Classification of Patients with Mild Cognitive Impairment vs. Normal Controls based on Experimental and Conventional Standardized Measures of Processing Speed and Working Memory. Erin Schlicting 1, Stephen Correia 2, Paul Malloy 2, Stephen Salloway 2 1 Department of Psychology, University of Rhode Island; 2 Department of Psychiatry and Human Behavior Brown Medical School & Butler Hospital, Providence, RI To determine if N-back and Self-Ordered Pointing Tasks (SOPT) improves classification of patients with amnestic mild cognitive impairment (MCI) vs. cognitively normal controls (NC) over and above standardized tests of processing speed and working memory. Acknowledgments: Support from: NIA ZAG1 FAS-5 (T32); Alzheimer’s Association NIRG ; NIMH K08MH01487W; The Human Brain Project (NIBIB & NIMH); Ittleson Fund at Brown; P20 NCRR ; Center for Translational Brain Research at Brown. Working memory (WM) and processing speed (PS) are often impaired in patients with amnestic MCI 1. Patients with MCI and deficits in WM and PS are at greater risk for conversion to dementia 2,3. Executive impairment (including WM and PS) adds to functional disability in Alzheimer’s disease 4,5. Experimental tests of WM and PS may improve discrimination between MCI and NC when combined with standardized WM and PS. Identifying patients at greatest risk for dementia is important for implementing early interventions. Background Objective Analysis Table 2: Cognitive Measures The results are consistent with prior findings of deficits in PS and WM in amnestic MCI 1,3. Performance on the SOPT and 3-Back tests improved discrimination of MCI from NC over and above standardized tests of PS and WM. WM performance is impaired in MCI and may help discriminating patients in the early stages of Alzheimer’s disease from controls 7. References 1.Nordlund, A. et al. The Goteborg MCI study: mild cognitive impairment is a heterogeneous condition. J Neurol Neurosurg Psychiatry 76, (2005). 2.Albert, M.S., Moss, M.B., Tanzi, R. & Jones, K. Preclinical prediction of AD using neuropsychological tests. J Int Neuropsychol Soc 7, (2001). 3.Tabert, M.H. et al. Neuropsychological prediction of conversion to Alzheimer disease in patients with mild cognitive impairment. Arch Gen Psychiatry 63, (2006). 4.Boyle, P.A. et al. Executive dysfunction and apathy predict functional impairment in Alzheimer disease. Am J Geriatr Psychiatry 11, (2003). 5.Cahn-Weiner, D.A., Boyle, P.A. & Malloy, P.F. Tests of executive function predict instrumental activities of daily living in community-dwelling older individuals. Appl Neuropsychol 9, (2002). 6.Petersen, R.C. et al. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol 56, (1999). 7. Germano, C. & Kinsella, G.J. Working memory and learning in early Alzheimer's disease. Neuropsychology review 15, 1-10 (2005). MeasureProcessing SpeedWorking MemoryExecutive Function StandardizedSymbol DigitDigit SpanDRS IP Subtest Trails ASpatial SpanDRS AC Subtest Grooved PegboardLetter-Number Seq.Trails B Working Memory IndexCOWA Trails B-Trails A Experimental0-back Nback Task1, 2, & 3 Nback tasksN/A* (correct responses) 0, 1, 2, & 3 NbackSOPT Designs (reaction time)and Words *Experimental measures of executive function were not examined in this study Participants were 26 patients with amnestic MCI (Petersen criteria 6 ) and 20 age matched cognitive normal elderly controls (Table 1). All participants undertook a battery of cognitive tests including standardized and experimental measures of executive function, WM, and PS (Table 2). Participants Standardized Measures* Processing SpeedESWorking MemoryESExecutive FunctionES Symbol Digit0.48Letter-Number Sequencing0.11COWA0.07 Trails A0.21Digit Span - Total0.22Trails B - Trails A0.10 Grooved Pegboard Digit Span - Backward0.20Trails B0.21 Dominant0.17Spatial Span -Total0.17 Non-Dominant0.20Spatial Span - Backward0.28 Experimental Measures* Processing SpeedESWorking MemoryESExecutive FunctionES 0-Back Rxn Time0.14SOPT Abstract Designs0.37N/A 1-Back Rxn Time0.10SOPT Abstract Words Back Rxn Time0.091-Back Correct Responses Back Correct Responses Back Correct Responses0.40 *Effect sizes determined from values for partial η 2 : = Medium Effect; >.12 = Large Effect Table 3: Variables selected from the MANOVA The groups did not significantly by age or education (Table 1). No measures were excluded due to collinearity (all r <.65). MANOVA revealed a significant main effect for group (NC vs. MCI) p<.001. Measures from the MANOVA with medium effect sizes (ES, partial η 2 >.06 were selected for each DFA (Table 3). Each DFA produced one significant function: 1.Standardized measures (Wilks’ λ =.48; p<.001) 2.Experimental measures (Wilks’ λ =.40, p<.001) 3.Combined measures (Wilks’ λ =.28, p<.001) Table 4 lists the effect size for each DFA and the tests retained with corresponding effect sizes (1-Wilks’ λ). The combination of standardized and experimental tests of PS and WM was the strongest discriminator of MCI from NC. Table 1: Participant Characteristics NormalMild CognitiveSignificant ControlsImpairmentDifferences (n = 20; 55% Female)(n = 26; 42% Female) Variable MeanSDMeanSDp Value Age Education Correlations among cognitive variables within groups were examined to evaluate for possible collinearity. MANOVA procedure was used to identify significant differences between MCI’s and NC’s on standardized and experimental tests of WM and PS. Three DFA procedures were conducted, one using the standardized tests of WM, PS, and EF, a second using experimental test of WM and PS, and a third DFA combining measures retained from the two prior DFA’s. The effect sizes for the three DFA’s were examined to determine if combining standardized and experimental measures improved classification accuracy (MCI vs. NC). DFA ProcedureMeasures RetainedEffect Size* 1. Standardized Measures 0.52 Processing SpeedSymbol Digit0.71 Working MemorySpatial Span - Backward Experimental Measures 0.60 Processing SpeedNS Working MemorySOPT Abstract Designs Back Correct Responses Combined Measures 0.72 Processing SpeedSymbol Digit0.25 Working MemorySpatial Span - Backward0.15 SOPT Abstract Designs Back Correct Responses0.25 *Effect sizes for the DFA’s and measures retained in each discriminant function Table 4: Discriminant Function Analyses Conclusions Results