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NINDS CDE Notice of Copyright
CDR System
Availability
The CDR System is owned by Bracket (www.bracketglobal.com) who license it for use in clinical trials.
 
Classification
Supplemental -- Highly Recommended: Parkinsons Disease (PD)
Short Description of Instrument
The Cognitive Drug Research computerized cognitive assessment system (CDR System) is an integrated set of cognitive tasks, developed in the 1980s to provide a practical, sensitive, reliable and repeatable method of assessing core aspects of cognitive function in healthy volunteers and any patient population. Responses are made via a simple YES/NO button box, and early work established that patients with Parkinson’s disease could reliably use the apparatus (Simpson et al., 1991). The 9 core tests assess attention, information processing, executive control, working memory (articulatory & spatial) and episodic memory (verbal & visual). It does not require specialist administration and can be completed within 20 minutes, with the data being stored and processed automatically. There are over 60 parallel forms of all tasks and it is available in over 50 languages. The System is modular, allowing subsets of tests to be employed. It has been widely used in a variety of trials in PD (see references). The System includes a pattern separation task, sensitive to neurogenesis in the dentate gyrus, which has provided the first behavioral data of neurogenesis deficits in PD (Wesnes & Burn, 2013a).
 
Comments/Special Instructions
There is also a CDR System version for use with patients with PDD, which contains the same tasks but fewer stimuli. This version has been successfully used in clinical trials with rivastigmine, donepezil and memantine to demonstrate treatment related improvements in cognitive function, particularly to attention. Further, in a population of 451 PDD patients when compared to other tests (ADAS-cog, MMSE and Delis Kaplan Verbal Fluency), the CDR attention tests were the single strongest cognitive predictor of ADL status, matching the strength of motor disability (Bronnick et al., 2005).
 
Scoring
The accuracy and speed of each response in every task is automatically captured. These are transferred electronically to Bracket, where the various scores for each task are calculated using in-house software. These summary scores are provided in pre-agreed formats, together with a range of core domain scores derived from the various test scores. These domain scores have been validated by factor analysis, and cover major aspects of attention, information processing, working and episodic memory. Age and gender matched normative data are available from the extensive Bracket databases, including a large population of healthy volunteers as well as a wide range of clinical conditions including PD and all of the major dementias.
 
Rationale/Justification
The CDR System is the embodiment of the advantages of automated testing over pencil and paper procedures. Test administration is standardized, and the automatic capture and scoring of data overcomes the majority of the problems experienced in clinical trials with non-automated tests. The precise measurement of the speed of information processing in attentional tasks confers a strong advantage to the CDR System. The system can identify a characteristic profile of attentional impairment in PD, even in recently diagnosed untreated patients (Moon et al., 2003). In a population of 484 PD patients, using the 2012 MDS task force Diagnostic Criteria for PD-MCI Level II, data from the system identified attentional PD-MCI in 59%, amnestic in 15% and visuospatial in 51% of patients (Wesnes & Burn, 2013b). This contrasted sharply to an analysis using the same criteria of 1,346 patients from 8 cohorts which identified attentional PD-MCI in 10%, amnesic in 13% and visuospatial in 11% of patients (Aarsland et al., 2010). Further, the CDR System attention tests predict cognitive decline over 3 years in PD (Taylor et al., 2008), as well as the frequency of falls (Allcock et al., 2009). Finally, deep brain stimulation has been found to improve speed on CDR System tests of attention in PD (Thevathasan et al., 2010).
 
References
CDR System publications containing data from PD patients:
 
Allcock LM, Rowan EN, Steen IN, Wesnes K, Kenny RA, Burn DJ. Impaired attention predicts falling in Parkinson's disease. Parkinsonism Relat Disord. 2009;15(2):110–115.
 
Allcock LM, Kenny RA, Mosimann UP, Tordoff S, Wesnes KA, Hildreth AJ, Burn DJ. Orthostatic hypotension in Parkinson's disease: association with cognitive decline? Int J Geriatr Psychiatry. 2006;21(8):778–783.
 
Almeida OP, Burton EJ, McKeith I, Gholkar A, Burn D, O'Brien JT. MRI study of caudate nucleus volume in Parkinson's disease with and without dementia with Lewy bodies and Alzheimer's disease. Dement Geriatr Cogn Disord. 2003;16(2):57–63.
 
Ballard CG, Aarsland D, McKeith I, O'Brien J, Gray A, Cormack F, Burn D, Cassidy T, Starfeldt R, Larsen JP, Brown R, Tovee M. Fluctuations in attention: PD dementia vs DLB with parkinsonism. Neurology. 2002;59(11):1714–1720.
 
Hudson G, Stutt A, Eccles M, Robinson L, Allcock LM, Wesnes KA, Chinnery PF, Burn DJ. Genetic variation of CHRNA4 does not modulate attention in Parkinson's disease. Neurosci Lett. 2010;479(2):123–125.
 
Mace JL, Porter RJ, Dalrymple-Alford JC, Wesnes KA, Anderson TJ. Effects of acute tryptophan depletion on neuropsychological and motor function in Parkinson's disease. J Psychopharmacol. 2010;24(10):1465–1472.
 
Molloy SA, Rowan EN, O'Brien JT, McKeith IG, Wesnes K, Burn DJ. Effect of levodopa on cognitive function in Parkinson's disease with and without dementia and dementia with Lewy bodies. J Neurol Neurosurg Psychiatry. 2006;77(12):1323–1328.
 
Moon G, Wesnes KA, Manktelow TC. Cognitive deficits in recently diagnosed untreated patients with Parkinson’s disease. J Psychopharmacol. 2002;16: A31
 
Mosimann UP, Mather G, Wesnes KA, O'Brien JT, Burn DJ, McKeith IG. Visual perception in Parkinson disease dementia and dementia with Lewy bodies. Neurology. 2004;63(11):2091–2096.
 
Simpson PM, Surmon DJ, Wesnes KA, Wilcock GK. The Cognitive Drug Research computerised assessment system for demented patients: A validation study. Int J Geriatric Psych. 1991;6: 95–102.
 
Taylor JP, Rowan EN, Lett D, O'Brien JT, McKeith IG, Burn DJ. Poor attentional function predicts cognitive decline in patients with non-demented Parkinson's disease independent of motor phenotype. J Neurol Neurosurg Psych. 2008;79(12):1318–1323
 
Thevathasan W, Silburn PA, Brooker H, Coyne TJ, Khan S, Gill SS, Aziz TZ, Brown P. The impact of low-frequency stimulation of the pedunculopontine nucleus region on reaction time in parkinsonism. J Neurol Neurosurg Psych. 2010;81(10):1099–1104.
 
Wesnes KA, Burn DJ. Compromised object pattern separation performance in Parkinson’s disease suggests dentate gyrus neurogenesis may be compromised in the condition. J Alzheim Dis Parkinsonism 2013a;3:131.
 
Wesnes KA, Burn DJ The frequency of Mild Cognitive Impairment in Parkinson’s disease as assessed with automated cognitive tests. Paper selected for Blue Ribbon Highlights Session at: 17th International Congress of Parkinson’s Disease and Movement Disorders, Sydney, Australia, June 2013b.
 
Yarnall AJ, Breen DP, Duncan GW, Khoo TK, Coleman SY, Firbank MJ, NombelaOtero C, Rowe J, Mollenhauer B, Hudson G, Chinnery PF, O’Brien JT, Robbins TW, Wesnes KA, Brooks DJ, Barker RA, Burn JA. Characterising Mild Cognitive Impairment in Incident Parkinson’s Disease: The ICICLE-PD Study. Neurology. 2014;82:308–316.
 
Additonal Papers with CDR System data in PDD patients:
 
Barone P, Burn DJ, van Laar T, Hsu C, Poewe W, Lane RM. Rivastigmine versus placebo in hyperhomocysteinemic Parkinson's disease dementia patients. Mov Disord. 2008;23:1532–1540.
 
Bronnick K, Ehrt U, Emre M, De Deyn PP, Wesnes KA, Tekin S, Aarsland D. Attentional deficits affect activities of daily living in dementia associated with Parkinson's disease. J Neurol Neurosurg Psych. 2006;77:1136–1142.
 
Burn D, Emre M, McKeith IG, De Deyn PP, Aarsland D, Hsu C, Lane R. Effects of rivastigmine in patients with and without visual hallucinations in dementia associated with Parkinson's disease. Mov Disord. 2006;21:1899–1907.
 
Dujardin K, Devos D, Duhem S, Desté A, Marié R-M, Durif F, Lacomblez L, Touchon J, Pollak P, Péré J-J. Utility of the Mattis dementia rating scale to assess the efficacy of rivastigmine in dementia associated with Parkinson’s disease. J Neurol. 2006;253:1154–1159.
 
Emre M, Aarsland D, Albanese A, Byrne EJ, Deuschl G, De Deyn PP, Durif F, Kulisevsky J, van Laar T, Lees A, Poewe W, Robillard A, Rosa MM, Wolters E, Quarg P, Tekin S, Lane R. Rivastigmine for dementia associated with Parkinson's disease. NEJM. 2004;351:2509–2518.
 
Harvey PD, Ferris SH, Cummings JL, Wesnes KA, Hsu C, Lane RM, Tekin S. Evaluation of Dementia Rating Scales in Parkinson’s Disease Dementia. Am J Alzheimers Dis Other Demen. 2010;25:142–148.
 
Rowan EN, McKeith IG, Saxby BK, O'Brien JT, Burn D, Mosimann U, Newby J, Daniel S, Sanders J, Wesnes KA. Effects of donepezil on central processing speed and attentional measures in Parkinson's disease with Dementia and Dementia with Lewy Bodies. Dement Geriatr Cogn Disord. 2007;23:161–167.
 
Schmitt FA, Aarsland D, Brønnick KS, Meng X, Tekin S, Olin JT. Evaluating rivastigmine in mild-to-moderate Parkinson's disease dementia using ADAS-cog items. Am J Alzheimers Dis Other Demen. 2010;25(5):407–413.
 
Tekin S, Lane R. Rivastigmine in the treatment of dementia associated with Parkinson’s disease: a randomized, double-blind, placebo-controlled study. Prog Neurotherapeutics Neuropsychopharmacol. 2005;1:1–13.
 
Wesnes KA. Rivastigmine tartrate with a focus on dementia associated with Parkinson's disease. Drugs of Today. 2007;43:349–359.
 
Wesnes KA, McKeith IG, Edgar C, Emre M, Lane R. Benefits of rivastigmine on attention in dementia associated with Parkinson disease. Neurology. 2005;65:1654–1656.
 
Wesnes KA, Aarsland D, Ballard C, Londos E. Memantine improves attention and episodic memory in Parkinson's disease dementia and dementia with Lewy bodies. Int J Geriatr Psychiatry. 2015;30(1):46–54.
 
Williams-Gray CH, Barker RA. Visual hallucinations predict increased benefits from rivastigmine in Parkinson's disease dementia. Nat Clin Pract Neurol. 2007;3(5):250–251.
 
Zaffalon M, Wesnes K, Petrini O. Reliable diagnoses of dementia by the naïve creedal classifier inferred from incomplete cognitive data. Artif Intell Med. 2003;29(1–2):61–79
 
Papers commenting upon or using CDR Sytem Data in PD or PD Dementia:
 
Aarsland D, Bronnick K, Williams-Gray C, Weintraub D, Marder K, Kulisevsky J, Burn D, Barone P, Pagonabarraga J, Allcock L, Santangelo G, Foltynie T, Janvin C, Larsen JP, Barker RA, Emre M. Mild cognitive impairment in Parkinson disease: a multicenter pooled analysis. Neurology. 2010;75(12):1062–1069.
 
Emre M. Dementia Associated with Parkinson’s disease. Lancet Neurol. 2004;2:229–237.
 
Emre M, Aarsland D, Brown R, Burn DJ, Duyckaerts C, Mizuno Y, Broe GA, Cummings J, Dickson DW, Gauthier S, Goldman J, Goetz C, Korczyn A, Lees A, Levy R, Litvan I, McKeith I, Olanow W, Poewe W, Quinn N, Sampaio C, Tolosa E, Dubois B. Clinical diagnostic criteria for dementia associated with Parkinson's disease. Mov Disord. 2007;22(12):1689–1707.
 
Press DZ. Parkinson's disease dementia--a first step? N Engl J Med. 2004;351(24):2547–2549.
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