Last, variability in ADAS-Cog scores can exceed the annual rate of change in clinical trials, with variability in uninformative subscales potentially obscuring changes on items that can actually track mild deficits.Īnother endpoint-related challenge for disease-modifying trials is the precedent set in symptomatic antidementia trials requiring statistical significance on separate primary endpoints of cognition and function. Limited coverage of early cognitive deficits compounds the insensitivity of ADAS-Cog to mild progression. Up to half of ADAS-Cog subscales demonstrate ceiling effects in subjects with mild or moderate AD, which makes these items likely to be uninformative in earlier stages of the disease. There is a nonlinear relationship between disease severity and rate of decline, with the fastest rate of decline seen in patients with moderate AD, and slower rates of decline in patients with mild AD or MCI. Īlthough the ADAS-Cog has been used successfully in trials of symptomatic treatments for mild-to-moderate AD, certain features of the ADAS-Cog limit its use in earlier stages. In its original configuration, the ADAS-Cog assessed learning and memory, language, and spatial cognition, but lacked coverage of executive function an expanded version was developed in an attempt to address this concern. The standard research tool for cognitive assessment in clinical trials is the Alzheimer’s Disease Assessment Scale-Cognitive (ADAS-Cog), which provides a single score based on arbitrary weightings of performance on test items relevant to AD. Among the challenges faced by disease-modifying strategies targeting early disease stages is uncertainty over appropriate endpoints for early AD and mild cognitive impairment (MCI) trials. Alzheimer’s disease (AD) clinical research has entered a new era of therapeutics that aim to modify underlying disease pathology rather than ameliorate symptoms.
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