Attenuated neural activity in processing decision-making feedback in uncertain conditions in patients with mild cognitive impairment.

The present study aimed to explore the potential neural correlates during feedback evaluation during decision-making under risk and ambiguity in MCI. Nineteen individuals with MCI and twenty age-matched HCs were enrolled. Decision-making performance under risk and ambiguity was examined with the modified game of dice task (GDT) and an Iowa gambling task (IGT). Using task-related EEG data, reward positivity (RewP) and feedback P3 (fb-P3) were used to characterize participants' motivation and allocation of cognitive resources. Also, response time and event-related oscillation (ERO) were used to evaluate information processing speed, and the potent of post-feedback information integration and behavioral modulation. MCI patients had lower RewP (p = 0.022) and fb-P3 (p = 0.045) amplitudes in the GDT than HCs. Moreover, the amount and valence of feedback modulated the RewP (p = 0.008; p = 0.017) and fb-P3 (p < 0.001; p < 0.001). In the IGT, in addition to the significantly reduced fb-P3 observed in MCI patients (p = 0.010), the amount and valence of feedback modulated the RewP (p = 0.002; p = 0.020). Furthermore, MCI patients took longer to make decisions (t = 2.15, p = 0.041). The ERO analysis revealed that delta power was reduced in MCI (GDT: p = 0.045; p = 0.011). The findings suggest that, during feedback evaluation when making risky and ambiguous decisions, motivation, allocation of cognitive resources, information processing and neuronal excitability were attenuated in MCI. It implies that neural activity related to decision making was compromised in MCI.

A Stable and Scalable Digital Composite Neurocognitive Test for Early Dementia Screening Based on Machine Learning: Model Development and Validation Study.

BACKGROUND: Dementia has become a major public health concern due to its heavy disease burden. Mild cognitive impairment (MCI) is a transitional stage between healthy aging and dementia. Early identification of MCI is an essential step in dementia prevention. OBJECTIVE: Based on machine learning (ML) methods, this study aimed to develop and validate a stable and scalable panel of cognitive tests for the early detection of MCI and dementia based on the Chinese Neuropsychological Consensus Battery (CNCB) in the Chinese Neuropsychological Normative Project (CN-NORM) cohort. METHODS: CN-NORM was a nationwide, multicenter study conducted in China with 871 participants, including an MCI group (n=327, 37.5%), a dementia group (n=186, 21.4%), and a cognitively normal (CN) group (n=358, 41.1%). We used the following 4 algorithms to select candidate variables: the F-score according to the SelectKBest method, the area under the curve (AUC) from logistic regression (LR), P values from the logit method, and backward stepwise elimination. Different models were constructed after considering the administration duration and complexity of combinations of various tests. Receiver operating characteristic curve and AUC metrics were used to evaluate the discriminative ability of the models via stratified sampling cross-validation and LR and support vector classification (SVC) algorithms. This model was further validated in the Alzheimer's Disease Neuroimaging Initiative phase 3 (ADNI-3) cohort (N=743), which included 416 (56%) CN subjects, 237 (31.9%) patients with MCI, and 90 (12.1%) patients with dementia. RESULTS: Except for social cognition, all other domains in the CNCB differed between the MCI and CN groups (P<.008). In feature selection results regarding discrimination between the MCI and CN groups, the Hopkins Verbal Learning Test-5 minutes Recall had the best performance, with the highest mean AUC of up to 0.80 (SD 0.02) and an F-score of up to 258.70. The scalability of model 5 (Hopkins Verbal Learning Test-5 minutes Recall and Trail Making Test-B) was the lowest. Model 5 achieved a higher level of discrimination than the Hong Kong Brief Cognitive test score in distinguishing between the MCI and CN groups (P<.05). Model 5 also provided the highest sensitivity of up to 0.82 (range 0.72-0.92) and 0.83 (range 0.75-0.91) according to LR and SVC, respectively. This model yielded a similar robust discriminative performance in the ADNI-3 cohort regarding differentiation between the MCI and CN groups, with a mean AUC of up to 0.81 (SD 0) according to both LR and SVC algorithms. CONCLUSIONS: We developed a stable and scalable composite neurocognitive test based on ML that could differentiate not only between patients with MCI and controls but also between patients with different stages of cognitive impairment. This composite neurocognitive test is a feasible and practical digital biomarker that can potentially be used in large-scale cognitive screening and intervention studies.

Characteristics and Potential Neural Substrates of Encoding and Retrieval During Memory Binding in Amnestic Mild Cognitive Impairment.

BACKGROUND: Whether encoding or retrieval failure contributes to memory binding deficit in amnestic mild cognitive impairment (aMCI) has not been elucidated. Also, the potential brain structural substrates of memory binding remained undiscovered. OBJECTIVE: To investigate the characteristics and brain atrophy pattern of encoding and retrieval performance during memory binding in aMCI. METHODS: Forty-three individuals with aMCI and 37 cognitively normal controls were recruited. The Memory Binding Test (MBT) was used to measure memory binding performance. The immediate and delayed memory binding indices were computed by using the free and cued paired recall scores. Partial correlation analysis was performed to map the relationship between regional gray matter volume and memory binding performance. RESULTS: The memory binding performance in the learning and retrieval phases was worse in the aMCI group than in the control group (F = 22.33 to 52.16, all p < 0.001). The immediate and delayed memory binding index in the aMCI group was lower than that in the control group (p < 0.05). The gray matter volume of the left inferior temporal gyrus was positively correlated with memory binding test scores (r = 0.49 to 0.61, p < 0.05) as well as the immediate (r = 0.39, p < 0.05) and delayed memory binding index (r = 0.42, p < 0.05) in the aMCI group. CONCLUSION: aMCI may be primarily characterized by a deficit in encoding phase during the controlled learning process. Volumetric losses in the left inferior temporal gyrus may contribute to encoding failure.

Decision-Making Profiles and Their Associations with Cognitive Performance in Mild Cognitive Impairment.

BACKGROUND: It is crucial for older adults, especially those with mild cognitive impairment (MCI), to make profitable decisions routinely. However, the results regarding decision-making (DM) remain inconsistent. OBJECTIVE: The present study assessed DM profiles under uncertainty conditions in individuals with MCI and their associations with multi-domain cognitive performance. METHOD: Fifty-three patients with MCI and forty-two age-, gender-, and education level-matched healthy controls (HCs) were administered a comprehensive neuropsychological battery test. The Iowa Gambling Task (IGT) and Game of Dice Task (GDT) were used to assess DM competence in conditions involving ambiguity and risk, respectively. In addition, Spearman's correlations were used to examine relationships between GDT and multi-domain cognitive performance. RESULT: The final capital (FC) and frequency of utilization of negative feedback (FUNF) and positive feedback (FUPF) in the GDT were lower in MCI patients than in HCs. In addition, the number of shifts between safe and risky alternatives was significantly different across groups. However, IGT performance was comparable across groups. In the MCI patients, risky DM performance was associated with language, whereas in HCs was correlated with memory and executive functions. Besides, in MCI, performance on IGT was significantly correlated with social cognition. CONCLUSION: Individuals with mild cognitive impairment have difficulty utilizing feedback to make optimal decisions under risky situations. The association between decision-making performance and cognitive function is divergent regarding situational uncertainty and individuals' cognitive status. In mild cognitive impairment and normal aging, decision-making under ambiguity needs further investigation.

Heterogenous Subtypes of Late-Life Depression and Their Cognitive Patterns: A Latent Class Analysis.

Background: Late-life depression (LLD), characterized by cognitive deficits, is considered heterogeneous across individuals. Previous studies have identified subtypes with diverse symptom profiles, but their cognitive patterns are unknown. This study aimed to investigate the subtypes of LLD and the cognitive profile of each group. Methods: In total, 109 depressed older adults were enrolled. We performed latent class analysis using Geriatric Depression Scale items as indicators to generate latent classes. We compared the sociodemographic and clinical characteristics with cognitive functions between groups and conducted regression analysis to investigate the association between class membership and variables with significant differences. Results: Two classes were identified: the "pessimistic" group was characterized by pessimistic thoughts and the "worried" group with a relatively high prevalence of worry symptoms. The two groups did not differ in sociodemographic characteristics. The "pessimistic" group showed a higher rate of past history of depression and lower age of onset. The "worried" group had more physical comorbidities and a higher rate of past history of anxiety. The "pessimistic" group was more impaired in general cognitive function, executive function, information processing speed, and attention. Lower general and executive functions were associated with the membership in the "pessimistic" group. Conclusions: Subjects with pessimistic symptoms and subjects with a propensity to worry may form two distinct subtypes of late-life depression with different cognitive profiles. Further, the cognitive evaluation of subjects with pessimistic symptoms is of utmost importance.