Heterogeneous cortical atrophy patterns in MCI not captured by conventional diagnostic criteria

Abstract

Objective: We investigated differences in regional cortical thickness between previously identified empirically derived mild cognitive impairment (MCI) subtypes (amnestic MCI, dysnomic MCI, dysexecutive/mixed MCI, and cluster-derived normal) in order to determine whether these cognitive subtypes would show different patterns of cortical atrophy.Methods: Participants were 485 individuals diagnosed with MCI and 178 cognitively normal individuals from the Alzheimer's Disease Neuroimaging Initiative. Cortical thickness estimates were computed for 32 regions of interest per hemisphere. Statistical group maps compared each MCI subtype to cognitively normal participants and to one another. Results:The pattern of cortical thinning observed in each MCI subtype corresponded to their cognitive profile. No differences in cortical thickness were found between the cluster-derived normal MCI subtype and the cognitively normal group. Direct comparison between MCI subtypes suggested that the cortical thickness patterns reflect increasing disease severity. Conclusions:There is an ordered pattern of cortical atrophy among patients with MCI that coincides with their profiles of increasing cognitive dysfunction. This heterogeneity is not captured when patients are grouped by conventional diagnostic criteria. Results in the cluster-derived normal group further support the premise that the conventional MCI diagnostic criteria are highly susceptible to false-positive diagnostic errors. Findings suggest a need to (1) improve the diagnostic criteria by reducing reliance on conventional screening measures, rating scales, and a single memory measure in order to avoid false-positive errors; and (2) divide MCI samples into meaningful subgroups based on cognitive and biomarkers profiles-a method that may provide better staging of MCI and inform prognosis. Mild cognitive impairment (MCI), a prodromal state between normal aging and dementia, 1 is typically divided into amnestic or nonamnestic subtypes, with single-domain or multi-domain distinctions.2,3 A limitation of this conventional classification system is that it combines patients with very different cognitive profiles. Previous research has identified considerable heterogeneity beyond the amnestic/nonamnestic distinction with respect to neuropsychological performance in MCI samples. [4][5][6][7] In a recent study, 7 cluster analysis was performed on 825 individuals with MCI from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Although nearly all participants (99.8%) were originally classified simply as amnestic MCI by conventional criteria, 2,8 results showed 4 cognitive phenotypes. This included 3 impaired subtypes: amnestic MCI (34.9%), dysnomic MCI (18.5%), and dysexecutive/mixed MCI (12.5%). A large fourth cluster

Increasing Inaccuracy of Self-Reported Subjective Cognitive Complaints Over 24 Months in Empirically Derived Subtypes of Mild Cognitive Impairment

“…These results add to the accumulating body of evidence that the CDN group – which accounts for a significant proportion of the ADNI MCI cohort – represents false positive diagnostic errors (Bangen et al, 2016; Bondi et al, 2014; Edmonds et al, 2014, 2015, 2016; Eppig et al, 2017; Thomas et al, 2017). Previous studies have suggested that MCI patients have intact awareness of their cognitive abilities (for review, see Piras et al, 2016), which appears contrary to our results.…”

Sex differences in the association between apolipoprotein E ε4 allele and Alzheimer's disease markers

“…When comparing Jak/Bondi and conventional criteria, conventional MCI diagnostic methods resulted in about 33% false‐positive and 7% false‐negative error rates [28,29,50]. In support of the Jak/Bondi criteria, the “false‐positive” subgroup performed within normal limits across the cognitive battery and showed cerebrospinal fluid biomarker levels, cortical thickness maps, and rates of progression to dementia that were comparable to a robust NC group [28,29,51]. The “false‐negative” group showed cerebrospinal fluid biomarker levels that were comparable to the MCI group and progressed to dementia at double the rate of the overall NC sample [50].…”

Identifying the neural basis of a language‐impaired phenotype of temporal lobe epilepsy

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