Dataset Information

The Cognitive-Functional Composite is sensitive to clinical progression in early dementia: Longitudinal findings from the Catch-Cog study cohort.

ABSTRACT:

Introduction

In an attempt to capture clinically meaningful cognitive decline in early dementia, we developed the Cognitive-Functional Composite (CFC). We investigated the CFC's sensitivity to decline in comparison to traditional clinical endpoints.

Methods

This longitudinal construct validation study included 148 participants with subjective cognitive decline, mild cognitive impairment, or mild dementia. The CFC and traditional tests were administered at baseline, 3, 6, and 12 months. Sensitivity to change was investigated using linear mixed models and r ² effect sizes.

Results

CFC scores declined over time (? = -.16, P < .001), with steepest decline observed in mild Alzheimer's dementia (? = -.25, P < .001). The CFC showed medium-to-large effect sizes at succeeding follow-up points (r ²= .08-.42), exhibiting greater change than the Clinical Dementia Rating scale (r ²= .02-.12). Moreover, change on the CFC was significantly associated with informant reports of cognitive decline (? = .38, P < .001).

Discussion

By showing sensitivity to decline, the CFC could enhance the monitoring of disease progression in dementia research and clinical practice.

SUBMITTER: Jutten RJ

PROVIDER: S-EPMC7164406 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

The Cognitive-Functional Composite is sensitive to clinical progression in early dementia: Longitudinal findings from the Catch-Cog study cohort.

Jutten Roos J RJ Harrison John E JE Brunner A J AJ Vreeswijk R R van Deelen R A J RAJ de Jong Frank Jan FJ Opmeer Esther M EM Ritchie Craig W CW Aleman André A Scheltens Philip P Sikkes Sietske A M SAM

Alzheimer's & dementia (New York, N. Y.) 20200417 1

<h4>Introduction</h4>In an attempt to capture clinically meaningful cognitive decline in early dementia, we developed the Cognitive-Functional Composite (CFC). We investigated the CFC's sensitivity to decline in comparison to traditional clinical endpoints.<h4>Methods</h4>This longitudinal construct validation study included 148 participants with subjective cognitive decline, mild cognitive impairment, or mild dementia. The CFC and traditional tests were administered at baseline, 3, 6, and 12 mo ...[more]

PMID: 32313832

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Project description:BackgroundThe cognitive-functional composite (CFC) was designed to improve the measurement of clinically relevant changes in predementia and early dementia stages. We have previously demonstrated its good test-retest reliability and feasibility of use. The current study aimed to evaluate several quality aspects of the CFC, including construct validity, clinical relevance, and suitability for the target population.MethodsBaseline data of the Capturing Changes in Cognition study was used: an international, prospective cohort study including participants with subjective cognitive decline (SCD), mild cognitive impairment (MCI), Alzheimer's disease (AD) dementia, and dementia with Lewy bodies (DLB). The CFC comprises seven existing cognitive tests focusing on memory and executive functions (EF) and the informant-based Amsterdam Instrumental Activities of Daily Living Questionnaire (A-IADL-Q). Construct validity and clinical relevance were assessed by (1) confirmatory factor analyses (CFA) using all CFC subtests and (2) linear regression analyses relating the CFC score (independent) to reference measures of disease severity (dependent), correcting for age, sex, and education. To assess the suitability for the target population, we compared score distributions of the CFC to those of traditional tests (Alzheimer's Disease Assessment Scale-Cognitive subscale, Alzheimer's Disease Cooperative Study-Activities of Daily Living scale, and Clinical Dementia Rating scale).ResultsA total of 184 participants were included (age 71.8 ± 8.4; 42% female; n = 14 SCD, n = 80 MCI, n = 78 AD, and n = 12 DLB). CFA showed that the hypothesized three-factor model (memory, EF, and IADL) had adequate fit (CFI = .931, RMSEA = .091, SRMR = .06). Moreover, worse CFC performance was associated with more cognitive decline as reported by the informant (β = .61, p < .001), poorer quality of life (β = .51, p < .001), higher caregiver burden (β = - .51, p < .001), more apathy (β = - .36, p < .001), and less cortical volume (β = .34, p = .02). Whilst correlations between the CFC and traditional measures were moderate to strong (ranging from - .65 to .83, all p < .001), histograms showed floor and ceiling effects for the traditional tests as compared to the CFC.ConclusionsOur findings illustrate that the CFC has good construct validity, captures clinically relevant aspects of disease severity, and shows no range restrictions in scoring. It therefore provides a more useful outcome measure than traditional tests to evaluate cognition and function in MCI and mild AD.

Project description:BackgroundClinical endpoints for upcoming therapeutic trials in frontotemporal dementia (FTD) are increasingly urgent. Cognitive composite scores are often used as endpoints but are lacking in genetic FTD. We aimed to create cognitive composite scores for genetic frontotemporal dementia (FTD) as well as recommendations for recruitment and duration in clinical trial design.MethodsA standardized neuropsychological test battery covering six cognitive domains was completed by 69 C9orf72, 41 GRN, and 28 MAPT mutation carriers with CDR® plus NACC-FTLD ≥ 0.5 and 275 controls. Logistic regression was used to identify the combination of tests that distinguished best between each mutation carrier group and controls. The composite scores were calculated from the weighted averages of test scores in the models based on the regression coefficients. Sample size estimates were calculated for individual cognitive tests and composites in a theoretical trial aimed at preventing progression from a prodromal stage (CDR® plus NACC-FTLD 0.5) to a fully symptomatic stage (CDR® plus NACC-FTLD ≥ 1). Time-to-event analysis was performed to determine how quickly mutation carriers progressed from CDR® plus NACC-FTLD = 0.5 to ≥ 1 (and therefore how long a trial would need to be).ResultsThe results from the logistic regression analyses resulted in different composite scores for each mutation carrier group (i.e. C9orf72, GRN, and MAPT). The estimated sample size to detect a treatment effect was lower for composite scores than for most individual tests. A Kaplan-Meier curve showed that after 3 years, ~ 50% of individuals had converted from CDR® plus NACC-FTLD 0.5 to ≥ 1, which means that the estimated effect size needs to be halved in sample size calculations as only half of the mutation carriers would be expected to progress from CDR® plus NACC FTLD 0.5 to ≥ 1 without treatment over that time period.DiscussionWe created gene-specific cognitive composite scores for C9orf72, GRN, and MAPT mutation carriers, which resulted in substantially lower estimated sample sizes to detect a treatment effect than the individual cognitive tests. The GENFI-Cog composites have potential as cognitive endpoints for upcoming clinical trials. The results from this study provide recommendations for estimating sample size and trial duration.

Dataset Information

The Cognitive-Functional Composite is sensitive to clinical progression in early dementia: Longitudinal findings from the Catch-Cog study cohort.

Introduction

Methods

Results

Discussion

Publications

The Cognitive-Functional Composite is sensitive to clinical progression in early dementia: Longitudinal findings from the Catch-Cog study cohort.

Similar Datasets

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