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      Is intraindividual reaction time variability an independent cognitive predictor of mortality in old age? Findings from the Sydney Memory and Ageing Study

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          Abstract

          Intraindividual variability of reaction time (IIV RT), a proposed cognitive marker of neurobiological disturbance, increases in old age, and has been associated with dementia and mortality. The extent to which IIV RT is an independent predictor of mortality, however, is unclear. This study investigated the association of IIV RT and all-cause mortality while accounting for cognitive level, incident dementia and biomedical risk factors in 861 participants aged 70–90 from the Sydney Memory and Ageing Study. Participants completed two computerised reaction time (RT) tasks (76 trials in total) at baseline, and comprehensive medical and neuropsychological assessments every 2 years. Composite RT measures were derived from the two tasks—the mean RT and the IIV RT measure computed from the intraindividual standard deviation of the RTs (with age and time-on-task effects partialled out). Consensus dementia diagnoses were made by an expert panel of clinicians using clinical criteria, and mortality data were obtained from a state registry. Cox proportional hazards models estimated the association of IIV RT and mean RT with survival time over 8 years during which 191 (22.2%) participants died. Greater IIV RT but not mean RT significantly predicted survival time after adjusting for age, sex, global cognition score, cardiovascular risk index and apolipoprotein ɛ4 status. After excluding incident dementia cases, the association of IIV RT with mortality changed very little. Our findings suggest that greater IIV RT uniquely predicts shorter time to death and that lower global cognition and prodromal dementia in older individuals do not explain this relationship.

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          General cardiovascular risk profile for use in primary care: the Framingham Heart Study.

          Separate multivariable risk algorithms are commonly used to assess risk of specific atherosclerotic cardiovascular disease (CVD) events, ie, coronary heart disease, cerebrovascular disease, peripheral vascular disease, and heart failure. The present report presents a single multivariable risk function that predicts risk of developing all CVD and of its constituents. We used Cox proportional-hazards regression to evaluate the risk of developing a first CVD event in 8491 Framingham study participants (mean age, 49 years; 4522 women) who attended a routine examination between 30 and 74 years of age and were free of CVD. Sex-specific multivariable risk functions ("general CVD" algorithms) were derived that incorporated age, total and high-density lipoprotein cholesterol, systolic blood pressure, treatment for hypertension, smoking, and diabetes status. We assessed the performance of the general CVD algorithms for predicting individual CVD events (coronary heart disease, stroke, peripheral artery disease, or heart failure). Over 12 years of follow-up, 1174 participants (456 women) developed a first CVD event. All traditional risk factors evaluated predicted CVD risk (multivariable-adjusted P<0.0001). The general CVD algorithm demonstrated good discrimination (C statistic, 0.763 [men] and 0.793 [women]) and calibration. Simple adjustments to the general CVD risk algorithms allowed estimation of the risks of each CVD component. Two simple risk scores are presented, 1 based on all traditional risk factors and the other based on non-laboratory-based predictors. A sex-specific multivariable risk factor algorithm can be conveniently used to assess general CVD risk and risk of individual CVD events (coronary, cerebrovascular, and peripheral arterial disease and heart failure). The estimated absolute CVD event rates can be used to quantify risk and to guide preventive care.
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            Aging cognition: from neuromodulation to representation.

            Basic cognitive functions, such as the abilities to activate, represent, maintain, focus and process information, decline with age. A paradigm shift towards cross-level conceptions is needed in order to obtain an integrative understanding of cognitive aging phenomena that cuts across neural, information-processing, and behavioral levels. We review empirical data at these different levels, and computational theories proposed to enable their integration. A theoretical link is highlighted, relating deficient neuromodulation with noisy information processing, which might result in less distinctive cortical representations. These less distinctive representations might be implicated in working memory and attentional functions that underlie the behavioral manifestations of cognitive aging deficits.
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              Variability in reaction time performance of younger and older adults.

              Age differences in three basic types of variability were examined: variability between persons (diversity), variability within persons across tasks (dispersion), and variability within persons across time (inconsistency). Measures of variability were based on latency performance from four measures of reaction time (RT) performed by a total of 99 younger adults (ages 17--36 years) and 763 older adults (ages 54--94 years). Results indicated that all three types of variability were greater in older compared with younger participants even when group differences in speed were statistically controlled. Quantile-quantile plots showed age and task differences in the shape of the inconsistency distributions. Measures of within-person variability (dispersion and inconsistency) were positively correlated. Individual differences in RT inconsistency correlated negatively with level of performance on measures of perceptual speed, working memory, episodic memory, and crystallized abilities. Partial set correlation analyses indicated that inconsistency predicted cognitive performance independent of level of performance. The results indicate that variability of performance is an important indicator of cognitive functioning and aging.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: ResourcesRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Funding acquisitionRole: MethodologyRole: Project administrationRole: Writing – original draftRole: Writing – review & editing
                Role: Funding acquisitionRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                9 August 2017
                2017
                : 12
                : 8
                : e0181719
                Affiliations
                [1 ] Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales (UNSW) Australia, Sydney, NSW, Australia
                [2 ] Neuropsychiatric Institute, Prince of Wales Hospital, Randwick, NSW, Australia
                [3 ] School of Psychology, Faculty of Medicine and Health, University of Leeds, Leeds, United Kingdom
                [4 ] Dementia Collaborative Research Centre–Assessment and Better Care (DCRC-ABC), School of Psychiatry, UNSW Australia, Sydney, NSW, Australia
                Nathan S Kline Institute, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-8630-6398
                Article
                PONE-D-17-06978
                10.1371/journal.pone.0181719
                5549897
                28792946
                6419c676-2c99-440e-9fe0-a4a27dfaafaf
                © 2017 Kochan et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 21 February 2017
                : 6 July 2017
                Page count
                Figures: 0, Tables: 3, Pages: 11
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100000925, National Health and Medical Research Council;
                Award ID: 350833
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100000925, National Health and Medical Research Council;
                Award ID: 350833
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100000925, National Health and Medical Research Council;
                Award ID: 123148
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100002986, Dementia Collaborative Research Centres, Australia;
                Award Recipient :
                Funded by National Health and Medical Research Council of Australia Program Grant (grant number 350833) (HB PS), National Health and Medical Research Council of Australia Early Career Fellowship (grant number 123148) (NK), and Dementia Collaborative Research Centre (NK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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                Custom metadata
                Data may be available to interested researchers upon request to the Sydney Memory and Ageing Study (MAS) Governance Committee (via email: chebadata@ 123456unsw.edu.au ). This is required because of the conditions of the MAS ethics approval and the consent forms which only allows data to be passed onto third parties following review and approval by the study governance committee.

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