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Toward rational use of cognitive training in those with mild cognitive impairment.

ABSTRACT: The term cognitive training includes a range of techniques that hold potential for treating cognitive impairment caused by neurologic injury and disease. Our central premise is that these techniques differ in their mechanisms of action and therefore engage distinct brain regions (or neural networks). We support this premise using data from a single-blind randomized-controlled trial in which patients with mild cognitive impairment were randomized to either mnemonic strategy training (MST) or spaced retrieval training (SRT) as they learned ecologically relevant object-location associations. Both training approaches were highly effective in the short term, but MST demonstrated a clear advantage after days to weeks. MST also increased activation in and functional connectivity between frontal, temporal, and parietal regions as well as the hippocampus. In contrast, patterns of reduced activation and functional connectivity were evident following SRT. These findings support the rational development of cognitive training techniques.

SUBMITTER: Hampstead BM

PROVIDER: S-EPMC9816345 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Toward rational use of cognitive training in those with mild cognitive impairment.

Hampstead Benjamin M BM Stringer Anthony Y AY Iordan Alexandru D AD Ploutz-Snyder Robert R Sathian K K

Alzheimer's & dementia : the journal of the Alzheimer's Association 20220706 3

The term cognitive training includes a range of techniques that hold potential for treating cognitive impairment caused by neurologic injury and disease. Our central premise is that these techniques differ in their mechanisms of action and therefore engage distinct brain regions (or neural networks). We support this premise using data from a single-blind randomized-controlled trial in which patients with mild cognitive impairment were randomized to either mnemonic strategy training (MST) or spac ...[more]

PMID: 35791724

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Project description:ObjectivesAlzheimer's disease (AD) is the most prevalent neurodegenerative disorder and the most common form of dementia in the elderly. Certain genes have been identified as important clinical risk factors for AD, and technological advances in genomic research, such as genome-wide association studies (GWAS), allow for analysis of polymorphisms and have been widely applied to studies of AD. However, shortcomings of GWAS include sensitivity to sample size and hereditary deletions, which result in low classification and predictive accuracy. Therefore, this paper proposes a novel deep-learning genomics approach and applies it to multitasking classification of AD progression, with the goal of identifying novel genetic biomarkers overlooked by traditional GWAS analysis.MethodsIn this study, we selected genotype data from 1461 subjects enrolled in the Alzheimer's Disease Neuroimaging Initiative, including 622 AD, 473 mild cognitive impairment (MCI), and 366 healthy control (HC) subjects. The proposed deep-learning genomics (DLG) approach consists of three steps: quality control, coding of single-nucleotide polymorphisms, and classification. The ResNet framework was used for the DLG model, and the results were compared with classifications by simple convolutional neural network structure. All data were randomly assigned to one training/validation group and one test group at a ratio of 9 : 1. And fivefold cross-validation was used.ResultsWe compared classification results from the DLG model to those from traditional GWAS analysis among the three groups. For the AD and HC groups, the accuracy, sensitivity, and specificity of classification were, respectively, 98.78 ± 1.50%, 98.39% ± 2.50%, and 99.44% ± 1.11% using the DLG model, while 71.38% ± 0.63%, 63.13% ± 2.87%, and 85.59% ± 6.66% using traditional GWAS. Similar results were obtained from the other two intergroup classifications.ConclusionThe DLG model can achieve higher accuracy and sensitivity when applied to progression of AD. More importantly, we discovered several novel genetic biomarkers of AD progression, including rs6311 and rs6313 in HTR2A, rs1354269 in NAV2, and rs690705 in RFC3. The roles of these novel loci in AD should be explored in future research.

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.).

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.

Dataset Information

Toward rational use of cognitive training in those with mild cognitive impairment.

Publications

Toward rational use of cognitive training in those with mild cognitive impairment.

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