Deficits in color detection in patients with Alzheimer disease.

Deficits in color vision and related retinal changes hold promise as early screening biomarkers in patients with Alzheimer's disease. This study aimed to determine a cut-off score that can screen for Alzheimer's dementia using a novel color vision threshold test named the red, green, and blue (RGB) modified color vision plate test (RGB-vision plate). We developed the RGB-vision plate consisting of 30 plates in which the red and green hues of Ishihara Plate No.22 were sequentially adjusted. A total of 108 older people participated in the mini-mental state examination (MMSE), Ishihara plate, and RGB-vision plate. For the analyses, the participants were divided into two groups: Alzheimer's dementia (n = 42) and healthy controls (n = 38). K-means cluster analysis and ROC curve analysis were performed to identify the most appropriate cut-off score. As a result, the cut-off screening score for Alzheimer's dementia on the RGB-vision plate was set at 25, with an area under the curve of 0.773 (p<0.001). Moreover, there was a negative correlation between the RGB-vision plate thresholds and MMSE scores (r = -0.36, p = 0.02). In conclusion, patients with Alzheimer's dementia had a deficit in color vision. The RGB-vision plate is a potential early biomarker that may adequately detect Alzheimer's dementia.

Functional Dysconnectivity in Ventral Striatocortical Systems in 22q11.2 Deletion Syndrome.

22q11.2 deletion syndrome (22q11.2DS) is a genetic neurodevelopmental disorder that represents one of the greatest known risk factors for psychosis. Previous studies in psychotic subjects without the deletion have identified a dopaminergic dysfunction in striatal regions, and dysconnectivity of striatocortical systems, as an important mechanism in the emergence of psychosis. Here, we used resting-state functional MRI to examine striatocortical functional connectivity in 22q11.2DS patients. We used a 2 × 2 factorial design including 125 subjects (55 healthy controls, 28 22q11.2DS patients without a history of psychosis, 10 22q11.2DS patients with a history of psychosis, and 32 subjects with a history of psychosis without the deletion), allowing us to identify network effects related to the deletion and to the presence of psychosis. In line with previous results from psychotic patients without 22q11.2DS, we found that there was a dorsal to ventral gradient of hypo- to hyperstriatocortical connectivity related to psychosis across both patient groups. The 22q11.2DS was additionally associated with abnormal functional connectivity in ventral striatocortical networks, with no significant differences identified in the dorsal system. Abnormalities in the ventral striatocortical system observed in these individuals with high genetic risk to psychosis may thus reflect a marker of illness risk.

Utility of Machine Learning Approach with Neuropsychological Tests in Predicting Functional Impairment of Alzheimer's Disease.

BACKGROUND: In assessing the levels of clinical impairment in dementia, a summary index of neuropsychological batteries has been widely used in describing the overall functional status. OBJECTIVE: It remains unexamined how complex patterns of the test performances can be utilized to have specific predictive meaning when the machine learning approach is applied. METHODS: In this study, the neuropsychological battery (CERAD-K) and assessment of functioning level (Clinical Dementia Rating scale and Instrumental Activities of Daily Living) were administered to 2,642 older adults with no impairment (n = 285), mild cognitive impairment (n = 1,057), and Alzheimer's disease (n = 1,300). Predictive accuracy on functional impairment level with the linear models of the single total score or multiple subtest scores (Model 1, 2) and support vector regression with low or high complexity (Model 3, 4) were compared across different sample sizes. RESULTS: The linear models (Model 1, 2) showed superior performance with relatively smaller sample size, while nonlinear models with low and high complexity (Model 3, 4) showed an improved accuracy with a larger dataset. Unlike linear models, the nonlinear models showed a gradual increase in the predictive accuracy with a larger sample size (n > 500), especially when the model training is allowed to exploit complex patterns of the dataset. CONCLUSION: Our finding suggests that nonlinear models can predict levels of functional impairment with a sufficient dataset. The summary index of the neuropsychological battery can be augmented for specific purposes, especially in estimating the functional status of dementia.

Chronic Beneficial Effect of Makeup Therapy on Cognitive Function of Dementia and Facial Appearance Analyzed by Artificial Intelligence Software.

BACKGROUND: Makeup greatly impacts normal social lives but can also be a non-pharmacological form of therapy for dementia. OBJECTIVE: To evaluate the therapeutic effect of makeup therapy. METHODS: We carried out a prospective interventional study on female nursing home residents with dementia, focusing on the chronic therapeutic effect of makeup therapy. Thirty-four patients who received either only skin care (control group, n = 16) or skin care plus makeup therapy (makeup therapy group, n = 18) once every 2 weeks for 3 months were assessed. RESULTS: Three months of makeup therapy significantly improved the Mini-Mental State Examination (MMSE) score compared with control patients (*p < 0.05). Artificial intelligence (AI) software revealed that the appearance of age decreased significantly in the makeup group compared with the control, especially among patients without depression (*p < 0.05). Furthermore, a larger AI happiness score was significantly correlated with a greater improvement of ADL in the makeup therapy group (r = 0.43, *p < 0.05). CONCLUSION: Makeup therapy had a chronic beneficial effect on the cognitive function of female dementia patients, while the chronic effect of makeup therapy on facial appearance was successfully detected by the present AI software.

Assessment of Cognitive Symptoms in Brain Bank-Registered Control Subjects: Feasibility and Utility of a Telephone-Based Screening.

BACKGROUND: For neuroscience research, the study of brain tissue of neurologically unimpaired subjects is crucial to interpret findings in neurodegenerative diseases. Sub-optimal neurological follow-up and the presence of neuropathological lesions in supposedly asymptomatic subjects casts doubt as to whether these subjects present an undetected underlying neurodegenerative disease or are resilient to neurodegeneration. OBJECTIVE: We aimed to assess whether the control donors registered in the Neurological Tissue Bank-Hospital Clínic-IDIBAPS (NTB-HCI) are still free of cognitive symptoms at follow-up and to evaluate the feasibility and utility of a telephone-based screening. METHODS: All control subjects older than 65 years registered at the NTB-HCI database were selected for the study. After a structured telephone interview, those subjects already diagnosed with a neurological disease were excluded. Then, a cognitive screening was performed, including the telephone version of the Mini-Mental State Examination (t-MMSE) and the eight-item interview (AD-8) to the subject and to one informant (AD-8i). RESULTS: In total, 73.8% of the registered donors collaborated in the study. Only 21.4% had at least one of the three cognitive screening tools impaired, and 2.7% had a profile highly suggestive of cognitive impairment. AD-8i correlated moderately with t-MMSE. CONCLUSION: Telephone-based neurologic screening in control donors is feasible and was within the normal range in most of the subjects in our cohort. Albeit, the involvement of neurologists and periodic neurological screenings are desirable in a control subjects brain donor program, AD8-i could be used to screen the control's neurological status in the absence of accurate clinical data at the time of the death.

A Novel Game-Based Intelligent Test for Detecting Elderly Cognitive Function Impairment.

PURPOSES: This research explores the game-based intelligent test (GBIT), predicts the possibilities of Mini-Mental State Examination (MMSE) scores and the risk of cognitive impairment, and then verifies GBIT as one of the reliable and valid cognitive assessment tools. METHODS: This study recruited 117 elderly subjects in Taiwan (average age is 79.92 ± 8.68, average height is 156.91 ± 8.01, average weight is 59.14 ± 9.67, and average MMSE score is 23.33 ± 6.16). A multiple regression model was used to analyze the GBIT parameters of the elderly's reaction, attention, coordination, and memory to predict their MMSE performance. The binary logistic regression was then utilized to predict their risk of cognitive impairment. The statistical significance level was set as α = 0.05. RESULTS: Multiple regression analysis showed that gender, the correct number of reactions, and the correct number of memory have a significantly positive predictive power on MMSE of the elderly (F = 37.60, R 2 = 0.69, and p < 0.05). Binary logistic regression analysis noted that the correct average number of reactions falls by one question, and the ratio of cognitive dysfunction risk increases 1.09 times (p < 0.05); the correct average number of memory drops by one question, the ratio of cognitive dysfunction risk increases 3.76 times (p < 0.05), and the overall model predictive power is 88.20% (sensitivity: 84.00%; specificity: 92.30%). CONCLUSIONS: This study verifies that GBIT is reliable and can effectively predict the cognitive function and risk of cognitive impairment in the elderly. Therefore, GBIT can be used as one of the feasible tools for evaluating older people's cognitive function.

Validation of the Korean Quick Dementia Rating System (K-QDRS).

BACKGROUND: The Quick Dementia Rating System (QDRS) is a brief and rapid dementia staging tool that does not require a trained rater. OBJECTIVE: The purpose of this study is to demonstrate the validity, reliability, and diagnostic usefulness of the Korean version of the QDRS (K-QDRS). METHODS: We collected a total of 411 subject-informant dyads including cognitively unimpaired (CU, n = 22), mild cognitive impairment (MCI, n = 198), and dementia (n = 191). The Clinical Dementia Rating (CDR) scale, Korean version of the Mini-Mental State Examination (K-MMSE), Korean version of instrumental activity of daily living (K-IADL), Short Form of the Geriatric Depression Scale, Caregiver-Administered Neuropsychiatric Inventory (CGA-NPI), and detailed neuropsychological tests were administered as gold standards of dementia staging, cognition, function, mood, and behavior. RESULTS: Internal consistency of the K-QDRS was excellent with Cronbach's alpha of 0.933. Concurrent validity was also satisfactory, with the K-QDRS correlating highly with the CDR Sum of Boxes (Pearson's r = 0.791), K-MMSE (Pearson's r = -0.518), K-IADL (Pearson's r = 0.727), and CGA-NPI (Pearson's r = 0.700). The K-QDRS was highly correlated with the global CDR, K-IADL, and CGA-NPI. We suggested two types of comparisons (for initial diagnosis and for follow-up evaluation). The cutoff scores for follow-up were 1.0 for MCI, 3.5 for very mild dementia, 6.5 for mild dementia, and 11.0 for moderate dementia. CONCLUSION: The K-QDRS is a valid and reliable dementia rating questionnaire and can be used, briefly and rapidly, in various settings like clinical practices, longitudinal cohort studies, and community primary care.

Age-Related Cognitive Decline and Prevalence of Mild Cognitive Impairment in the Iwaki Health Promotion Project.

BACKGROUND: The Iwaki Health Promotion Project (IHPP) is a community-based study for the prevention of lifestyle-related diseases and improvement of quality of life. OBJECTIVE: Between 2014 and 2017, a total of 4,442 Iwaki town residents from 19 to 93 years of age participated in annual surveys to clarify the natural course of age-related cognitive decline and mild cognitive impairment (MCI). METHODS: Modified OLD and SED-11Q questionnaires, MMSE, Logical Memory II, educational history, and APOE genotypes were examined at the first screening. MCI and dementia were diagnosed at the second examination by detailed neurological examination, CDR, and MRI, and followed for 3 years. Spline regression analyses based on a linear mixed model was adopted for statistical analysis. RESULTS: MMSE scores declined with age from 55 to 64 years. There was also interaction between levels of education and ages. At the second examination, 56 MCI and 5 dementia patients were identified. None of the MCI cases progressed to dementia during the 3 years. During follow-up examinations, 13 cases showed improved MMSE scores (0.95 point/year), 5 remained stable, and 7 deteriorated (-0.83 point/year). Five cases showed improved CDR-SOB scores (-0.28 point/year), 9 remained stable, and 6 deteriorated (0.3 point/year). CONCLUSION: IHPP revealed that age- and education-related cognitive decline began and advanced from 55 years of age. The prevalence of MCI and dementia was estimated to be 5.9%in the Iwaki town cohort over 60 yeas of age. About 30%of MCI cases showed progression of cognitive decline.

The Efficacy and Cognitive Effects of Acute Course Electroconvulsive Therapy Are Equal in Adolescents, Transitional Age Youth, and Young Adults.

Objective: Electroconvulsive therapy (ECT) is the most effective acute treatment for depression, but its use in younger patients is rare and heavily regulated in many U.S. states. It is unclear whether age modifies treatment response or tolerability in adolescents, transitional age youth, and young adults. We examined the effects of ECT on depression and cognition in patients aged 16-30 years. Methods: A retrospective cohort study of patients aged 16-30 years receiving ECT between 2011 and 2020 who were evaluated with the Quick Inventory of Depressive Symptomatology (QIDS), the Behavior and Symptom Identification Scale-24 (BASIS-24), and the Montreal Cognitive Assessment (MoCA) at baseline and following treatment #10. Results: Among the 424 patients who met the inclusion criteria, ECT was associated with a decrease in depression symptoms (ΔQIDS -6.7; Kruskal-Wallis rank sum test; χ2 = 293.37; df = 2; p < 0.0001) and improvement in overall self-reported mental health status (ΔBASIS-24 - 0.70; Kruskal-Wallis rank sum test; χ2 = 258.5; df = 2; p < 0.0001) during the first 10 treatments, with a slight reduction in cognition as measured by the MoCA (ΔMoCA -1.1; Kruskal-Wallis rank sum test; χ2 = 33.7; df = 1; p < 0.0001). Age was not a significant predictor of QIDS, BASIS-24, or MoCA changes. Conclusions: Among 424 patients aged 16-30 years receiving acute course ECT, age was not a significant predictor of improvement in depression, change in overall self-reported mental health status, or change in cognition. These results support the utility of ECT in the treatment of adolescents and young adults.

Investigating Changes in the Serum Inflammatory Factors in Alzheimer's Disease and Their Correlation with Cognitive Function.

BACKGROUND: Serum levels of inflammatory factors, such as C3, C4, C-reactive protein (CRP), immunoglobulin (Ig) G, IgA, and IgM, in patients with Alzheimer's disease (AD) and their correlation with cognitive function remain unexplored. OBJECTIVE: To investigate the expression of serum inflammatory factors in patients with AD and its correlation with cognitive function. METHODS: Serum levels of C3, C4, CRP, IgG, IgA, and IgM in 200 patients with AD (mild, moderate, and severe) and those in 174 normal controls were assessed. Spearman's rank correlation analysis was used to explore the relationships among biomarker levels, cognitive function, and activities of daily living (ADL). RESULTS: Among these inflammatory factors, C3 and CRP levels were significantly lower, and IgG and IgA levels were significantly higher in the AD group than in the control group (p < 0.05). There were no significant differences in C4 and IgM levels between the two groups (p > 0.05). In all participants, CRP level was positively correlated with the Mini-Mental State Examination and Montreal Cognitive Assessment scores (p < 0.05). In the AD group, IgA level was negatively associated with ADL scores (p < 0.05). No significant correlation was detected between the other factors and different cognitive scores (p > 0.05). CONCLUSION: Inflammatory factors C3, CRP, IgG, and IgA have the potential to serve as biomarkers for AD. Furthermore, serum IgA was not only correlated with AD but also with ADL. These results support the hypothesis that inflammation is involved in the occurrence and development of AD.

Long-Known Music Exposure Effects on Brain Imaging and Cognition in Early-Stage Cognitive Decline: A Pilot Study.

BACKGROUND: Repeated exposure to long-known music has been shown to have a beneficial effect on cognitive performance in patients with AD. However, the brain mechanisms underlying improvement in cognitive performance are not yet clear. OBJECTIVE: In this pilot study we propose to examine the effect of repeated long-known music exposure on imaging indices and corresponding changes in cognitive function in patients with early-stage cognitive decline. METHODS: Participants with early-stage cognitive decline were assigned to three weeks of daily long-known music listening, lasting one hour in duration. A cognitive battery was administered, and brain activity was measured before and after intervention. Paired-measures tests evaluated the longitudinal changes in brain structure, function, and cognition associated with the intervention. RESULTS: Fourteen participants completed the music-based intervention, including 6 musicians and 8 non-musicians. Post-baseline there was a reduction in brain activity in key nodes of a music-related network, including the bilateral basal ganglia and right inferior frontal gyrus, and declines in fronto-temporal functional connectivity and radial diffusivity of dorsal white matter. Musician status also significantly modified longitudinal changes in functional and structural brain measures. There was also a significant improvement in the memory subdomain of the Montreal Cognitive Assessment. CONCLUSION: These preliminary results suggest that neuroplastic mechanisms may mediate improvements in cognitive functioning associated with exposure to long-known music listening and that these mechanisms may be different in musicians compared to non-musicians.

Caregiving for a Spouse with Cognitive Impairment: Effects on Nutrition and Other Lifestyle Factors.

BACKGROUND: Being a spousal caregiver (SCG) for a patient with cognitive impairment is well known to be associated with increased risk for dementia and cognitive decline. OBJECTIVE: This study examined the impact of the care-recipient's cognitive status on lifestyle factors influencing cognitive decline in SCGs, focusing on nutritional status and blood biomarkers. METHODS: Fifty-one SCGs participated (mean age 73.5±7.0 years) in this study. All participants underwent clinical assessment including the Mini Nutritional Assessment (MNA), Geriatric Depression Scale, Pittsburgh Sleep Quality Index, and International Physical Activity Questionnaire to evaluate lifestyle factors, and the Mini-Mental State Examination to assess global cognition. Also, nutritional blood biomarkers were measured. RESULTS: SCGs caring for a demented spouse showed significantly higher depression scores (t = -3.608, p = 0.001) and malnutrition risk (t = 2.894, p = 0.006) compared to those caring for a non-demented spouse. Decreased care recipients' cognition was significantly correlated with higher GDS (ß= -0.593, t = -4.471, p < 0.001) and higher MNA scores (ß= 0.315, t = 2.225, p = 0.031) and lower level of high-density lipoprotein (HDL) cholesterol (ß= 0.383, t = 2.613, p = 0.012) in their SCGs. Gender had moderating effects on association of care-recipients' cognition with sleep quality (B[SE] = 0.400[0.189], p = 0.041) and HDL cholesterol (B[SE] = -1.137[0.500], p = 0.028) among SCGs. Poorer care-recipient's cognition was associated with worse sleep quality and low HDL cholesterol among wives but not husband caregivers. CONCLUSION: This study provides substantial evidence that SCGs are at risk for depression and malnutrition, which can further affect cognitive decline. As such, these factors should be well assessed and monitored among SCGs for patient with cognitive impairment.

Sleep Characteristics and Cognitive Function in Older Adults Without Dementia: The CABLE Study.

BACKGROUND: The associations between sleep characteristics and cognition are complicated. Alzheimer's disease (AD) pathologies have been proven to be associated with sleep characteristics. OBJECTIVE: We aimed to investigate the associations between sleep characteristics and cognitive function and examine the roles of AD pathologies in modulating the association of sleep duration with cognition. METHODS: A total of 974 participants who had measurements of cerebrospinal fluid (CSF) amyloid-ß (Aß), phosphorylated tau (P-tau), total tau proteins (T-tau), cognitive function, and sleep characteristics were included from the Chinese Alzheimer's Biomarker and Lifestyle (CABLE) study. Linear regression analyses were utilized to explore the associations of sleep characteristics with cognition. Non-linear regression analyses were utilized to explore the associations of sleep habits with cognition. Causal mediation analyses were conducted to explore the mediation effects of AD pathologies on cognition. RESULTS: The Pittsburgh Sleep Quality Index (PSQI) total score was significantly negatively correlated with Montreal Cognitive Assessment (MoCA) score (p = 0.0176). Long latency (p = 0.0054) and low efficiency (p = 0.0273) were associated with cognitive impairment. Habitual nap behavior was associated with lower MoCA scores (p = 0.0045). U-shaped associations were observed between sleep habits (bedtime and nocturnal sleep duration) and cognition. A causal mediation analysis indicated that P-tau/Aß42 mediated the association of sleep duration with cognition. CONCLUSION: These findings showed sleep characteristics were associated with cognitive functions. Sleep habits (duration, bedtime) had U-shaped associations with cognition. AD core pathologies might partially mediate the influence of sleep duration on cognitive impairments.

Medical and Social Determinants of Brain Health and Dementia in a Multicultural Community Cohort of Older Adults.

BACKGROUND: Socioeconomic status (SES), race, ethnicity, and medical comorbidities may contribute to Alzheimer's disease and related disorders (ADRD) health disparities. OBJECTIVE: Analyze effects of social and medical determinants on cognition in 374 multicultural older adults participating in a community-based dementia screening program. METHODS: We used the Montreal Cognitive Assessment (MoCA) and AD8 as measures of cognition, and a 3-way race/ethnicity variable (White, African American, Hispanic) and SES (Hollingshead index) as predictors. Potential contributors to health disparities included: age, sex, education, total medical comorbidities, health self-ratings, and depression. We applied K-means cluster analyses to study medical and social dimension effects on cognitive outcomes. RESULTS: African Americans and Hispanics had lower SES status and cognitive performance compared with similarly aged Whites. We defined three clusters based on age and SES. Cluster #1 and #3 differed by SES but not age, while cluster #2 was younger with midlevel SES. Cluster #1 experienced the worse health outcomes while cluster #3 had the best health outcomes. Within each cluster, White participants had higher SES and better health outcomes, African Americans had the worst physical performance, and Hispanics had the most depressive symptoms. In cross-cluster comparisons, higher SES led to better health outcomes for all participants. CONCLUSION: SES may contribute to disparities in access to healthcare services, while race and ethnicity may contribute to disparities in the quality and extent of services received. Our study highlights the need to critically address potential interactions between race, ethnicity, and SES which may better explain disparities in ADRD health outcomes.

Adaptation and Validation of the Memory Alteration Test (M@T) in Greek Middle-Aged, Older, and Older-Old Population with Subjective Cognitive Decline and Mild Cognitive Impairment.

BACKGROUND: The Memory Alteration Test (M@T) is a verbal episodic and semantic memory screening test able to detect subjective cognitive decline (SCD) and Mild Cognitive Impairment (MCI). OBJECTIVE: To adapt M@T, creating a Greek version of the Memory Alteration Test (M@T-GR), and to validate M@T-GR compared to the Mini-Mental State Examination (MMSE), and Subjective Cognitive Decline- Questionnaire (SCD-Q) MyCog and TheirCog. METHODS: 232 people over 55 years old participated in the study and they were classified as healthy controls (HC, n = 65), SCD (n = 78), or MCI (n = 89). RESULTS: The ANCOVA showed that the M@T-GR's total score was significantly different in HC and SCD (I-J = 2.26, p = 0.032), HC and MCI (I-J = 6.16, p < 0.0001), and SCD compared to MCI (I-J = 3.90, p < 0.0001). In particular, a cut-off score of 46.50 points had an 81%sensitivity and 61%specificity for discriminating HC from SCD (AUC = 0.76, p < 0.0001), while a cut-off score of 45.50 had a sensitivity of 92%and a specificity of 73%for discriminating MCI (AUC = 0.88, p < 0.0001), and a cut-off score of 45.50 points had a sensitivity of 63%and a specificity of 73%for discriminating SCD from those with MCI (AUC = 0.69, p < 0.0021). Exploratory factor analysis indicated that there was one factor explaining 38.46%of the total variance. Internal consistency was adequate (α= 0.75), while convergent validity was found between M@T-GR and MMSE (r = 0.37, p < 0.0001) and SCD-Q TheirCog (r = -0.32, p < 0.0001). CONCLUSION: The M@T-GR is a good to fair screening tool with adequate discriminant validity for administration in people with SCD and MCI in Greece.

White Matter but not Gray Matter Volumes Are Associated with Cognition in Community-Dwelling Chinese Populations.

BACKGROUND: Few studies have investigated the association between cognition and brain volume associated with cerebral small vessel disease (CSVD). OBJECTIVE: We investigated the association between cognition and brain volume and neuroimaging markers of CSVD in a community-dwelling population. METHODS: Participants (n = 993, age≥35 years) from the community-based Shunyi Study were included to investigate the association between neuroimaging markers and cognition cross-sectionally. Magnetic resonance imaging markers included brain volume measurements of the total cerebrum, white matter, gray matter, and CSVD imaging markers. Cognitive performance was assessed using neuropsychological tests of the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Fuld Object Memory, digit span, Trail Making Test (TMT)-A, and TMT-B. RESULTS: For brain volume measurement, subcortical white matter fraction was positively associated with MMSE score (ß= 0.034, p = 0.0062) and MoCA score (ß= 0.034, p = 0.0174), and negatively associated with TMT-A and TMT-B completion time (ß= -2.319, p = 0.0002; ß= -2.827, p = 0.0073, respectively). For evaluation of CSVD imaging markers, the presence of lacunes was positively associated with TMT-B completion time (ß= 17.241, p = 0.0028). CONCLUSION: In community-dwelling populations, reduced white matter volumes, as a consequence of aging and vascular damage, are associated with worse global cognition and executive function. Our findings provide potential insights into the correlation between cognition and CSVD-associated subcortical white matter injury.

Are Video Games Effective to Promote Cognition and Everyday Functional Capacity in Mild Cognitive Impairment/Dementia Patients? A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Mild cognitive impairment (MCI) and dementia are associated with increased age. MCI is a clinical entity described as a transitional state between normal cognition and dementia. Video games (VGs) can potentially promote cognition and functional capacity since multiple cognitive domains are recruited during gameplay. However, there is still a lack of consensus regarding the efficacy of VGs as therapeutic tools, particularly in neurodegenerative diseases. OBJECTIVE: We aimed to analyze the impact of VGs on cognition and functional capacity outcomes in MCI/dementia patients. METHODS: We conducted a systematic review and meta-analysis study (PROSPERO [CRD42021229445]). PubMed, Web of Science, Epistemonikos, CENTRAL, and EBSCO electronic databases were searched for RCT (2000-2021) that analyzed the impact of VGs on cognitive and functional capacity outcomes in MCI/dementia patients. RESULTS: Nine studies were included (n = 409 participants), and Risk of Bias (RoB2) and quality of evidence (GRADE) were assessed. Data regarding attention, memory/learning, visual working memory, executive functions, general cognition, functional capacity, quality of life were identified, and pooled analyses were conducted. An effect favoring VGs interventions was observed on Mini-Mental State Examination (MMSE) score (MD = 1.64, 95%CI 0.60 to 2.69). CONCLUSION: Although promising, the effects observed should be interpreted with caution since serious methodological shortcomings were identified in the studies included. Nonetheless, the effect observed is higher than the minimum clinically important difference (1.4 points) established to MMSE. Future studies on the current topic urge. Recommendations for the design and conduction of cognitive RCT studies are presented.

Influence of Cognitive Impairment on Rehabilitation Received and Its Mediating Effect on Functional Recovery.

BACKGROUND: Cognitive impairment (CI) has been reported to negatively impact rehabilitation outcomes. Knowledge about differences in rehabilitation received in dependence of CI as a potential mediating factor is limited. OBJECTIVE: To analyze whether CI affects amount and frequency of rehabilitation received and if associations between CI and rehabilitation outcome are mediated by the provided amount of therapy. METHODS: Observational cohort study in ward-based geriatric rehabilitation consecutively including 373 patients (mean age 82.0±6.69 years, mean MMSE 23.66±5.31). Outcome measures were amount, frequency, and type of multi-professional therapy sessions and rehabilitation outcome assessed with the Barthel Index (BI). Cognitive status was measured with the Mini-Mental-State Examination (MMSE) classifying three patient subgroups according to cognitive status. RESULTS: Patients with more severe CI received least total therapy hours (TTH) (MMSE < 17, 13.67±6.58 versus MMSE 17-26, 16.12±7.19 and MMSE > 26, 17.79±8.88 h, p = 0.014) and were less often included in occupational therapy (MMSE < 17, 48.9%versus MMSE 17-26, 65.5%and MMSE > 26, 71.4%, p = 0.019) and group-based physiotherapy (MMSE < 17, 73.3%versus MMSE 17-26, 88.5%and MMSE > 26, 81.2%, p = 0.027). Regression models showed that CI negatively impacted TTH (ß= 0.24, p = 0.003) and rehabilitation outcome (ß= 0.41, p = 0.008). In the mediation model, TTH accounted for 23.18%(p < 0.001) of the relationship between CI and rehabilitation outcome. CONCLUSION: Cognitive impairment negatively impacted rehabilitation received. The lower TTH partly mediated the negative association between CI and rehabilitation outcome. Future research should identify specific barriers to therapy provision and optimal length, intensity, and dosage of rehabilitation programs to optimize rehabilitation outcomes in CI.

Association of Thyroid Dysfunction With Cognitive Function: An Individual Participant Data Analysis.

Importance: In clinical guidelines, overt and subclinical thyroid dysfunction are mentioned as causal and treatable factors for cognitive decline. However, the scientific literature on these associations shows inconsistent findings. Objective: To assess cross-sectional and longitudinal associations of baseline thyroid dysfunction with cognitive function and dementia. Design, Setting, and Participants: This multicohort individual participant data analysis assessed 114 267 person-years (median, 1.7-11.3 years) of follow-up for cognitive function and 525 222 person-years (median, 3.8-15.3 years) for dementia between 1989 and 2017. Analyses on cognitive function included 21 cohorts comprising 38 144 participants. Analyses on dementia included eight cohorts with a total of 2033 cases with dementia and 44 573 controls. Data analysis was performed from December 2016 to January 2021. Exposures: Thyroid function was classified as overt hyperthyroidism, subclinical hyperthyroidism, euthyroidism, subclinical hypothyroidism, and overt hypothyroidism based on uniform thyrotropin cutoff values and study-specific free thyroxine values. Main Outcomes and Measures: The primary outcome was global cognitive function, mostly measured using the Mini-Mental State Examination. Executive function, memory, and dementia were secondary outcomes. Analyses were first performed at study level using multivariable linear regression and multivariable Cox regression, respectively. The studies were combined with restricted maximum likelihood meta-analysis. To overcome the use of different scales, results were transformed to standardized mean differences. For incident dementia, hazard ratios were calculated. Results: Among 74 565 total participants, 66 567 (89.3%) participants had normal thyroid function, 577 (0.8%) had overt hyperthyroidism, 2557 (3.4%) had subclinical hyperthyroidism, 4167 (5.6%) had subclinical hypothyroidism, and 697 (0.9%) had overt hypothyroidism. The study-specific median age at baseline varied from 57 to 93 years; 42 847 (57.5%) participants were women. Thyroid dysfunction was not associated with global cognitive function; the largest differences were observed between overt hypothyroidism and euthyroidism-cross-sectionally (-0.06 standardized mean difference in score; 95% CI, -0.20 to 0.08; P = .40) and longitudinally (0.11 standardized mean difference higher decline per year; 95% CI, -0.01 to 0.23; P = .09). No consistent associations were observed between thyroid dysfunction and executive function, memory, or risk of dementia. Conclusions and Relevance: In this individual participant data analysis of more than 74 000 adults, subclinical hypothyroidism and hyperthyroidism were not associated with cognitive function, cognitive decline, or incident dementia. No rigorous conclusions can be drawn regarding the role of overt thyroid dysfunction in risk of dementia. These findings do not support the practice of screening for subclinical thyroid dysfunction in the context of cognitive decline in older adults as recommended in current guidelines.

Levels of Receptor for Advanced Glycation End Products and Glyoxalase-1 in the Total Circulating Extracellular Vesicles from Mild Cognitive Impairment and Different Stages of Alzheimer's Disease Patients.

BACKGROUND: Growing evidence supports that receptor for advanced glycation end products (RAGE) and glyoxalase-1 (GLO-1) are implicated in the pathophysiology of Alzheimer's disease (AD). Extracellular vesicles (EVs) are nanovesicles secreted by almost all cell types, contribute to cellular communication, and are implicated in AD pathology. Recently, EVs are considered as promising tools to identify reliable biomarkers in AD. OBJECTIVE: The aim of our study was to determine the levels of RAGE and GLO-1 in circulating EVs from mild cognitive impairment (MCI) and AD patients and to analyze their correlation with the clinical Mini-Mental State Examination and Montreal Cognitive Assessment scores. We have studied the possibility that neuronal cells could release and transfer GLO-1 through EVs. METHODS: RAGE and GLO-1 levels were measured in circulating EVs, respectively, by Luminex assay and western blot. Released-EVs from SK-N-SH neuronal cells were isolated and GLO-1 levels were determined by western blot. RESULTS: Our data showed higher levels of RAGE in EVs from late AD patients while GLO-1 levels in EVs from early AD were lower as compared to control and MCI patients. Interestingly, levels of RAGE and GLO-1 in EVs were correlated with the cognitive scores regardless of age. For the first time, we demonstrated that GLO-1 was released from neuronal cells through EVs. CONCLUSION: Although more samples will be needed, our preliminary results support the use of peripheral EVs cargo as new tools for the discovery of peripheral AD biomarkers.