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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.

SUBMITTER: Brooker H

PROVIDER: S-EPMC7560493 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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FLAME: A computerized neuropsychological composite for trials in early dementia.

Brooker Helen H Williams Gareth G Hampshire Adam A Corbett Anne A Aarsland Dag D Cummings Jeffrey J Molinuevo Jose Luis JL Atri Alireza A Ismail Zahinoor Z Creese Byron B Fladby Tormod T Thim-Hansen Charlotte C Wesnes Keith K Ballard Clive C

Alzheimer's & dementia (Amsterdam, Netherlands) 20201014 1

<h4>Introduction</h4>Sensitive neuropsychological tests are needed to improve power for clinical trials in early Alzheimer's disease (AD).<h4>Methods</h4>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 anal ...[more]

PMID: 33088895

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Project description:Voice processing in neurodegenerative disease is poorly understood. Here we undertook a systematic investigation of voice processing in a cohort of patients with clinical diagnoses representing two canonical dementia syndromes: temporal variant frontotemporal lobar degeneration (n = 14) and Alzheimer's disease (n = 22). Patient performance was compared with a healthy matched control group (n = 35). All subjects had a comprehensive neuropsychological assessment including measures of voice perception (vocal size, gender, speaker discrimination) and voice recognition (familiarity, identification, naming and cross-modal matching) and equivalent measures of face and name processing. Neuroanatomical associations of voice processing performance were assessed using voxel-based morphometry. Both disease groups showed deficits on all aspects of voice recognition and impairment was more severe in the temporal variant frontotemporal lobar degeneration group than the Alzheimer's disease group. Face and name recognition were also impaired in both disease groups and name recognition was significantly more impaired than other modalities in the temporal variant frontotemporal lobar degeneration group. The Alzheimer's disease group showed additional deficits of vocal gender perception and voice discrimination. The neuroanatomical analysis across both disease groups revealed common grey matter associations of familiarity, identification and cross-modal recognition in all modalities in the right temporal pole and anterior fusiform gyrus; while in the Alzheimer's disease group, voice discrimination was associated with grey matter in the right inferior parietal lobe. The findings suggest that impairments of voice recognition are significant in both these canonical dementia syndromes but particularly severe in temporal variant frontotemporal lobar degeneration, whereas impairments of voice perception may show relative specificity for Alzheimer's disease. The right anterior temporal lobe is likely to have a critical role in the recognition of voices and other modalities of person knowledge.

Dataset Information

FLAME: A computerized neuropsychological composite for trials in early dementia.

Publications

FLAME: A computerized neuropsychological composite for trials in early dementia.

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