Dataset Information

Up-regulation of DMN Connectivity in Mild Cognitive Impairment Via Network-based Cognitive Training.

ABSTRACT: BACKGROUND:Previous work designed a network-based protocol of cognitive training. This programme exploits a mechanism of induced task-oriented co-activation of multiple regions that are part of the default mode network (DMN), to induce functional rewiring and increased functional connectivity within this network. OBJECTIVE:In this study, the programme was administered to patients with a diagnosis of mild cognitive impairment to test its effects in a clinical sample. METHOD:Twenty-three patients with mild cognitive impairment (mean age: 73.74 years, standard deviation 5.13, female/male ratio 13/10) allocated to the experimental condition, underwent one month of computerised training, while fourteen patients (mean age: 73.14 years, standard deviation 6.16, female/ male ratio 7/7) assigned to the control condition underwent a regime of intense social engagement. Patients were in the prodromal stage of Alzheimer's disease (AD) as confirmed by clinical follow ups for at least two years. The DMN was computed at baseline and retest, together with other, control patterns of connectivity, grey matter maps and neuropsychological profiles. RESULTS:A condition-by-timepoint interaction indicating increased connectivity triggered by the programme was found in left parietal DMN regions. No decreases as well as no changes in the other networks or morphology were found. Although between-condition cognitive changes did not reach statistical significance, they correlated positively with changes in DMN connectivity in the left parietal region, supporting the hypothesis that parietal changes were beneficial. CONCLUSION:This programme of cognitive training up-regulates a pattern of connectivity which is pathologically down-regulated in AD. We argue that, when cognitive interventions are conceptualised as tools to induce co-activation repeatedly, they can lead to clinically relevant improvements in brain functioning, and can be of aid in support of pharmacological and other interventions in the earliest stages of AD.

SUBMITTER: De Marco M

PROVIDER: S-EPMC5898032 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Up-regulation of DMN Connectivity in Mild Cognitive Impairment Via Network-based Cognitive Training.

De Marco Matteo M Meneghello Francesca F Pilosio Cristina C Rigon Jessica J Venneri Annalena A

Current Alzheimer research 20180101 6

<h4>Background</h4>Previous work designed a network-based protocol of cognitive training. This programme exploits a mechanism of induced task-oriented co-activation of multiple regions that are part of the default mode network (DMN), to induce functional rewiring and increased functional connectivity within this network.<h4>Objective</h4>In this study, the programme was administered to patients with a diagnosis of mild cognitive impairment to test its effects in a clinical sample.<h4>Method</h4> ...[more]

PMID: 29231140

Similar Datasets

Project description:Background: The spectrum of early Alzheimer's disease (AD) is thought to include subjective cognitive impairment, early mild cognitive impairment (eMCI), and late mild cognitive impairment (lMCI). Choline dysfunction affects the early progression of AD, in which the basal nucleus of Meynert (BNM) is primarily responsible for cortical cholinergic innervation. The aims of this study were to determine the abnormal patterns of BNM-functional connectivity (BNM-FC) in the preclinical AD spectrum (SCD, eMCI, and lMCI) and further explore the relationships between these alterations and neuropsychological measures. Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) was used to investigate FC based on a seed mask (BNM mask) in 28 healthy controls (HC), 30 SCD, 24 eMCI, and 25 lMCI patients. Furthermore, the relationship between altered FC and neurocognitive performance was examined by a correlation analysis. The receiver operating characteristic (ROC) curve of abnormal BNM-FC was used to specifically determine the classification ability to differentiate the early AD disease spectrum relative to HC (SCD and HC, eMCI and HC, lMCI and HC) and pairs of groups in the AD disease spectrum (eMCI and SCD, lMCI and SCD, eMCI and lMCI). Results: Compared with HC, SCD patients showed increased FC in the bilateral SMA and decreased FC in the bilateral cerebellum and middle frontal gyrus (MFG), eMCI patients showed significantly decreased FC in the bilateral precuneus, and lMCI individuals showed decreased FC in the right lingual gyrus. Compared with the SCD group, the eMCI group showed decreased FC in the right superior frontal gyrus (SFG), while the lMCI group showed decreased FC in the left middle temporal gyrus (MTG). Compared with the eMCI group, the lMCI group showed decreased FC in the right hippocampus. Interestingly, abnormal FC was associated with certain cognitive domains and functions including episodic memory, executive function, information processing speed, and visuospatial function in the disease groups. BNM-FC of SFG in distinguishing eMCI from SCD; BNM-FC of MTG in distinguishing lMCI from SCD; BNM-FC of the MTG, hippocampus, and cerebellum in distinguishing SCD from HC; and BNM-FC of the hippocampus and MFG in distinguishing eMCI from lMCI have high sensitivity and specificity. Conclusions: The abnormal BNM-FC patterns can characterize the early disease spectrum of AD (SCD, eMCI, and lMCI) and are closely related to the cognitive domains. These new and reliable findings will provide a new perspective in identifying the early disease spectrum of AD and further strengthen the role of cholinergic theory in AD.

Project description:Patients with amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) show functional and structural connectivity alterations in the default mode network (DMN) while cerebrovascular disease (CeVD) shows functional and structural connectivity changes in the executive control network (ECN). Such disruptions are associated with memory and executive function impairment, respectively. Concurrent AD and CeVD pathology is associated with a higher rate of cognitive decline and differential neurodegenerative patterns. Together, such findings are likely reflective of different underlying pathology in AD with and without CeVD. However, few studies have examined the effect of CeVD on network functional connectivity (task-free functional magnetic resonance imaging (fMRI)) and structural connectivity (diffusion MRI) of the DMN and ECN in aMCI and AD using a hypothesis-driven multiple seed-based approach.We examined functional and structural connectivity network changes in 39 aMCI, 50 aMCI+CeVD, 47 AD, 47 AD+CeVD, and 65 healthy controls (HCs) and their associations with cognitive impairment in the executive/attention and memory domains.We demonstrate divergent DMN and ECN functional connectivity changes in CeVD and non-CeVD subjects. Compared with controls, intra-DMN hippocampal functional connectivity reductions were observed in both AD and AD+CeVD, while intra-DMN parietal and medial prefrontal-parietal functional connectivity was higher in AD+CeVD and aMCI+CeVD, but lower in AD. Intra-ECN frontal functional connectivity increases and fronto-parietal functional connectivity decreases occurred in CeVD but not non-CeVD subjects. Such functional connectivity alterations were related with cognitive impairment in a dissociative manner: intra-DMN functional connectivity changes were associated with worse cognition primarily in non-CeVD groups, while intra-ECN functional connectivity changes were associated with worse cognition primarily in CeVD groups. Additionally, CeVD and non-CeVD groups showed overlapping and distinct alterations in inter-network DMN-ECN functional connectivity depending on disease severity. In contrast to functional connectivity, CeVD groups had greater network structural connectivity damage compared with non-CeVD groups in both aMCI and AD patients. Network structural connectivity damage was associated with worse cognition.We demonstrate differential functional and structural network changes between aMCI and AD patients with and without CeVD through diverging and deleterious network-based degeneration underlying domain-specific cognitive impairment.

Project description:BackgroundMild cognitive impairment (MCI) increases the risk of dementia. The efficacy of cognitive training in patients with MCI is unclear.MethodsIn a two-site, single-blinded, 78-week trial, participants with MCI - stratified by age, severity (early/late MCI), and site - were randomly assigned to 12 weeks of intensive, home-based, computerized training with Web-based cognitive games or Web-based crossword puzzles, followed by six booster sessions. In mixed-model analyses, the primary outcome was change from baseline in the 11-item Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) score, a 70 point scale in which higher scores indicate greater cognitive impairment at 78 weeks, adjusted for baseline. Secondary outcomes included change from baseline in neuropsychological composite score, University of California San Diego Performance-Based Skills Assessment (functional outcome) score, and Functional Activities Questionnaire (functional outcome) score at 78 weeks, adjusted for baseline. Changes in hippocampal volume and cortical thickness on magnetic resonance imaging were assessed.ResultsAmong 107 participants (n=51 [games]; n=56 [crosswords]), ADAS-Cog score worsened slightly for games and improved for crosswords at week 78 (least squares [LS] means difference, -1.44; 95% confidence interval [CI], -2.83 to -0.06; P=0.04). From baseline to week 78, mean ADAS-Cog score worsened for games (9.53 to 9.93) and improved for crosswords (9.59 to 8.61). The late MCI subgroup showed similar results (LS means difference, -2.45; SE, 0.89; 95% CI, -4.21 to -0.70). Among secondary outcomes, the Functional Activities Questionnaire score worsened more with games than with crosswords at week 78 (LS means difference, -1.08; 95% CI, -1.97 to -0.18). Other secondary outcomes showed no differences. Decreases in hippocampal volume and cortical thickness were greater for games than for crosswords (LS means difference, 34.07; SE, 17.12; 95% CI, 0.51 to 67.63 [hippocampal volume]; LS means difference, 0.02; SE, 0.01; 95% CI, 0.00 to 0.04 [cortical thickness]).ConclusionsHome-based computerized training with crosswords demonstrated superior efficacy to games for the primary outcome of baseline-adjusted change in ADAS-Cog score over 78 weeks. (Supported by the National Institutes of Health, National Institute on Aging; ClinicalTrials.gov number, NCT03205709.).

Dataset Information

Up-regulation of DMN Connectivity in Mild Cognitive Impairment Via Network-based Cognitive Training.

Publications

Up-regulation of DMN Connectivity in Mild Cognitive Impairment Via Network-based Cognitive Training.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets