POSET based Cognitive Function Impairment (pCFI): a novel approach for delineating
heterogeneity of cognitive impairment in Parkinson's disease.
Deepak K. Gupta, MD1, Jennifer G. Goldman, MD, MS2, Judith Jaeger, PhD3, Curtis Tatsuoka, Phd*4
Department of Neurology, University Hospitals Case Medical Center & Case Western Reserve University, 2Neurology, Rush University, Chicago, IL, United States, 60612,
3
3Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, NY, United States, 10461, 4Neurology & Statistics, Case Western Reserve University, Cleveland, OH, United States, 44106
1
Objective
Apply partially ordered set (POSET) modeling for classifying impairment in cognitive functions in Parkinson's disease (PD).
paired. Compared to HC, PD group also had significantly higher number of subjects with
impairment in any of the four pCFI types.
Background
Mild cognitive impairment in PD (PD-MCI) is common and heterogeneous in nature. Current paradigms of classifying cognitive impairment lack specificity with regards to particular
cognitive functions as many neuropsychological measures tap into several different or overlapping cognitive domains. POSET models serve as a basis for novel methods to classify
the performance of subjects with respect to specific cognitive functions.
Methods
De novo PD subjects (n=418) and healthy controls (HC), n=195) from the Parkinson Progression Marker Initiative (PPMI) study were studied. PD subjects were classified as PDMCI level Ia (Montreal Cognitive Assessment, MoCA) and PD-MCI level Ib (< 5 domains
tested) as per Movement Disorders Society (MDS) Task Force PD-MCI criteria2.
Based on expert opinion, we mapped four specific cognitive functions, namely Attention
(ATTN), Visuospatial Judgment (VSJ), Cognitive Flexibility (CogFlex) and Episodic Memory
(EM), to 12 individual sub-scores from different cognitive tests, namely Benton Judgement
of Line Orientation (BJLO), Letter Number Sequencing (LNS), Semantic Fluency (SF),
Symbol Digit Modality (SDM), Hopkins Verbal Learning Memory Test (HVLT), and Montreal
Cognitive Assessment (MOCA).
ATTN was mapped to all 12 scores. Additionally, VSJ was mapped to BJLO, SDM and
MOCA Visuospatial executive scores; CogFlex was mapped to SF, HVLT Discrimination Recognition scores; EM was mapped to HVLT Delayed Recall, HVLT Discrimination
Recognition and MOCA Memory scores.
Cognitive function scores, representing posterior probabilities of a subject's highest level
of functioning, were derived for each subject through POSET models and Bayesian analysis. Based on 10th percentile cutoff of cognitive function scores of HC, and reported cognitive decline (from MDS-UPDRS Part I), the impairment in each cognitive function was classified and termed as POSET based cognitive function impairment (pCFI). We used t-tests
and chi-square statistics for testing significant differences between HC and PD.
Results
All four cognitive function scores were non-significantly lower in PD, compared to HC (Table
1).
Similar to PD-MCI, all four different pCFI types occurred more significantly in PD, compared
to controls (Table 2). Of the four pCFI types, episodic memory was the most frequently im-
Conclusions
We report for the first time a novel approach for distinguishing different cognitive phenotypes of PD-MCI. This may have important clinical and research implications (e.g., biomarkers discovery for cognitive impairment) in PD.
References:
1. Tatsuoka C, Tseng H, Jaeger J, et al. Modeling the heterogeneity in risk of progression
to Alzheimer’s disease across cognitive profiles in mild cognitive impairment. Alzheimers
Res Ther 2013;5:14.
2. Litvan I, Goldman JG, Tröster AI, et al. Diagnostic criteria for mild cognitive impairment
in Parkinson's disease: Movement Disorder Society Task Force guidelines. Movement Disorders 2012;27(3):349-356.
*Contact: [email protected].