Scales as outcome measures for Alzheimer's disease

Abstract

The assessment of patient outcomes in clinical trials of new therapeutics for Alzheimer's disease (AD) continues to evolve. In addition to assessing drugs for symptomatic relief, an increasing number of trials are focusing on potential disease-modifying agents. Moreover, participants with AD are being studied earlier in their course of disease. As a result, the limitations of current outcome measures have become more apparent, as has the need for better instruments. In recognition of the need to review and possibly revise current assessment measures, the Alzheimer's Association, in cooperation with industry leaders and academic investigators, convened a Research Roundtable meeting devoted to scales as outcome measures for AD clinical trials. The meeting included a discussion of methodological issues in the use of scales in AD clinical trials, including cross-cultural issues. Specific topics related to the use of cognitive, functional, global, and neuropsychiatric scales were also presented. Speakers also addressed academic and industry initiatives for pooling data from untreated and placebo-treated patients in clinical trials. A number of regulatory topics were also discussed with agency representatives. Panel discussions highlighted areas of controversy, in an effort to gain consensus on various topics.

Efficacy of a medical food on cognition in Alzheimer's Disease: Results from secondary analyses of a randomized, controlled trial

“…these observations are in line with recent publications that bring into question the sensitivity of adascog in mild cognitive impairment and mild ad (17)(18)(19). this may be due to the poor psychometric properties of the adascog measure, such as inadequate assessment of cognitive domains such as attention, working memory and executive function (19,20) and the presence of floor effects (17). Furthermore, several recent studies have reported slower rates of placebo decline in ad patients than traditionally assumed by older models and clinical trials (12,(21)(22)(23); they have also shown that baseline adas-cog significantly affects the rate of ad progression (23,24).…”

“…Within the group of patients with higher adas-cog scores at baseline, souvenaid significantly improved adas-cog scores compared with the control group. these observations are in line with recent publications that bring into question the sensitivity of adascog in mild cognitive impairment and mild ad (17)(18)(19). this may be due to the poor psychometric properties of the adascog measure, such as inadequate assessment of cognitive domains such as attention, working memory and executive function (19,20) and the presence of floor effects (17).…”

Current issues and future research priorities for health economic modelling across the full continuum of Alzheimer's disease

“…Instead, these effects have been modelled via intermediate outcomes given some critical assumptions on their relationship with the outcomes of interest [26]. Nevertheless, the effect on institutionalization appears difficult to validate as shown in the AD2000 study [35,36]. Differences in the availability of institutions across countries further increase the complexity of this outcome, as the relationship between dementia symptoms and institutionalization, therefore, likely varies across countries and contexts.…”

“…As noted earlier, ADAS-cog is usually the preferred primary cognitive end point in clinical trials in mild-to-moderate AD [47], but it has ceiling and floor effects making it less suitable in early and late stages of AD [35]. In moderate-to-severe AD, the Severe Impairment Battery [54] may be better suited, whereas in early AD, the Repeatable Battery for the Assessment of Neuropsychological Status [55] has been suggested [35]. The availability of data has caused many models to use the screening tool Mini-Mental State Examination (MMSE) [56] to represent cognitive decline.…”

Assessment of outcome in clinical trials in mild Alzheimer�s disease: Urgent time for a rethink?

“…Over recent years, questions have been raised regarding the suitability of the ADAS-Cog to assess those with mild AD [6][7][8] . These questions cover three main issues; the appropriateness of the cognitive domains tested, the psychometric properties and the variability in administration and scoring of the ADAS-Cog.…”