinesterase inhibitor treatment is associated with relatively slow cognitive decline in patients with Alzheimer’s disease and AD + DLB. J Alzheimers Dis 16:29–34PubMedGoogle Scholar
- 37.Tsuang D, Simpson K, Larson EB, Peskind E, Kukull W, Bowen JB, McCormick W, Teri L, Montine T, Thompson ML, Leverenz JB (2006) Predicting Lewy body pathology in a community-based sample with clinical diagnosis of Alzheimer’s disease. J Geriatr Psychiatry Neurol 19:195–201CrossRefPubMedGoogle Scholar