FLAME: A computerized neuropsychological composite for trials in early dementia

Abstract

Introduction Sensitive neuropsychological tests are needed to improve power for clinical trials in early Alzheimer's disease (AD). Methods To develop a neuropsychological composite (FLAME – Factors of Longitudinal Attention, Memory and Executive Function), we assessed, 10,714 participants over the age of 50 from PROTECT with validated computerized assessments for 2 years. A factorial analysis was completed to identify the key cognitive factors in all participants, and further analyses examined sensitivity to change in people with stage 2/3 early Alzheimer's disease (AD) according to the US Food and Drug Administration (FDA) framework. Results The FLAME composite score (speed of attention, accuracy of attention, memory, and executive function) distinguished between normal cognition and stage 2/3 early AD at baseline, and was sensitive to cognitive and global/functional decline over 2 years, with the potential to improve power for clinical trials. Discussion FLAME is sensitive to change, providing a straightforward approach to reduce sample size for RCTs in early AD. Conclusion FLAME is a useful computerized neuropsychology composite with utility for clinical trials focusing on cognition.

Parkinson disease-associated cognitive impairment

“…Digital computerized cognitive testing, which can be carried out remotely from patients' homes, has become an interesting alter native to traditional penandpaper testing 147 . Benefits of computerized testing include the opportunity for fre quent testing with less learning effects, which increases the sensitivity to detect decline 148 , costefficiency and the Questionnaire) independent of motor symptoms • Impairment in more than one cognitive domain, that is, at least two of the following aspects:…”

Multivariate profile and acute-phase correlates of cognitive deficits in a COVID-19 hospitalised cohort

“…Recently, we provided preliminary results addressing some of these limitations. Specifically, we used computerised cognitive assessment technology, 12,13 which has superior sensitivity and precision to gold-standard neuropsychological scales, 14 to investigate objectively measurable deficits across multiple cognitive domains in a large online cohort 15,16 that incidentally included people who reported infection with COVID-19 of varying severity. 17 Higher cognitive functions such as spatial planning and analogical reasoning appeared to be disproportionately impaired, especially in hospitalised patients.…”

Clinical outcome measures in dementia with Lewy bodies trials: critique and recommendations

“…These can include a stand-alone computerized test within a larger battery or a fully automated battery. Many computerized assessment measures can be administered remotely with generally similar results as in-clinic evaluations and can provide increased sensitivity to change compared to pen-and-paper tests, reducing the required sample sizes, which would be helpful in reducing the difficulty to recruit populations like DLB [ 103 ]. Computerized tests assessing reaction time and vigilance may be more sensitive in detection of cognitive fluctuations than traditional paper-and-pencil measures and may be better suited to capture cognitive fluctuations over short timescales, although they may not capture longer more profound fluctuations that occur over hours or days.…”