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Objective: This study aimed to develop and validate machine learning models (MLMs) to diagnose Alzheimer's disease (AD) using cortical complexity indicated by fractal dimension (FD). Methods: A total of 296 participants with normal cognitive (NC) function and 182 with AD from the AD Neuroimaging Initiative database were randomly divided into training and internal validation cohorts. Then, FDs, demographic characteristics, baseline global cognitive function scales [Montreal Cognitive Assessment (MoCA), Functional Activities Questionnaire (FAQ), Global Deterioration Scale (GDS), Neuropsychiatric Inventory (NPI)], phospho-tau (p-tau 181), amyloidß-42/40, apolipoprotein E (APOE) and polygenic hazard score (PHS) were collected to establish multiple MLMs. Receiver operating characteristic curves were used to evaluate model performance. Participants from our institution (n = 66; 33 with NC and 33 with AD) served as external validation cohorts to validate the MLMs. Decision curve analysis was used to estimate the models' clinical values. Results: The FDs from 30 out of 69 regions showed significant alteration. All MLMs were conducted based on the 30 significantly different FDs. The FD model had good accuracy in predicting AD in three cohorts [area under the receiver operating characteristic (ROC) curve (AUC) = 0.842, 0.808, and 0.803]. There were no statistically significant differences in AUC values between the FD model and the other combined models in the training and internal validation cohorts except MoCA + FD and FAQ + FD models. Among MLMs, the MoCA + FD model showed the best predictive efficiency in three cohorts (AUC = 0.951, 0.931, and 0.955) and had the highest clinical net benefit. Conclusion: The FD model showed favorable diagnostic performance for AD. Among MLMs, the MoCA + FD model can predict AD with the highest efficiency and could be used as a non-invasive diagnostic method. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment in the elderly may lead to potential increased sensitivity to anesthetic agents targeting receptors associated with cognition. This study aimed to explore the effect of cognitive status on propofol consumption during surgery in elderly patients. Methods: Sixty elderly patients scheduled for laparoscopic radical prostatectomy were allocated to either a cognitively normal [CogN, Montreal Cognitive Assessment (MoCA) score ≥26] or cognitively impaired (CogI, MoCA <26) group. Propofol was administered via target-controlled infusion to maintain a bispectral index (BIS) between 55-65 during surgery. Propofol consumption was recorded at three time points: T1 (abolished eyelash reflex), T2 (BIS = 50), T3 (extubation). BIS values at eyelash reflex abolition were also recorded. Postoperative MoCA, Visual Analogue Scale (VAS) scores, and remifentanil/sufentanil consumption were assessed. Results: BIS values before induction were similar between CogN and CogI groups. However, at eyelash reflex abolition, BIS was significantly higher in CogI than CogN (mean ± SD: 65.3 ± 7.2 vs. 61.1 ± 6.8, p = 0.031). Propofol requirement to reach BIS 50 was lower in CogI vs. CogN (1.24 ± 0.19 mg/kg vs. 1.46 ± 0.12 mg/kg, p = 0.003). Postoperative MoCA, VAS scores, and remifentanil/sufentanil consumption did not differ significantly between groups. Conclusion: Compared to cognitively intact elderly, those with cognitive impairment exhibited higher BIS at eyelash reflex abolition and required lower propofol doses to achieve the same BIS level, suggesting increased propofol sensitivity. Cognitive status may impact anesthetic medication requirements in the elderly. [ABSTRACT FROM AUTHOR]

Background and objective: Cognitive impairment (CI) is a substantial contributor to the disability associated with Parkinson's disease (PD). We aimed to assess the clinical features and explore the underlying biomarkers as predictors of CI in patients with newly diagnosed PD (NDPD; less than 2 years). Methods: We evaluated the cognitive function status using the Montreal Cognitive Assessment (MoCA) and a battery of neuropsychological tests at baseline and subsequent annual follow-up for 5 years from the Parkinson's Progression Markers Initiative (PPMI) database. We assessed the baseline clinical features, apolipoprotein (APO) E status, β-glucocerebrosidase (G6A) mutation status, cerebrospinal fluid findings, and dopamine transporter imaging results. Using a diagnosis of CI (combined mild cognitive impairment and dementia) developed during the 5-year follow-up as outcome measures, we assessed the predictive values of baseline clinical variables and biomarkers. We also constructed a predictive model for the diagnosis of CI using logistic regression analysis. Results: A total of 409 patients with NDPD with 5-year follow-up were enrolled, 232 with normal cognitive function at baseline, and 94 patients developed CI during the 5-year follow-up. In multivariate analyses, age, current diagnosis of hypertension, baseline MoCA scores, Movement disorder society Unified PD Rating Scale part III (MDS-UPDRS III) scores, and APOE status were associated with the development of CI. Predictive accuracy of CI using age alone improved by the addition of clinical variables and biomarkers (current diagnosis of hypertension, baseline MoCA scores, and MDS-UPDRS III scores, APOE status; AUC 0.80 [95% CI 0.74- 0.86] vs. 0.71 [0.64-0.77], p = 0.008). Cognitive domains that had higher frequencies of impairment were found in verbal memory (12.6 vs. 16.8%) and attention/processing speed (12.7 vs. 16.9%), however, no significant difference in the prevalence of CI at annual follow-up was found during the 5-year follow-up in NDPD patients. Conclusion: In NDPD, the development of CI during the 5-year follow-up can be predicted with good accuracy using a model combining age, current diagnosis of hypertension, baseline MoCA scores, MDS-UPDRS III scores, and APOE status. Our study underscores the need for the earlier identification of CI in NDPD patients in our clinical practice. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to develop and validate machine learning models (MLMs) to diagnose Alzheimer's disease (AD) using cortical complexity indicated by fractal dimension (FD)., Methods: A total of 296 participants with normal cognitive (NC) function and 182 with AD from the AD Neuroimaging Initiative database were randomly divided into training and internal validation cohorts. Then, FDs, demographic characteristics, baseline global cognitive function scales [Montreal Cognitive Assessment (MoCA), Functional Activities Questionnaire (FAQ), Global Deterioration Scale (GDS), Neuropsychiatric Inventory (NPI)], phospho-tau (p-tau 181), amyloidβ-42/40, apolipoprotein E (APOE) and polygenic hazard score (PHS) were collected to establish multiple MLMs. Receiver operating characteristic curves were used to evaluate model performance. Participants from our institution ( n  = 66; 33 with NC and 33 with AD) served as external validation cohorts to validate the MLMs. Decision curve analysis was used to estimate the models' clinical values., Results: The FDs from 30 out of 69 regions showed significant alteration. All MLMs were conducted based on the 30 significantly different FDs. The FD model had good accuracy in predicting AD in three cohorts [area under the receiver operating characteristic (ROC) curve (AUC) = 0.842, 0.808, and 0.803]. There were no statistically significant differences in AUC values between the FD model and the other combined models in the training and internal validation cohorts except MoCA + FD and FAQ + FD models. Among MLMs, the MoCA + FD model showed the best predictive efficiency in three cohorts (AUC = 0.951, 0.931, and 0.955) and had the highest clinical net benefit., Conclusion: The FD model showed favorable diagnostic performance for AD. Among MLMs, the MoCA + FD model can predict AD with the highest efficiency and could be used as a non-invasive diagnostic method., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jiang, Yang, Deng, Jiang and Xue.)

BackgroundThe commonly used screening tests for Parkinson’s disease (PD) are the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE), both of which only focus on cognitive function. A composite assessment that considers both cognitive and social dysfunction in PD would be helpful in detecting mild cognitive impairment (MCI) and PD dementia (PDD).ObjectiveWe aimed to simplify the commonly used tools and combine cognitive and social functioning tests to detect early MCI and PDD.Materials and MethodsA total of 166 participants (84 PD patients and 82 healthy) were recruited who completed the MMSE, MoCA, PD social functioning scale (PDSFS), clock drawing test, activities of daily living, comprehensive neuropsychological assessment (e.g., executive, attention, language, memory, and visuospatial functions), and movement disorder society (MDS)-unified PD rating scale. According to the MDS diagnostic criteria, the patients were grouped into PD-nonMCI, PD-MCI, or PDD.ResultsTo detect PD-MCI, the optimal cut-off scores for the simplified MoCA and the combined test were 9 and 35. The discrimination values measured by the area under the receiver operating characteristic curve (AUC) of the two tests were 0.767 (p < 0.001) and 0.790 (p < 0.001). When the simplified MoCA was 7 or the combined test 30, the patients would be classified as having PDD. The AUCs of the two tests were 0.846 (p < 0.001) and 0.794 (p = 0.003).ConclusionWe suggest considering both cognitive and social functions when detecting PD-MCI and PDD.

Background: To explore the prevalence and inequality of cognitive impairment among older adults in Macau and the contributions of influencing factors to inequality in cognitive impairment. Methods: The Montreal Cognitive Assessment (MoCA) was used to measure the prevalence of cognitive impairment. Socioeconomic status scores were used to describe economic level of the subjects. The concentration index was applied to measure the inequality of cognitive impairment associated with socioeconomic status (SES) and decomposed into its influencing factors. Results: The prevalence of cognitive impairment was 44.35% in Macau. The concentration index of cognitive impairment among the elderly was −0.165 (95% CI: −0.232 to −0.098), indicating that the prevalence of cognitive impairment was concentrated in households with poor SES. Older age, poor SES, long or short sleep duration, other marital status, poor appetite, no tea/coffee drinking, no religious belief, and depression contributed positively to the inequality of cognitive impairment. Among these factors, SES made the largest contribution to inequality, accounting for 76.74%. Conclusion: In Macau, the prevalence of cognitive impairment among people aged 65 years and older is concentrated among those who are in poor economic conditions. Reducing the gap between the rich and the poor at the source, increasing educational level of low SES population and improving their access to healthcare services will help to improve the inequity of cognitive impairment. [ABSTRACT FROM AUTHOR]

White matter hyperintensities (WMHs) are associated with cognitive decline. Assessing the effect of WMH on WM microstructural changes and its relationships with structural and functional connectivity to multiple cognitive domains are helpful to better understand the pathophysiological processes of cognitive impairment. 65 participants (49 normal and 16 MCI subjects, age: 67.4 ± 8.3 years, 44 females) were studied at 3T. The WMHs and fifty fiber tracts were automatically segmented from the T1/T2-weighted images and diffusion-weighted images, respectively. Tract-profiles of WMH were compared with those of apparent fiber density (AFD). The relationship between AFD and tract connectivity (TC) was assessed. Functional connectivity (FC) between tract ends obtained from resting-state functional MRI was examined in relation to TC. Tract-specific relationships of WMH, TC and FC with a multi-domain neuropsychological test battery and Montreal Cognitive Assessment (MoCA) were also separately assessed by lasso linear regression. Indirect pathways of TC and FC between WMH and multiple cognitive measures were tested using the mediation analysis. Higher WMH loads in WM tracts were locally matched with the reduced AFD, which was related to decrease in TC. However, no direct relationship was found between TC and FC. Tract-specific changes on WMH, TC and FC for each cognitive performance may explain that macro- and microstructural and functional changes are associated differently with each cognitive domain in a fiber specific manner. In these identified tracts, the differences between normal and MCI for WMH and TC were increased, and the relationships of WMH, TC and FC with cognitive outcomes were more significant, compared to the results from all tracts. Indirect pathways of two-step (TC-FC) between WMH and all cognitive domains were significant (p < 0.0083 with Bonferroni correction), while the separated indirect pathways through TC and through FC were different depending on cognitive domain. Deterioration in specific cognitive domains may be affected by alterations in a set of different tracts that are differently associated with macrostructural, microstructural, and function changes. Thus, assessments of WMH and its associated changes on specific tracts help for better understanding of the interrelationships of multiple changes in cognitive impairment. [ABSTRACT FROM AUTHOR]

White matter integrity and structural connectivity may be altered in mild cognitive impairment (MCI), and these changes may closely reflect decline in specific cognitive domains. Multi-shell diffusion data in healthy control (HC, n = 31) and mild cognitive impairment (MCI, n = 19) cohorts were downloaded from the ADNI3 database. The data were analyzed using an advanced approach to assess both white matter microstructural integrity and structural connectivity. Compared with HC, lower intracellular compartment (IC) and higher isotropic (ISO) values were found in MCI. Additionally, significant correlations were found between IC and Montreal Cognitive Assessment (MoCA) scores in the MCI cohort. Network analysis detected structural connectivity differences between the two groups, with lower connectivity in MCI. Additionally, significant differences between HC and MCI were observed for global network efficiency. Our results demonstrate the potential of advanced diffusion MRI biomarkers for understanding brain changes in MCI. [ABSTRACT FROM AUTHOR]

Background and Objective: Cystatin C is indicated to be involved in the pathogenesis of Alzheimer's disease (AD) and cognitive impairment. Our objective is to examine the serum Cystatin C levels, and to clarify the correlations between serum Cystatin C and cognitive performance in Chinese AD patients. Methods: The serum Cystatin C concentrations in AD patients and age, sex, and body mass index (BMI) matched-healthy controls were measured. The cognitive functions of the AD patients were evaluated by using the Mini-mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). The severity of dementia was determined with clinical dementia rating (CDR). Results: A total of 463 AD patients and 1,389 matched healthy subjects were included. AD patients had higher serum Cystatin C than healthy controls. Serum cystatin C levels were correlated with MoCA scores in AD patients. In an ordinal logistic regression model, AD patients with higher serum cystatin C levels had increased odds of severe cognitive dysfunction. Conclusion: Our study suggested that AD patients had higher levels of serum cystatin C than age/sex/BMI-matched normal control subjects. Higher serum cystatin C may be associated with worse cognitive performance, but more studies are required to verify such association. [ABSTRACT FROM AUTHOR]

Introduction: The exact relationship between long-term shift work (SW) and cognitive impairment (CI) has been poorly understood. The effects of the long-term rotating night SW (RNSW) combining daytime recharge (DTR) on cognitive function were investigated. Methods: A total 920 retired nurses and 656 retired female teachers aged ≥50 years were analyzed. Participants who worked at least once per week for 8 hat night for more than 1 year were defined as the SW group, and those without a regular nighttime shift were defined as the control group. The associations among duration, frequency, and DTR of RNSW, and neuropsychological assessments were ascertained by regression models. Results: Participants with RNSW had a significantly higher proportion of mild CI (MCI), both amnestic MCI (aMCI) (14.4% in 11–20 years, p < 0.05, and 17.8% in > 20 years, p < 0.001) and non-amnestic MCI (naMCI) (8.1% in 11–20 years, p < 0.05), as well as dementia (1.5% in 1–10 years, and 11.7% in > 20 years, p < 0.05) compared to controls (8.4% with aMCI, 4.4% with naMCI, and 7.0% with dementia, respectively). There were significant negative relationships between general times of night SW and scores of Mini-Mental State Examination (MMSE) (R squared = 0.01, p = 0.0014) and Montreal Cognitive Assessment (MoCA) (R squared = 0.01, p = 0.0054). Participants with ≥1 h of DTR and ≥ 11 years of RNSW were about 2-fold more likely to experience MCI compared with the subjects in the control group, especially with 3–5 h (odds ratio [OR]: 2.35; 95% confidence interval: 1.49–3.68, p < 0.001). Conclusion: The long-term RNSW was associated with a higher risk of CI, especially aMCI and dementia, and the problem cannot be improved by DTR. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the relationship between serum cortisol, cerebral small vessel disease (CSVD) neuroimaging markers, and cognitive performance. Methods: We recruited patients over 50 years old who attended our hospital for physical examination between November 2020 and July 2021. All participants were subject to brain magnetic resonance imaging (MRI), serum cortisol examination, and the Montreal cognitive function assessment (MoCA). On brain MRI, we scored the presence of each marker of CSVD, including white matter hyperintensity (WMH), lacunes, cerebral microbleeds (CMBs), and enlarged perivascular spaces (EPVS). One point was awarded for the presence of each marker, producing a score between 0 and 4. Results: In total, 158 participants were included in this study with a mean age of 60.5 (56.0–66.3) years; 55.1% were male. In the multivariable analyses, serum cortisol level was an independent predictor of WMH severity, the presence of lacunes/CMBs, moderate-severe EPVS and total CSVD burden after adjusting for confounding factors. Serum cortisol level had positive associations with periventricular/deep Fazekas score, burdens of lacunes/CMBs, moderate-severe EPVS, and total CSVD burden in dose-dependent manner, and was an independent predictor of cognitive impairment. Furthermore, the results of the receiver operating characteristic (ROC) curve analysis revealed an area under curve (AUC) of 0.745 with 64.1% sensitivity and 82.5% specificity, and an AUC of 0.705 with 52.1% sensitivity and 85.5 specificity of cortisol in detecting patients with high CSVD burden and MCI, respectively. Conclusions: Serum cortisol level is independently associated with each CSVD MRI markers, total CSVD burden and cognitive impairment. These findings provide clues for pathological mechanisms and suggest serum cortisol as a promising biomarker associated with CSVD. [ABSTRACT FROM AUTHOR]

The rate of progression from Mild Cognitive Impairment (MCI) to Alzheimer's disease (AD) is estimated at >10% per year, reaching up to 80–90% after 6 years. MCI is considered an indicator of early-stage AD. In this context, the diagnostic screening of MCI is crucial for detecting individuals at high risk of AD before they progress and manifest further severe symptoms. Typically, MCI has been determined using neuropsychological assessment tools such as the Montreal Cognitive Assessment (MoCA) or Mini-Mental Status Examination (MMSE). Unfortunately, other diagnostic methods are not available or are unable to identify MCI in its early stages. Therefore, identifying new biomarkers for MCI diagnosis and prognosis is a significant challenge. In this framework, miRNAs in serum, plasma, and other body fluids have emerged as a promising source of biomarkers for MCI and AD-related cognitive impairments. Interestingly, miRNAs can regulate several signaling pathways via multiple and diverse targets in response to pathophysiological stimuli. This systematic review aims to describe the current state of the art regarding AD-related target genes modulated by differentially expressed miRNAs in peripheral fluids samples in MCI subjects to identify potential miRNA biomarkers in the early stages of AD. We found 30 articles that described five miRNA expression profiles from peripheral fluid in MCI subjects, showing possible candidates for miRNA biomarkers that may be followed up as fluid biomarkers or therapeutic targets of early-stage AD. However, additional research is needed to validate these miRNAs and characterize the precise neuropathological mechanisms. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to investigate the role of the high-frequency cochlear dysfunction in the cognitive-ear link. Methods: Seventy-four presbycusis patients (PC group) and seventy-one age-, sex-, and education-level matched normal hearing controls (NH group) were recruited in this study. Participants underwent a battery of cognitive tests estimated by Montreal Cognitive Assessment (MoCA), Stroop Color-Word Interference Test (Stroop), Symbol Digit Modalities Test (SDMT), Auditory Verbal Learning Test (AVLT), and Trail-Making Test (TMT-A and B), as well as auditory tests including distortion product otoacoustic emission (DPOAE), pure tone (PT) thresholds, and speech reception thresholds (SRT). Data were analyzed using the factor analysis, partial correlation analysis, multiple linear regression models, and mediation models. Results: Distortion product otoacoustic emission detection amplitudes and PT thresholds performed worse gradually from low to high frequencies in both the NH and PC groups. High-frequency DPOAE (H-DPOAE) was significantly correlated with cognitive domains in the PC group (AVLT: r = 0.30, p = 0.04; SDMT: r = 0.36, p = 0.01; Stroop: r = –0.32, p = 0.03; TMT-A: r = –0.40, p = 0.005; TMT-B: r = –0.34, p = 0.02). Multiple linear regression models showed that H-DPOAE predicted cognitive impairment effectively for aspects of memory (R 2 = 0.27, 95% CI, 0.03 to 1.55), attention (R 2 = 0.32, 95% CI, –6.18 to –0.40), processing speed (R 2 = 0.37, 95% CI, 0.20 to 1.64), and executive function (TMT-A: R 2 = 0.34, 95% CI, –5.52 to 1.03; TMT-B: R 2 = 0.29, 95% CI, –11.30 to –1.12). H-DPOAE directly affected cognition and fully mediated the relationship between pure tone average (PTA)/SRT and cognitive test scores, excluding MoCA. Conclusion: This study has demonstrated that the high-frequency cochlear amplifier dysfunction has a direct predictive effect on the cognitive decline and makes a large contribution to the cognitive-ear link. [ABSTRACT FROM AUTHOR]

Background: The efficacy of virtual reality (VR)-based intervention for improving cognition in patients with the chronic stage of stroke is controversial. The aims of this meta-analysis were to evaluate the effect of VR-based training combined with traditional rehabilitation on cognition, motor function, mood, and activities of daily living (ADL) after chronic stroke. Methods: The search was performed in the Cochrane Library (CENTRAL), EBSCO, EMBASE, Medline (OVID), Web of Science databases, PubMed, CINAHL Ovid, and Scopus from inception to May 31, 2021. All included studies were randomized controlled trials (RCTs) examining VR-based intervention combined with traditional rehabilitation for chronic stroke. The main outcomes of this study were cognition, including overall cognition (combined with all cognitive measurement results), global cognition (measured by the Montreal Cognitive Assessment, MoCA, and/or Mini-Mental State Examination, MMSE), and attention/execution. The additional outcomes were motor function, mood, and ADL. Subgroup analyses were conducted to verify the potential factors for heterogeneity. Results: Six RCTs including 209 participants were included for systematic review, and five studies of 177 participants were included in meta-analyses. Main outcome analyses showed large and significant effect size (ES) of VR-based training on overall cognition (g = 0.642; 95% CI = 0.134–1.149; and P = 0.013) and attention/execution (g = 0.695; 95% CI = 0.052–1.339; and P = 0.034). Non-significant result was found for VR-based intervention on global cognition (g = 0.553; 95% CI = −0.273–1.379; and P = 0.189). Additional outcome analyses showed no superiority of VR-based intervention over traditional rehabilitation on motor function and ADL. The ES of VR-based intervention on mood (g = 1.421; 95% CI = 0.448–2.393; and P = 0.004) was large and significant. In the subgroup analysis, large effects for higher daily intensity, higher weekly frequency, or greater dose of VR intervention were found. Conclusion: Our findings indicate that VR-based intervention combined with traditional rehabilitation showed better outcomes for overall cognition, attention/execution, and depressive mood in individuals with chronic stroke. However, VR-based training combined with traditional rehabilitation showed a non-significant effect for global cognition, motor function, and ADL in individuals with chronic stroke. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to systematically evaluate the effects of mind–body exercise on global cognitive function, depression, sleep disorders, fatigue level, and quality of life (QOL) in a Parkinson's disease (PD) population. Methods: Total six English and Chinese databases were searched for articles published up to May 2021. Randomized controlled trials (RCTs) evaluating mind–body excises on non-motor symptoms of PD were included. The Cochrane risk of bias tool was used to assess the methodological quality, and we defined high-quality studies as having a low risk of bias in four or more domains. Global cognitive function was considered the primary outcome and was assessed using the Montreal Cognitive Assessment (MoCA). The secondary outcomes included QOL, fatigue, depression, and sleep quality, which were measured using the Parkinson's Disease Questionnaire (PDQ-39), 16-item Parkinson's Disease Fatigue Scale (PFS-16), Beck Depression Inventory (BDI), and revised Parkinson's Disease Sleep Scale (PDSS-2), respectively. Subgroup analyses were conducted for global cognitive function and QOL to assess the optimal treatment measure across the various mind–body exercises. Results: Fourteen RCTs with 404 patients were finally included in the meta-analysis. Eight (57.14%) studies were of high quality. The pooled results showed that mind–body exercises generally had a significant advantage over the control intervention in improving global cognitive function (MD = 1.68; P = 0.0008). The dose subgroup analysis revealed that the low dose (60–120 min per week) and moderate dose (120–200 min per week) significantly increased MoCA scores compared with the control group (MD = 2.11, P = 0.01; MD = 1.27, P = 0.02, respectively). The duration subgroup analysis indicated a significant difference in the effect of the duration (6–10 and >15 weeks) on increasing MoCA scores compared with the control group (MD = 3.74, P < 0.00001; MD = 1.45, P = 0.01, respectively). Conclusion: Mind–body exercise may improve global cognitive function, sleep quality, and QOL in the PD population. In addition, low to moderate doses and appropriate durations significantly improved global cognitive function. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [CRD42021275522]. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment in the elderly may lead to potential increased sensitivity to anesthetic agents targeting receptors associated with cognition. This study aimed to explore the effect of cognitive status on propofol consumption during surgery in elderly patients., Methods: Sixty elderly patients scheduled for laparoscopic radical prostatectomy were allocated to either a cognitively normal [CogN, Montreal Cognitive Assessment (MoCA) score ≥26] or cognitively impaired (CogI, MoCA <26) group. Propofol was administered via target-controlled infusion to maintain a bispectral index (BIS) between 55-65 during surgery. Propofol consumption was recorded at three time points: T1 (abolished eyelash reflex), T2 (BIS = 50), T3 (extubation). BIS values at eyelash reflex abolition were also recorded. Postoperative MoCA, Visual Analogue Scale (VAS) scores, and remifentanil/sufentanil consumption were assessed., Results: BIS values before induction were similar between CogN and CogI groups. However, at eyelash reflex abolition, BIS was significantly higher in CogI than CogN (mean ± SD: 65.3 ± 7.2 vs. 61.1 ± 6.8, p  = 0.031). Propofol requirement to reach BIS 50 was lower in CogI vs. CogN (1.24 ± 0.19 mg/kg vs. 1.46 ± 0.12 mg/kg, p  = 0.003). Postoperative MoCA, VAS scores, and remifentanil/sufentanil consumption did not differ significantly between groups., Conclusion: Compared to cognitively intact elderly, those with cognitive impairment exhibited higher BIS at eyelash reflex abolition and required lower propofol doses to achieve the same BIS level, suggesting increased propofol sensitivity. Cognitive status may impact anesthetic medication requirements in the elderly., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhuge, Zhou, Qiu and Huang.)

Introduction: We aimed to determine whether in vivo tau deposits and monoamine oxidase B (MAO-B) detection using 18F-THK5351 positron emission tomography (PET) can assist in the differential distribution in patients with corticobasal syndrome (CBS), progressive supranuclear palsy (PSP), and Alzheimer's disease (AD) and whether 18F-THK5351 retention of lesion sites in CBS and PSP can correlate with clinical parameters. Methods: 18F-THK5351 PET was performed in 35 participants, including 7, 9, and 10 patients with CBS, PSP, and AD, respectively, and 9 age-matched normal controls. In CBS and PSP, cognitive and motor functions were assessed using the Montreal Cognitive Assessment, Addenbrooke's Cognitive Examination–Revised, and Frontal Assessment Battery, Unified Parkinson's Disease Rating Scale Motor Score, and PSP Rating Scale. Results: 18F-THK5351 retention was observed in sites susceptible to disease-related pathologies in CBS, PSP, and AD. 18F-THK5351 uptake in the precentral gyrus clearly differentiated patients with CBS from those with PSP and AD. Furthermore, 18F-THK5351 uptake in the inferior temporal gyrus clearly differentiated patients with AD from those with CBS and PSP. Regional 18F-THK5351 retention was associated with the cognitive function in CBS and PSP. Conclusion: Measurement of the tau deposits and MAO-B density in the brain using 18F-THK5351 may be helpful for the differential diagnosis of tauopathies and for understanding disease stages. [ABSTRACT FROM AUTHOR]

Introduction: Dementia is increasingly prevalent globally. Existing questionnaire-based cognitive assessment tools may not comprehensively assess cognitive function and real-time task-performance across all cognitive domains. CAVIRE (Cognitive Assessment by VIrtual REality), a fully immersive virtual reality system incorporating automated audio-visual instructions and a scoring matrix was developed to assess the six cognitive domains, with potential to maintain consistency in execution of the testing environment and possibly time-saving in busy primary care practice. Aims: This is a feasibility study to compare the completion times of the questionnaire-based Montreal Cognitive Assessment (MoCA) and the CAVIRE in cognitively-healthy Asian adults aged between 35 and 74 years, overall, and in and across each 10-year age group (35–44; 45–54; 55–64; 65–74). Methods: A total of 100 participants with a MoCA score of 26 or more were recruited equally into the four 10-year age groups at a primary care clinic in Singapore. Completion time for the MoCA assessment for each participant was recorded. They were assessed using the CAVIRE, comprising 13 segments featuring common everyday activities assessing all six cognitive domains, and the completion time was also recorded through the embedded automated scoring and timing framework. Results: Completion time for CAVIRE as compared to MoCA was significantly (p < 0.01) shorter, overall (mean difference: 74.9 (SD) seconds) and in each age group. Younger, vs. older, participants completed both the MoCA and CAVIRE tasks in a shorter time. There was a greater variability in the completion time for the MoCA, most markedly in the oldest group, whereas completion time was less variable for the CAVIRE tasks in all age groups, with most consistency in the 45–54 year-age group. Conclusion: We demonstrate almost equivalent completion times for a VR and a questionnaire-based cognition assessment, with inter-age group variation in VR completion time synonymous to that in conventional screening methods. The CAVIRE has the potential to be an alternative screening modality for cognition in the primary care setting. [ABSTRACT FROM AUTHOR]

Given the limited power of neuropsychological tests, there is a need for a simple, reliable means, such as gait, to identify mild dementia and its subtypes. However, gait characteristics of patients with post-stroke dementia (PSD) and Alzheimer's disease (AD) are unclear. We sought to describe their gait signatures and to explore gait parameters distinguishing PSD from post-stroke non-dementia (PSND) and patients with AD. We divided 3-month post-stroke patients into PSND and PSD groups based on the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and the activity of daily living (ADL). Thirty-one patients with AD and thirty-two healthy controls (HCs) were also recruited. Ten gait parameters in one single and two dual-task gait tests (counting-backward or naming-animals while walking) were compared among the groups, with adjustment for baseline demographic covariates and the MMSE score. The area under the receiver operating characteristic curve (AUC) was used to identify parameters discriminating PSD from individuals with PSND and AD. Patients with PSD and patients with AD showed impaired stride length, velocity, stride time, and cadence while patients with PSD had altered stance and swing phase proportions (all p ≤ 0.01, post hoc). Patients with AD had smaller toe-off (ToA) and heel-to-ground angles (HtA) (p ≤ 0.01) than HCs in dual-task gait tests. Individuals with PSD had a shorter stride length, slower velocity, and altered stance and swing phase percentages in all tests (p ≤ 0.01), but a higher coefficient of variation of stride length (CoVSL) and time (CoVST) only in the naming animals-task gait test (p ≤ 0.001) than individuals with PSND. ToA and HtA in the naming animals-task gait test were smaller in individuals with AD than those with PSD (p ≤ 0.01). Statistical significance persisted after adjusting for demographic covariates, but not for MMSE. The pace and the percentage of stance or swing phase in all tests, CoVST in the dual-task paradigm, and CoVSL only in the naming animals-task gait test (moderate accuracy, AUC > 0.700, p ≤ 0.01) could distinguish PSD from PSND. Furthermore, the ToA and HtA in the naming animals-task gait paradigm discriminated AD from PSD (moderate accuracy, AUC > 0.700, p ≤ 0.01). Thus, specific gait characteristics could allow early identification of PSD and may allow non-invasive discrimination between PSD and AD, or even other subtypes of dementia. [ABSTRACT FROM AUTHOR]

Purpose: This study investigates the usability of a stepping exergame in older adults with major neurocognitive disorder (MNCD) residing in a long-term care facility. Materials and Methods: A mixed methods study was conducted. Participants played exergames for 30 min on one try-out session. During the exergames, the think aloud method was used, and field notes were taken by the facilitator. Following the exergames, participants completed the System Usability Scale (SUS) and a semi-structured in-depth interview about usability including their personal experiences. Audio files were transcribed and a thematic content analysis of the think aloud data, field notes and interviews were performed using NVivo 12. Results: Twenty-two participants with MNCD were included [mean age = 84.3 ± 5.5 (70–95) years; 81.8% women; Short Physical Performance Battery score = 7.5 ± 3.2 (1–12), Montreal Cognitive Assessment score = 11.9 ± 4.4 (2–19)]. System usability was rated "ok to good" with a mean SUS score of 57.8 (SD = 12.3) with scores ranging from 37.5 to 90.0. Five main themes emerged from the thematic content analysis: (1) perceived user friendliness and acceptability of the exergames; (2) interactional experience; (3) motivational factors; (4) training modalities; and (5) risks. There were no adverse events nor dropouts. Conclusion: Participants evaluated the usability of the exergames positively. The results indicate that the stepping exergame is usable in older adults with MNCD. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease is a common neurodegenerative disorder with motor and non-motor symptoms. Recently, as adjuvant therapy, transcranial direct current stimulation (tDCS) has been shown to improve the motor and non-motor function of patients with Parkinson's disease (PD). This systematic review aimed to evaluate the existing evidence for the efficacy of tDCS for PD. We included English databases (PubMed, the Cochrane Library, Embase, and Web of Science) and Chinese databases [Wanfang database, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and China Biology Medicine (CBM)] without restricting the year of publication. Twenty-one tDCS studies, with a total of 736 participants, were included in the analysis. Two independent researchers extracted the data and characteristics of each study. There was a significant pooled effect size (−1.29; 95% CI = −1.60, −0.98; p < 0.00001; I 2 = 0%) in the Unified PD Rating Scale (UPDRS) I and the Montreal cognitive assessment (SMD = 0.87, 95% CI = 0.50 to 1.24; p < 0.00001; I 2 = 0%). The poor effect size was observed in the UPDRS III scores (SMD = −0.13; 95% CI = −0.64, 0.38; p = 0.61; I 2 = 77%), and similar results were observed for the timed up and go (TUG) test, Berg balance scale, and gait assessment. The results of this meta-analysis showed that there was insufficient evidence that tDCS improves the motor function of patients with PD. However, tDCS seemed to improve their cognitive performance. Further multicenter research with a larger sample size is needed. In addition, future research should focus on determining the tDCS parameters that are most beneficial to the functional recovery of patients with PD. [ABSTRACT FROM AUTHOR]

Background: Cerebral small vessel disease (cSVD) and neurodegeneration are the two main causes of dementia and are considered distinct pathological processes, while studies have shown overlaps and interactions between the two pathological pathways. Medial temporal atrophy (MTA) is considered a classic marker of neurodegeneration. We aimed to investigate the relationship of total cSVD burden and MTA on MRI using a total cSVD score and to explore the impact of the two MRI features on cognition. Methods: Patients in a memory clinic were enrolled, who underwent brain MRI scan and cognitive evaluation within 7 days after the first visit. MTA and total cSVD score were rated using validated visual scales. Cognitive function was assessed by using Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scales. Spearman's correlation and regression models were used to test (i) the association between MTA and total cSVD score as well as each cSVD marker and (ii) the correlation of the MRI features and cognitive status. Results: A total of 312 patients were finally enrolled, with a median age of 75.0 (66.0–80.0) years and 40.7% (127/312) males. All of them finished MRI and MMSE, and 293 subjects finished MoCA. Of note, 71.8% (224/312) of the patients had at least one of the cSVD markers, and 48.7% (152/312) of them had moderate–severe MTA. The total cSVD score was independently associated with MTA levels, after adjusting for age, gender, years of education, and other vascular risk factors (OR 1.191, 95% CI 1.071–1.324, P = 0.001). In regard to individual markers, a significant association existed only between white matter hyperintensities and MTA after adjusting for the factors mentioned above (OR 1.338, 95% CI 1.050–1.704, P = 0.018). Both MTA and total cSVD score were independent risk factors for MMSE ≤ 26 (MTA: OR 1.877, 95% CI 1.407–2.503, P < 0.001; total cSVD score: OR 1.474, 95% CI 1.132–1.921, P = 0.004), and MoCA < 26 (MTA: OR 1.629, 95% CI 1.112–2.388, P = 0.012; total cSVD score: OR 1.520, 95% CI 1.068–2.162, P = 0.020). Among all the cSVD markers, microbleed was found significantly associated with MMSE ≤ 26, while no marker was demonstrated a relationship with MoCA < 26. Conclusion: Cerebral small vessel disease was related to MTA in patients of a memory clinic, and both the MRI features had a significant association with cognitive impairment. [ABSTRACT FROM AUTHOR]

Objectives: The Clinical Dementia Rating (CDR) Scale is the gold standard for the staging of dementia due to Alzheimer's disease (AD). However, the application of CDR for the staging of subjective cognitive decline (SCD) and mild cognitive impairment (MCI) in AD remains controversial. This study aimed to use the sum of boxes of the CDR (CDR-SB) plus an SCD single questionnaire to operationally determine the different stages of cognitive impairment (CI) due to AD and non-AD. Methods: This was a two-phase study, and we retrospectively analyzed the Show Chwan Dementia registry database using the data selected from 2015 to 2020. Individuals with normal cognition (NC), SCD, MCI, and mild dementia (MD) due to AD or non-AD with a CDR < 2 were included in the analysis. Results: A total of 6,946 individuals were studied, including 875, 1,009, 1,585, and 3,447 with NC, SCD, MCI, and MD, respectively. The cutoff scores of CDR-SB for NC/SCD, SCD/MCI, and MCI/dementia were 0/0.5, 0.5/1.0, and 2.5/3.0, respectively. The receiver operating characteristic (ROC) analysis showed that the area under the curve (AUC) values of the test groups were 0.85, 0.90, and 0.92 for discriminating NC from SCD, SCD from MCI, and MCI from dementia, respectively. Compared with the Cognitive Abilities Screening Instrument or the Montreal Cognitive Assessment, the use of CDR-SB is less influenced by age and education. Conclusion: Our study showed that the operational determination of SCD, MCI, and dementia using the CDR-SB is practical and can be applied in clinical settings and research on CI or dementia. [ABSTRACT FROM AUTHOR]

Background: Acupuncture may be a promising complementary therapy for vascular cognitive impairment (VCI) and has been extensively applied in China. However, its potential effects remain uncertain, and the clinical findings are inconsistent. This review aimed to systematically appraise the overall effectiveness and safety of acupuncture in treating VCI.Methods: To investigate the effects of acupuncture on VCI from inception to February 28, 2021 using randomized clinical trials (RCTs), seven electro-databases [Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), VIP, and Wanfang] were searched. Two independent investigators identified the eligible RCTs and extracted data into predesigned forms. The risk of bias (ROB) within each individual trial was evaluated using the Cochrane Collaboration's tool. Meta-analyses were conducted for calculating comparative effects in the RevMan software (version 5.3). The strength of attained evidence was rated using the online GRADEpro approach.Results: A total of 48 RCTs involving 3,778 patients with VCI were included. The pooled data demonstrated that acupuncture was more beneficial for a global cognitive function [mean difference (MD) 1.86, 95% CI 1.19–2.54, p < 0.01] and activities of daily living (MD −3.08, 95% CI −4.81 to −1.35, p < 0.01) compared with western medicine (WM). The favorable results were also observed when acupuncture was combined with WM (MD 2.37, 95% CI 1.6–3.14, p < 0.01) or usual care (UC, MD 4.4, 95% CI 1.61–7.19, p = 0.002) in comparison with the corresponding control conditions. Meanwhile, the subgroup analysis did not indicate a statistical effect difference between manual acupuncture (MA) and electroacupuncture (EA) (inter-group I2 < 50% and p > 0.1) when comparing acupuncture with WM. There were no significant differences in the occurrence of adverse events (AEs) between the acupuncture group and the control group (p > 0.05). Owing to the poor methodological quality and considerable heterogeneity among studies, the certainty of the evidence was low or very low.Conclusions: This review suggests that acupuncture as a monotherapy or an adjuvant therapy may play a positive role in improving the cognition and daily performance of VCI patients associated with few side effects. The difference in styles may not significantly influence its effectiveness. More rigorously designed and preregistered RCTs are highly desirable to verify the therapeutic benefits and determine an optimal acupuncture paradigm. The methodological and reporting quality of future researches should be enhanced by adhering to authoritative standardized statements.Systematic Review Registration: [PROSPERO], identifier [No. CRD42017071820].

Background : Oroxylum indicum has been used in traditional Ayurvedic medicine for the prevention and treatment of several diseases and may have neuroprotective effects. Purpose : Examine the effects of Oroxylum indicum on cognitive function in older adults with self-reported cognitive complaints. Study Design : Two-arm, parallel-group, 12-week, randomized, double-blind, placebo-controlled trial. Methods : Eighty-two volunteers received either 500 mg, twice daily of a standardized Oroxylum indicum extract or placebo. Outcome measures included several computer-based cognitive tasks, the Control, Autonomy, Self-Realization, and Pleasure scale (CASP-19), Cognitive Failures Questionnaire (CFQ), and the Montreal Cognitive Assessment (MoCA). Changes in the concentration of brain-derived neurotrophic factor (BDNF) were also examined. Results : Compared to the placebo, Oroxylum indicum was associated with greater improvements in episodic memory, and on several computer-based cognitive tasks such as immediate word recall and numeric working memory, and a faster rate of learning on the location learning task. However, there were no other significant differences in performance on the other assessed cognitive tests, the MoCA total score, or other self-report questionnaires. BDNF concentrations increased significantly in both groups, with no statistically-significant between-group differences. Oroxylum indicum was well tolerated except for an increased tendency for mild digestive complaints and headaches. Conclusion : The results of this first human trial on the cognitive-enhancing effects of Oroxylum indicum suggest that it is a promising herbal candidate for the improvement of cognitive function in older adults with self-reported cognitive complaints. [ABSTRACT FROM AUTHOR]

Background : Abnormal spontaneous neural activity is often found in patients with Parkinson's disease with mild cognitive impairment (PD-MCI). However, the frequency dependence of neuronal interaction activities, especially the fractional amplitude of low-frequency fluctuation (fALFF) and degree centrality (DC), in PD-MCI is still unclear. Thus, this study aimed to explore the frequency dependence of PD-MCI based on fALFF and DC maps. Methods : Twenty-four patients with PD-MCI, 42 PD patients with normal cognition (PD-NC), and 33 healthy controls (HCs) were enrolled. Neuropsychological assessments and resting-state functional MRI (rs-fMRI) were performed. The fALFF and DC values in the conventional, slow4 and slow5 frequency bands were compared among the groups. Results : In the conventional frequency band, the DC value in the left precentral area was decreased in PD-MCI patients, while that in the right fusiform area was increased in PD-NC patients compared with HCs. Regarding fALFFs, both the PD-MCI and PD-NC patients had decreased values in the right precentral area compared with those of the HCs. The fALFFs did not differ between PD-MCI and PD-NC patients. The fALFF results in the slow4 subfrequency band were consistent with those in the conventional frequency band. In the slow5 band, the DC value in the left middle temporal lobe was higher in PD-MCI patients than in PD-NC patients and was positively correlated with the performance of the PD-MCI patients on the Montreal Cognitive Assessment (MoCA). Additionally, both PD-MCI and PD-NC patients showed lower fALFF values in the bilateral putamen than the HCs, and the fALFF in the bilateral putamen was negatively correlated with the Hoehn and Yahr stages of PD-MCI. The fALFF in the left putamen was negatively correlated with the scores of PD-MCI patients on the Movement Disorder Society-Unified Parkinson Disease Rating Scale Part III (MDS-UPRDS-III). Conclusion : Our results suggested that abnormal neuronal activities, such as fALFF and DC, are dependent on frequency in PD-MCI. Some subfrequency bands could distinguish PD-MCI from PD. Our findings may be helpful for further revealing the frequency-dependent resting functional disruption in PD-MCI. [ABSTRACT FROM AUTHOR]

Objectives: This research aims to validate a modified visually based Montreal Cognitive Assessment for hearing-aid users (MoCA-HA). This population should be the target of cognitive screening due to high risk of developing dementia. Design: Case-control study. Setting: The participants were recruited from referral hearing-aid center and memory clinic in central London, United Kingdom. Participant: 75 hearing-aid users were recruited. Of these, thirty were cognitively intact controls with hearing impairment (NC-HI); thirty had mild cognitive impairment with hearing impairment (MCI-HI); fifteen had dementia with hearing impairment (D-HI). Measurements: The baseline characteristics and analysis of the MoCA-HA for the NC-HI were recorded. The MoCA-HA performance of the MCI-HI cohort and D-HI cohort were also studied. Results: The cutpoint of <26 yields 93.3% sensitivity with 80% specificity in distinguishing MCI-HI from NC-HI. The specificity increased to 95.6% in screening for all cognitive impairment (MCI-HI and D-HI) from NC-HI. Conclusion: The MoCA-HA has been validated with a cutpoint which is comparable to the traditional MoCA. This tool may help clinicians to early identify older adult hearing-aid users for appropriate cognitive evaluation. [ABSTRACT FROM AUTHOR]

Background: Acupuncture may be a promising complementary therapy for vascular cognitive impairment (VCI) and has been extensively applied in China. However, its potential effects remain uncertain, and the clinical findings are inconsistent. This review aimed to systematically appraise the overall effectiveness and safety of acupuncture in treating VCI. Methods: To investigate the effects of acupuncture on VCI from inception to February 28, 2021 using randomized clinical trials (RCTs), seven electro-databases [Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), VIP, and Wanfang] were searched. Two independent investigators identified the eligible RCTs and extracted data into predesigned forms. The risk of bias (ROB) within each individual trial was evaluated using the Cochrane Collaboration's tool. Meta-analyses were conducted for calculating comparative effects in the RevMan software (version 5.3). The strength of attained evidence was rated using the online GRADEpro approach. Results: A total of 48 RCTs involving 3,778 patients with VCI were included. The pooled data demonstrated that acupuncture was more beneficial for a global cognitive function [mean difference (MD) 1.86, 95% CI 1.19–2.54, p < 0.01] and activities of daily living (MD −3.08, 95% CI −4.81 to −1.35, p < 0.01) compared with western medicine (WM). The favorable results were also observed when acupuncture was combined with WM (MD 2.37, 95% CI 1.6–3.14, p < 0.01) or usual care (UC, MD 4.4, 95% CI 1.61–7.19, p = 0.002) in comparison with the corresponding control conditions. Meanwhile, the subgroup analysis did not indicate a statistical effect difference between manual acupuncture (MA) and electroacupuncture (EA) (inter-group I 2 < 50% and p > 0.1) when comparing acupuncture with WM. There were no significant differences in the occurrence of adverse events (AEs) between the acupuncture group and the control group (p > 0.05). Owing to the poor methodological quality and considerable heterogeneity among studies, the certainty of the evidence was low or very low. Conclusions: This review suggests that acupuncture as a monotherapy or an adjuvant therapy may play a positive role in improving the cognition and daily performance of VCI patients associated with few side effects. The difference in styles may not significantly influence its effectiveness. More rigorously designed and preregistered RCTs are highly desirable to verify the therapeutic benefits and determine an optimal acupuncture paradigm. The methodological and reporting quality of future researches should be enhanced by adhering to authoritative standardized statements. Systematic Review Registration: [PROSPERO], identifier [No. CRD42017071820]. [ABSTRACT FROM AUTHOR]

Objective: Although previous studies postulated that physical and cognitive decline codeveloped in preclinical dementia, the interconnected relationship among subjective cognitive complaints (SCCs), objective cognitive performance, and physical activity remained hazy. We investigated the mediating roles of physical activity between subjective and objective cognition. Diffusion tensor imaging (DTI) was utilized to test our hypothesis that brain white matter microstructural changes underlie the physical-cognitive decline in subjective cognitive decline (SCD). Methods: We enrolled cognitively normal older adults aged > 50 years in the Community Medicine Research Center of Keelung Chang Gung Memorial Hospital during 2017–2020. Regression models analyzed mediation effects of physical activity between subjective and objective cognition. The self-reported AD8 questionnaire assessed SCCs. The SCD group, defined by AD8 score ≥ 2, further underwent diffusion MRI scans. Those who agreed to record actigraphy also wore the SOMNOwatch™ for 72 h. Spearman's correlation coefficients evaluated the associations of diffusion indices with physical activity and cognitive performance. Results: In 95 cognitively normal older adults, the AD8 score and the Montreal Cognitive Assessment (MoCA) score were mediated partially by the metabolic equivalent of the International Physical Activity Questionnaire-Short Form (IPAQ-SF MET) and fully by the sarcopenia score SARC-F. That is, the relation between SCCs and poorer cognitive performance was mediated by physical inactivity. The DTI analysis of 31 SCD participants found that the MoCA score correlated with mean diffusivity at bilateral inferior cerebellar peduncles and the pyramids segment of right corticospinal tract [ p < 0.05, false discovery rate (FDR) corrected]. The IPAQ-SF MET was associated with fractional anisotropy (FA) at the right posterior corona radiata (PCR) (p < 0.05, FDR corrected). In 15 SCD participants who completed actigraphy recording, the patterns of physical activity in terms of intradaily variability and interdaily stability highly correlated with FA of bilateral PCR and left superior corona radiata (p < 0.05, FDR corrected). Conclusions: This study addressed the role of physical activity in preclinical dementia. Physical inactivity mediated the relation between higher SCCs and poorer cognitive performance. The degeneration of specific white matter tracts underlay the co-development process of physical-cognitive decline in SCD. [ABSTRACT FROM AUTHOR]

Objective: Emerging evidence suggests that white matter (WM) disruption is associated with the incidence of subcortical vascular cognitive impairment (SVCI). However, our knowledge regarding this relationship in the early stage of SVCI is limited. We aimed to investigate the associations between WM disruptions and cognitive declines at the early stage of SVCI. Method: We performed a case–control study, involving 22 cases and 19 controls. The cases were patients at the early stage of SVCI, which was defined as subcortical ischemic vascular disease with normal global cognitive measures (pre-SVCI). The controls were healthy people matched by age, sex, and education years. We assessed the differences in a battery of neuropsychological tests between the two groups, investigated the diffusion changes in 40 WM tracts among the participants via an atlas-based segmentation strategy, and compared the differences between the cases and controls by multiple linear regression analysis. We then evaluated the relationships between diffusion indices and cognitive assessment scores by Pearson's correlation. Results: The pre-SVCI group exhibited significant differences in the Montreal cognitive assessment (MoCA), Rey–Osterrieth Complex Figure (R-O)-copy, and Trail Making Test (TMT)-B test compared with the controls. Compared with the controls, some long associative and projective bundles, such as the right anterior corona radiata (ACR), the right inferior fronto-occipital fasciculus (IFOF), and the left external capsule (EC), were extensively damaged in cases after Bonferroni correction (p < 0.05/40). Damages to specific fibers, such as the right ACR, IFOF, and posterior thalamic radiation (PTR), exhibited significant correlations with declines in MoCA, R-O delay, and the Mini-Mental State Examination (MMSE), respectively, after Bonferroni correction (p < 0.05/14). Conclusion: Long WM tracts, especially those in the right hemisphere, were extensively damaged in the pre-SVCI patients and correlated with declines in executive functions and spatial processing. Patients of pre-SVCI are likely at an ultra-early stage of SVCI, and there is a very high risk of this condition becoming SVCI. [ABSTRACT FROM AUTHOR]

The mild cognitive impairment (MCI) stage plays an essential role in preventing the progression of older adults to Alzheimer's disease. In this study, neurofeedback training (NFT) is applied to improve MCI brain cognitive function. To assess the improvement effect, a novel algorithm called Weighted Multiple Multiscale Entropy (WMMSE) is proposed to extract and analyze the electroencephalogram (EEG) features of patients with MCI. To overcome the information loss problem of traditional multiscale entropy (MSE), WMMSE fully considered the correlation of the sequence and the contribution of each sequence to the total entropy. The experimental group composed of 39 patients with MCI was subjected to NFT for 10 days during two sessions. The control group included 21 patients with MCI without any intervention. The Lempel-Ziv complexity (LZC) was used for primary assessment, and WMMSE was used to accurately analyze the effect of NFT. The results show that the WMMSE values of F4, C3, C4, O1, and T5 channels post-NFT are higher compared with pre-NFT and significant differences (P < 0.05). Moreover, the cognitive subscale of the Montreal Cognitive Assessment (MoCA) results shows that the post-NFT score is higher than the pre-NFT in the vast majority of the patients with MCI and significant differences (P < 0.05). When compared with the control group, the WMMSE values of the experimental group increased in each channel. Therefore, the NFT intervention method contributes to brain cognitive functional recovery, and WMMSE can be used as a biomarker to evaluate the state of MCI brain cognitive function. [ABSTRACT FROM AUTHOR]

Introduction: The number of elective surgeries for patients who are over 70 years of age is continuously growing. At the same time, postoperative delirium (POD) is common in older patients (5–60%) depending on predisposing risk factors, such as multimorbidity, cognitive impairment, neurodegenerative disorders and other dementing disorders, and precipitating factors, such as duration of surgery. Knowledge of individual risk profiles prior to elective surgery may help to identify patients at increased risk for development of POD. In this study, clinical and cognitive risk factors for POD were investigated in patients undergoing various elective cardiac and non-cardiac surgeries. Methods: The PAWEL study is a prospective, interventional trial on delirium prevention. At baseline, 880 inpatients at five surgical centers were recruited for sub-sample PAWEL-R. Multimodal assessments included clinical renal function, medication, American Society of Anesthesiologists (ASA) Physical Status Classification System, geriatric and cognitive assessments, which comprised the Montreal Cognitive Assessment Scale (MoCA), Trail-making Test, and Digit Span backward. Delirium incidence was monitored postoperatively by the Confusion Assessment Method (CAM) and a chart review for up to a week or until discharge. Multivariate regression models and Chi-square Automatic Interaction Detectors (CHAID) analyses were performed using delirium incidence as the primary outcome. Results: Eighteen risk factors were investigated in elective cardiovascular and orthopedic or general surgery. A total of 208 out of 880 patients (24%) developed POD. A global regression model that included all risk variables predicted delirium incidence with high accuracy (AUC = 0.81; 95% CI 0.77, 0.85). A simpler model (clinical and cognitive variables; model CLIN-COG) of 10 factors that only included surgery type, multimorbidity, renal failure, polypharmacy, ASA, cut-to-suture time, and cognition (MoCA, Digit Span backward, and preexisting dementia), however, exhibited similar predictive accuracy (AUC = 0.80; 95% CI 0.76, 0.84). Conclusion: The risk of developing POD can be estimated by preoperative assessments, such as ASA classification, expected cut-to-suture time, and short cognitive screenings. This rather efficient approach predicted POD risk over all types of surgery. Thus, a basic risk assessment including a cognitive screen can help to stratify patients at low, medium, or high POD risk to provide targeted prevention and/or management strategies for patients at risk. [ABSTRACT FROM AUTHOR]

Background: There is a strong need for short and effective methods to screen for cognitive impairment. Recent studies have created short forms of the Montreal Cognitive Assessment (s-MoCA) in English-speaking populations. It is also important to develop a validated Chinese short version to detect cognitive impairment. Methods: Item response theory and computerized adaptive testing analytics were used to construct abbreviated MoCAs across a large neurological sample comprising 6,981 community-dwelling Chinese veterans. Results: Six MoCA items with high discrimination and appropriate difficulty were included in the s-MoCA. The Chinese short versions (sensitivity 0.89/0.90, specificity 0.72/0.77) are similar in performance to the full MoCA in identifying cognitive impairment (sensitivity 0.91, specificity 0.82). Conclusions: These short variants of the MoCA may serve as quick and effective instruments when the original MoCA cannot be feasibly administered in clinical services with a high patient burden and limited cognitive testing resources. [ABSTRACT FROM AUTHOR]

Background: The estimated absolute cardiovascular disease (CVD) risk level is known to be a useful surrogate marker for future cognitive impairment; however, evidence regarding its predictive validity in terms of cognitive subtypes is limited. We aimed to examine subtype-dependent differences in the associations between absolute CVD risk and the incidence of cognitive impairment in a community-dwelling older Japanese cohort. Methods and Results: This study comprised 1,641 cognitively intact older Japanese participants without CVDs at baseline. We estimated absolute CVD risk using WHO region-specific risk estimation charts and included age, sex, diabetes mellitus, smoking, systolic blood pressure, and total cholesterol at baseline, and the CVD risk level was stratified into the three following risk categories: low (<10%), moderate (10 to <20%), and high (≥20%). Objective cognitive screening was performed using a multicomponent neurocognitive test at baseline and follow-up, and the incidence of cognitive impairment over 48 ± 2 months was determined. The incidence of cognitive impairment in low-, moderate-, and high-CVD risk participants was 1.2, 3.0, and 5.4%, respectively, for amnestic subtypes and 5.8, 10.1, and 14.0%, respectively, for non-amnestic subtypes. After adjusting for potential confounding factors, the absolute CVD risk level was significantly associated with non-amnestic impairment but not with amnestic impairment. Conclusions: The absolute CVD risk estimated using region-specific risk estimation charts in old age is useful to predict incidence of cognitive impairment. Strategies to screen populations at risk of cognitive impairment and to prevent progression to dementia should be cognitive subtype-specific. [ABSTRACT FROM AUTHOR]

Mild cognitive impairment (MCI) is a common global health problem. Recently, the potential of mind-body intervention for MCI has drawn the interest of investigators. This study aims to comparatively explore the modulation effect of Baduanjin, a popular mind-body exercise, and physical exercise on the cognitive function, as well as the norepinephrine and dopamine systems using the resting state functional connectivity (rsFC) method in patients with MCI. 69 patients were randomized to the Baduanjin, brisk walking, or healthy education control group for 6 months. The Montreal Cognitive Assessment (MoCA) and magnetic resonance imaging (MRI) scans were applied at baseline and at the end of the experiment. Results showed that (1) compared to the brisk walking, the Baduanjin significantly increased MoCA scores; (2) Baduanjin significantly increased the right locus coeruleus (LC) and left ventral tegmental area (VTA) rsFC with the right insula and right amygdala compared to that of the control group; and the right anterior cingulate cortex (ACC) compared to that of the brisk walking group; (3) the increased right LC-right insula rsFC and right LC-right ACC rsFC were significantly associated with the corresponding MoCA score after 6-months of intervention; (4) both exercise groups experienced an increased effective connectivity from the right ACC to the left VTA compared to the control group; and (5) Baduanjin group experienced an increase in gray matter volume in the right ACC compared to the control group. Our results suggest that Baduanjin can significantly modulate intrinsic functional connectivity and the influence of the norepinephrine (LC) and dopamine (VTA) systems. These findings may shed light on the mechanisms of mind-body intervention and aid the development of new treatments for MCI. [ABSTRACT FROM AUTHOR]

Purpose: Imaging of the choroid may detect the microvascular changes associated with early-onset dementia (EOD) and may represent an indicator for detection of the disease. We aimed to analyze the in vivo choriocapillaris (CC) flow density in EOD patients using optical coherence tomography angiography (OCTA) and evaluate the association with its clinical measures.Methods: This cross-sectional study used the OCTA to image and analyze the choriocapillaris (CC) of 25 EOD patients and 20 healthy controls. Choriocapillaris flow density in the 3 mm area and 6 mm area was measured by an inbuilt algorithm in the OCT tool. Brain volume using magnetic resonance imaging and cognitive assessment was done and recorded.Results: Significantly reduced capillary flow density of the choriocapillaris was seen in EOD patients when compared to healthy controls in the 3.0 mm (P = 0.001) and 6.0 mm (P < 0.001) area respectively. Montreal Cognitive Assessment (MoCA) scores in EOD patients positively correlated with choriocapillaris flow density in the 3 mm area (Rho = 0.466, P = 0.021). Disease duration of EOD patients also negatively correlated with choriocapillaris density in the 3 mm area (Rho = −0.497, P = 0.008).Discussion: Our report suggests that choriocapillaris damage may be a potential indicator of early-onset dementia. Microvascular impairment may be involved in the early phase of dementia without aging playing a role in its impairment.Clinical Trial Registration: www.ClinicalTrials.gov, ChiCTR2000041386.

Cognitive impairment in type 2 diabetes mellitus (T2DM) is associated with functional and structural abnormalities in the intrinsic brain network. The salience network (SN) is a neurocognitive network that maintains normal cognitive function, but it has received little attention in T2DM. We explored SN changes in patients with T2DM with normal cognitive function (DMCN) and in patients with T2DM with mild cognitive impairment (DMCI). Sixty-five T2DM patients and 31 healthy controls (HCs) underwent a neuropsychological assessment, independent component analysis (ICA), and voxel-based morphometry (VBM) analysis. The ICA extracted the SN for VBM to compare SN functional connectivity (FC) and gray matter (GM) volume (GMV) between groups. A correlation analysis examined the relationship between abnormal FC and GMV and clinical/cognitive variables. Compared with HCs, DMCN patients demonstrated increased FC in the left frontoinsular cortex (FIC), right anterior insula, and putamen, while DMCI patients demonstrated decreased right middle/inferior frontal gyrus FC. Compared with DMCN patients, DMCI patients showed decreased right FIC FC. There was no significant difference in SN GMV in DMCN and DMCI patients compared with HCs. FIC GMV was decreased in the DMCI patients compared with DMCN patients. In addition, right FIC FC and SN GMV positively correlated with Montreal Cognitive Assessment and Mini-Mental State Examination (MMSE) scores. These findings indicate that changes in SN FC, and GMV are complex non-linear processes accompanied by increased cognitive dysfunction in patients with T2DM. The right FIC may be a useful imaging biomarker for supplementary assessment of early cognitive dysfunction in patients with T2DM. [ABSTRACT FROM AUTHOR]

Background: Abnormal cholesterol metabolism is common in type 2 diabetes mellitus (T2DM) and causes dementia. Cholesterol 24S-hydroxylase (CYP46A1) converts cholesterol into 24S-hydroxycholesterol (24-OHC) and maintains cholesterol homeostasis in the brain. Objective: This study aimed to investigate the roles of 24-OHC and the CYP46A1 (rs754203) polymorphism in patients with T2DM and mild cognitive impairment (MCI). Methods: A total of 193 Chinese patients with T2DM were recruited into two groups according to the Montreal Cognitive Assessment (MoCA). Demographic and clinical data were collected, and neuropsychological tests were conducted. Enzyme-linked immunosorbent assay (ELISA) and Seqnome method were used to detect the concentration of plasma 24-OHC and the CYP46A1 rs754203 genotype, respectively. Results: Compared with 118 healthy cognition participants, patients with MCI (n = 75) displayed a higher plasma level of 24-OHC and total cholesterol concentration (all p = 0.031), while no correlation was found between them. In the overall diabetes population, the plasma level of 24-OHC was negatively correlated with MoCA (r = −0.150, p = 0.039), and it was further proved to be an independent risk factor of diabetic MCI (OR = 1.848, p = 0.001). Additionally, patients with MCI and the CC genotype of CYP46A1 rs754203 showed the highest plasma level of 24-OHC even though the difference was not statistically significant, and they obtained low scores in both the verbal fluency test and Stroop color and word test A (p = 0.008 and p = 0.029, respectively). Conclusion: In patients with T2DM, high plasma level of 24-OHC and the CC genotype carrier of CYP46A1 rs754203 may portend a high risk of developing early cognitive impairment, including attention and executive deficits. [ABSTRACT FROM AUTHOR]

Background: Cognitive reserve explains why subjects with more years of education, professional achievement, or participation in recreational activities show less cognitive decline with aging. We hypothesize that levels of recreational travel, education, occupation, systemic health, physical performance, and current cognitive activity levels affect the trajectory of cognitive function in older, healthy people in Poland. Materials and Methods: Healthy, older people (N = 205) were examined and followed-up at 2 years. Participants completed physical and cognitive function assessments: including the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and its two subtests Delayed Recall (DR) and Verbal Fluency (VF), and Trail Making Test Part B (TMT B). Factors associated with cognitive functioning were also examined. Results: The MMSE result significantly decreased over 2 years. No significant decrease in other cognitive tests was noted. However, the trajectory of cognitive tests results varied between individual participants. Percentage of variance of change was explained by the following predictors: 21 in MMSE, 24 in MoCA, 8 in DR, 25 in VF, and 24 in TMT B. Age and the presence of varicose veins were significantly linked to negative changes in MMSE and MoCA scores, while working in a professional occupational status associated with a higher score. The subgroup with varicose veins did worse on the Delayed Recall subtest of MoCA. Conclusion: Cognitive reserve could be extended by proxies of reserve that are related to systemic health and travel activity. The latter is a combination of social, physical, and cognitive activity and potentially might serve as an intervention to improve cognitive function in older people. However, due to the limitations of this study, results should be interpreted with caution and needs to be replicated in the further studies. [ABSTRACT FROM AUTHOR]

Purpose : Imaging of the choroid may detect the microvascular changes associated with early-onset dementia (EOD) and may represent an indicator for detection of the disease. We aimed to analyze the in vivo choriocapillaris (CC) flow density in EOD patients using optical coherence tomography angiography (OCTA) and evaluate the association with its clinical measures. Methods : This cross-sectional study used the OCTA to image and analyze the choriocapillaris (CC) of 25 EOD patients and 20 healthy controls. Choriocapillaris flow density in the 3 mm area and 6 mm area was measured by an inbuilt algorithm in the OCT tool. Brain volume using magnetic resonance imaging and cognitive assessment was done and recorded. Results : Significantly reduced capillary flow density of the choriocapillaris was seen in EOD patients when compared to healthy controls in the 3.0 mm (P = 0.001) and 6.0 mm (P < 0.001) area respectively. Montreal Cognitive Assessment (MoCA) scores in EOD patients positively correlated with choriocapillaris flow density in the 3 mm area (Rho = 0.466, P = 0.021). Disease duration of EOD patients also negatively correlated with choriocapillaris density in the 3 mm area (Rho = −0.497, P = 0.008). Discussion : Our report suggests that choriocapillaris damage may be a potential indicator of early-onset dementia. Microvascular impairment may be involved in the early phase of dementia without aging playing a role in its impairment. Clinical Trial Registration : www.ClinicalTrials.gov, ChiCTR2000041386. [ABSTRACT FROM AUTHOR]

Objective: This cross-sectional study aimed to distinguish patients with mild cognitive impairment (MCI) from patients with normal controls (NCs) by measuring the levels of N -acetyl aspartate (NAA), total creatinine (tCr), and choline (Cho) in their hippocampus (HIP) and their posterior cingulate gyrus (PCG) by using proton magnetic resonance spectroscopy (MRS) and to predict the cutoff value on the ratios of metabolites. We further aimed to provide a reference for the diagnosis of MCI in elderly patients in China. Methods: About 69 patients who underwent a clinical diagnosis of the MCI group and 67 patients with NCs, the Mini-Mental Status Examination (MMSE) score, the Montreal Cognitive Assessment (MoCA) score, and MRS of the bilateral HIP and bilateral PCG were considered. The ratio of NAA/tCr and Cho/tCr in the bilateral HIP and bilateral PCG was calculated. The relationship between the ratios of metabolites and the scores of MMSE and MoCA was analyzed, and the possible brain metabolite cutoff point for the diagnosis of MCI was evaluated. Results: Compared with the NC group, the scores of MMSE and MoCA in the MCI group decreased significantly (p < 0.05); the ratio of NAA/tCr in the bilateral HIP and bilateral PCG and the ratio of Cho/tCr at the right HIP in the MCI group decreased significantly (p < 0.05); however, there was no significant difference in the ratio of Cho/tCr in the left HIP and bilateral PCG between the two groups (p > 0.05). The correlation coefficient between MMSE/MoCA and the ratio of NAA/tCr was 0.49–0.56 in the bilateral HIP (p < 0.01). The best cutoff value of NAA/creatine (Cr) in the left HIP and the right HIP was 1.195 and 1.19. Sensitivity, specificity, and the Youden index (YDI) in the left HIP and the right HIP were (0.725, 0.803, 0.528) and (0.754, 0.803, 0.557), respectively. Conclusion: The level of metabolites in the HIP and the PCG of patients with MCI and of those with normal subjects has a certain correlation with the score of their MMSE and MoCA. When the value of NAA/tCr in the left HIP and right HIP is <1.19, it suggests that MCI may have occurred. According to this cutoff point, elderly patients with MCI in China could be screened. [ABSTRACT FROM AUTHOR]

Background: Dementia, as a global public health problem, is becoming increasingly serious. As a precursor of dementia, mild cognitive impairment (MCI) plays an important role in the diagnosis and prevention of dementia. Recent studies have found a correlation between gamma-glutamyl transferase (GGT) levels and cognitive function in men. The relationship between GGT levels and cognitive function in women remains unclear because GGT activity and expression differ between the sexes. Method: We recruited a total of 2,943 Chinese women from Jidong and Taian in 2019. We grouped the participants according to GGT levels, diagnosed MCI using the Montreal Cognitive Assessment (MOCA) scale, and modeled the study outcomes using logistic regression to explore the relationship between GGT level and MCI. We also analyzed the interaction of obesity, sleep duration, and hyperuricemia with GGT in the development of MCI. Results: The prevalence of MCI increased with increasing GGT level, from the lowest quartile to the highest quartile of GGT: 8.4% (66/786), 14.2% (119/840), 17.6% (108/613), and 21.4% (151/704), respectively. At the same time, as GGT levels increased, so did the risk of MCI. In the fully adjusted model, compared with those for participants in the lowest GGT quartiles, the odds ratios (ORs), and 95% confidence intervals (CIs) for MCI for participants in the second, third, and fourth GGT quartiles were 1.49 (1.04–2.12), 1.53(1.06–2.21), and 1.88 (1.33–2.65), respectively. The risk of developing MCI was further increased in people with high GGT levels who were obese (OR = 1.96, 95% CI: 1.39–2.76, P < 0.001), slept less (OR = 1.91, 95% CI: 1.35–2.71, P < 0.001), had high levels of uric acid (OR = 1.55, 95% CI: 1.03–2.32, P < 0.001), or after menopause (OR = 2.92, 95% CI: 2.07–4.12, P < 0.001). Conclusion: We found that MCI is more common in women with elevated GGT levels, so GGT could be a potential diagnostic marker for MCI. Meanwhile, our findings indicated that women with high GGT levels had an increased risk of MCI when they were obese, sleep deprived, had high serum uric acid (SUA) levels or underwent menopause. [ABSTRACT FROM AUTHOR]

Objective: We investigated the prevalence, evolution, associated factors, and risk factors of apathy in a cohort of patients with early-stage Parkinson's disease (PD), who underwent a 4-years prospective follow-up. Methods: This study included 188 patients with PD (baseline disease duration <3 years) who underwent an annual evaluation using the Lille Apathy Rating Scale (LARS). Based on the cut-off value of −21 observed on the LARS, patients were categorized as PD with and without apathy. The generalized estimating equations (GEE) model was utilized to determine the factors associated with apathy, and the Cox proportional-hazards regression model was used to determine the predictors of apathy. Results: Apathy increased from a baseline rate of 18.6–28.8% after 4 years; notably, this rate was not persistent across patients' visits. The LARS score was independently associated with the male sex (B 8.131, p = 0.009), low Frontal Assessment Battery (FAB) scores (B 0.567, p = 0.011), low attention scores on the Montreal Cognitive Assessment (MOCA) test (B 0.217, p = 0.026), high Hamilton Depression Rating Scale (HDRS) scores (B 1.362, p < 0.001), high Unified Parkinson's Disease Rating Scale (UPDRS) part III scores (B 1.147, p < 0.001), and prolonged follow-up time (B 1.785, p = 0.048). A high HDRS score was the only predictor of apathy in PD [hazard ratio (HR) 1.043, p = 0.026]. Conclusions: The risk of apathy is higher in men with progressive PD accompanied by disease-specific motor and non-motor symptoms. Depression during early-stage PD is a primary risk factor for apathy in PD. [ABSTRACT FROM AUTHOR]

Background: The substantial heterogeneity of clinical symptoms and lack of reliable progression markers in Parkinson's disease (PD) present a major challenge in predicting accurate progression and prognoses. Increasing evidence indicates that each component of the neurovascular unit (NVU) and blood-brain barrier (BBB) disruption may take part in many neurodegenerative diseases. Since some portions of CSF are eliminated along the neurovascular unit and across the BBB, disturbing the pathways may result in changes of these substances. Methods: Four hundred seventy-four participants from the Parkinson's Progression Markers Initiative (PPMI) study (NCT01141023) were included in the study. Thirty-six initial features, including general information, brief clinical characteristics and the current year's classical scale scores, were used to build five regression models to predict PD motor progression represented by the coming year's Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III score after redundancy removal and recursive feature elimination (RFE)-based feature selection. Then, a threshold range was added to the predicted value for more convenient model application. Finally, we evaluated the CSF and blood biomarkers' influence on the disease progression model. Results: Eight hundred forty-nine cases were included in the study. The adjusted R 2 values of three different categories of regression model, linear, Bayesian and ensemble, all reached 0.75. Models of the same category shared similar feature combinations. The common features selected among the categories were the MDS-UPDRS Part III score, Montreal Cognitive Assessment (MOCA) and Rapid Eye Movement Sleep Behavior Disorder Questionnaire (RBDSQ) score. It can be seen more intuitively that the model can achieve certain prediction effect through threshold range. Biomarkers had no significant impact on the progression model within the data in the study. Conclusions: By using machine learning and routinely gathered assessments from the current year, we developed multiple dynamic models to predict the following year's motor progression in the early stage of PD. These methods will allow clinicians to tailor medical management to the individual and identify at-risk patients for future clinical trials examining disease-modifying therapies. [ABSTRACT FROM AUTHOR]

Background and Objective: Alzheimer's disease (AD) has been shown to affect vision in human patients and animal models. This study was conducted to explore ocular abnormalities in the primary visual pathway and their relationship with hippocampal atrophy in patients with AD and mild cognitive impairment (MCI). The aim of this study was to investigate the potential value of ocular examinations as a biomarker during the AD progression. Methods: Patients with MCI (n = 23) or AD (n = 17) and age-matched cognitively normal controls (NC; n = 19) were enrolled. Pattern visual-evoked potentials (PVEP), flash electroretinogram (FERG) recordings and optical coherence tomography (OCT) were performed for all participants. Hippocampal volumes were measured by 3T magnetic resonance imaging. Cognitive function was assessed by Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog). Pearson correlation was employed to analyze the potential associations between ocular abnormalities and hippocampal volumes. Hierarchical regression models were conducted to determine associations between cognitive performances and ocular abnormalities as well as hippocampal volumes after adjusting for confounding factors including age, sex, cognitive reserve, and APOE4 status. Results: PVEP amplitude of P100 waveform was significantly decreased in AD patients compared to MCI and normal individuals. In FERG test, delayed latencies of rod response, rod cone response and 3.0 flicker time were found in cognitively impaired groups, indicating dysfunctions of both the rod and cone systems in the disease progression. OCT test revealed reduced macular retinal nerve fiber layer (m-RNFL) thickness in MCI and AD patients, which significantly correlated with brain structure of hippocampus particularly vulnerable during the progression of AD. Interestingly, P100 amplitude showed a significant association with hippocampal volumes even after adjusting confounding factors including age, sex, and cognitive reserve. Hierarchical regression analysis further demonstrated that m-RNFL thickness, as well as hippocampal volumes, significantly associated with ADAS-cog scores. Conclusion: P100 amplitude and m-RNFL thickness showed significant correlations with brain structure involved in AD-related neurodegeneration, and therefore proved to be potential indicators of brain imaging pathologies. [ABSTRACT FROM AUTHOR]

Background: Cognitive frailty is a particular state of cognitive vulnerability toward dementia with neuropathological hallmarks. The hippocampus is a complex, heterogeneous structure closely relates to the cognitive impairment in elderly which is composed of 12 subregions. Atrophy of these subregions has been implicated in a variety of neurodegenerative diseases. The aim of this study was to explore the changes in hippocampal subregions in older adults with cognitive frailty and the relationship between subregions and cognitive impairment as well as physical frailty. Methods: Twenty-six older adults with cognitive frailty and 26 matched healthy controls were included in this study. Cognitive function was evaluated by the Montreal Cognitive Assessment (MoCA) scale (Fuzhou version) and Wechsler Memory Scale-Revised Chinese version (WMS-RC), while physical frailty was tested with the Chinese version of the Edmonton Frailty Scale (EFS) and grip strength. The volume of the hippocampal subregions was measured with structural brain magnetic resonance imaging. Partial correlation analysis was carried out between the volumes of hippocampal subregions and MoCA scores, Wechsler's Memory Quotient and physical frailty indexes. Results: A significant volume decrease was found in six hippocampal subregions, including the bilateral presubiculum, the left parasubiculum, molecular layer of the hippocampus proper (molecular layer of the HP), and hippocampal amygdala transition area (HATA), and the right cornu ammonis subfield 1 (CA1) area, in older adults with cognitive frailty, while the proportion of brain parenchyma and total number of white matter fibers were lower than those in the healthy controls. Positive correlations were found between Wechsler's Memory Quotient and the size of the left molecular layer of the HP and HATA and the right presubiculum. The sizes of the left presubiculum, molecular of the layer HP, and HATA and right CA1 and presubiculum were found to be positively correlated with MoCA score. The sizes of the left parasubiculum, molecular layer of the HP and HATA were found to be negatively correlated with the physical frailty index. Conclusion: Significant volume decrease occurs in hippocampal subregions of older adults with cognitive frailty, and these changes are correlated with cognitive impairment and physical frailty. Therefore, the atrophy of hippocampal subregions could participate in the pathological progression of cognitive frailty. [ABSTRACT FROM AUTHOR]

Introduction: Dementia is increasing in prevalence in aging populations. Current questionnaire-based cognitive assessments may not comprehensively assess cognitive function and real-time task-performance. Virtual reality (VR) technology has been used in cognitive assessments but existing systems have limited scope in evaluating all cognitive domains. We have developed a novel, fully-immersive VR system (CAVIRE: Cognitive Assessment by VIrtual REality), which incorporates automated audio-visual instructions. An automated scoring matrix to assess the six cognitive domains—perceptual-motor function, executive function, complex attention, social cognition, learning and memory, and language—is embedded in the CAVIRE system. Aims: The primary aim is to evaluate the feasibility of using the CAVIRE system to assess cognitive function of participants across different age groups from 35 to 84 years old. The secondary aims are to determine the CAVIRE performance-indices (completion time and scores) of the participants and to assess their acceptability toward the use of CAVIRE as a modality for cognitive assessment. Methods: One hundred and seventy-five participants will be assessed by CAVIRE at a primary care clinic in Singapore. They will be first assessed using questionnaires: Montreal Cognitive Assessment (MoCA), Abbreviated Mental Test (AMT), Mini-Mental State Examination (MMSE), Basic Activities of Daily Living (BADLs), Instrumental Activities of Daily Living (IADLs). Those aged 65–84 years will be grouped into cognitively intact (n = 50, MoCA score ≥ 26) and cognitively impaired (n = 50, MoCA < 26). The CAVIRE performance-indices of cognitively healthy younger participants aged 35–64 years (n = 75) will serve as benchmark references. CAVIRE auto-computes the participant's performance-indices in 13 different segments. The tasks include domestic chores, memory, shopping, and social interactions. The proportion of participants who complete the entire VR assessment in each age group will be evaluated as feasibility indicators. The CAVIRE performance-indices will be compared across the different age groups. Feedback on the acceptability of the CAVIRE system will be collated and compared among the participants across the age groups. Significance: CAVIRE is designed to assess the six domains of cognitive function using VR. The results of this feasibility study will provide insights for the implementation of the CAVIRE system as an alternative modality of cognitive assessment in the community. [ABSTRACT FROM AUTHOR]

Objective: To assess the value of the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) during acute phase in predicting post-stroke cognitive impairment (PSCI) at 3–6 months.Methods: We prospectively recruited 229 patients who had suffered their first-ever ischemic stroke. PSCI was determined in 104 of these patients by a comprehensive neuropsychological battery performed at 3–6 months. Receiver operating characteristic (ROC) curve analysis was then performed to compare the discriminatory ability of the MMSE and MoCA. Also, we applied a decision tree generated by the classification and regression tree methodology.Results: In total, 66 patients had PSCI when evaluated 3–6 months after the onset of minor stroke. Logistic regression analysis revealed that education, body mass index (BMI), and baseline MoCA scores were independently associated with PSCI. ROC curve analysis showed that the ability to predict PSCI was similar when compared between baseline MoCA scores [area under curve (AUC), 0.821; 95% confidence interval (CI), 0.743–0.898] and baseline MMSE scores (AUC, 0.809; 95% CI, 0.725–0.892, P = 0.75). Both MMSE and MoCA exhibited similar predictive values at their optimal cut-off points (MMSE ≤27; sensitivity, 0.682; specificity, 0.816; MoCA ≤21; sensitivity, 0.636; specificity, 0.895). Classification and regression tree-derived analysis yielded an AUC of 0.823 (sensitivity, 0.803; specificity, 0.842).Conclusion: When applied within 2 weeks of stroke, the MMSE and MoCA are both useful and have similar predictive value for PSCI 3–6 months after the onset of minor stroke.

Alzheimer disease (AD) has an insidious onset and heterogeneous clinical symptoms. The well-accepted biomarkers for clinical diagnosis of AD include β-amyloid (Aβ) deposition and pathologic tau level within cerebral spinal fluid (CSF) and imaging AD pathology such as positive emission tomography (PET) imaging of the amyloid-binding agent Pittsburgh compound B (PET-PiB). However, the high expense and invasive nature of these methods highly limit their wide usage in clinic practice. Therefore, it is imperious to develop less expensive and invasive methods, and plasma biomarkers are the premium targets. In the current study, we utilized a single-blind comparison method; all the probable AD cases met the core clinical National Institute on Aging and Alzheimer’s Association (NIA-AA) criteria and validated by PET-PiB. We used ultrasensitive immunomagnetic reduction (IMR) assays to measure plasma Aβ42 and total-tau (t-tau) levels, in combination with different variables including Aβ42 × t-tau value, Montreal Cognitive Assessment (MoCA), and Mini Mental State Examination (MMSE). We used logistic regression to analyze the effect of all these variables in the algorism. Our results showed that (1) plasma Aβ42 and t-tau are efficient biomarkers for AD diagnosis using IMR platform, whereas Aβ42 × t-tau value is more efficient for discriminating control and AD; (2) in the control group, Aβ42 level and age demonstrated strong negative correlation; Aβ42 × t-tau value and age demonstrated significant negative correlation; (3) in the AD group, t-tau level and MMSE score demonstrated strong negative correlation; (4) using the model that Aβ42, Aβ42 × t-tau, and MoCA as the variable to generate receiver operating characteristic (ROC) curve, cutoff value = 0.48, sensitivity = 0.973, specificity = 0.982, area under the curve (AUC) = 0.986, offered better categorical efficacy, sensitivity, specificity, and AUC. The multifactor model of plasma Aβ42 and t-tau in combination with MoCA can be a viable model separate health and AD subjects in clinical practice.

Objective: The current study aimed at comparing the effects of Tai Chi (a motor-cognitive exercise) with walking (an exercise without cognitive demands) on cognitive performance, brain structure, and brain function in the elderly. Methods: This cross-sectional study included 42 healthy elderly women within two groups: Tai Chi (n = 20; mean age = 62.90 ± 2.38 years) and brisk walking exercise (n = 22; mean age = 63.27 ± 3.58 years). All the participants underwent a cognitive assessment via the Montreal Cognitive Assessment and brain structural and resting state functional magnetic resonance imaging (rsfMRI) assessments. Results: Episodic memory in the Tai Chi group was superior to that of the walking group. Higher gray matter density in the inferior and medial temporal regions (including the hippocampus) and higher ReHo in temporal regions (specifically the fusiform gyrus and hippocampus) were found in the Tai Chi group. Significant partial correlations were found between the gray matter density of the left hippocampus and episodic memory in the whole sample. Significant partial correlations were observed between the ReHo in left hippocampus, left parahippocampal, left fusiform, and delayed memory task, which was observed among all subjects. Conclusion: The present study suggests that long-term Tai Chi practice may improve memory performance via remodeling the structure and function of the hippocampus. [ABSTRACT FROM AUTHOR]