UNASSIGNED: With advancing age, cognitive decline is frequently associated with endothelial dysfunction, but data on vascular performance prior to the onset of mild cognitive impairment (MCI) is scarce.
UNASSIGNED: To investigate the relationship between endothelial function, vital parameters and cognitive performance in older adults with subjective cognitive decline (SCD).
UNASSIGNED: Forty-five volunteers aged 65 years and older with SCD underwent comprehensive geriatric assessment-based prognosis evaluation by means of the Multidimensional Prognostic Index (MPI), full neuropsychological examination and peripheral arterial tonometry measurement by means of EndoPAT™2000 to evaluate endothelial flexibility and vital parameters. Six months after initial evaluation, participants were contacted by phone and a telephone-administered version of the MPI (TELE-MPI) was conducted.
UNASSIGNED: Fifteen study participants scored below the cutoff score of 26 on the Montreal Cognitive Assessment, suggesting MCI (26.56±2.23). Nominal significant correlations were found between heart rate (HR) and trail making test (TMT) A (β= -0.49, p = 0.03), between heart rate variability (HRV) and TMT B (β= 0.78, p = 0.041), between power of low-frequency band (LF) HRV and Mini Nutritional Assessment-Short Form (β= 0.007, p = 0.037) as well as between augmentation index (AI) and CogState Detection Test (β= 0.002, p = 0.034).
UNASSIGNED: HR, HRV, and AI, but not endothelial flexibility are associated with cognitive performance in SCD and suspected MCI patients and may serve as clinical biomarkers in the early diagnosis of neurodegenerative disorders with advancing age.

UNASSIGNED: Mild cognitive impairment (MCI) is a critical transitional phase from healthy cognitive aging to dementia, offering a unique opportunity for early intervention. However, few studies focus on the correlation of brain structure and functional activity in patients with MCI due to Alzheimer\'s disease (AD). Elucidating the complex interactions between structural-functional (SC-FC) brain connectivity and glymphatic system function is crucial for understanding this condition.
UNASSIGNED: The aims of this study were to explore the relationship among SC-FC coupling values, glymphatic system function and cognitive function. 23 MCI patients and 18 healthy controls (HC) underwent diffusion tensor imaging (DTI) and resting-state functional MRI (fMRI). DTI analysis along the perivascular space (DTI-ALPS) index and SC-FC coupling values were calculated using DTI and fMRI. Correlation analysis was conducted to assess the relationship between Mini-Mental State Examination (MMSE) scores, DTI-ALPS index, and coupling values. Receiver operating characteristic (ROC) curves was conducted on the SC-FC coupling between the whole brain and subnetworks. The correlation of coupling values with MMSE scores was also analyzed.
UNASSIGNED: MCI patients (67.74 ± 6.99 years of age) exhibited significantly lower coupling in the whole-brain network and subnetworks, such as the somatomotor network (SMN) and ventral attention network (VAN), than HCs (63.44 ± 6.92 years of age). Whole-brain network coupling was positively correlated with dorsal attention network (DAN), SMN, and visual network (VN) coupling. MMSE scores were significantly positively correlated with whole-brain coupling and SMN coupling. In MCI, whole-brain network demonstrated the highest performance, followed by the SMN and VAN, with the VN, DAN, limbic network (LN), frontoparietal network (FPN), and default mode network (DMN). Compared to HCs, lower DTI-ALPS index was observed in individuals with MCI. Additionally, the left DTI-ALPS index showed a significant positive correlation with MMSE scores and coupling values in the whole-brain network and SMN.
UNASSIGNED: These findings reveal the critical role of SC-FC coupling values and the ALPS index in cognitive function of MCI. The positive correlations observed in the left DTI-ALPS and whole-brain and SMN coupling values provide a new insight for investigating the asymmetrical nature of cognitive impairments.

OBJECTIVE: To investigate motor, non-motor and cognitive progression in early Parkinson\'s disease (PD) patients with Mild Cognitive Impairment (MCI).
METHODS: PD patients were recruited within 1 year of diagnosis and were classified into PD-MCI group and PD with normal cognition (PD-NC) group. H&Y staging scale, MDS-UPDRS part III were used to assess disease severity and motor progression. Non-motor symptom scale (NMSS) was used to evaluate the NMS progression. Cognitive progression was assessed from 5 cognitive domains. Annual progression changes in the longitudinal outcomes were examined via linear mixed model with random intercept effect. False discovery rate (FDR) method was performed to control for multiple testing comparison and q-value was calculated. We set the threshold of q-values as 0.1.
RESULTS: A total of 205 PD patients, including 107 PD-MCI and 98 PD-NC patients were assessed prospectively over a 5-year period. PD-MCI patients, compared to PD-NC group, had a significantly higher progression rate in H&Y score (0.11 vs. 0.06, p=0.03, q=0.08), MDS-UPDRS motor score (3.11 vs. 1.90 p<0.001, q=0.06) and postural instability gait difficulty (PIGD) score (0.40 vs. 0.20, p=0.02, q=0.07). PD-MCI group also exhibited significantly faster deterioration in NMSS perceptual domain (PD-MCI vs. PD-NC: 0.38 vs. -0.04, p=0.01, q=0.06) and cognitive visuospatial domain (PD-MCI vs. PD-NC: 0.13 vs. -0.06, p=0.048, q=0.09) after adjustment for confounders and multiple comparisons.
CONCLUSIONS: PD-MCI patients had faster decline in motor functions, visuo-perceptual and visuospatial performance. These findings provide a more comprehensive prognosis of PD-MCI, which could be helpful for clinician to manage PD-MCI patients.

BACKGROUND: This study aimed to explore the associations between brain structures, cognition, and motor control in participants with mild cognitive impairment (MCI), with a focus on dual-task performance.
METHODS: Thirty MCI patients and thirty healthy controls were enrolled. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Structural magnetic resonance imaging data were analyzed using voxel-based morphometry (VBM) to calculate brain parenchyma volume and gray matter volume (GMV). Participants performed single- and dual-task Timed Up and Go (TUG) tests, and the correlations between significant GMV differences and task execution time was analyzed.
RESULTS: MCI patients showed significantly lower MoCA scores, particularly in visuospatial/executive, attention, and delayed recall domains (p < 0.05). Dual-task TUG execution time was significantly increased in MCI patients (p < 0.05). The GMV in the right anterior lobe of the cerebellum and both insulae was positively correlated with visuospatial/executive scores (FDR-corrected, p < 0.05). The GMV of the right cerebellar anterior lobe and insula were significantly reduced in MCI patients (p < 0.05). The GMV of the right cerebellar anterior lobe was negatively correlated with dual-task execution time (r = -0.32, p = 0.012).
CONCLUSIONS: Smaller GMV in the right anterior lobe of the cerebellum was associated with impaired dual-task performance, which may provide more evidence for the neural mechanisms of cognitive and motor function impairments in MCI.

BACKGROUND: We investigated the link between habitual caffeine intake with memory impairments and cerebrospinal fluid (CSF) biomarkers in mild cognitive impairment (MCI) and Alzheimer\'s disease (AD) patients.
METHODS: MCI (N = 147) and AD (N = 116) patients of the Biomarker of AmyLoid pepTide and AlZheimer\'s diseAse Risk (BALTAZAR) cohort reported their caffeine intake at inclusion using a dedicated survey. Associations of caffeine consumption with memory impairments and CSF biomarkers (tau, p-tau181, amyloid beta 1-42 [Aβ1-42], Aβ1-40) were analyzed using logistic and analysis of covariance models.
RESULTS: Adjusted on Apolipoprotein E (APOE ε4), age, sex, education level, and tobacco, lower caffeine consumption was associated with higher risk to be amnestic (OR: 2.49 [95% CI: 1.13 to 5.46]; p = 0.023) and lower CSF Aβ1-42 (p = 0.047), Aβ1-42/Aβ1-40 (p = 0.040), and Aβ1-42/p-tau181 (p = 0.020) in the whole cohort.
CONCLUSIONS: Data support the beneficial effect of caffeine consumption to memory impairments and CSF amyloid markers in MCI and AD patients.
CONCLUSIONS: We studied the impact of caffeine consumption in the BALTAZAR cohort. Low caffeine intake is associated with higher risk of being amnestic in MCI/AD patients. Caffeine intake is associated with CSF biomarkers in AD patients.

BACKGROUND: Older adults often face loneliness due to chronic illness or loss of close ones, a situation worsened by the COVID-19 pandemic. Increased loneliness heightens the risk of diseases, especially dementia, necessitating urgent action.
OBJECTIVE: This study aims to assess the impact of a virtual reality (VR)-based open-air bath program on depression and loneliness in older individuals with subjective cognitive decline/mild cognitive impairment attending the Dementia Medical Center in Kyoto, Japan. We further aim to evaluate the feasibility of the program (participant recruitment and adherence) and to measure program enjoyment and satisfaction.
METHODS: The study design is a crossover trial with a 1:1 ratio, wherein 12 participants will be randomly assigned to groups 1 and 2, with group 2 serving as a waitlist control and group 1 receiving the VR program from the onset for 6 months; the VR program will be conducted 6 times (monthly). Program completion for group 1 will be followed by an observation period from months 7 to 12. Group 2 will participate in the VR program from months 7 to 12, with an observation period from months 1 to 6. Cognitive tests, psychiatric assessments, and the University of California, Los Angeles Loneliness Scale will be conducted before the study, at 6 months, and at 12 months. Results will be analyzed using repeated-measures ANOVA. Head magnetic resonance imaging and single-photon emission computed tomography scans will be performed before and after the VR program to evaluate changes and effects on brain regions.
RESULTS: Recruitment began in September 2023 and data collection is expected to be completed by March 2025. Complete study results will be published by September 2025.
CONCLUSIONS: This study examines the preliminary effects of VR on loneliness in older adults with predementia through open-air bath simulations. VR experiences could benefit this population, particularly those with limited outdoor activities. Quantifying VR\'s impact will aid in determining the size for a larger clinical trial. Qualitative results will inform participation mechanisms and guide the implementation and design of future trials.
BACKGROUND: University hospital Medical Information Network UMIN000052667; https://tinyurl.com/3yaccay5.
UNASSIGNED: DERR1-10.2196/57101.

BACKGROUND: Mild Cognitive Impairment (MCI) is considered a decline in cognitive functions, which becomes more pronounced with age. These patients may benefit from cognitive treatments that help attenuate or slow down a potential progression towards dementia.
OBJECTIVE: To assess the feasibility, fidelity, satisfaction, and effectiveness of the Memory Training and Cognitive Stimulation Program (PEMEC, by its Spanish acronym) in individuals with MCI in an online setting.
METHODS: A non-probabilistic convenience sample of 14 patients with MCI received the PEMEC (PEMEC online) through an electronic device, were assessed with MoCA, NEUROPSI Brief, Yesavage Geriatric Depression Scale before and after treatment, comparing these measurements with those of a waiting list control group.
RESULTS: 92,85% completed the treatment; with an average of 92% fidelity to the original intervention, an average of 91,61% for satisfaction with the activities of each session and the perceived usefulness was 97,98%. Statistically significant differences were found in the NEUROPSI Brief and the MoCA, before and after treatment in the intervention group and, when comparing the scores with the waiting list control group, a statistically significant difference was found in the MoCA scores.
CONCLUSIONS: Following the cultural adaptation of the program (from a Spanish to a Mexican treatment group), these results establish a precedent that systematic group cognitive interventions are feasible and effective in virtual tele-neuropsychology contexts for older adults.

OBJECTIVE: This study aims to assess and contrast cognitive and psychological aspects of patients with burning mouth syndrome (BMS-MCI) and geriatric patients (G-MCI) with mild cognitive impairment, focusing on potential predictors like pain, mood disorders, blood biomarkers, and age-related white matter changes (ARWMCs).
METHODS: The study enrolled 40 BMS-MCI and 40 geriatric G-MCI, matching them by age, gender, and educational background. Participants underwent psychological, sleepiness, and cognitive assessment including the Mini-Mental State Exam (MMSE), Trail Making Test (TMT), Corsi Block-Tapping Task, Rey Auditory Verbal Learning Test, Copying Geometric Drawings Test, Frontal Assessment Battery, and Digit Cancellation Test.
RESULTS: G-MCI patients exhibited higher ARWMCs scores in right (p = 0.005**) and left (p < 0.001**) temporal regions, which may relate to specific neurodegenerative processes. Conversely, BMS-MCI patients showed higher levels of depression and anxiety and lower MMSE scores(p < 0.001**), also struggling more with tasks requiring processing speed and executive function, as evidenced by their higher TMT-A scores (p < 0.001**).
CONCLUSIONS: The study highlights particular deficits in global cognition and processing speed for BMS-MCI. The influence of educational background, pain levels, cholesterol, sleep disturbances, and anxiety on these cognitive assessments underscores the need for personalized therapeutic strategies addressing both cognitive and emotional aspects of MCI.

Cognitive impairment among older adults is a growing public health challenge and environmental chemicals may be modifiable risk factors. A wide array of chemicals has not yet been tested for association with cognition in an environment-wide association framework. In the US National Health and Nutrition Examination Survey (NHANES) 1999-2000 and 2011-2014 cross-sectional cycles, cognition was assessed using the Digit Symbol Substitution Test (DSST, scores 0-117) among participants aged 60 years and older. Concentrations of environmental chemicals measured in blood or urine were log2 transformed and standardized. Chemicals with at least 50% of measures above the lower limit of detection were included (nchemicals=147, nclasses=14). We tested for associations between chemical concentrations and cognition using parallel survey-weighted multivariable linear regression models adjusted for age, sex, race/ethnicity, education, smoking status, fish consumption, cycle year, urinary creatinine, and cotinine. Participants with at least one chemical measurement (n=4,982) were mean age 69.8 years, 55.0% female, 78.2% non-Hispanic White, and 77.0% at least high school educated. The mean DSST score was 50.4 (standard deviation (SD)=17.4). In adjusted analyses, 5 of 147 exposures were associated with DSST at p-value<0.01. Notably, a SD increase in log2-scaled cotinine concentration was associated with 2.71 points lower DSST score (95% CI -3.69, -1.73). A SD increase in log2-scaled urinary tungsten concentration was associated with 1.34 points lower DSST score (95% CI -2.11, -0.56). Exposure to environmental chemicals, particularly heavy metals and tobacco smoke, may be modifiable factors for cognition among older adults.

UNASSIGNED: The prevalence of Alzheimer\'s disease (AD) is increasing, therefore, identifying biomarkers to predict those vulnerable to AD is imperative. Type 2 diabetes (T2D) serves as an independent risk factor for AD. Early prediction of T2D patients who may be more susceptible to AD, so as to achieve early intervention, is of great significance to reduce the prevalence of AD.
UNASSIGNED: To establish periphery biomarkers that could predict conversion of T2D into pre-AD-like cognitive decline.
UNASSIGNED: A follow-up study was carried out from 159 T2D patients at baseline. The correlations of cognitive states (by MMSE score) with multi-periphery biomarkers, including APOE genotype, plasma amyloid-β level, platelet GSK-3β activity, and olfactory score were analyzed by logistic regression. ROC curve was used for establishing the prediction model. Additionally, MRI acquired from 38 T2D patients for analyzing the correlation among cognitive function, biomarkers and brain structure.
UNASSIGNED: Compared with the patients who maintained normal cognitive functions during the follow-up period, the patients who developed MCI showed worse olfactory function, higher platelet GSK-3β activity, and higher plasma Aβ42/Aβ40 ratio. We conducted a predictive model which T2D patients had more chance of suffering from pre-AD-like cognitive decline. The MRI data revealed MMSE scores were positively correlated with brain structures. However, platelet GSK-3β activity was negatively correlated with brain structures.
UNASSIGNED: Elevated platelet GSK-3β activity and plasma Aβ42/Aβ40 ratio with reduced olfactory function are correlated with pre-AD-like cognitive decline in T2D patients, which used for predicting which T2D patients will convert into pre-AD-like cognitive decline in very early stage.