Abstract
BackgroundDevelopment of new treatments for Alzheimer’s disease (AD) has broadened into early interventions in individuals with modest cognitive impairment and a slow decline. The 11-item version of the Alzheimer’s Disease Assessment Scale–Cognitive subscale (ADAS-Cog) was originally developed to measure cognition in patients with mild to moderate AD. Attempts to improve its properties for early AD by removing items prone to ceiling and/or by adding cognitive measures known to be impaired early have yielded a number of ADAS-Cog variants. Using Alzheimer’s Disease Neuroimaging Initiative data, we compared the performance of the 3-, 5-, 11- and 13-item ADAS-Cog variants in subjects with early AD. Given the interest in enrichment strategies, we also examined this aspect with a focus on cerebrospinal fluid (CSF) markers.MethodsSubjects with mild cognitive impairment (MCI) and mild AD with available ADAS-Cog 13 and CSF data were analysed. The decline over time was defined by change from baseline. Direct cross-comparison of the ADAS-Cog variants was performed using the signal-to-noise ratio (SNR), with higher values reflecting increased sensitivity to detect change over time.ResultsThe decline over time on any of the ADAS-Cog variants was minimal in subjects with MCI. Approximately half of subjects with MCI fulfilled enrichment criteria for positive AD pathology. The impact of enrichment was detectable but subtle in MCI. The annual decline in mild AD was more pronounced but still modest. More than 90 % of subjects with mild AD had positive AD pathology. SNRs were low in MCI but greater in mild AD. The numerically largest SNRs were seen for the ADAS-Cog 5 in MCI and for both the 5- and 13-item ADAS-Cog variants in mild AD, although associated confidence intervals were large.ConclusionsThe possible value of ADAS-Cog expansion or reduction is less than compelling, particularly in MCI. In mild AD, adding items known to be impaired at early stages seems to provide more benefit than removing items on which subjects score close to ceiling.Electronic supplementary materialThe online version of this article (doi:10.1186/s13195-016-0170-5) contains supplementary material, which is available to authorized users.
Highlights
Development of new treatments for Alzheimer’s disease (AD) has broadened into early interventions in individuals with modest cognitive impairment and a slow decline
The primary goal of Alzheimer’s Disease Neuroimaging Initiative (ADNI) has been to test whether serial magnetic resonance imaging (MRI), positron emission tomography (PET), other biological markers, and clinical and neuropsychological assessment can be combined to measure the progression of mild cognitive impairment (MCI) and early Alzheimer’s disease (AD)
To maintain a sufficient number of subjects in the analyses, the focus was on change from baseline to 12 months in mild AD, while the change to 24 months was analysed for subjects diagnosed with MCI
Summary
Development of new treatments for Alzheimer’s disease (AD) has broadened into early interventions in individuals with modest cognitive impairment and a slow decline. In response to criticism of the ADAS-Cog’s inability to measure relevant cognitive domains, Mohs et al [8] suggested the use of additional tests, such as Digit Cancellation, Delayed Word Recall and a Maze test. This has led to the creation of ADAS-Cog variants such as the ADAS-Cog 13. The ADAS-Cog 5 variant combines the ADAS-Cog 3 items with Delayed Recall and Digit Cancellation from ADAS-Cog 13 This tactic could improve detection of cognitive decline over time because it measures more relevant domains impacted in early stages of the disease than the ADAS-Cog 3.
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