Classification of Patients with Mild Cognitive Impairment vs. Normal Controls based on Experimental and Conventional Standardized Measures of Processing Speed and Working Memory.

Erin Schlicting1, Stephen Correia2, Paul Malloy2, Stephen Salloway2

1Department of Psychology, University of Rhode Island; 2Department 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-03-6195; NIMH K08MH01487W; The Human Brain Project (NIBIB & NIMH); Ittleson Fund at Brown; P20 NCRR15578-01; Center for Translational Brain Research at Brown.

Working memory (WM) and processing speed (PS) are often impaired in patients with amnestic MCI1.

Patients with MCI and deficits in WM and PS are at greater risk for conversion to dementia2,3.

Executive impairment (including WM and PS) adds to functional disability in Alzheimer’s disease4,5.

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 MCI1,3.

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 controls7.

References1.Nordlund, A. et al. The Goteborg MCI study: mild cognitive impairment is a heterogeneous condition. J Neurol Neurosurg Psychiatry 76, 1485-90 (2005).2.Albert, M.S., Moss, M.B., Tanzi, R. & Jones, K. Preclinical prediction of AD using neuropsychological tests. J Int Neuropsychol Soc 7, 631-9 (2001).3.Tabert, M.H. et al. Neuropsychological prediction of conversion to Alzheimer disease in patients with mild cognitive impairment. Arch Gen Psychiatry 63, 916-24 (2006).4.Boyle, P.A. et al. Executive dysfunction and apathy predict functional impairment in Alzheimer disease. Am J Geriatr Psychiatry 11, 214-21 (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, 187-91 (2002).6.Petersen, R.C. et al. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol 56, 303-8 (1999).7. Germano, C. & Kinsella, G.J. Working memory and learning in early Alzheimer's disease. Neuropsychology review 15, 1-10 (2005).

Measure Processing Speed Working Memory Executive Function

Standardized Symbol Digit Digit Span DRS IP Subtest

Trails A Spatial Span DRS AC Subtest

Grooved Pegboard Letter-Number Seq. Trails B

  Working Memory Index COWA

      Trails B-Trails A

Experimental 0-back Nback Task 1, 2, & 3 Nback tasks N/A*

(correct responses) (correct responses)

0, 1, 2, & 3 Nback SOPT Designs

  (reaction time) and Words  *Experimental measures of executive function were not examined in this study

Participants were 26 patients with amnestic MCI (Petersen criteria6) 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 Speed ES Working Memory ES Executive Function ES

Symbol Digit 0.48 Letter-Number Sequencing 0.11 COWA 0.07

Trails A 0.21 Digit Span - Total 0.22 Trails B - Trails A 0.10

Grooved Pegboard   Digit Span - Backward 0.20 Trails B 0.21

Dominant 0.17 Spatial Span -Total 0.17

Non-Dominant 0.20 Spatial Span - Backward 0.28    

Experimental Measures*        

Processing Speed ES Working Memory ES Executive Function ES

0-Back Rxn Time 0.14 SOPT Abstract Designs 0.37 N/A N/A

1-Back Rxn Time 0.10 SOPT Abstract Words 0.08

2-Back Rxn Time 0.09 1-Back Correct Responses 0.21

  2-Back Correct Responses 0.24

    3-Back Correct Responses 0.40    *Effect sizes determined from values for partial η2: .06-.12 = 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 η2 >.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

  Normal Mild Cognitive Significant

  Controls Impairment Differences

  (n = 20; 55% Female) (n = 26; 42% Female)  

Variable Mean SD Mean SD p Value

Age 71.5 10.0 75.6 7.6 0.144

Education 14.9 3.0 14.2 3.4 0.940

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 Procedure Measures Retained Effect Size*

1. Standardized Measures   0.52

Processing Speed Symbol Digit 0.71

Working Memory Spatial Span - Backward 0.30

2. Experimental Measures   0.60

Processing Speed NS NS

Working Memory SOPT Abstract Designs 0.59

3-Back Correct Responses 0.62

3. Combined Measures   0.72

Processing Speed Symbol Digit 0.25

Working Memory Spatial Span - Backward 0.15

SOPT Abstract Designs 0.35

3-Back Correct Responses 0.25*Effect sizes for the DFA’s and measures retained in each discriminant function

Table 4: Discriminant Function Analyses

Conclusions

Results