Data-Driven vs Consensus Diagnosis of MCI

Abstract

Objective:Given prior work demonstrating that mild cognitive impairment (MCI) can be empirically differentiated into meaningful cognitive subtypes, we applied actuarial methods to comprehensive neuropsychological data from the University of California San Diego (UCSD) Alzheimer’s Disease Research Center (ADRC) in order to identify cognitive subgroups within nondemented ADRC participants, and to examine cognitive, biomarker, and neuropathological trajectories.Methods:Cluster analysis was performed on baseline neuropsychological data (n=738; mean age=71.8). Survival analysis examined progression to dementia (mean follow-up=5.9 years). CSF AD biomarker status and neuropathological findings at follow-up were examined in a subset with available data.Results:Five clusters were identified: “optimal” cognitively normal (CN; n=130) with above-average cognition, “typical” CN (n=204) with average cognition, non-amnestic MCI (naMCI; n=104), amnestic MCI (aMCI; n=216), and mixed MCI (mMCI; n=84). Progression to dementia differed across MCI subtypes (mMCI>aMCI>naMCI), with the mMCI group demonstrating the highest rate of CSF biomarker positivity and AD pathology at autopsy. Actuarial methods classified 29.5% more of the sample with MCI and outperformed consensus diagnoses in capturing those who had abnormal biomarkers, progressed to dementia, or had AD pathology at autopsy.Conclusions:We identified subtypes of MCI and CN with differing cognitive profiles, clinical outcomes, CSF AD biomarkers, and neuropathological findings over more than 10 years of follow-up. Results demonstrate that actuarial methods produce reliable cognitive phenotypes, with data from a subset suggesting unique biological and neuropathological signatures. Findings indicate that data-driven algorithms enhance diagnostic sensitivity relative to consensus diagnosis for identifying older adults at risk for cognitive decline.

Trajectory of Unawareness of Memory Decline in Individuals With Autosomal Dominant Alzheimer Disease

“…This later finding may have clinical relevance because it is directly associated with the reliability of a patient's complaints of dysfunction. 10 Paradoxically, there seems to be a period in which individuals may experience increased awareness of subtle changes in their memory function despite performing well on standardized memory tests (often referred to as subjective cognitive decline [SCD]). 11 This SCD only takes the participant's complaints into account, whereas increased awareness compares the participant's complaints with the informant's complaints or objective memory function.…”

“…Of importance, SCD, increased awareness, and reduced awareness in the predementia stage are associated with biomarker and neuroimaging abnormalities consistent with AD pathology [6][7][8][12][13][14][15][16][17][18][19][20] as well as an increased risk of prospective AD dementia. 8,10,[21][22][23] A consensus is lacking regarding the presence and evolution of altered awareness of memory function across the preclinical and prodromal stages of AD. In particular, the findings of variability of awareness may have implications for the use of SCD in the predementia stages of AD because loss of awareness is associated with reduced validity of the subjective experience of cognitive abilities.…”

Decreased Electroencephalography Global Field Synchronization in Slow-Frequency Bands Characterizes Synaptic Dysfunction in Amnestic Subtypes of Mild Cognitive Impairment

“…It is interesting that the biological profile of clinically defined sd-aMCI in this study is closer to the biological profile of AD in contrast to the empirically data-driven classification of sd-aMCI recently published by Edmonds et al (2021). This discrepancy emphasizes a need for validation of different diagnostic criteria in diverse clinical populations.…”

Uncovering heterogeneous cognitive trajectories in mild cognitive impairment: a data-driven approach

“…Delano-Wood was one of the first to provide evidence that distinct subgroups of MCI can be empirically derived based on cognitive data using a clinical sample of 70 [ 20 ]. Subsequent studies applying empirical methods to neuropsychological test scores have identified multiple MCI subgroups in clinic-based [ 21 – 28 ], community-based [ 29 , 30 ], and clinical trial [ 12 ] samples. However, given the progressive nature of cognitive aging or AD, considering the longitudinal progression and not just a snapshot of the current state may provide a more comprehensive picture of the prodrome stage of the disease.…”