Xinyi Zhu

Multimodal intervention in older adults improves resting-state functional connectivity between the medial prefrontal cortex and medial temporal lobe

The prefrontal cortex and medial temporal lobe are particularly vulnerable to the effects of aging. The disconnection between them is suggested to be an important cause of cognitive decline in normal aging. Here, using multimodal intervention training, we investigated the functional plasticity in resting-state connectivity of these two regions in older adults. The multimodal intervention, comprised of cognitive training, Tai Chi exercise, and group counseling, was conducted to explore the regional connectivity changes in the default-mode network, as well as changes in prefrontal-based voxel-wise connectivity in the whole brain. Results showed that the intervention selectively affected resting-state functional connectivity between the medial prefrontal cortex and medial temporal lobe. Moreover, the strength of resting-state functional connectivity between these regions correlated with individual cognitive performance. Our results suggest that multimodal intervention could postpone the effects of aging and improve the function of the regions that are most heavily influenced by aging, as well as play an important role in preserving the brain and cognition during old age.

Intervention-induced enhancement in intrinsic brain activity in healthy older adults

This study examined the effects of a multimodal intervention on spontaneous brain activity in healthy older adults. Seventeen older adults received a six-week intervention that consisted of cognitive training, Tai Chi exercise, and group counseling, while 17 older adults in a control group attended health knowledge lectures. The intervention group demonstrated enhanced memory and social support compared to the control group. The amplitude of low frequency fluctuations (ALFF) in the middle frontal gyrus, superior frontal gyrus, and anterior cerebellum lobe was enhanced for the intervention group, while the control group showed reduced ALFF in these three regions. Moreover, changes in trail-making performance and well-being could be predicted by the intervention-induced changes in ALFF. Additionally, individual differences in the baseline ALFF were correlated with intervention-related changes in behavioral performance. These findings suggest that a multimodal intervention is effective in improving cognitive functions and well-being and can induce functional changes in the aging brain. The study extended previous training studies by suggesting resting-state ALFF as a marker of intervention-induced plasticity in older adults.

Combined Cognitive-Psychological-Physical Intervention Induces Reorganization of Intrinsic Functional Brain Architecture in Older Adults

Mounting evidence suggests that enriched mental, physical, and socially stimulating activities are beneficial for counteracting age-related decreases in brain function and cognition in older adults. Here, we used functional magnetic resonance imaging (fMRI) to demonstrate the functional plasticity of brain activity in response to a combined cognitive-psychological-physical intervention and investigated the contribution of the intervention-related brain changes to individual performance in healthy older adults. The intervention was composed of a 6-week program of combined activities including cognitive training, Tai Chi exercise, and group counseling. The results showed improved cognitive performance and reorganized regional homogeneity of spontaneous fluctuations in the blood oxygen level-dependent (BOLD) signals in the superior and middle temporal gyri, and the posterior lobe of the cerebellum, in the participants who attended the intervention. Intriguingly, the intervention-induced changes in the coherence of local spontaneous activity correlated with the improvements in individual cognitive performance. Taken together with our previous findings of enhanced resting-state functional connectivity between the medial prefrontal cortex and medial temporal lobe regions following a combined intervention program in older adults, we conclude that the functional plasticity of the aging brain is a rather complex process, and an effective cognitive-psychological-physical intervention is helpful for maintaining a healthy brain and comprehensive cognition during old age.

The more the better? A meta-analysis on effects of combined cognitive and physical intervention on cognition in healthy older adults.

Both cognitive intervention and physical exercise benefit cognitive function in older adults. It has been suggested that combined cognitive and physical intervention may induce larger effects than cognitive or physical intervention alone, but existing literature has shown mixed results. This meta-analysis aimed at assessing the efficacy of combined intervention on cognition by comparing combined intervention to control group, cognitive intervention and physical exercise. Eligible studies were controlled trials examining the effects of combined intervention on cognition in older adults without known cognitive impairment. Twenty interventional studies comprising 2667 participants were included. Results showed that the overall effect size for combined intervention versus control group was 0.29 (random effects model, p=0.001). Compared to physical exercise, combined intervention produced greater effects on overall effect size (0.22, p<0.01), while no significant difference was found between combined intervention and cognitive intervention. Effects of combined intervention were moderated by age of participants, intervention frequency and setting. The findings suggest that combined intervention demonstrates advantages over control group and physical exercise, while evidence is still lacking for superiority when compared combined intervention to cognitive intervention. More well-designed studies with long follow-ups are needed to clarify the potential unique efficacy of combined intervention for older adults.

Smaller gray matter volume of hippocampus/parahippocampus in elderly people with subthreshold depression: a cross-sectional study.

BackgroundHippocampal/parahippocampal structural changes accompany major depressive disorders in the elderly, but whether subthreshold depression (StD) at an advanced age is also accompanied by similar changes in hippocampal/parahippocampal volumes is still unknown. By using voxel-based morphometry (VBM) analysis of the gray matter, we explored whether there are structural alterations of the hippocampus/parahippocampus and the correlations between its volume and participants’ self-reported depressive symptoms.MethodsParticipants were 19 community-dwelling older adults with StD assessed by the Center for Epidemiologic Studies Depression scale (CES-D) scores. We collected magnetic resonance images of their brain compared to images of 17 healthy aged-matched adults. We used VBM to analyze differences in gray matter volume (GMV) of the hippocampus/parahippocampus between the two groups. Moreover, we examined the correlation between the GMV of the hippocampus/parahippocampus and participants’ self-reported depressive symptoms.ResultsVBM revealed that elderly individuals with StD had substantially reduced volumes of the right parahippocampus compared to healthy controls. Furthermore, the volumes of the hippocampus/parahippocampus were significantly associated with participants’ self-reported depressive symptoms in StD.ConclusionsGray matter volume alterations in the hippocampus/parahippocampus are correlated with subthreshold depression suggesting that early structural changes in the hippocampus/parahippocampus can constitute a risk indicator of depression.

Aberrant functional connectivity of the hippocampus in older adults with subthreshold depression

Major depression disorder (MDD) is closely associated with functional and structural changes in the hippocampus (HC). Neuroimaging studies have demonstrated abnormal functional connectivity (FC) of the HC in patients with MDD, but it remains unknown whether this abnormal hippocampal FC pattern occurs in individuals with subthreshold depression (StD) who are at high risk of MDD. Resting-state functional magnetic resonance imaging data were collected from 19 elderly individuals with StD and 18 normal controls. Whole brain voxel-wise FC analyses were conducted to investigate the hippocampal FC pattern by selecting the HC as the region of interest, and correlation analyses were performed to explore the association of altered FC of the HC with self-reported depressive symptoms. The results showed that elderly individuals with StD had substantially decreased FC of the HC to the prefrontal and cuneus cortices compared with healthy normal controls. Moreover, the strength of HC-cuneus connectivity was correlated with self-reported depressive symptoms in elderly individuals with StD. These findings suggest that dysfunctional integration within the HC and cortical regions may occur at an early stage of depression.

Spontaneous activity in the precuneus predicts individual differences in verbal fluency in cognitively normal elderly.

OBJECTIVE The precuneus is 1 of the major cortical hubs and plays an important role in normal aging and verbal fluency processing. The main aim of present study was to investigate how intrinsic brain activity in the precuneus at rest predicts individual differences in verbal fluency ability among elderly adults. METHOD Regional amplitude of low-frequency fluctuations (ALFF) analysis and a correlation-based functional connectivity (FC) approach were used to analyze data acquired from 101 cognitively normal elderly. RESULTS ALFF in the precuneus declined with normal aging and was significantly correlated with individual differences in performance on the verbal fluency test (VFT). Specifically, ALFF in the precuneus was reduced in elderly with high fluency (HF) ability compared with those with low fluency (LF) ability. In addition, the HF individuals displayed increased functional connectivity of the precuneus with the lateral temporal area and prefrontal lobe, including the inferior frontal, medial frontal, superior temporal, middle temporal, and superior frontal gyri. CONCLUSION Spontaneous activity in the precuneus could predict individual differences in verbal fluency processing. Our results suggest that spontaneous activity in the precuneus is an indicator of aging-related changes in semantic verbal fluency processing, or even a potential biomarker for the early detection of semantic verbal fluency deterioration.

Visuospatial characteristics of an elderly Chinese population: results from the WAIS-R block design test

Visuospatial deficits have long been recognized as a potential predictor of dementia, with visuospatial ability decline having been found to accelerate in later stages of dementia. We, therefore, believe that the visuospatial performance of patients with mild cognitive impairment (MCI) and dementia (Dem) might change with varying visuospatial task difficulties. This study administered the Wechsler Adult Intelligence Scale-Revised (WAIS-R) Block Design Test (BDT) to determine whether visuospatial ability can help discriminate between MCI patients from Dem patients and normal controls (NC). Results showed that the BDT could contribute to the discrimination between MCI and Dem. Specifically, simple BDT task scores could best distinguish MCI from Dem patients, while difficult BDT task scores could contribute to discriminating between MCI and NC. Given the potential clinical value of the BDT in the diagnosis of Dem and MCI, normative data stratified by age and education for the Chinese elderly population are presented for use in research and clinical settings.

The Age Effects on the Cognitive Processes of Intention-Based and Stimulus-Based Actions: An ERP Study

The functional decline in action among older adults is caused not only by physical weakness but also by cognitive decline. In this study, we aimed to compare the cognitive effects of age between intention-based and stimulus-based action modes electrophysiologically. Because age-related declines in cognitive function might proceed distinctly according to specific action modes and processes, four specific cognitive processes, action-effect binding, stimulus-response linkage, action-effect feedback control, and effect-action retrieval, were investigated. We recorded event-related potentials (ERPs) during a modified acquisition-test paradigm in young (mean age = 21, SD = 2) and old (mean age = 69, SD = 5) groups. A temporal bisection task and a movement pre-cuing task were used during the acquisition and test phases, respectively. Using ERP indices including readiness potential (RP), P3, N2 and contingent negative variation (CNV) to identify these four specific processes for the two action modes, we revealed the effects of age on each ERP index. The results showed similar patterns of waveforms but consistently decreasing amplitudes of all four ERP indices in the old age group compared with the young age group, which indicates not only generally declining functions of action preparation in older adults but also age effects specific to the action modes and processes that might otherwise be mixed together under confounding experimental conditions. Particularly, an interference effect indexed by the differences in the amplitudes of CNV between congruent and incongruent tasks was observed in the young age group, which is consistent with previous behavioral reports. However, this effect was absent in the old age group, indicating a specific age-related deficit in the effect-action retrieval process of intention-based action, which might be caused by an age-related deficit in associative memory. In sum, this study investigated the cognitive processes of two action modes from a developmental perspective and suggests the importance of adding associative memory training to interventions for older adults with the aim of improving intention-based action.

Linking Inter-Individual Variability in Functional Brain Connectivity to Cognitive Ability in Elderly Individuals

Increasing evidence suggests that functional brain connectivity is an important determinant of cognitive aging. However, the fundamental concept of inter-individual variations in functional connectivity in older individuals is not yet completely understood. It is essential to evaluate the extent to which inter-individual variability in connectivity impacts cognitive performance at an older age. In the current study, we aimed to characterize individual variability of functional connectivity in the elderly and to examine its significance to individual cognition. We mapped inter-individual variability of functional connectivity by analyzing whole-brain functional connectivity magnetic resonance imaging data obtained from a large sample of cognitively normal older adults. Our results demonstrated a gradual increase in variability in primary regions of the visual, sensorimotor, and auditory networks to specific subcortical structures, particularly the hippocampal formation, and the prefrontal and parietal cortices, which largely constitute the default mode and fronto-parietal networks, to the cerebellum. Further, the inter-individual variability of the functional connectivity correlated significantly with the degree of cognitive relevance. Regions with greater connectivity variability demonstrated more connections that correlated with cognitive performance. These results also underscored the crucial function of the long-range and inter-network connections in individual cognition. Thus, individual connectivity–cognition variability mapping findings may provide important information for future research on cognitive aging and neurocognitive diseases.