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Both Reaction Time and Accuracy Measures of Intraindividual Variability Predict Cognitive Performance in Alzheimer's Disease.

ABSTRACT: Dementia researchers around the world prioritize the urgent need for sensitive measurement tools that can detect cognitive and functional change at the earliest stages of Alzheimer's disease (AD). Sensitive indicators of underlying neural pathology assist in the early detection of cognitive change and are thus important for the evaluation of early-intervention clinical trials. One method that may be particularly well-suited to help achieve this goal involves the quantification of intraindividual variability (IIV) in cognitive performance. The current study aimed to directly compare two methods of estimating IIV (fluctuations in accuracy-based scores vs. those in latency-based scores) to predict cognitive performance in AD. Specifically, we directly compared the relative sensitivity of reaction time (RT)-and accuracy-based estimates of IIV to cognitive compromise. The novelty of the present study, however, centered on the patients we tested [a group of patients with Alzheimer's disease (AD)] and the outcome measures we used (a measure of general cognitive function and a measure of episodic memory function). Hence, we compared intraindividual standard deviations (iSDs) from two RT tasks and three accuracy-based memory tasks in patients with possible or probable Alzheimer's dementia (n = 23) and matched healthy controls (n = 25). The main analyses modeled the relative contributions of RT vs. accuracy-based measures of IIV toward the prediction of performance on measures of (a) overall cognitive functioning, and (b) episodic memory functioning. Results indicated that RT-based IIV measures are superior predictors of neurocognitive impairment (as indexed by overall cognitive and memory performance) than accuracy-based IIV measures, even after adjusting for the timescale of measurement. However, one accuracy-based IIV measure (derived from a recognition memory test) also differentiated patients with AD from controls, and significantly predicted episodic memory performance. The findings suggest that both RT- and accuracy-based IIV measures may be useful indicators of underlying neuropathology. The present study therefore contributes toward an understanding of the relative utility of RT- and accuracy-based IIV measures in detecting neurocognitive impairment in older adults, and also advances the empirical evaluation of sensitive markers of cognitive change in patients with AD.

SUBMITTER: Christ BU

PROVIDER: S-EPMC5900796 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Both Reaction Time and Accuracy Measures of Intraindividual Variability Predict Cognitive Performance in Alzheimer's Disease.

Christ Björn U BU Combrinck Marc I MI Thomas Kevin G F KGF

Frontiers in human neuroscience 20180409

Dementia researchers around the world prioritize the urgent need for sensitive measurement tools that can detect cognitive and functional change at the earliest stages of Alzheimer's disease (AD). Sensitive indicators of underlying neural pathology assist in the early detection of cognitive change and are thus important for the evaluation of early-intervention clinical trials. One method that may be particularly well-suited to help achieve this goal involves the quantification of intraindividual ...[more]

PMID: 29686610

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Project description:IntroductionParkinson's disease (PD) is a neurodegenerative disorder that commonly results in cognitive impairments and dementia. Intraindividual variability of neuropsychological performance is a sensitive marker of cognitive decline in other neurologic populations. However, studies have not examined the longitudinal utility of intraindividual variability in predicting future cognitive impairments among individuals with PD. In the current study, we hypothesized that increased intraindividual variability would predict future cognitive decline independent of traditional neuropsychological markers of cognitive impairment.MethodsThe sample included 423 newly diagnosed PD patients and 175 healthy controls, who were followed up to 5 years (baseline, first, second, third, fourth, and fifth annual follow-up). Participants underwent tests of learning, memory, processing speed, attention, verbal fluency, and visuospatial functioning. Cognitive status (cognitive intact, mild cognitive impairment, and dementia) was classified based on previously established criteria. Multilevel models were computed to examine the longitudinal relationship between intraindividual variability, cognitive status, and general cognitive functioning.ResultsAnalyses revealed that increased intraindividual variability was predictive of incident cognitive decline among individuals with PD. Specifically, greater dispersion in neuropsychological performance was associated with greater risk of transitioning from cognitively intact to mild cognitive impairment or transitioning from mild cognitive impairment to dementia. Additional analyses revealed a significant Intraindividual Variability × Group (PD or control) interaction, meaning that intraindividual variability was predictive of declines in cognitive functioning among PD participants only but not healthy controls.ConclusionIntraindividual variability may be a harbinger for future cognitive decline among individuals with PD. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Project description:ObjectiveThe current study was designed to achieve 2 primary objectives: (a) determine the moderating effect of mild cognitive impairments (MCI) on intraindividual variability in semantic and letter fluency performance taking into account longitudinal annual assessments; and (b) establish predictive utility for intraindividual variability in semantic and letter fluency performance as a risk factor of incident MCI.MethodsParticipants were community-residing older adults (n = 514; M age = 75.89 ± 6.45; 55.1% female). Sixty participants were diagnosed with MCI at baseline and 50 developed incident MCI during the follow-up. We operationalized intraindividual variability as word generation slopes derived from 3 consecutive time intervals during the standard 1-min administration of both letter and semantic fluency tasks (i.e., 0-20 s, 21-40 s, and 41-60 s).ResultsLinear mixed effects models revealed significant within task slope effects for semantic (estimate = -8.350; p < .0001; 95% confidence interval [CI] = -8.604, -8.095) and letter (estimate = -5.068; p < .0001; 95% CI [-5.268, -4.869]) fluency indicating that word generation declined over the course of both tasks. The two-way interactions of MCI × Slope were significant for semantic (estimate = 1.34; p = .001; 95% CI [0.551, 2.126]) and letter (estimate = 0.733; p = .020; 95% CI [0.116, 1.350]) fluency indicating attenuated slopes among MCI participants compared to controls taking into account repeated annual assessments. Cox proportional-hazards models revealed that attenuated word generation slope, at baseline, in semantic (hazard ratio [HR] = 2.063; p = .015; 95% = 1.149 to 3.702) but not letter (HR = 0.704; p = .243; 95% CI [0.391, 1.269]) fluency was associated with increased risk of incident MCI.ConclusionIntraindividual variability in verbal fluency performance has clinical and predictive utility; it can be easily incorporated into testing batteries in clinical and research settings. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Project description:Intraindividual variability (IIV) across neuropsychological measures within a single testing session is a promising marker predictive of cognitive decline and development of Alzheimer's disease (AD). We have previously shown that greater IIV is cross-sectionally associated with reduced cerebral blood flow (CBF), but not with cortical thickness or brain volume, in older adults without dementia who were amyloid beta (Aβ) positive. However, there is little known about the association between change in IIV and CBF over time. Therefore, we examined 12-month longitudinal change in IIV and interactions of IIV and AD biomarker status on changes in regional CBF. Fifty-three non-demented Alzheimer's Disease Neuroimaging Initiative (ADNI) participants underwent lumbar puncture to obtain cerebrospinal fluid (CSF) at baseline and neuropsychological testing and magnetic resonance imaging (MRI) exams at baseline and 12-month follow-up evaluation. IIV was calculated as the intraindividual standard deviation across 6 demographically-corrected neuropsychological measures. Pulsed arterial spin labeling (ASL) MRI was acquired to quantify CBF and FreeSurfer-derived a priori CBF regions of interest (ROIs) were examined. AD biomarker positivity was determined using a published CSF p-tau/Aβ ratio cut-score. Change scores were calculated for IIV, CBF, and mean neuropsychological performance from baseline to 12 months. Hierarchical linear regression models showed that after adjusting for age and gender, there was a significant interaction between IIV change and biomarker-positivity (p-tau/Aβ+) for change in entorhinal and hippocampal CBF but not for the other ROIs. Specifically, increases in IIV were associated with reductions in entorhinal and hippocampal CBF among individuals who were biomarker-positive (n = 21). In contrast, there were no significant associations between change in IIV and CBF among those who were biomarker-negative (n = 32). Findings remained similar when analyses were performed adjusting for change in mean level of neuropsychological performance. Changes in IIV may be sensitive to changes in regional hypoperfusion in AD-vulnerable regions among AD biomarker-positive individuals, above and beyond demographics and mean neuropsychological performance. These findings provide further evidence supporting IIV as a potential marker of cerebrovascular brain changes in individuals at risk for dementia.

Project description:Objective: Increased intraindividual variability (IIV) in function has been linked to various age-related outcomes including cognitive decline and dementia. Most studies have operationalized IIV as fluctuations across trials (e.g., response latencies) for a single task, with comparatively few studies examining variability across multiple tasks for a given individual. In the present study, we derive a multivariable operationalization of dispersion across a broad profile of neuropsychological measures and use this index along with degree of engaged lifestyle to predict risk of cognitive impairment. Participants and Methods: Participants (n = 60) were community-dwelling older adults aged 65+ years (M = 74.1, SD = 6.5) participating in a cross-sectional investigation of risk factors for amnestic mild cognitive impairment (a-MCI) and probable Alzheimer's Disease (AD). Participants were classified into three subgroups based on test performance and clinical judgement. Healthy controls (n = 30) scored better than -1 SD relative to existing norms on all classification measures, in the absence of memory complaints or functional impairments. The a-MCI group (n = 23) had self- or informant-reported memory complaints and scored 1 SD or more below the mean for at least one memory task while scoring better than 1 SD below the mean for all other cognitive domains, in the absence of functional impairments. The AD group (n = 7) scored at least 2 SD below the mean for two cognitive domains (including memory) with impairments in functioning. Measures spanned a range of cognitive domains (episodic memory, executive function, language), with the derived dispersion estimates reflecting variability across an individual's neuropsychological profile relative to the group average. Further, an Activities Lifestyle Questionnaire, indexing social, cognitive, and physical behaviors, was administered to assess the protective benefits of engaged lifestyle. Results: Multinomial logistic regression models examined the risk of being classified as a-MCI or AD as a function of increased dispersion, (dis)engaged lifestyle, and their interaction. Greater dispersion was associated with an increased likelihood of being classified with AD, with protective engaged-lifestyle benefits apparent for a-MCI individuals only. Conclusion: As a measure of IIV, dispersion across neuropsychological profiles holds promise for the detection of cognitive impairment.

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Both Reaction Time and Accuracy Measures of Intraindividual Variability Predict Cognitive Performance in Alzheimer's Disease.

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Both Reaction Time and Accuracy Measures of Intraindividual Variability Predict Cognitive Performance in Alzheimer's Disease.

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