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Biological Factors Contributing to the Response to Cognitive Training in Mild Cognitive Impairment.

ABSTRACT: In mild cognitive impairment (MCI), small benefits from cognitive training were observed for memory functions but there appears to be great variability in the response to treatment. Our study aimed to improve the characterization and selection of those participants who will benefit from cognitive intervention. We evaluated the predictive value of disease-specific biological factors for the outcome after cognitive training in MCI (n?=?25) and also considered motivation of the participants. We compared the results of the cognitive intervention group with two independent control groups of MCI patients (local memory clinic, n?=?20; ADNI cohort, n?=?302). The primary outcome measure was episodic memory as measured by verbal delayed recall of a 10-word list. Episodic memory remained stable after treatment and slightly increased 6 months after the intervention. In contrast, in MCI patients who did not receive an intervention, episodic memory significantly decreased during the same time interval. A larger left entorhinal cortex predicted more improvement in episodic memory after treatment and so did higher levels of motivation. Adding disease-specific biological factors significantly improved the prediction of training-related change compared to a model based simply on age and baseline performance. Bootstrapping with resampling (n?=?1000) verified the stability of our finding. Cognitive training might be particularly helpful in individuals with a bigger left entorhinal cortex as individuals who did not benefit from intervention showed 17% less volume in this area. When extended to alternative treatment options, stratification based on disease-specific biological factors is a useful step towards individualized medicine.

SUBMITTER: Peter J

PROVIDER: S-EPMC5734129 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Biological Factors Contributing to the Response to Cognitive Training in Mild Cognitive Impairment.

Peter Jessica J Schumacher Lena V LV Landerer Verena V Abdulkadir Ahmed A Kaller Christoph P CP Lahr Jacob J Klöppel Stefan S

Journal of Alzheimer's disease : JAD 20180101 1

In mild cognitive impairment (MCI), small benefits from cognitive training were observed for memory functions but there appears to be great variability in the response to treatment. Our study aimed to improve the characterization and selection of those participants who will benefit from cognitive intervention. We evaluated the predictive value of disease-specific biological factors for the outcome after cognitive training in MCI (n = 25) and also considered motivation of the participants. We com ...[more]

PMID: 29154279

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Project description:BackgroundMild cognitive impairment (MCI) is generally regarded as the borderline between cognitive changes of aging and very early Alzheimer's disease (AD). It is important to develop easily available interventions to delay the progression of MCI to AD. We investigated factors contributing to the cognitive improvement effects of acupuncture to obtain data for developing optimized acupuncture treatments for MCI.MethodsThis outcome assessor-blinded, randomized controlled trial included a full analysis for comparing the efficacy of different acupuncture methods. Thirty-two participants with MCI (i.e., fulfilling the Peterson diagnostic criteria for MCI, K-MMSE scores of 20-23, and MoCA-K scale scores of 0-22) were randomly assigned to basic acupuncture (BA; GV20, EX-HN1, GB20, and GV24 for 30 min), acupoint specificity (AS; adding KI3 to BA), needle duration (ND; BA for 20 min), or electroacupuncture (EA; electrical stimulation to BA) groups (n=8/group) via 1:1:1:1 allocation and administered acupuncture once daily, three times a week for 8 weeks. The measured outcomes included scores on the Korean version of the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-K-cog), Korean version of the Montreal Cognitive Assessment scale (MoCA-K), Center for Epidemiological Studies-Depression Scale, Korean Activities of Daily Living scale, Korean Instrumental Activities of Daily Living scale, and European Quality of Life Five Dimension Five Level Scale. Outcome measurements were recorded at baseline (week 0), intervention endpoint (week 8), and 12 weeks after intervention completion (week 20).ResultsTwenty-five patients with MCI completed the trial (BA group, 8; AS group, 6; ND group, 5; EA group, 6). MoCA-K scores were significantly increased in the BA group compared with the ND (p=0.008, week 8-week 0) and EA groups (p=0.003, week 8-week 0; p=0.043, week 20-week 0). ADAS-K-cog scores were significantly decreased in the BA group compared with the ND group (p=0.019, week 20-week 0).ConclusionsThe BA group showed significant improvement in cognitive function compared to the ND and EA groups. Electrical stimulation and needle duration may contribute to the cognitive improvement effects of acupuncture in patients with MCI.Trial registrationClinical Research Information Service; URL:cris.nih.go.kr .; unique identifier: KCT0003430 (registration date: January 16, 2019).

Project description: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.

Project description:Background:Transcranial direct current stimulation (tDCS), a non-invasive stimulation, represents a potential intervention to enhance cognition across clinical populations including Alzheimer's disease and mild cognitive impairment (MCI). This randomized clinical trial in MCI investigated the effects of anodal tDCS (a-tDCS) delivered to left inferior frontal gyrus (IFG) combined with gist-reasoning training (SMART) versus sham tDCS (s-tDCS) plus SMART on measures of cognitive and neural changes in resting cerebral blood flow (rCBF). We were also interested in SMART effects on cognitive performance regardless of the tDCS group. Methods:Twenty-two MCI participants, who completed the baseline cognitive assessment (T1), were randomized into one of two groups: a-tDCS + SMART and s-tDCS + SMART. Of which, 20 participants completed resting pCASL MRI scan to measure rCBF. Eight SMART sessions were administered over 4 weeks with a-tDCS or s-tDCS stimulation for 20 min before each session. Participants were assessed immediately (T2) and 3-months after training (T3). Results:Significant group × time interactions showed cognitive gains at T2 in executive function (EF) measure of inhibition [DKEFS- Color word (p = 0.047)], innovation [TOSL (p = 0.01)] and on episodic memory [TOSL (p = 0.048)] in s-tDCS + SMART but not in a-tDCS + SMART group. Nonetheless, the gains did not persist for 3 months (T3) after the training. A voxel-based analysis showed significant increase in regional rCBF in the right middle frontal cortex (MFC) (cluster-wise p = 0.05, k = 1,168 mm3) in a-tDCS + SMART compared to s-tDCS + SMART. No significant relationship was observed between the increased CBF with cognition. Irrespective of group, the combined MCI showed gains at T2 in EF of conceptual reasoning [DKEFS card sort (p = 0.033)] and category fluency [COWAT (p = 0.055)], along with gains at T3 in EF of verbal fluency [COWAT (p = 0.009)]. Conclusion:One intriguing finding is a-tDCS to left IFG plus SMART increased blood flow to right MFC, however, the stimulation seemingly blocked cognitive benefits of SMART on EF (inhibition and innovation) and episodic memory compared to s-tDCS + SMART group. Although the sample size is small, this paper contributes to growing evidence that cognitive training provides a way to significantly enhance cognitive performance in adults showing memory loss, where the role of a-tDCS in augmenting these effects need further study.

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Biological Factors Contributing to the Response to Cognitive Training in Mild Cognitive Impairment.

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Biological Factors Contributing to the Response to Cognitive Training in Mild Cognitive Impairment.

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