Characteristics of patients misdiagnosed with Alzheimer’s disease and their medication use: an analysis of the NACC-UDS database

BMC Geriatrics

Thomas G Beach⁵  Andrew Siderowf⁴  Tolulope Fafowora²  David L Roth²  Haya Ascher-Svanum³  Joseph E Gaugler¹ 

[1] Center on Aging, School of Nursing, University of Minnesota, Minneapolis, MN, USA;Center on Aging and Health, School of Medicine, Johns Hopkins University, Baltimore, MD, USA;Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA;Avid Radiopharmaceuticals Inc, Philadelphia, PA, USA;Banner Sun Health Research Institute, Sun City, AZ, USA

关键词: Neuropathology;    Autopsy;    Misdiagnosis;    Diagnosis;    Alzheimer disease;   

Others  :  855549
DOI  :  10.1186/1471-2318-13-137

 received in 2013-07-15, accepted in 2013-12-17,  发布年份 2013

【 摘 要 】

Background

This study compared individuals whose clinical diagnosis of Alzheimer’s disease (AD) matched or did not match neuropathologic results at autopsy on clinical and functional outcomes (cognitive impairment, functional status and neuropsychiatric symptoms). The study also assessed the extent of potentially inappropriate medication use (using potentially unnecessary medications or potentially inappropriate prescribing) among misdiagnosed patients.

Methods

Longitudinal data from the National Alzheimer’s Coordinating Center Uniform Data Set (NACC-UDS, 2005–2010) and corresponding NACC neuropathological data were utilized to compare 88 misdiagnosed and 438 accurately diagnosed patients.

Results

Following adjustment of sociodemographic characteristics, the misdiagnosed were found to have less severe cognitive and functional impairment. However, after statistical adjustment for sociodemographics, dementia severity level, time since onset of cognitive decline and probable AD diagnosis at baseline, the groups significantly differed on only one outcome: the misdiagnosed were less likely to be depressed/dysphoric. Among the misdiagnosed, 18.18% were treated with potentially inappropriate medication. An additional analysis noted this rate could be as high as 67.10%.

Conclusions

Findings highlight the importance of making an accurate AD diagnosis to help reduce unnecessary treatment and increase appropriate therapy. Additional research is needed to demonstrate the link between potentially inappropriate treatment and adverse health outcomes in misdiagnosed AD patients.

【 授权许可】

   
2013 Gaugler et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Grand JH, Caspar S, Macdonald SW: Clinical features and multidisciplinary approaches to dementia care. J Multidiscip Healthc 2011, 4:125-147.
• [2]Hyman BT, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Carrillo MC, Dickson DW, Duyckaerts C, Frosch MP, Masliah E, Mirra SS, Nelson PT, Schneider JA, Thal DR, Thies B, Trojanowski JQ, Vinters HV, Montine TJ: National Institute on Aging-Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease. Alzheimers Dement 2012, 8(1):1-13.
• [3]McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, Mohs RC, Morris JC, Rossor MN, Scheltens P, Carrillo MC, Thies B, Weintraub S, Phelps CH: The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011, 7(3):263-269.
• [4]Beach TG, Monsell SE, Phillips LE, Kukull W: Accuracy of the clinical diagnosis of Alzheimer disease at National Institute on Aging Alzheimer Disease Centers, 2005–2010. J Neuropathol Exp Neurol 2012, 71(4):266-273.
• [5]Lim A, Tsuang D, Kukull W, Nochlin D, Leverenz J, McCormick W, Bowen J, Teri L, Thompson J, Peskind ER, Raskind M, Larson EB: Clinico-neuropathological correlation of Alzheimer’s disease in a community-based case series. J Am Geriatr Soc 1999, 47(5):564-569.
• [6]Mayeux R, Saunders AM, Shea S, Mirra S, Evans D, Roses AD, Hyman BT, Crain B, Tang MX, Phelps CH: Utility of the apolipoprotein E genotype in the diagnosis of Alzheimer’s disease. Alzheimer’s disease centers consortium on apolipoprotein E and Alzheimer’s disease. N Engl J Med 1998, 338(8):506-511.
• [7]Ranginwala NA, Hynan LS, Weiner MF, White CL III: Clinical criteria for the diagnosis of Alzheimer disease: still good after all these years. Am J Geriatr Psychiatry 2008, 16((5):384-388.
• [8]Pearl GS: Diagnosis of Alzheimer’s disease in a community hospital-based brain bank program. South Med J 1997, 90(7):720-722.
• [9]Klatka LA, Schiffer RB, Powers JM, Kazee AM: Incorrect diagnosis of Alzheimer’s disease. A clinicopathologic study. Arch Neurol 1996, 53(1):35-42.
• [10]Piccini C, Bracco L, Amaducci L: Treatable and reversible dementias: an update. J Neurol Sci 1998, 153(2):172-181.
• [11]Hejl A, Hogh P, Waldemar G: Potentially reversible conditions in 1000 consecutive memory clinic patients. J Neurol Neurosurg Psychiatry 2002, 73(4):390-394.
• [12]Wang BW, Lu E, Mackenzie IR, Assaly M, Jacova C, Lee PE, Beattie BL, Hsiung GY: Multiple pathologies are common in Alzheimer patients in clinical trials. Can J Neurol Sci 2012, 39(5):592-599.
• [13]Gay BE, Taylor KI, Hohl U, Tolnay M, Staehelin HB: The validity of clinical diagnoses of dementia in a group of consecutively autopsied memory clinic patients. J Nutr Health Aging 2008, 12(2):132-137.
• [14]Jellinger KA: Clinicopathological analysis of dementia disorders in the elderly–an update. J Alzheimers Dis 2006, 9(3 Suppl):61-70.
• [15]Brunnstrom H, Englund E: Clinicopathological concordance in dementia diagnostics. Am J Geriatr Psychiatry 2009, 17(8):664-670.
• [16]Boxer AL, Boeve BF: Frontotemporal dementia treatment: current symptomatic therapies and implications of recent genetic, biochemical, and neuroimaging studies. Alzheimer Dis Assoc Disord 2007, 21(4):S79-S87.
• [17]Irwin D, Lippa CF, Rosso A: Effects of prescribed medications on cognition and behavior in frontotemporal lobar degeneration. Am J Alzheimers Dis Other Demen 2010, 25(7):566-571.
• [18]Lomen-Hoerth C, Murphy J, Langmore S, Kramer JH, Olney RK, Miller B: Are amyotrophic lateral sclerosis patients cognitively normal? Neurology 2003, 60(7):1094-1097.
• [19]Lomen-Hoerth C, Anderson T, Miller B: The overlap of amyotrophic lateral sclerosis and frontotemporal dementia. Neurology 2002, 59(7):1077-1079.
• [20]Kerchner GA, Tartaglia MC, Boxer A: Abhorring the vacuum: use of Alzheimer’s disease medications in frontotemporal dementia. Expert Rev Neurother 2011, 11(5):709-717.
• [21]McKeith I, Mintzer J, Aarsland D, Burn D, Chiu H, Cohen-Mansfield J, Dickson D, Dubois B, Duda JE, Feldman H, Gauthier S, Halliday G, Lawlor B, Lippa C, Lopez OL, Machado JC, O’Brien J, Playfer J: Dementia with Lewy bodies. Lancet Neurol 2004, 3(1):19-28.
• [22]Baskys A: Lewy body dementia: the litmus test for neuroleptic sensitivity and extrapyramidal symptoms. J Clin Psychiatry 2004, 65(Suppl 11):16-22.
• [23]Shim YS, Roe CM, Buckles VD, Morris JC: Clinicopathologic study of Alzheimer’s disease: Alzheimer mimics. J Alzheimers Dis 2013, 35(4):799-811.
• [24]Morris JC, Weintraub S, Chui HC, Cummings J, Decarli C, Ferris S, Foster NL, Galasko D, Graff-Radford N, Peskind ER, Beekly D, Ramos EM, Kukull WA: The Uniform Data Set (UDS): clinical and cognitive variables and descriptive data from Alzheimer Disease Centers. Alzheimer Dis Assoc Disord 2006, 20(4):210-216.
• [25]Mirra SS, Heyman A, McKeel D, Sumi SM, Crain BJ, Brownlee LM, Vogel FS, Hughes JP, van Belle G, Berg L: The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer’s disease. Neurology 1991, 41(4):479-486.
• [26]McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM: Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA work group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s disease. Neurology 1984, 34(7):939-944.
• [27]Braak H, Braak E: Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 1991, 82(4):239-259.
• [28]Folstein MF, Folstein SE, McHugh PR: Mini-Mental State: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975, 12:189-198.
• [29]Pfeffer RI, Kurosaki TT, Harrah CH Jr, Chance JM, Filos S: Measurement of functional activities in older adults in the community. J Gerontol 1982, 37(3):323-329.
• [30]Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J: The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology 1994, 44(12):2308-2314.
• [31]Yesavage JA, Brink TL, Rose TL, Lum O, Huang V, Adey M, Leirer VO: Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res 1982, 17(1):37-49.
• [32]Di Napoli M: Benefits of statins in cerebrovascular disease. Curr Opin Investig Drugs 2004, 5(3):295-305.
• [33]Mendez MF: Frontotemporal dementia: therapeutic interventions. Front Neurol Neurosci 2009, 24:168-178.
• [34]Hodges JR: Hope abandoned: memantine therapy in frontotemporal dementia. Lancet Neurol 2013, 12(2):121-123.
• [35]Lewy Body Dementia Association, Inc: Treatment options. http://www.lbda.org/content/treatment-options webcite. Updated 2012. Accessed January 27th, 2013
• [36]Rolinski M, Fox C, Maidment I, McShane R: Cholinesterase inhibitors for dementia with Lewy bodies, Parkinson’s disease dementia and cognitive impairment in Parkinson’s disease. Cochrane Database Syst Rev 2012., 3CD006504
• [37]SAS Institute Inc: Base SAS® 9.3 Procedures Guide. Cary, NC: SAS Institute Inc; 2011.
• [38]Bloudek LM, Spackman DE, Blankenburg M, Sullivan SD: Review and meta-analysis of biomarkers and diagnostic imaging in Alzheimer’s disease. J Alzheimers Dis 2011, 26(4):627-645.
• [39]Zhang S, Han D, Tan X, Feng J, Guo Y, Ding Y: Diagnostic accuracy of 18 F-FDG and 11C-PIB-PET for prediction of short-term conversion to Alzheimer’s disease in subjects with mild cognitive impairment. Int J Clin Pract 2012, 66(2):185-198.
• [40]Grundman M, Pontecorvo MJ, Salloway SP, Doraiswamy PM, Fleisher AS, Sadowsky CH, Nair AK, Siderowf A, Lu M, Arora AK, Agbulos A, Flitter ML, Krautkramer MJ, Sarsour K, Skovronsky DM, Mintun MA, for the AV45-A17 Study Group: Potential impact of amyloid imaging on diagnosis and intended management in patients with progressive cognitive decline. Alzheimer Dis Assoc Disord 2013, 27(1):4-15.
• [41]Schipke CG, Peters O, Heuser I, Grimmer T, Sabbagh MN, Sabri O, Hock C, Kunz M, Kuhlmann J, Reininger C, Blankenburg M: Impact of beta-amyloid-specific florbetaben PET imaging on confidence in early diagnosis of Alzheimer’s disease. Dement Geriatr Cogn Disord 2012, 33(6):416-422.