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Normative Data for the Cognitively Intact Oldest-Old: The Framingham Heart Study.

ABSTRACT: UNLABELLED:BACKGROUND/STUDY CONTEXT: The number of individuals who reach extreme age is quickly increasing. Much of the current literature focuses on impaired cognition in extreme age, and debate continues regarding what constitutes "normal" cognition in extreme age. This study aimed to provide oldest-old normative data and to compare cognitive performances of cognitively intact elderly individuals from the Framingham Heart Study. METHODS:A total of 1302 individuals aged 65+ years from the Framingham Heart Study were separated into 5-year age bands and compared on cognitive tests. Multivariate linear regression analyses were conducted, adjusting for gender, the Wide Range Achievement Test-Third Edition (WRAT-III) Reading score, and cohort. Analyses also included comparisons between 418 individuals aged 80+ and 884 individuals aged 65-79, and comparisons within oldest-old age bands. RESULTS:Normative data for all participants are presented. Significant differences were found on most tests between age groups in the overall analysis between young-old and oldest-old, and analysis of oldest-old age bands also revealed select significant differences (all ps <.05). CONCLUSION:As aging increases, significant cognitive differences and increased variability in performances are evident. These results support the use of age-appropriate normative data for oldest-old individuals.

SUBMITTER: Miller IN

PROVIDER: S-EPMC5621515 | biostudies-literature | 2015 Jul-Sep

REPOSITORIES: biostudies-literature

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Normative Data for the Cognitively Intact Oldest-Old: The Framingham Heart Study.

Miller Ivy N IN Himali Jayandra J JJ Beiser Alexa S AS Murabito Joanne M JM Seshadri Sudha S Wolf Philip A PA Au Rhoda R

Experimental aging research 20150701 4

<h4>Unlabelled</h4>BACKGROUND/STUDY CONTEXT: The number of individuals who reach extreme age is quickly increasing. Much of the current literature focuses on impaired cognition in extreme age, and debate continues regarding what constitutes "normal" cognition in extreme age. This study aimed to provide oldest-old normative data and to compare cognitive performances of cognitively intact elderly individuals from the Framingham Heart Study.<h4>Methods</h4>A total of 1302 individuals aged 65+ years ...[more]

PMID: 26214098

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Project description:BACKGROUND:Recent findings suggest that Alzheimer's disease (AD) neuropathological features (neuritic plaques and NFTs) are not strongly associated with dementia in extreme old (over 90 years of age) and compel a search for neurobiological indices of dementia in this rapidly growing segment of the elderly population. We sought to characterize transcriptional and protein profiles of dementia in the oldest-old. METHODS AND FINDINGS:Gene and protein expression changes relative to non-demented age-matched controls were assessed by two microarray platforms, qPCR and Western blot in different regions of the brains of oldest-old and younger old persons who died at mild or severe stages of dementia. Our results indicate that: i) consistent with recent neuropathological findings, gene expression changes associated with cognitive impairment in oldest-old persons are distinct from those in cognitively impaired youngest-old persons; ii) transcripts affected in young-old subjects with dementia participate in biological pathways related to synaptic function and neurotransmission while transcripts affected in oldest-old subjects with dementia are associated with immune/inflammatory function; iii) upregulation of immune response genes in cognitively intact oldest-old subjects and their subsequent downregulation in dementia suggests a potential protective role of the brain immune-associated system against dementia in the oldest-old; iv) consistent with gene expression profiles, protein expression of several selected genes associated with the inflammatory/immune system in inferior temporal cortex is significantly increased in cognitively intact oldest-old persons relative to cognitively intact young-old persons, but impaired in cognitively compromised oldest-old persons relative to cognitively intact oldest-old controls. CONCLUSIONS:These results suggest that disruption of the robust immune homeostasis that is characteristic of oldest-old individuals who avoided dementia may be directly associated with dementia in the oldest-old and contrast with the synaptic and neurotransmitter system failures that typify dementia in younger old persons.

Project description:ObjectivesThe fraction of the population that reaches the age of 100 years is growing. At this age, dementia incidence is high and cognitive functioning is highly variable across individuals. Normative data for neuropsychological tests are lacking in centenarians, which hampers the ability to evaluate their cognitive functioning for both research and clinical practice. Here, we generated norms for neuropsychological tests in a sample of cognitively healthy centenarians while taking sensory impairments into account.DesignCross-sectional cohort study.SettingCentenarians who participate in the prospective 100-plus Study.ParticipantsA total of 235 centenarians (71.5% female), who self-reported to be cognitively healthy, which was confirmed by an informant and a trained researcher.MeasurementsWe generated normative data for 15 cognitive tests, measuring global cognition (Mini-Mental State Examination [MMSE]), premorbid intelligence, attention, language, memory, executive function, and visuospatial function by multiple linear regressions and/or by reporting percentiles.ResultsNormative data for global cognition resulted in a mean MMSE score of 25.6 ± 3.1 (range = 17-30; interquartile range = 24-28). Vision problems and fatigue often complicated the ability to complete tests, and these problems explained 41% and 22% of the missing test scores, respectively. In contrast, hearing problems (4%) and task incomprehension (6%) rarely complicated test performance. While educational level was associated with performance on the majority of the tests, sex and age were only weakly associated with test performance.ConclusionsWe generated normative data for 15 common neuropsychological tests in a large sample of cognitively healthy centenarians, while taking age-related sensory impairments into consideration. These normative data allow the detection of deficits across a wide range of cognitive domains. Our results suggest that, next to education level, vision ability and the level of fatigue should be taken into account when evaluating cognitive functioning in centenarians. J Am Geriatr Soc 67:759-767, 2019.

Project description:BackgroundStatistical methods for modeling longitudinal and time-to-event data has received much attention in medical research and is becoming increasingly useful. In clinical studies, such as cancer and AIDS, longitudinal biomarkers are used to monitor disease progression and to predict survival. These longitudinal measures are often missing at failure times and may be prone to measurement errors. More importantly, time-dependent survival models that include the raw longitudinal measurements may lead to biased results. In previous studies these two types of data are frequently analyzed separately where a mixed effects model is used for the longitudinal data and a survival model is applied to the event outcome.MethodsIn this paper we compare joint maximum likelihood methods, a two-step approach and a time dependent covariate method that link longitudinal data to survival data with emphasis on using longitudinal measures to predict survival. We apply a Bayesian semi-parametric joint method and maximum likelihood joint method that maximizes the joint likelihood of the time-to-event and longitudinal measures. We also implement the Two-Step approach, which estimates random effects separately, and a classic Time Dependent Covariate Model. We use simulation studies to assess bias, accuracy, and coverage probabilities for the estimates of the link parameter that connects the longitudinal measures to survival times.ResultsSimulation results demonstrate that the Two-Step approach performed best at estimating the link parameter when variability in the longitudinal measure is low but is somewhat biased downwards when the variability is high. Bayesian semi-parametric and maximum likelihood joint methods yield higher link parameter estimates with low and high variability in the longitudinal measure. The Time Dependent Covariate method resulted in consistent underestimation of the link parameter. We illustrate these methods using data from the Framingham Heart Study in which lipid measurements and Myocardial Infarction data were collected over a period of 26 years.ConclusionsTraditional methods for modeling longitudinal and survival data, such as the time dependent covariate method, that use the observed longitudinal data, tend to provide downwardly biased estimates. The two-step approach and joint models provide better estimates, although a comparison of these methods may depend on the underlying residual variance.

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Normative Data for the Cognitively Intact Oldest-Old: The Framingham Heart Study.

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Normative Data for the Cognitively Intact Oldest-Old: The Framingham Heart Study.

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