Dataset Information

Cognitive Variability during Middle-Age: Possible Association with Neurodegeneration and Cognitive Reserve.

ABSTRACT: Objective: Increased variability in cognition with age has been argued as an indication of pathological processes. Focusing on early detection of neurodegenerative disorders, we investigated variability in cognition in healthy middle-aged adults. In order to understand possible determinants of this variability, we also investigated associations with cognitive reserve, neuroimaging markers, subjective memory complaints, depressive symptomatology, and gender. Method: Thirty-one 50 ± 2 years old individuals were investigated as target group and deviation was studied in comparison to a reference younger group of 30 individuals 40 ± 2 years old. Comprehensive neuropsychological and structural imaging protocols were collected. Brain regional volumes and cortical thickness were calculated with FreeSurfer, white matter hyperintensities with CASCADE, and mean diffusivity with FSL. Results: Across-individuals variability showed greater dispersion in lexical access, processing speed, executive functions, and memory. Variability in global cognition correlated with, reduced cortical thickness in the right parietal-temporal-occipital association cortex, and increased mean diffusivity in the cingulum bundle and right inferior fronto-occipital fasciculus. A trend was also observed for the correlation between global cognition and hippocampal volume and female gender. All these associations were influenced by cognitive reserve. No correlations were found with subjective memory complaints, white matter hyperintensities and depressive symptomatology. Across-domains and across-tasks variability was greater in several executive components and cognitive processing speed. Conclusion: Variability in cognition during middle-age is associated with neurodegeneration in the parietal-temporal-occipital association cortex and white matter tracts connecting this to the prefrontal dorsolateral cortex and the hippocampus. Moreover, this effect is influenced by cognitive reserve. Studying variability offers valuable information showing that differences do not occur in the same magnitude and direction across individuals, cognitive domains and tasks. These findings may have important implications for early detection of subtle cognitive impairment and clinical interpretation of deviation from normality.

SUBMITTER: Ferreira D

PROVIDER: S-EPMC5465264 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Cognitive Variability during Middle-Age: Possible Association with Neurodegeneration and Cognitive Reserve.

Ferreira Daniel D Machado Alejandra A Molina Yaiza Y Nieto Antonieta A Correia Rut R Westman Eric E Barroso José J

Frontiers in aging neuroscience 20170609

<b>Objective:</b> Increased variability in cognition with age has been argued as an indication of pathological processes. Focusing on early detection of neurodegenerative disorders, we investigated variability in cognition in healthy middle-aged adults. In order to understand possible determinants of this variability, we also investigated associations with cognitive reserve, neuroimaging markers, subjective memory complaints, depressive symptomatology, and gender. <b>Method:</b> Thirty-one 50 ± ...[more]

PMID: 28649200

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Project description:Cognitive Reserve (CR), according to a recent consensus definition of the NIH-funded Reserve and Resilience collaboratory, is constituted by any mechanism contributing to cognitive performance beyond, or interacting with, brain structure in the widest sense. To identity multivariate activation patterns fulfilling this postulate, we investigated a verbal Sternberg fMRI task and imaged 181 people with age coverage in the ranges 20-30 (44 participants) and 55-70 (137 participants). Beyond task performance, participants were characterized in terms of demographics, and neuropsychological assessments of vocabulary, episodic memory, perceptual speed, and abstract fluid reasoning. Participants studied an array of either one, three, or six upper-case letters for 3 s (=encoding phase), then a blank fixation screen was presented for 7 s (=maintenance phase), to be probed with a lower-case letter to which they responded with a differential button press whether the letter was part of the studied array or not (=retrieval phase). We focused on identifying maintenance-related activation patterns showing memory load increases in pattern score on an individual participant level for both age groups. We found such a pattern that increased with memory load for all but one person in the young participants (p < 0.001), and such a pattern for all participants in the older group (p < 0.001). Both patterns showed broad topographic similarities; however, relationships to task performance and neuropsychological characteristics were markedly different and point to individual differences in Cognitive Reserve. Beyond the derivation of group-level activation patterns, we also investigated the inter-subject spatial similarity of individual working memory rehearsal patterns in the older participants' group as a function of neuropsychological and task performance, education, and mean cortical thickness. Higher task accuracy and neuropsychological function was reliably associated with higher inter-subject similarity of individual-level activation patterns in older participants.

Project description:Background: Preoperative cognitive reserve and brain integrity may explain commonly observed intraoperative fluctuations seen on a standard anesthesia depth monitor used ubiquitously in operating rooms throughout the nation. Neurophysiological variability indicates compromised regulation and organization of neural networks. Based on theories of neuronal integrity changes that accompany aging, we assessed the relative contribution of: 1) premorbid cognitive reserve, 2) current brain integrity (gray and white matter markers of neurodegenerative disease), and 3) current cognition (specifically domains of processing speed/working memory, episodic memory, and motor function) on intraoperative neurophysiological variability as measured from a common intraoperative tool, the Bispectral Index Monitor (BIS).Methods: This sub-study included participants from a parent study of non-demented older adults electing unilateral Total Knee Arthroplasty (TKA) with the same surgeon and anesthesia protocol, who also completed a preoperative neuropsychological assessment and preoperative 3T brain magnetic resonance imaging scan. Left frontal two-channel derived EEG via the BIS was acquired preoperatively (un-medicated and awake) and continuously intraoperatively with time from tourniquet up to tourniquet down. Data analyses used correlation and regression modeling.Results: Fifty-four participants met inclusion criteria for the sub-study. The mean (SD) age was 69.5 (7.4) years, 54% were male, 89% were white, and the mean (SD) American Society of Anesthesiologists score was 2.76 (0.47). We confirmed that brain integrity positively and significantly associated with each of the cognitive domains of interest. EEG intra-individual variability (squared deviation from the mean BIS value between tourniquet up and down) was significantly correlated with cognitive reserve (r = -.40, p = .003), brain integrity (r = -.37, p = .007), and a domain of processing speed/working memory (termed cognitive efficiency; r = -.31, p = .021). Hierarchical regression models that sequentially included age, propofol bolus dose, cognitive reserve, brain integrity, and cognitive efficiency found that intraoperative propofol bolus dose (p = .001), premorbid cognitive reserve (p = .008), and current brain integrity (p = .004) explained a significant portion of intraoperative intra-individual variability from the BIS monitor.Conclusions: Older adults with higher premorbid reserve and less brain disease were more stable intraoperatively on a depth of anesthesia monitor. Researchers need to replicate findings within larger cohorts and other surgery types.

Dataset Information

Cognitive Variability during Middle-Age: Possible Association with Neurodegeneration and Cognitive Reserve.

Publications

Cognitive Variability during Middle-Age: Possible Association with Neurodegeneration and Cognitive Reserve.

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