Memory Support System training in mild cognitive impairment: Predictors of learning and adherence.
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ABSTRACT:
SUBMITTER: De Wit L
PROVIDER: S-EPMC8180362 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background: Effective treatment for Alzheimer’s disease (AD) remains an unmet need. Thus, identifying patients with mild cognitive impairment (MCI) who are at high-risk of progressing to AD is crucial for early intervention. Methods: Blood-based transcriptomics analyses were performed using a longitudinal study cohort to compare progressive MCI (P-MCI, n=28), stable MCI (S-MCI, n=39), and AD patients (n=49). Statistical DESeq2 analysis and machine learning methods were employed to identify differentially expressed genes (DEGs) and develop prediction models. Results: We discovered a remarkable gender-specific difference in DEGs that distinguish P-MCI from S-MCI. Machine learning models achieved high accuracy in distinguishing P-MCI from S-MCI (AUC 0.93), AD from S-MCI (AUC 0.94), and AD from P-MCI (AUC 0.92). An 8-gene signature was identified for distinguishing P-MCI from S-MCI.
2024-11-30 | GSE282742 | GEO
Project description:Reliable biomarkers of memory decline are critical for the early detection of Alzheimer's disease. Previous work has found three EEG measures, namely the event-related brain potential P600, suppression of oscillatory activity in the alpha frequency range (∼10 Hz) and cross-frequency coupling between low theta/high delta and alpha/beta activity, each of which correlates strongly with verbal learning and memory abilities in healthy elderly and patients with mild cognitive impairment or prodromal Alzheimer's disease. In the present study, we address the question of whether event-related or oscillatory measures, or a combination thereof, best predict the decline of verbal memory in mild cognitive impairment and Alzheimer's disease. Single-trial correlation analyses show that despite a similarity in their time courses and sensitivities to word repetition, the P600 and the alpha suppression components are minimally correlated with each other on a trial-by-trial basis (generally |r s| < 0.10). This suggests that they are unlikely to stem from the same neural mechanism. Furthermore, event-related brain potentials constructed from bandpass filtered (delta, theta, alpha, beta or gamma bands) single-trial data indicate that only delta band activity (1-4 Hz) is strongly correlated (r = 0.94, P < 0.001) with the canonical P600 repetition effect; event-related potentials in higher frequency bands are not. Importantly, stepwise multiple regression analyses reveal that the three event-related brain potential/oscillatory measures are complementary in predicting California Verbal Learning Test scores (overall R 2 ' s in 0.45-0.63 range). The present study highlights the importance of combining EEG event-related potential and oscillatory measures to better characterize the multiple mechanisms of memory failure in individuals with mild cognitive impairment or prodromal Alzheimer's disease.
| S-EPMC7749791 | biostudies-literature
Project description:BackgroundAdaptive computerized working memory (WM) training has shown favorable effects on cerebral cortical thickness as compared to non-adaptive training in healthy individuals. However, knowledge of WM training-related morphological changes in mild cognitive impairment (MCI) is limited.ObjectiveThe primary objective of this double-blind randomized study was to investigate differences in longitudinal cortical thickness trajectories after adaptive and non-adaptive WM training in patients with MCI. We also investigated the genotype effects on cortical thickness trajectories after WM training combining these two training groups using longitudinal structural magnetic resonance imaging (MRI) analysis in Freesurfer.MethodMagnetic resonance imaging acquisition at 1.5 T were performed at baseline, and after four- and 16-weeks post training. A total of 81 individuals with MCI accepted invitations to undergo 25 training sessions over 5 weeks. Longitudinal Linear Mixed effect models investigated the effect of adaptive vs. non-adaptive WM training. The LME model was fitted for each location (vertex). On all statistical analyzes, a threshold was applied to yield an expected false discovery rate (FDR) of 5%. A secondary LME model investigated the effects of LMX1A and APOE-ε4 on cortical thickness trajectories after WM training.ResultsA total of 62 participants/patients completed the 25 training sessions. Structural MRI showed no group difference between the two training regimes in our MCI patients, contrary to previous reports in cognitively healthy adults. No significant structural cortical changes were found after training, regardless of training type, across all participants. However, LMX1A-AA carriers displayed increased cortical thickness trajectories or lack of decrease in two regions post-training compared to those with LMX1A-GG/GA. No training or training type effects were found in relation to the APOE-ε4 gene variants.ConclusionThe MCI patients in our study, did not have improved cortical thickness after WM training with either adaptive or non-adaptive training. These results were derived from a heterogeneous population of MCI participants. The lack of changes in the cortical thickness trajectory after WM training may also suggest the lack of atrophy during this follow-up period. Our promising results of increased cortical thickness trajectory, suggesting greater neuroplasticity, in those with LMX1A-AA genotype need to be validated in future trials.
| S-EPMC9014119 | biostudies-literature
Project description:Dementia is a common medical condition in the ageing population, and cognitive intervention is a non-pharmacologic strategy to improve cognitive functions. This meta-analysis evaluated the benefits of computerized cognitive training (CCT) on memory functions in individuals with MCI or dementia. The study was registered prospectively with PROSPERO under CRD42022363715 and received no funding. The search was conducted on MEDLINE, Embase, and PsycINFO on Sept 19, 2022, and Google Scholar on May 9, 2023, to identify randomized controlled trials that examined the effects of CCT on memory outcomes in individuals with MCI or dementia. Mean differences and standard deviations of neuropsychological assessment scores were extracted to derive standardized mean differences. Our search identified 10,678 studies, of which 35 studies were included. Among 1489 participants with MCI, CCT showed improvements in verbal memory (SMD (95%CI) = 0.55 (0.35-0.74)), visual memory (0.36 (0.12-0.60)), and working memory (0.37 (0.10-0.64)). Supervised CCT showed improvements in verbal memory (0.72 (0.45-0.98)), visual memory (0.51 (0.22-0.79)), and working memory (0.33 (0.01-0.66)). Unsupervised CCT showed improvement in verbal memory (0.21 (0.04-0.38)) only. Among 371 participants with dementia, CCT showed improvement in verbal memory (0.64 (0.02-1.27)) only. Inconsistency due to heterogeneity (as indicated by I2 values) is observed, which reduces our confidence in MCI outcomes to a moderate level and dementia outcomes to a low level. The results suggest that CCT is efficacious on various memory domains in individuals with MCI. Although the supervised approach showed greater effects, the unsupervised approach can improve verbal memory while allowing users to receive CCT at home without engaging as many healthcare resources.
| S-EPMC10764827 | biostudies-literature
Project description:An activated plasma contact system is an abnormality observed in many Alzheimer's disease (AD) patients. Since mild cognitive impairment (MCI) patients often develop AD, we analyzed the status of contact system activation in MCI patients. We found that kallikrein activity, high molecular weight kininogen cleavage, and bradykinin levels- measures of contact system activation- were significantly elevated in MCI patient plasma compared to plasma from age- and education-matched healthy individuals. Changes were more pronounced in MCI patients with impaired short-term recall memory, indicating the possible role of the contact system in early cognitive changes.
| S-EPMC7587041 | biostudies-literature
Project description:OBJECTIVE:To identify a neuroimaging signature predictive of brain amyloidosis as a screening tool to identify individuals with mild cognitive impairment (MCI) that are most likely to have high levels of brain amyloidosis or to be amyloid-free. METHODS:The prediction model cohort included 62 MCI subjects screened with structural magnetic resonance imaging (MRI) and (11) C-labeled Pittsburgh compound B positron emission tomography (PET). We identified an anatomical shape variation-based neuroimaging predictor of brain amyloidosis and defined a structural MRI-based brain amyloidosis score (sMRI-BAS). Amyloid beta positivity (A?(+) ) predictive power of sMRI-BAS was validated on an independent cohort of 153 MCI patients with cerebrospinal fluid A?1-42 biomarker data but no amyloid PET scans. We compared the A?(+) predictive power of sMRI-BAS to those of apolipoprotein E (ApoE) genotype and hippocampal volume, the 2 most relevant candidate biomarkers for the prediction of brain amyloidosis. RESULTS:Anatomical shape variations predictive of brain amyloidosis in MCI embraced a characteristic spatial pattern known for high vulnerability to Alzheimer disease pathology, including the medial temporal lobe, temporal-parietal association cortices, posterior cingulate, precuneus, hippocampus, amygdala, caudate, and fornix/stria terminals. A?(+) prediction performance of sMRI-BAS and ApoE genotype jointly was significantly better than the performance of each predictor separately (area under the curve [AUC] = 0.88 vs AUC = 0.70 and AUC = 0.81, respectively) with >90% sensitivity and specificity at 20% false-positive rate and false-negative rate thresholds. Performance of hippocampal volume as an independent predictor of brain amyloidosis in MCI was only marginally better than random chance (AUC = 0.56). INTERPRETATION:As one of the first attempts to use an imaging technique that does not require amyloid-specific radioligands for identification of individuals with brain amyloidosis, our findings could lead to development of multidisciplinary/multimodality brain amyloidosis biomarkers that are reliable, minimally invasive, and widely available.
| S-EPMC4603555 | biostudies-literature
Project description:Objectives: To identify learning effects and meaningful changes in amnestic mild cognitive impairment (aMCI) at a follow-up assessment. Method: The Spanish version of the California Verbal Learning Test (CVLT) was administered to a sample of 274 adults of age over 50 years with subjective memory complains (SMC), including single and multiple domain aMCI groups and participants with SMC but without cognitive impairment (SMC group). The Wilcoxon test was used to compare results at baseline and after 18 months in short and long recall, and standardized regression-based (SRB) methods were used to study meaningful changes. Results: Scores were significantly higher at follow-up for short and long-delayed recall in all groups indicating generalized practice effect. SRB scores indicated a significant decline in recall in a higher proportion of participants with aMCI than in SMC group. Discussion: Patients with multiple and single domain aMCI benefit from practice in a verbal learning memory test. The SRB approach revealed a higher incidence of meaningful decline in short and long-delay recall and recognition in the aMCI groups than in the SMC group. Specifically, compared to SMC participants, single-domain aMCI individuals declined in a higher proportion in all measures, and multiple-domain aMCI individuals in long delay free recall.
| S-EPMC5518168 | biostudies-other
Project description:BackgroundAlmost 60% of adults with amnestic mild cognitive impairment (aMCI) have obstructive sleep apnea (OSA). Treatment with continuous positive airway pressure (CPAP) may delay cognitive decline, but CPAP adherence is often suboptimal. In this study, we report predictors of CPAP adherence in older adults with aMCI who have increased odds of progressing to dementia, particularly due to Alzheimer's disease.MethodsThe data are from Memories 2, "Changing the Trajectory of Mild Cognitive Impairment with CPAP Treatment of Obstructive Sleep Apnea." Participants had moderate to severe OSA, were CPAP naïve, and received a telehealth CPAP adherence intervention. Linear and logistic regression models examined predictors.ResultsThe 174 participants (mean age 67.08 years, 80 female, 38 Black persons) had a mean apnea-hypopnea index of 34.78, and 73.6% were adherent, defined as an average of ≥4 hours of CPAP use per night. Only 18 (47.4%) Black persons were CPAP adherent. In linear models, White race, moderate OSA, and participation in the tailored CPAP adherence intervention were significantly associated with higher CPAP use at 3 months. In logistic models, White persons had 9.94 times the odds of adhering to CPAP compared to Black persons. Age, sex, ethnicity, education, body mass index, nighttime sleep duration, daytime sleepiness, and cognitive status were not significant predictors.ConclusionsOlder patients with aMCI have high CPAP adherence, suggesting that age and cognitive impairment should not be a barrier to prescribing CPAP. Research is needed to improve adherence in Black patients, perhaps through culturally tailored interventions.
| S-EPMC11007392 | biostudies-literature
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.).
| S-EPMC10457124 | biostudies-literature
Project description:Young and older adults experience benefits in attention and memory for emotional compared to neutral information, but this memory benefit is greatly diminished in Alzheimer's disease (AD). Little is known about whether this impairment arises early or late in the time course between healthy aging and AD. This study compared memory for positive, negative, and neutral items with neutral backgrounds between patients with mild cognitive impairment (MCI) and healthy older adults. We also used a divided attention condition in older adults as a possible model for the deficits observed in MCI patients. Results showed a similar pattern of selective memory for emotional items while forgetting their backgrounds in older adults and MCI patients, but MCI patients had poorer memory overall. Dividing attention during encoding disproportionately reduced memory for backgrounds (versus items) relative to a full attention condition. Participants performing in the lower half on the divided attention task qualitatively and quantitatively mirrored the results in MCI patients. Exploratory analyses comparing lower- and higher-performing MCI patients showed that only higher-performing MCI patients had the characteristic scene memory pattern observed in healthy older adults. Together, these results suggest that the effects of emotion on memory are relatively well preserved for patients with MCI, although emotional memory patterns may start to be altered once memory deficits become more pronounced.
| S-EPMC5303668 | biostudies-literature