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A Machine Learning Approach to Design an Efficient Selective Screening of Mild Cognitive Impairment
Published on: January 11, 2020
Mild cognitive impairment can be distinguished from Alzheimer disease and normal aging for clinical trials
Michael Grundman1, Ronald C Petersen, Steven H Ferris
1Alzheimer's Disease Cooperative Study, Department of Neurosciences, University of California-San Diego, 8950 Villa La Jolla Drive, Suite 227, La Jolla, CA 92037, USA. mgrundman@ucsd.edu
Background:
Mild cognitive impairment (MCI) represents a transitional state between the cognitive changes of normal aging and very early dementia and is becoming increasingly recognized as a risk factor for Alzheimer disease (AD). The Memory Impairment Study (MIS) is a multicenter clinical trial in patients with MCI designed to evaluate whether vitamin E or donepezil is effective at delaying the time to a clinical diagnosis of AD.
Objective:
To describe the baseline characteristics of patients with MCI recruited for the MIS and compare them with those of elderly controls and patients with AD in another clinical trial.
Design:
Descriptive and comparative study of patients with MCI participating in a multicenter clinical trial.
Setting:
Memory disorder centers in the United States and Canada.
Patients:
A total of 769 patients with MCI, 107 cognitively normal elderly controls, 122 patients with very mild AD (Clinical Dementia Rating [CDR] 0.5), and 183 patients with mild AD (CDR 1.0) were evaluated. Patients in the MIS met operational criteria for amnestic MCI. Controls were recruited in parallel with the MCI group, underwent the same assessments, and had a CDR of 0.
Main Outcome Measures:
Clinical, neuropsychologic, functional, neuroimaging, and genetic measures.
Results:
Mean +/- SD Alzheimer's Disease Assessment Scale-Cognitive Subscale scores were 5.6 +/- 3.3 for controls, 11.3 +/- 4.4 for patients with MCI, 18.0 +/- 6.2 for the AD CDR 0.5 group, and 25.2 +/- 8.8 for the AD CDR 1.0 group. Compared with controls, patients with MCI were most impaired on memory tasks, with less severe impairments in other cognitive domains. Patients with MCI were more likely than controls but less likely than patients with AD to carry the apolipoprotein E epsilon4 allele. Patients with MCI had hippocampal volumes that were intermediate between those of controls and patients with AD.
Conclusions:
Patients with MCI had a predominant memory impairment with relative sparing of other cognitive domains and were intermediate between clinically normal individuals and patients with AD on cognitive and functional ratings. These results demonstrate the successful implementation of operational criteria for this unique group of at-risk patients in a multicenter clinical trial.
Insights
Mild cognitive impairment (MCI) patients show memory deficits, intermediate between healthy individuals and Alzheimer's disease (AD) patients. This study successfully characterized MCI patients for clinical trials investigating potential AD treatments.
Area of Science:
- Neuroscience
- Gerontology
- Clinical Trials
Background:
- Mild cognitive impairment (MCI) is a transitional stage between normal aging and Alzheimer's disease (AD).
- MCI is increasingly recognized as a significant risk factor for AD.
- The Memory Impairment Study (MIS) is a clinical trial evaluating vitamin E and donepezil for delaying AD diagnosis in MCI patients.
Purpose of the Study:
- To characterize baseline features of MCI patients in the MIS trial.
- To compare MCI patients with cognitively normal elderly controls.
- To compare MCI patients with individuals diagnosed with very mild and mild AD.
Main Methods:
- A descriptive and comparative study design was employed.
- 769 MCI patients, 107 controls, 122 very mild AD, and 183 mild AD patients were evaluated.
- Assessments included clinical, neuropsychological, functional, neuroimaging, and genetic measures.
Main Results:
- MCI patients exhibited primary memory impairment with relative preservation of other cognitive domains.
- Alzheimer's Disease Assessment Scale-Cognitive Subscale scores were intermediate for MCI patients compared to controls and AD patients.
- MCI patients showed intermediate hippocampal volumes and apolipoprotein E epsilon4 allele frequency between controls and AD patients.
Conclusions:
- MCI patients represent a distinct group with predominant memory issues, bridging normal cognition and AD.
- The study successfully implemented operational criteria for recruiting at-risk MCI patients in a multicenter trial.
- These findings support MCI as a crucial stage for therapeutic interventions aimed at preventing or delaying AD progression.
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