Abstract
Background: Amnestic mild cognitive impairment (aMCI) and mild-to-moderate Alzheimer’s disease (AD) are clinically distinct but impact cognitive and functional ability similarly. Comprehensive assessment of cognitive and functional deficits may prove useful in informing differential diagnosis in early stages of dementia and in informing endpoint selection in therapeutic AD trials. Objective: The objective of this study was to characterize patterns of cognitive and functional impairment in aMCI and mild-to-moderate AD subjects compared to cognitively intact healthy elderly (HE). Methods: Thirty-one healthy elderly, 20 aMCI and 19 AD participants were administered a cognitive test battery that included the ADAS-Cog and functional assessments. Z-scores were calculated for all endpoints based on the HE reference group. Results: Cognitive deficits were observed in AD and aMCI participants relative to the referent group. On average, aMCI participants performed 1 - 2 standard deviations below HE on cognitive tests, and AD participants performed 2 - 3 standard deviations below HE. Domain-specific functional deficits among AD participants (z- score -0.4 to -6.4) were consistently greater than those of aMCI participants (z-score 0 to -1.7). Conclusion: This study provides further support for comprehensive assessment and monitoring of cognitive and functional domain scores in the diagnosis and treatment of aMCI and mild AD. Domain-specific cognitive scores may be more useful than composite scores in characterizing impairment and decline. Measuring domains such as attention, processing speed and executive function may increase the sensitivity of detecting disease progression and therapeutic effects, particularly in mild-moderate AD where memory decline may be too slow to detect drug effects during a typical clinical trial.
Highlights
Mild Cognitive Impairment (MCI) is characterized by changes in cognition which are less severe and widespread than those of Alzheimer’s disease (AD), but represent a decline from cognitive functioning of normal aging and predisposes one to the risk of developing AD [1]
Domain-specific cognitive scores may be more useful than composite scores in characterizing impairment and decline. Measuring domains such as attention, processing speed and executive function may increase the sensitivity of detecting disease progression and therapeutic effects, in mild-moderate AD where memory decline may be too slow to detect drug effects during a typical clinical trial
Standardizing the Amnestic mild cognitive impairment (aMCI) and mild-to-moderate AD performance to a z-score based on a healthy elderly (HE) sample allows all test and domain scores to be reported based on the same scale with mean of 0 and a standard deviation of 1
Summary
Mild Cognitive Impairment (MCI) is characterized by changes in cognition which are less severe and widespread than those of Alzheimer’s disease (AD), but represent a decline from cognitive functioning of normal aging and predisposes one to the risk of developing AD [1]. The criteria include memory impairment as assessed with sensitive episodic memory tests. This new diagnostic framework has stimulated debate about the definition of AD and related conditions. Objective: The objective of this study was to characterize patterns of cognitive and functional impairment in aMCI and mild-to-moderate AD subjects compared to cognitively intact healthy elderly (HE). Methods: Thirty-one healthy elderly, 20 aMCI and 19 AD participants were administered a cognitive test battery that included the ADAS-Cog and functional assessments. Conclusion: This study provides further support for comprehensive assessment and monitoring of
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