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Cognitive composite score association with Alzheimer's disease plaque and tangle pathology.

ABSTRACT: Cognitive composite scores are used as the primary outcome measures for Alzheimer's disease (AD) prevention trials; however, the extent to which these composite measures correlate with AD pathology has not been fully investigated. Since many on-going AD prevention studies are testing therapies that target either amyloid or tau, we sought to establish an association between a cognitive composite score and the underlying pathology of AD.Data from 192 older deceased and autopsied persons from the Rush Religious Order Study were used in this study. All participants were classified at their initial evaluations with a clinical diagnosis of no cognitive impairment (NCI). Of these individuals, 105 remained NCI at the time of their death while the remaining 87 progressed to mild cognitive impairment (MCI) or AD. A cognitive composite score composed of eight cognitive tests was used as the outcome measure. Individuals were classified into groups based on Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropathological diagnosis and Braak stage.The rate of annualized composite score decline was significantly greater for the high CERAD (p?

SUBMITTER: Malek-Ahmadi M

PROVIDER: S-EPMC6134796 | biostudies-other | 2018 Sep

REPOSITORIES: biostudies-other

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Cognitive composite score association with Alzheimer's disease plaque and tangle pathology.

Malek-Ahmadi Michael M Chen Kewei K Perez Sylvia E SE He Anna A Mufson Elliott J EJ

Alzheimer's research & therapy 20180911 1

<h4>Background</h4>Cognitive composite scores are used as the primary outcome measures for Alzheimer's disease (AD) prevention trials; however, the extent to which these composite measures correlate with AD pathology has not been fully investigated. Since many on-going AD prevention studies are testing therapies that target either amyloid or tau, we sought to establish an association between a cognitive composite score and the underlying pathology of AD.<h4>Methods</h4>Data from 192 older deceas ...[more]

PMID: 30205840

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Project description:IntroductionThe Alzheimer's disease (AD) composite score (ADCOMS) has been shown to be a more sensitive measure of cognitive change in early AD (i.e., mild cognitive impairment [MCI] and mild AD) than commonly used measures. This study derived ADCOMS value ranges associated with different disease severity stages across the predementia and AD continuum.MethodsData from patients enrolled in the Alzheimer's Disease Neuroimaging Initiative were assessed at baseline and month 24. Data were randomly split into derivation and validation samples. Receiver-operating characteristic (ROC) curves of ADCOMS values were generated in the derivation sample to assess the sensitivity and specificity of ADCOMS cutoff values compared with existing disease severity cutoff scores using the Clinical Dementia Rating (CDR) global, CDR Sum of Boxes, Alzheimer's Disease Assessment Scale-Cognitive Subscale, and Mini-Mental State Examination. Optimal ADCOMS cutoff values for each disease stage were compared between the derivation and the validation samples using a χ2 test. The diagnostic accuracy of the derived ADCOMS cutoff values was then assessed. The analyses were repeated for the subset with positive amyloid β confirmation (Aβ +).ResultsThe following ADCOMS value ranges for the total population and Aβ + population were identified: < 0.29 indicative of normal cognition, 0.29 to < 0.45 indicative of MCI, 0.45-0.77 indicative of mild AD, and > 0.77 indicative of at least moderate AD. The reliability of these ADCOMS value ranges was supported by diagnostic accuracy tests and tests indicating no significant difference in the ROC curves between the derivation and validation samples.ConclusionADCOMS values ranges can be used to assess the severity of cognitive decline. The derived severity threshold score ranges for ADCOMS will enable its use as an endpoint in clinical trials assessing disease progression and clinical outcomes of disease-modifying therapies in persons with MCI or early AD, including patients with Aβ + confirmation.

Dataset Information

Cognitive composite score association with Alzheimer's disease plaque and tangle pathology.

Publications

Cognitive composite score association with Alzheimer's disease plaque and tangle pathology.

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