Early versus late MCI: Improved MCI staging using a neuropsychological approach

Abstract

Introduction: The Alzheimer's Disease Neuroimaging Initiative (ADNI) separates "early" and "late" mild cognitive impairment (MCI) based on a single memory test. We compared ADNI's MCI classifications to our neuropsychological approach, which more broadly assesses cognitive abilities.

Methods: Three hundred thirty-six ADNI-2 participants were classified as "early" or "late" MCI. Cluster analysis was performed on neuropsychological test data, and participants were reclassified based on cluster results. These two staging approaches were compared on progression rates, cerebrospinal fluid biomarkers, and cortical thickness profiles.

Results: There was little correspondence between the two staging methods. ADNI's early MCI group included a large proportion of false-positive diagnostic errors. The reclassified neuropsychological MCI groups showed steeper survival curves and more abnormal biomarkers.

Conclusions: Our novel neuropsychological approach improved the staging of MCI by (1) capturing individuals at an early symptomatic stage, (2) minimizing false-positive cases, and (3) identifying a late MCI group further along the disease trajectory.

Keywords: Alzheimer's disease; Cluster analysis; Dementia; Early-stage MCI; False positive; Late-stage MCI; Mild cognitive impairment; Misdiagnosis; Neuropsychology.

Fig. 1.

Neuropsychological performance of cluster-derived groups and CN group. Error bars denote standard error of the mean. The horizontal dotted line indicates the typical cutoff for impairment (−1.5 SDs). BNT=Boston Naming Test; TMT=Trail Making Test; RAVLT=Rey Auditory Verbal Learning Test; NP=neuropsychological; MCI=mild cognitive impairment.

Fig. 2.

Percentage of participants in the early and late MCI groups by staging method.

Fig. 3.

Kaplan-Meier survival curves showing rate of progression to AD in the MCI groups by staging method.

Fig. 4.

Proportion of CSF AD biomarker positive individuals in each group by staging method. Cut-offs used to determine biomarker positivity [21]: <977 pg/ml for Aβ_1-42, >.025 for pTau/ Aβ_1-42, and >.27 for tTau/Aβ_1-42.

Fig. 5.

T-value surface maps showing regional cortical thickness on the left and right lateral and medial pial surfaces for each group relative to the CN group with FDR correction for multiple comparisons. The cyan/blue shades represent areas where the MCI subgroup has thinner cortex than the CN group, while the red regions represent areas were the subgroup has thicker cortex than the CN group.