Distributed functional connectivity predicts neuropsychological test performance among older adults.
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ABSTRACT:
SUBMITTER: Kwak S
PROVIDER: S-EPMC8193511 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Excessive brain iron negatively affects working memory and related processes but the impact of cortical iron on task-relevant, cortical brain networks is unknown. We hypothesized that high cortical iron concentration may disrupt functional circuitry within cortical networks supporting working memory performance. Fifty-five healthy older adults completed an N-Back working memory paradigm while functional magnetic resonance imaging (fMRI) was performed. Participants also underwent quantitative susceptibility mapping (QSM) imaging for assessment of non-heme brain iron concentration. Additionally, pseudo continuous arterial spin labeling scans were obtained to control for potential contributions of cerebral blood volume and structural brain images were used to control for contributions of brain volume. Task performance was positively correlated with strength of task-based functional connectivity (tFC) between brain regions of the frontoparietal working memory network. However, higher cortical iron concentration was associated with lower tFC within this frontoparietal network and with poorer working memory performance after controlling for both cerebral blood flow and brain volume. Our results suggest that high cortical iron concentration disrupts communication within frontoparietal networks supporting working memory and is associated with reduced working memory performance in older adults.
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Project description:OBJECTIVE:Studies of postoperative cognitive dysfunction (POCD) rely on repeat neuropsychological testing. The stability of the applied instruments, which are affected by natural variability in performance and measurement imprecision, is often unclear. We determined the stability of a neuropsychological test battery using a sample of older adults from the general population. Forty-five participants aged 65 to 89 years performed six computerized and non-computerized neuropsychological tests at baseline and again at 7 day and 3 months follow-up sessions. Mean scores on each test were compared across time points using repeated measures analyses of variance (ANOVA) with pairwise comparison. Two-way mixed effects, absolute agreement analyses of variance intra-class correlation coefficients (ICC) determined test-retest reliability. RESULTS:All tests had moderate to excellent test-retest reliability during 7-day (ICC range 0.63 to 0.94; all p < 0.01) and 3-month intervals (ICC range 0.60 to 0.92; all p < 0.01) though confidence intervals of ICC estimates were large throughout. Practice effects apparent at 7 days eased off by 3 months. No substantial differences between computerized and non-computerized tests were observed. We conclude that the present six-test neuropsychological test battery is appropriate for use in POCD research though small sample size of our study needs to be recognized as a limitation. Trial registration ClinicalTrials.gov Identifier NCT02265263 (15th October 2014).
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Project description:OBJECTIVES:Hippocampal hyperactivation marks preclinical dementia pathophysiology, potentially due to differences in the connectivity of specific medial temporal lobe structures. Our aims were to characterize the resting-state functional connectivity of medial temporal lobe sub-structures in older adults, and evaluate whether specific substructural (rather than global) functional connectivity relates to memory function. METHODS:In 15 adults (mean age: 69 years), we evaluated the resting state functional connectivity of medial temporal lobe substructures: dentate/Cornu Ammonis (CA) 4, CA1, CA2/3, subiculum, the molecular layer, entorhinal cortex, and parahippocampus. We used 7-Tesla susceptibility weighted imaging and magnetization-prepared rapid gradient echo sequences to segment substructures of the hippocampus, which were used as structural seeds for examining functional connectivity in a resting BOLD sequence. We then assessed correlations between functional connectivity with memory performance (short and long delay free recall on the California Verbal Learning Test [CVLT]). RESULTS:All the seed regions had significant connectivity within the temporal lobe (including the fusiform, temporal, and lingual gyri). The left CA1 was the only seed with significant functional connectivity to the amygdala. The left entorhinal cortex was the only seed to have significant functional connectivity with frontal cortex (anterior cingulate and superior frontal gyrus). Only higher left dentate-left lingual connectivity was associated with poorer CVLT performance (Spearman r?=?-0.81, p?=?0.0003, Benjamini-Hochberg false discovery rate: 0.01) after multiple comparison correction. CONCLUSIONS:Rather than global hyper-connectivity of the medial temporal lobe, left dentate-lingual connectivity may provide a specific assay of medial temporal lobe hyper-connectivity relevant to memory in aging.
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Project description:The expression of microRNA (miRNA) is influenced by ongoing biological processes, including aging, and has begun to play a role in the measurement of neurodegenerative processes in central nervous system. The purpose of this study is to utilize machine learning approaches to determine whether miRNA can be utilized as a blood-based biomarker of cognitive aging. A random forest regression combining miRNA with biological (brain volume), clinical (comorbid conditions), and demographic variables in 115 typically aging older adults explained the greatest level of variance in cognitive performance compared to the other machine learning models explored. Three miRNA (miR-140-5p, miR-197-3p, and miR-501-3p) were top-ranked predictors of multiple cognitive outcomes (Fluid, Crystallized, and Overall Cognition) and past studies of these miRNA link them to cellular senescence, inflammatory signals for atherosclerotic formation, and potential development of neurodegenerative disorders (e.g., Alzheimer's disease). Several novel miRNAs were also linked to age and multiple cognitive functions, findings which together warrant further exploration linking these miRNAs to brain-derived metrics of neurodegeneration in typically aging older adults.
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Project description:The aim of this study is to investigate the validation of a sarcopenia screening test (Ishii's formula) for predicting long-term mortality among older adult inpatients. A prospective, observational study was conducted in acute geriatric wards at three hospitals in western China. Sarcopenia was estimated using Ishii's formula. Survival status was assessed at 12, 24, and 36 months after the baseline investigation. Cox proportional-hazard models were applied to calculate the hazard ratio for mortality associated with sarcopenia. Three hundred and eighty participants (100 women) with a mean age of 80.2?±?7.1 years were included. According to Ishii's formula, 264 participants (69.5%) were sarcopenic. The prevalence of sarcopenia was similar in men and women (71.1% vs. 65.0%, respectively, P?=?0.258). Sixty-seven participants (17.6%) died during the 3-year follow-up period. The all-cause mortality was significantly higher in the sarcopenia group than in the non-sarcopenia group (20.1% vs. 12.1%, respectively, P?<?0.05). Multivariate Cox proportional hazards analysis identified sarcopenia as a significant predictor of 3-year all-cause mortality (adjusted hazard ratio [HR]: 2.06; 95% confidence interval [CI]: 1.02-4.15). In conclusion, sarcopenia, estimated by Ishii's formula, can predict 3-year all-cause mortality in a study population of hospitalized older adults.
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Project description:"Resting-state" or task-free fMRI can assess intrinsic connectivity network (ICN) integrity in health and disease, suggesting a potential for use of these methods as disease-monitoring biomarkers. Numerous analytical options are available, including model-driven ROI-based correlation analysis and model-free, independent component analysis (ICA). High test-retest reliability will be a necessary feature of a successful ICN biomarker, yet available reliability data remains limited. Here, we examined ICN fMRI test-retest reliability in 24 healthy older subjects scanned roughly one year apart. We focused on the salience network, a disease-relevant ICN not previously subjected to reliability analysis, as well as the default mode network. Most ICN analytical methods proved reliable (intraclass coefficients>0.4) and were further improved by wavelet analysis. Seed-based ROI correlation analysis showed high scan-wise reliability, whereas graph theoretical analysis and temporal concatenation group ICA proved most reliable at the individual unit-wise level (voxels, ROIs). Including global signal regression in ROI-based correlation analyses reduced reliability. Our study provides a direct comparison between the most commonly used ICN fMRI methods and potential guidelines for measuring intrinsic connectivity in aging control and patient populations over time.
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Project description:BackgroundExercise training (ET) has neuroprotective effects in the hippocampus, a key brain region for memory that is vulnerable to age-related dysfunction.ObjectiveWe investigated the effects of ET on functional connectivity (FC) of the hippocampus in older adults with mild cognitive impairment (MCI) and a cognitively normal (CN) control group. We also assessed whether the ET-induced changes in hippocampal FC (Δhippocampal-FC) are associated with changes in memory task performance (Δmemory performance).Methods32 older adults (77.0±7.6 years; 16 MCI and 16 CN) participated in the present study. Cardiorespiratory fitness tests, memory tasks (Rey Auditory Verbal Learning Test (RAVLT) and Logical Memory Test (LM)), and resting-state fMRI were administered before and after a 12-week walking ET intervention. We utilized a seed-based correlation analysis using the bilateral anterior and posterior hippocampi as priori seed regions of interest. The associations of residualized ET-induced Δhippocampal-FC and Δmemory performance were assessed using linear regression.ResultsThere were significant improvements in RAVLT Trial 1 and LM test performance after ET across participants. At baseline, MCI, compared to CN, demonstrated significantly lower posterior hippocampal FC. ET was associated with increased hippocampal FC across groups. Greater ET-related anterior and posterior hippocampal FC with right posterior cingulate were associated with improved LM recognition performance in MCI participants.ConclusionOur findings indicate that hippocampal FC is significantly increased following 12-weeks of ET in older adults and, moreover, suggest that increased hippocampal FC may reflect neural network plasticity associated with ET-related improvements in memory performance in individuals diagnosed with MCI.
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Project description:Intrinsic functional connectivity MRI has become a widely used tool for measuring integrity in large-scale cortical networks. This study examined multiple cortical networks using Template-Based Rotation (TBR), a method that applies a priori network and nuisance component templates defined from an independent dataset to test datasets of interest. A priori templates were applied to a test dataset of 276 older adults (ages 65-90) from the Harvard Aging Brain Study to examine the relationship between multiple large-scale cortical networks and cognition. Factor scores derived from neuropsychological tests represented processing speed, executive function, and episodic memory. Resting-state BOLD data were acquired in two 6-min acquisitions on a 3-Tesla scanner and processed with TBR to extract individual-level metrics of network connectivity in multiple cortical networks. All results controlled for data quality metrics, including motion. Connectivity in multiple large-scale cortical networks was positively related to all cognitive domains, with a composite measure of general connectivity positively associated with general cognitive performance. Controlling for the correlations between networks, the frontoparietal control network (FPCN) and executive function demonstrated the only significant association, suggesting specificity in this relationship. Further analyses found that the FPCN mediated the relationships of the other networks with cognition, suggesting that this network may play a central role in understanding individual variation in cognition during aging.
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Project description:BackgroundPatterns of cognitive impairment in former American football players are uncertain because objective neuropsychological data are lacking. This study characterized the neuropsychological test performance of former college and professional football players.MethodsOne hundred seventy male former football players (n=111 professional, n=59 college; 45-74 years) completed a neuropsychological test battery. Raw scores were converted to T-scores using age, sex, and education-adjusted normative data. A T-score ≤ 35 defined impairment. A domain was impaired if 2+ scores fell in the impaired range except for the language and visuospatial domains due to the limited number of tests.ResultsMost football players had subjective cognitive concerns. On testing, rates of impairments were greatest for memory (21.2% two tests impaired), especially for recall of unstructured (44.7%) versus structured verbal stimuli (18.8%); 51.8% had one test impaired. 7.1% evidenced impaired executive functions; however, 20.6% had impaired Trail Making Test B. 12.1% evidenced impairments in the attention, visual scanning, and psychomotor speed domain with frequent impairments on Trail Making Test A (18.8%). Other common impairments were on measures of language (i.e., Multilingual Naming Test [21.2%], Animal Fluency [17.1%]) and working memory (Number Span Backward [14.7%]). Impairments on our tasks of visuospatial functions were infrequent.ConclusionsIn this sample of former football players (most of whom had subjective cognitive concerns), there were diffuse impairments on neuropsychological testing with verbal memory being the most frequently impaired domain.
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Project description:Functional connectivity (FC) has become a leading method for resting-state functional magnetic resonance imaging (rs-fMRI) analysis. However, the majority of the previous studies utilized pairwise, temporal synchronization-based FC. Recently, high-order FC (HOFC) methods were proposed with the idea of computing "correlation of correlations" to capture high-level, more complex associations among the brain regions. There are two types of HOFC. The first type is topographical profile similarity-based HOFC (tHOFC) and its variant, associated HOFC (aHOFC), for capturing different levels of HOFC. Instead of measuring the similarity of the original rs-fMRI signals with the traditional FC (low-order FC, or LOFC), tHOFC measures the similarity of LOFC profiles (i.e., a set of LOFC values between a region and all other regions) between each pair of brain regions. The second type is dynamics-based HOFC (dHOFC) which defines the quadruple relationship among every four brain regions by first calculating two pairwise dynamic LOFC "time series" and then measuring their temporal synchronization (i.e., temporal correlation of the LOFC fluctuations, not the BOLD fluctuations). Applications have shown the superiority of HOFC in both disease biomarker detection and individualized diagnosis than LOFC. However, no study has been carried out for the assessment of test-retest reliability of different HOFC metrics. In this paper, we systematically evaluate the reliability of the two types of HOFC methods using test-retest rs-fMRI data from 25 (12 females, age 24.48 ± 2.55 years) young healthy adults with seven repeated scans (with interval = 3-8 days). We found that all HOFC metrics have satisfactory reliability, specifically (1) fair-to-good for tHOFC and aHOFC, and (2) fair-to-moderate for dHOFC with relatively strong connectivity strength. We further give an in-depth analysis of the biological meanings of each HOFC metric and highlight their differences compared to the LOFC from the aspects of cross-level information exchanges, within-/between-network connectivity, and modulatory connectivity. In addition, how the dynamic analysis parameter (i.e., sliding window length) affects dHOFC reliability is also investigated. Our study reveals unique functional associations characterized by the HOFC metrics. Guidance and recommendations for future applications and clinical research using HOFC are provided. This study has made a further step toward unveiling more complex human brain connectome.
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