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This study explored the effect of different dual-task (DT) training programs on DT interference in adults with intellectual disability. Center-of-pressure (CoP) mean velocity in single-task (ST) and cognitive-DT conditions and the Timed Up-and-Go Test (TUGT) during ST, cognitive-DT, and motor-DT conditions were assessed before and after intervention in a cognitive–motor training group, a motor–motor training group, and a control group. Before training, CoP mean velocity and TUGT time increased (p <.001) in DT compared with the ST condition. After training, the CoP mean velocity values remained unchanged (p =.07) in DT compared with the ST condition among the cognitive–motor training group. Furthermore, compared with the ST condition, no increase (p = 1) was reported in the TUGT time during the cognitive-DT condition for the cognitive–motor training group and during the motor-DT for the motor–motor training group (p =.12). The effect of DT training on DT interference depends on the training modality. [ABSTRACT FROM AUTHOR]

The aim of this systematic review, meta-analysis, and meta-regression was to examine the effects of virtual reality–based training on global cognition and executive function compared with conventional training or information-based treatment in older adults, regardless of cognitive level. A systematic literature search was conducted using four databases. A total of 31 randomized controlled trials were identified. Pooled effect sizes were calculated, the risk of bias was assessed, and evidence was graded. The primary analyses showed a small but statistically significant effect of virtual reality–based training compared with control on global cognition (Hedges' g 0.42, 95% confidence interval [0.17, 0.68], I2 = 70.1%, n = 876, 20 randomized controlled trials, low evidence) and executive function (Hedges' g 0.35, 95% confidence interval [0.06, 0.65], I2 = 68.4%, n = 810, 16 randomized controlled trials, very low evidence). Meta-regression yielded inconclusive results. Virtual reality–based training may be more effective than control in improving cognition in older adults; however, more high-quality studies are needed. [ABSTRACT FROM AUTHOR]

Both navigation abilities and gait can be affected by the atrophy in the medial temporal cortex. This study aimed to determine whether navigation abilities could differentiate seniors with and without medial temporal lobe atrophy who complained about their cognitive status. The participants, classified to either the medial temporal atrophy group (n = 23) or the control group (n = 22) underwent neuropsychological assessment and performed a spatial navigation task while their gait parameters were recorded. The study showed no significant differences between the two groups in memory, fluency, and semantic knowledge or typical measures of navigating abilities. However, gait parameters, particularly the propulsion index during certain phases of the navigation task, distinguished between seniors with and without medial temporal lobe lesions. These findings suggest that the gait parameters in the navigation task may be a valuable tool for identifying seniors with cognitive complaints and subtle medial temporal atrophy. [ABSTRACT FROM AUTHOR]

This pragmatic review synthesises the current understanding of prodromal dementia with Lewy bodies (pDLB) and prodromal Alzheimers disease (pAD), including clinical presentations, neuropsychological profiles, neuropsychiatric symptoms, biomarkers, and indications for disease management. The core clinical features of dementia with Lewy bodies (DLB)-parkinsonism, complex visual hallucinations, cognitive fluctuations, and REM sleep behaviour disorder are common prodromal symptoms. Supportive clinical features of pDLB include severe neuroleptic sensitivity, as well as autonomic and neuropsychiatric symptoms. The neuropsychological profile in mild cognitive impairment attributable to Lewy body pathology (MCI-LB) tends to include impairment in visuospatial skills and executive functioning, distinguishing it from MCI due to AD, which typically presents with impairment in memory. pDLB may present with cognitive impairment, psychiatric symptoms, and/or recurrent episodes of delirium, indicating that it is not necessarily synonymous with MCI-LB. Imaging, fluid and other biomarkers may play a crucial role in differentiating pDLB from pAD. The current MCI-LB criteria recognise low dopamine transporter uptake using positron emission tomography or single photon emission computed tomography (SPECT), loss of REM atonia on polysomnography, and sympathetic cardiac denervation using meta-iodobenzylguanidine SPECT as indicative biomarkers with slowing of dominant frequency on EEG among others as supportive biomarkers. This review also highlights the emergence of fluid and skin-based biomarkers. There is little research evidence for the treatment of pDLB, but pharmacological and non-pharmacological treatments for DLB may be discussed with patients. Non-pharmacological interventions such as diet, exercise, and cognitive stimulation may provide benefit, while evaluation and management of contributing factors like medications and sleep disturbances are vital. There is a need to expand research across diverse patient populations to address existing disparities in clinical trial participation. In conclusion, an early and accurate diagnosis of pDLB or pAD presents an opportunity for tailored interventions, improved healthcare outcomes, and enhanced quality of life for patients and care partners.

IntroductionData-driven neuropsychological methods can identify mild cognitive impairment (MCI) subtypes with stronger associations to dementia risk factors than conventional diagnostic methods.MethodsCluster analysis used neuropsychological data from participants without dementia (mean age = 71.6 years) in the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (n = 26,255) and the "normal cognition" subsample (n = 16,005). Survival analyses examined MCI or dementia progression.ResultsFive clusters were identified: "Optimal" cognitively normal (oCN; 13.2%), "Typical" CN (tCN; 28.0%), Amnestic MCI (aMCI; 25.3%), Mixed MCI-Mild (mMCI-Mild; 20.4%), and Mixed MCI-Severe (mMCI-Severe; 13.0%). Progression to dementia differed across clusters (oCN

Sex disparities in serum bile acid (BA) levels and Alzheimer's disease (AD) prevalence have been established. However, the precise link between changes in serum BAs and AD development remains elusive. Here, authors quantitatively determined 33 serum BAs and 58 BA features in 4 219 samples collected from 1 180 participants from the Alzheimer's Disease Neuroimaging Initiative. The findings revealed that these BA features exhibited significant correlations with clinical stages, encompassing cognitively normal (CN), early and late mild cognitive impairment, and AD, as well as cognitive performance. Importantly, these associations are more pronounced in men than women. Among participants with progressive disease stages (n = 660), BAs underwent early changes in men, occurring before AD. By incorporating BA features into diagnostic and predictive models, positive enhancements are achieved for all models. The area under the receiver operating characteristic curve improved from 0.78 to 0.91 for men and from 0.76 to 0.83 for women for the differentiation of CN and AD. Additionally, the key findings are validated in a subset of participants (n = 578) with cerebrospinal fluid amyloid-beta and tau levels. These findings underscore the role of BAs in AD progression, offering potential improvements in the accuracy of AD prediction.

IntroductionReproductive health history may contribute to cognitive aging and risk for Alzheimer's disease, but this is understudied among Hispanic/Latina women.MethodsParticipants included 2126 Hispanic/Latina postmenopausal women (44 to 75 years) from the Study of Latinos-Investigation of Neurocognitive Aging. Survey linear regressions separately modeled the associations between reproductive health measures (age at menarche, history of oral contraceptive use, number of pregnancies, number of live births, age at menopause, female hormone use at Visit 1, and reproductive span) with cognitive outcomes at Visit 2 (performance, 7-year change, and mild cognitive impairment [MCI] prevalence).ResultsYounger age at menarche, oral contraceptive use, lower pregnancies, lower live births, and older age at menopause were associated with better cognitive performance. Older age at menarche was protective against cognitive change. Hormone use was linked to lower MCI prevalence.DiscussionSeveral aspects of reproductive health appear to impact cognitive aging among Hispanic/Latina women.

Leisure walking has been found to be positively associated with increased mental health. However, the benefits of leisure walking of varying intensities on the mental health of older adults (>50 years old) with mild cognitive impairment are not clear. This study employed 2020 Health and Retirement Study data to investigate the benefits of leisure walking for three groups based on levels of participation (low, mid, and high). We conducted a multivariate analysis of covariance (n = 834) to examine the group mean differences (MDs). The respondents in the high and mid groups presented higher life satisfaction and happiness than those in the low group. The high group had lower loneliness and stress scores than those in the low and mid groups. These findings indicate that older adults with mild cognitive impairment gained more mental health benefits and life satisfaction through moderate and vigorous leisure walking than through light leisure walking. [ABSTRACT FROM AUTHOR]

Mild cognitive impairment is an intermediate state between the cognitive decline often experienced in normal aging and dementia that affects 15% of Americans over 65 years of age. Our communities have an opportunity to support the development and adoption of evidence-based programs to help older adults preserve cognition and physical function. In partnership with a local urban YMCA in an underserved, predominantly minority neighborhood, we tested the appeal and therapeutic benefits of SMARTfit training among older adults with mild cognitive impairment. The participants reported a positive training experience. After 12 weeks of dual-task training, Trail-Making Test and Stroop Color–Word Interference Test scores improved, as did scores on the Short Physical Performance Battery. Results of our SMARTfit dual-task training intervention are encouraging. Larger randomized controlled trials must further investigate the development, implementation, and therapeutic impacts of SMARTfit dual-task training on cognitive and physical function in aging. [ABSTRACT FROM AUTHOR]

Inflammation is an important factor in Alzheimer's disease (AD). An NMR measurement in plasma, glycoprotein acetyls (GlycA), captures the overall level of protein production and glycosylation implicated in systemic inflammation. With its additional advantage of reducing biological variability, GlycA might be useful in monitoring the relationship between peripheral inflammation and brain changes relevant to AD. However, the associations between GlycA and these brain changes have not been fully evaluated. Here, we performed Spearman's correlation analyses to evaluate these associations cross-sectionally and determined whether GlycA can inform AD-relevant longitudinal measurements among participants in the Alzheimer's Disease Neuroimaging Initiative (n = 1506), with additional linear models and stratification analyses to evaluate the influences of sex or diagnosis status and confirm findings from Spearman's correlation analyses. We found that GlycA was elevated in AD patients compared to cognitively normal participants. GlycA correlated negatively with multiple concurrent regional brain volumes in females diagnosed with late mild cognitive impairment (LMCI) or AD. Baseline GlycA level was associated with executive function decline at 3-9 year follow-up in participants diagnosed with LMCI at baseline, with similar but not identical trends observed in the future decline of memory and entorhinal cortex volume. Results here indicated that GlycA is an inflammatory biomarker relevant to AD pathogenesis and that the stage of LMCI might be relevant to inflammation-related intervention.

The aging population of the world is increasing at an unprecedented rate which is expected to lead to a corresponding unparalleled increase in age related diseases. Of particular concern are the large number of older adults expected to develop Alzheimers disease (AD), which will require extraordinary local, national and worldwide healthcare resources. In this context, innovative interventions are needed urgently to delay AD onset and thereby give our healthcare systems time to prepare and provide meaningful care to our aging populations. This focused review discusses the crucial role of frontal gamma oscillations as a therapeutic target to delay or ameliorate cognitive decline in AD. Frontal gamma oscillations, including from prefrontal cortical areas, serve as a biomarker for working memory and other cognitive functions, and their impairment is observed before clinical symptoms manifest. This review evaluates evidence from animal models and human subjects to highlight the correlation between gamma wave abnormalities and cognitive deterioration. Furthermore, the review summarizes 11 clinical studies using neuromodulation techniques designed to stimulate gamma oscillations in mild cognitive impairment (MCI) and AD patients, including transcranial electrical stimulation, transcranial magnetic stimulation, and rhythmic sensory stimulation. These interventions have shown promise in mitigating early-stage cognitive decline, as evidenced by improved performance on memory tests, increased gamma oscillatory responses, and some have even shown reduced brain atrophy. These early studies suggest that treatments that strengthen frontal gamma oscillatory responses through neuromodulation are a promising approach to delay cognitive decline, that may serve as an adjunct to other therapies or as a standalone treatment in some populations.

BackgroundHypertension can have deleterious effects on cognitive function; however, few studies have examined its effects on cognition among Hispanics/Latinos.ObjectiveTo assess associations between hypertension status with 1) change in cognitive performance, and 2) having mild cognitive impairment (MCI) among diverse Hispanics/Latinos.MethodsThis population-based, prospective cohort, multisite study included Hispanic/Latino adults aged 45 to 72 years in enrolled in the Hispanic Community Health Study/Study of Latinos at Visit 1 (2008-2011; mean age of 63.40±8.24 years), and the Study of Latinos-Investigation of Neurocognitive Aging at Visit 2 (2016-2018), with a mean follow-up duration of 7 years (n = 6,173). Hypertension status was assessed at both visits: normotension (no hypertension), incident hypertension (only at Visit 2), and persistent hypertension (at both visits). We examined change in cognitive performance and having MCI (only assessed at Visit 2) relative to hypertension status and adjusted for demographics and cardiovascular disease risk factors.ResultsCompared to normotension, persistent hypertension was associated with significantly increased decline in verbal fluency (β= -0.08; CI = [-0.16;-0.01]; p

BACKGROUND: Unsupervised online cognitive assessments have demonstrated promise as an efficient and scalable approach for evaluating cognition in aging, and Alzheimers disease and related dementias. OBJECTIVES: The aim of this study was to evaluate the feasibility, usability, and construct validity of the Paired Associates Learning task from the Cambridge Neuropsychological Test Automated Battery® in adults enrolled in the Brain Health Registry. DESIGN, SETTING, PARTICIPANTS, MEASUREMENTS: The Paired Associates Learning task was administered to Brain Health Registry participants in a remote, unsupervised, online setting. In this cross-sectional analysis, we 1) evaluated construct validity by analyzing associations between Paired Associates Learning performance and additional participant registry data, including demographics, self- and study partner-reported subjective cognitive change (Everyday Cognition scale), self-reported memory concern, and depressive symptom severity (Patient Health Questionnaire-9) using multivariable linear regression models; 2) determined the predictive value of Paired Associates Learning and other registry variables for identifying participants who self-report Mild Cognitive Impairment by employing multivariable binomial logistic regressions and calculating the area under the receiver operator curve; 3) investigated feasibility by looking at task completion rates and statistically comparing characteristics of task completers and non-completers; and 4) evaluated usability in terms of participant requests for support from BHR related to the assessment. RESULTS: In terms of construct validity, in participants who took the Paired Associates Learning for the first time (N=14,528), worse performance was associated with being older, being male, lower educational attainment, higher levels of self- and study partner-reported decline, more self-reported memory concerns, greater depressive symptom severity, and self-report of Mild Cognitive Impairment. Paired Associates Learning performance and Brain Health Registry variables together identified those with self-reported Mild Cognitive Impairment with moderate accuracy (areas under the curve: 0.66-0.68). In terms of feasibility, in a sub-sample of 29,176 participants who had the opportunity to complete Paired Associates Learning for the first time in the registry, 14,417 started the task. 11,647 (80.9% of those who started) completed the task. Compared to those who did not complete the task at their first opportunity, those who completed were older, had more years of education, more likely to self-identify as White, less likely to self-identify as Latino, less likely to have a subjective memory concern, and more likely to report a family history of Alzheimers disease. In terms of usability, out of 8,395 received requests for support from BHR staff via email, 4.4% (n=374) were related to PAL. Of those, 82% were related to technical difficulties. CONCLUSIONS: Our findings support moderate feasibility, good usability, and construct validity of cross-sectional Paired Associates Learning in an unsupervised online registry, but also highlight the need to make the assessment more inclusive and accessible to individuals from ethnoculturally and socioeconomically diverse communities. A future, improved version could be a scalable, efficient method to assess cognition in many different settings, including clinical trials, observational studies, healthcare, and public health.

BACKGROUND: Anatomic total shoulder arthroplasty (ATSA) and reverse total shoulder arthroplasty (RTSA) reliably alleviate pain and restore shoulder function for a variety of indications. However, these procedures are not well-studied in patients with neurocognitive impairment. Therefore, the purpose of this study was to investigate whether patients with dementia or mild cognitive impairment (MCI) have increased odds of surgical or medical complications following arthroplasty. METHODS: The PearlDiver database was queried from 2010 through October 2021 to identify a cohort of patients who underwent either ATSA or RTSA and had a minimum 2-year follow-up. Current Procedural Terminology and International Classification of Diseases codes were used to stratify this cohort into three groups: (1) patients with dementia, (2) patients with MCI, and (3) patients with neither condition. Surgical and medical complication rates were compared among these three groups. RESULTS: The overall prevalence of neurocognitive impairment among patients undergoing total shoulder arthroplasty was 3.0% in a cohort of 92,022 patients. Patients with dementia had increased odds of sustaining a periprosthetic humerus fracture (odds ratio [OR] = 1.46, P

INTRODUCTION: Virtually all people with Down syndrome (DS) develop neuropathology associated with Alzheimers disease (AD). Atrophy of the hippocampus and entorhinal cortex (EC), as well as elevated plasma concentrations of neurofilament light chain (NfL) protein, are markers of neurodegeneration associated with late-onset AD. We hypothesized that hippocampus and EC gray matter loss and increased plasma NfL concentrations are associated with memory in adults with DS. METHODS: T1-weighted structural magnetic resonance imaging (MRI) data were collected from 101 participants with DS. Hippocampus and EC volume, as well as EC subregional cortical thickness, were derived. In a subset of participants, plasma NfL concentrations and modified Cued Recall Test scores were obtained. Partial correlation and mediation were used to test relationships between medial temporal lobe (MTL) atrophy, plasma NfL, and episodic memory. RESULTS: Hippocampus volume, left anterolateral EC (alEC) thickness, and plasma NfL were correlated with each other and were associated with memory. Plasma NfL mediated the relationship between left alEC thickness and memory as well as hippocampus volume and memory. DISCUSSION: The relationship between MTL gray matter and memory is mediated by plasma NfL levels, suggesting a link between neurodegenerative processes underlying axonal injury and frank gray matter loss in key structures supporting episodic memory in people with DS.

Mild cognitive impairment (MCI) is a prodromal stage of Alzheimer's disease (AD) that causes a significant burden in caregiving and medical costs. Clinically, the diagnosis of MCI is determined by the impairment statuses of five cognitive domains. If one of these cognitive domains is impaired, the patient is diagnosed with MCI, and if two out of the five domains are impaired, the patient is diagnosed with AD. In medical records, most of the time, the diagnosis of MCI/AD is given, but not the statuses of the five domains. We may treat the domain statuses as missing variables. This diagnostic procedure relates MCI/AD status modeling to multiple‐instance learning, where each domain resembles an instance. However, traditional multiple‐instance learning assumes common predictors among instances, but in our case, each domain is associated with different predictors. In this article, we generalized the multiple‐instance logistic regression to accommodate the heterogeneity in predictors among different instances. The proposed model is dubbed heterogeneous‐instance logistic regression and is estimated via the expectation‐maximization algorithm because of the presence of the missing variables. We also derived two variants of the proposed model for the MCI and AD diagnoses. The proposed model is validated in terms of its estimation accuracy, latent status prediction, and robustness via extensive simulation studies. Finally, we analyzed the National Alzheimer's Coordinating Center‐Uniform Data Set using the proposed model and demonstrated its potential. [ABSTRACT FROM AUTHOR]

ABSTRACT Family caregivers of persons with mild cognitive impairment attempt to understand the behavioural and functional changes exhibited by their relative. However, how caregivers respond to initial changes and changes over time has not been explored. The purpose of this qualitative study was to explore the experience of family caregivers responding to changes in their relative's memory, behaviours, and physical functions over 2 years. Eleven family caregivers of a relative with mild cognitive impairment were purposively recruited from neurological clinics in Taiwan. Face‐to‐face semi‐structured interviews were conducted within 6‐months of referral; three follow‐ups were conducted at 6‐month intervals. Content analysis of 41 transcribed audio‐recorded interviews revealed the longitudinal changes in their relative with cognitive impairment was made caregiving challenging. Three themes described the challenges: (1) Changes related to their relative's cognitive impairment, which included increases in mood fluctuations, erratic behaviours, and reductions in physical abilities; (2) changes in their relative's comorbidities, which included adapting to new symptoms and treatments for a chronic disease, monitoring medication adherence and drug interactions; and (3) changes in caregiver burden, which increased levels of stress, uncertainty, and anxiety resulting in greater role strain. Caregiving became more challenging with time, especially caregivers whose relative developed dementia during the study period. These findings offer insight into the trajectory of the experience of family caregivers attempting to understand changes in cognition, behaviours, and physical functions for their relative with mild cognitive impairment over 2 years, which could help mental healthcare providers develop support services to reduce caregiver role strain. [ABSTRACT FROM AUTHOR]

Introduction: Subjective cognitive decline (SCD) and mild cognitive impairment (MCI) are stages 2 and 3, respectively, of the Alzheimer's continuum. The Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog's) tenwords recall test is a validated method for the early detection of cognitive impairment in Alzheimer's disease. However, limited studies have investigated its ability to differentiate between SCD and MCI. Methods: 203 participants with SCD and 62 participants with MCI underwent multiple neuropsychological assessments. The Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment-Basic (MOCA-B) served as brief global cognition tests. A binary logistic regression model was used to analyze the potential factors affecting MCI. The accuracy of the ten-words recall test was assessed using the area under the receiver operating characteristic (ROC) and the area under the curve (AUC). Results: The neuropsychological assessment revealed significant differences in the ten-words recall test scores between the SCD (median age 61 years; 70.44% female) and MCI (median age 64 years; 61.29% female) groups (p < 0.001), with the MCI group scoring the highest. Using a cut-off value of 3.15 for the ten-words recall test, sensitivity for distinguishing MCI from SCD reached 87%, while specificity stood at 61% (AUC 0.777, p < 0.001). DeLong's test indicated no statistically significant difference in the ten-words recall test's ability to distinguish between SCD and MCI compared to the total score of ADAS-Cog (AUC 0.833, p) and MMSE (AUC 0.784, p > 0.05). However, a significant difference was observed when compared to MoCA-B (AUC 0.973, p < 0.001). In the population with an education level of = 9 years, the optimal cut-off value for the ten-words recall test was 3.15, yielding a sensitivity of 91% and a specificity of 45% (AUC = 0.674, p = 0.030). In the population with an education level > 9 years, the optimal cut-off value was 3.63, resulting in a sensitivity of 79% and a specificity of 71% (AUC = 0.785, p < 0.001). Discussion: The ten-words recall test from the ADAS-cog may detect MCI early owing to its simplicity and quick administration. It is an effective and convenient tool for rapidly identifying mild cognitive impairment. [ABSTRACT FROM AUTHOR]

Emerged evidence indicated that stimulating hippocampal neurogenesis is a potential strategy for restoring cognition in AD. Mitogen‐activated protein kinases (MAPKs) play an essential role in neurogenesis. Meanwhile, the enzymatic power of the phosphatases is much greater than that of kinases. Dual‐specificity phosphatase 16 (DUSP16), known to as a phosphatase negatively regulate MAPKs, may be implicated in neural differentiation. Nevertheless, the effect of DUSP16 on cognitive disorders by stimulating neural progenitor cell (NPC) differentiation in AD mice remains unclear. Our study demonstrates an association between DUSP16 SNPs and clinical progression in individuals with mild cognitive impairment (MCI). Besides, increased DUSP16 expression was detected in both 3xTg and SAMP8 mouse models of AD, accompanied by NPC neural differentiation impairments. By silencing DUSP16, the induction of neural differentiation, synaptic transmission, and cognitive benefits were observed in both AD mice. Furthermore, DUSP16 was involved in the process of NPC differentiation through regulating c‐Jun N‐terminal kinase (JNK) phosphorylation and SOX2 expression. Moreover, ETS transcription factor (ELK1) was involved in the DUSP16 transcription, which resulted in the upregulation of DUSP16 at the state of AD. Our data uncovers a potential regulatory role for DUSP16 in adult hippocampal neurogenesis (AHN) and provides a possibility to find a novel strategy for AD intervention. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a global healthcare challenge lacking a simple and affordable detection method. We propose a novel deep learning framework, Eye-AD, to detect Early-onset Alzheimer's Disease (EOAD) and Mild Cognitive Impairment (MCI) using OCTA images of retinal microvasculature and choriocapillaris. Eye-AD employs a multilevel graph representation to analyze intra- and inter-instance relationships in retinal layers. Using 5751 OCTA images from 1671 participants in a multi-center study, our model demonstrated superior performance in EOAD (internal data: AUC = 0.9355, external data: AUC = 0.9007) and MCI detection (internal data: AUC = 0.8630, external data: AUC = 0.8037). Furthermore, we explored the associations between retinal structural biomarkers in OCTA images and EOAD/MCI, and the results align well with the conclusions drawn from our deep learning interpretability analysis. Our findings provide further evidence that retinal OCTA imaging, coupled with artificial intelligence, will serve as a rapid, noninvasive, and affordable dementia detection. [ABSTRACT FROM AUTHOR]

Background: With the recent surge in the utilization of electronic health records for cognitive decline, the research community has turned its attention to conducting fine-grained analyses of dementia onset using advanced techniques. Previous works have mostly focused on machine learning-based prediction of dementia, lacking the analysis of dementia progression and its associations with risk factors over time. The black box nature of machine learning models has also raised concerns regarding their uncertainty and safety in decision making, particularly in sensitive domains like healthcare. Objective: We aimed to characterize the progression of health conditions, such as chronic diseases and neuropsychiatric symptoms, of the participants in Mayo Clinic Study of Aging (MCSA) from initial mild cognitive impairment (MCI) diagnosis to dementia onset through network analysis. Methods: We used the data from the MCSA, a prospective population-based cohort study of cognitive aging, and examined the changing association among variables (i.e., participants' health conditions) from the first visit of MCI diagnosis to the visit of dementia onset using network analysis. The number of participants for this study are 97 with the number of visits ranging from 2 visits (30 months) to 7 visits (105 months). We identified the network communities among variables from three-fold collection of instances: (i) the first MCI diagnosis, (ii) progression to dementia, and (iii) dementia diagnosis. We determine the variables that play a significant role in the dementia onset, aiming to identify and prioritize specific variables that prominently contribute towards developing dementia. In addition, we explore the sex-specific impact of variables in relation to dementia, aiming to investigate potential differences in the influence of certain variables on dementia onset between males and females. Results: We found correlation among certain variables, such as neuropsychiatric symptoms and chronic conditions, throughout the progression from MCI to dementia. Our findings, based on patterns and changing variables within specific communities, reveal notable insights about the time-lapse before dementia sets in, and the significance of progression of correlated variables contributing towards dementia onset. We also observed more changes due to certain variables, such as cognitive and functional scores, in the network communities for the people who progressed to dementia compared to those who does not. Most changes for sex-specific analysis are observed in clinical dementia rating and functional activities questionnaire during MCI onset are followed by chronic diseases, and then by NPI-Q scores. Conclusions: Network analysis has shown promising potential to capture significant longitudinal changes in health conditions, spanning from the MCI diagnosis to dementia progression. It can serve as a valuable analytic approach for monitoring the health status of individuals in cognitive impairment assessment. Furthermore, our findings indicate a notable sex difference in the impact of specific health conditions on the progression of dementia. [ABSTRACT FROM AUTHOR]

The Bio-Hermes Study was a cross-sectional observational study designed to develop a database of blood-based and digital biomarkers to improve detection of Alzheimer's disease (AD) and mild cognitive impairment (MCI). We examined the ability of Cognivue Clarity to (a) detect MCI and AD in clinical diagnostics groups, (b) determine the presence of amyloid, and (c) distinguish between biomarker-confirmed groups. Bio-Hermes enrolled 887 participants who completed both Cognivue Clarity and amyloid PET scans (388 Cognitively Normal, 282 MCI, 217 Probable AD). Cognivue Clarity differentiated between Cognitively Normal, MCI, and probable AD in clinical cohorts, amyloid positive from amyloid negative individuals, and True Controls from MCI due to AD and AD in biomarker-confirmed cohorts (all p < 0.001) with large effect sizes. Cognivue Clarity correlated with amyloid PET and plasma amyloid and pTau (all p < 0.001). In biomarker confirmed groups, Cognivue Clarity had a positive likelihood ratio of 2.17, a negative likelihood ratio of 0.29, and a diagnostic odds ratio of 7.48. Cognivue Clarity detected cognitive impairment and differentiated between both clinically and biomarker defined MCI and AD groups. The use of Cognivue Clarity could assist with identification of MCI-AD or AD for inclusion into current treatment protocols or for enriching recruitment into clinical trials. Trial registration ClinicalTrials.gov (NCT04733989). [ABSTRACT FROM AUTHOR]

Background: Tau-PET is a diagnostic tool with high sensitivity and specificity for discriminating Alzheimer's disease (AD) dementia from other neurodegenerative disorders in well-controlled research environments. The role of tau-PET in real-world clinical practice, however, remains to be established. The aim of the TAP-TAU study is therefore to investigate the impact of tau-PET in clinical practice. Methods: TAP-TAU is a prospective, longitudinal multi-center study in 300 patients (≥ 50 years old) with mild cognitive impairment or mild dementia across five Dutch memory clinics. Patients are eligible if diagnostic certainty is < 85% after routine dementia screening and if the differential diagnosis includes AD. More specifically, we will include patients who (i) are suspected of having mixed pathology (e.g., AD and vascular pathology), (ii) have an atypical clinical presentation, and/or (iii) show conflicting or inconclusive outcomes on other tests (e.g., magnetic resonance imaging or cerebrospinal fluid). Participants will undergo a [18F]flortaucipir tau-PET scan, blood-based biomarker sampling, and fill out questionnaires on patient reported outcomes and experiences. The primary outcomes are change (pre- versus post- tau-PET) in diagnosis, diagnostic certainty, patient management and patient anxiety and uncertainty. Secondary outcome measures are head-to-head comparisons between tau-PET and less invasive and lower cost diagnostic tools such as novel blood-based biomarkers and artificial intelligence-based classifiers. Results: TAP-TAU has been approved by the Medical Ethics Committee of the Amsterdam UMC. The first participant is expected to be included in October 2024. Conclusions: In TAP-TAU, we will investigate the added clinical value of tau-PET in a real-world clinical setting, including memory clinic patients with diagnostic uncertainty after routine work-up. Findings of our study may contribute to recommendations regarding which patients would benefit most from assessment with tau-PET. This study is timely in the dawning era of disease modifying treatments as an accurate etiological diagnosis becomes increasingly important. Trial registration: This trial is registered and authorized on December 21st, 2023 in EU Clinical Trials with registration number 2023-505430-10-00. [ABSTRACT FROM AUTHOR]

Objective: Mild Cognitive Impairment (MCI) is a recognized precursor to Alzheimer's Disease (AD), presenting a significant risk of progression. Early detection and intervention in MCI can potentially slow disease advancement, offering substantial clinical benefits. This study employed radiomics and machine learning methodologies to distinguish between MCI and Normal Cognition (NC) groups. Methods: The study included 172 MCI patients and 183 healthy controls from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, all of whom had 3D-T1 weighted MRI structural images. The cerebellar gray and white matter were segmented automatically using volBrain software, and radiomic features were extracted and screened through Pyradiomics. The screened features were then input into various machine learning models, including Random Forest (RF), Logistic Regression (LR), eXtreme Gradient Boosting (XGBoost), Support Vector Machines (SVM), K Nearest Neighbors (KNN), Extra Trees, Light Gradient Boosting Machine (LightGBM), and Multilayer Perceptron (MLP). Each model was optimized for penalty parameters through 5-fold cross-validation to construct radiomic models. The DeLong test was used to evaluate the performance of different models. Results: The LightGBM model, which utilizes a combination of cerebellar gray and white matter features (comprising eight gray matter and eight white matter features), emerges as the most effective model for radiomics feature analysis. The model demonstrates an Area Under the Curve (AUC) of 0.863 for the training set and 0.776 for the test set. Conclusion: Radiomic features based on the cerebellar gray and white matter, combined with machine learning, can objectively diagnose MCI, which provides significant clinical value for assisted diagnosis. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) affects the hippocampus during its progression, but the specific observable changes of hippocampal subfields during disease progression remain poorly understood. In this study, we employed an event‐based model (EBM) to determine the sequence of occurrence of hippocampal subfield atrophy in mild cognitive impairment (MCI) and AD cohorts. Subjects (207) were included: 86 MCI, 53 AD, and 68 healthy controls from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Participants underwent structural magnetic resonance imaging (MRI) scans to analyse the hippocampal subfields. We assigned each patient to a specific EBM stage, based on the number of their abnormal subfields. A combination of 2‐year follow‐up MRI scans were applied to demonstrate the longitudinal consistency and utility of the model's staging system. The model estimated that the earliest atrophy occurs in the hippocampal fissure, then spreading to other subregions in both MCI and AD. We identified a marked divergence between the sequences of left and right hippocampal subfields atrophy, so inter‐hemispheric asymmetry pattern was further analysed. The sequence of asymmetry index (AI) increases beginning in the molecular and granule cell layers of the dentate gyrus (GC‐ML‐DG), cornus ammonis (CA) 4, and the molecular layer (ML). Longitudinal analysis confirms the efficacy of the model. In addition, the model stages were significantly correlated with patients' memory scores (p <.05). Collectively, we used a data‐driven method to provide new insight into AD hippocampal progression. The present model could aid in understanding of the disease stages, as well as tracking memory decline. [ABSTRACT FROM AUTHOR]

Mild cognitive impairment is associated with many neurodegenerative diseases. It is essential to detect mild cognitive impairment on time to reduce the prevalence of such disorders. Nevertheless, present clinically employed test scales and biomarkers are time-consuming, user-unfriendly, and expensive. Hence, we developed a neuropsychological test system based on virtual reality in this study, the Virtual Reality Neuropsychological Mild Cognitive Impairment Test (VRNPT). The diagnosis and classification of MCI were achieved by effectively combining digital cognitive parameters and EEG signal features obtained during the VRNPT cognitive task. The VRNPT contains three head-mounted display-based cognitive tasks that assess participants' attention, memory, spatial perception, working memory, and visuospatial executive ability across multiple cognitive domains of functioning. We investigated how to design and optimize these tasks. We conducted a field study by recruiting 80 participants (40 MCI patients and 40 normal older adults). The results showed that the classification accuracy of combining digitized cognitive parameters and EEG signals during VRNPT was 91.3%, higher than using only digitized parameters from VRNPT and applying EEG signals alone, demonstrating the validity and feasibility of this method for diagnosing MCI. The user satisfaction survey showed that the subjects were satisfied with VRNPT. [ABSTRACT FROM AUTHOR]

Introduction: Insomnia is associated with mild cognitive impairment, although the mechanisms of this impairment are not well-understood. Timing of slow-wave and rapid eye movement sleep may help explain cognitive impairments common in insomnia. This investigation aimed to determine whether cognitive changes following continuous theta-burst stimulation (cTBS) are attributable to active stimulation, polysomnographic parameters of sleep, or both. Method: Data presented here are part of a pilot clinical trial aiming to treat insomnia by targeting a node in the defaultmode network using an inhibitory 40-s (cTBS). A double-blind counterbalanced sham-controlled crossover design was conducted. Participants (N = 20) served as their own controls on two separate in-laboratory visits--one with active cTBS and the other with sham cTBS. Each visit included cognitive assessments before and after stimulation and following a night of sleep in the lab monitored with polysomnography. Results: Slowwave sleep duration influenced workingmemory in the active cTBS condition, with shorter duration predicting improvements in working memory post sleep (B = -0.003, p = 0.095). Onset latency to rapid eye movement sleep predicted subsequent working memory, regardless of treatment condition (B = -0.001, p = 0.040). Results suggest that changes in attention and processing speed were primarily due to slow wave sleep onset (B = -0.001, p = 0.017) and marginally predicted by slowwave sleep duration (B=0.002, p=0.081) and sleep efficiency (B = 0.006, p = 0.090). Conclusions: Findings emphasize the important role that timing of slow-wave and rapid eye movement sleep have on information processing. Future work using larger sample sizes and more stimulation sessions is needed to determine optimal interactions between timing and duration of slow wave and rapid eye movement throughout the sleep period. Clinical trial registration: This study is registered on ClinicalTrials.gov (NCT04953559). https://clinicaltrials.gov/study/NCT04953559?locStr=Arizona& country=United%20States&state=Arizona&cond=insomnia&intr=tms%20& rank=1. [ABSTRACT FROM AUTHOR]

Background: With the increasing global aging population, the health and welfare of elderly individuals, especially individuals with prevalent mild cognitive impairment (MCI) living in nursing homes, have become critical concerns. These concerns highlight the urgency of developing effective interventions to address the cognitive and psychological needs of elderly individuals, ensuring their well-being and alleviating the burden on their caregivers. Objective: This study investigates the impact of wooden toy training on mitigating cognitive decline in elderly individuals with cognitive impairment. It evaluates how this training influences cognitive functions and psychological well-being, exploring whether it can slow or reverse the progression of cognitive decline. This outcome will be assessed in a randomized controlled trial, in which changes in cognitive ability and psychological health indicators among the participants will be measured. Design: A two-arm, open-label, cluster-randomized controlled trial. Setting(s): The study was conducted in two nursing homes, which served as both the recruitment sites for participants and the intervention locations. These nursing homes were selected for their ability to facilitate the intervention and for their representative demographic characteristics of the elderly population. The settings provided a controlled environment that was conducive to implementing the wooden toy training program and observing its effects on the participants. Participants: A total of 76 elderly participants with mild cognitive impairment but functional independence were recruited. Methods: Participants were randomized into an intervention group and a control group. The intervention group engaged in an 8-week wooden toy training program, whereas those in the control cohort received customary nursing care. Standardized cognitive and psychological well-being measures were used to assess improvements in cognitive performance and mental health. Results: Significant improvements were observed in the cognitive functions of the intervention group from a baseline score of M = 13.11 to M = 16.29 postintervention (95% CI [-4.44, -1.93]), along with reductions in depressive symptoms from a baseline score of M = 8.63 to M = 7.18 (95% CI [0.38, 2.51]). Additionally, engagement in activities with wooden toys significantly satisfied their need for competence, increasing from a baseline of M = 16.29 to M = 20 postintervention (95% CI [-5.92, -1.51]), and relatedness, which improved from a baseline of M = 20.32 to M = 22.95 (95% CI [-4.73, -0.53]). Conclusions: This study underscores the potential of a wooden toy intervention in nursing homes that combines cognitive challenges with traditional cultural elements to improve cognitive functions in elderly individuals with mild cognitive impairment. Our findings suggest a novel method of promoting the cognitive and psychological health of nursing home residents through emotional comfort and social interaction. [ABSTRACT FROM AUTHOR]

Objectives: This study examined the impact of the Center of Healthy Aging Program (CHAP) on the cognitive function and economic burden associated with dementia. Methods: This observational study utilised Iwaki cohort data. We included participants with mini-mental state examination (MMSE) scores and categorised them into pre- and post-CHAP groups based on their year of entry into the cohort (before 2013 or after) (index year). We defined participants with suspected severe cognitive impairment and suspected mild cognitive impairment using their MMSE scores, with their incidence being the first observation meeting these definitions during the follow-up period. We compared the incidence rates between the pre- and post-CHAP groups using Cox proportional hazard analysis. Medical and caregiving costs were estimated based on the projected number of residents in Iwaki area with suspected mild cognitive impairment and sSCI during hypothetical 10 years of the CHAP implemented or not and compared. Results: Of the 2,569 participants, 1716 and 853 were included in the pre- and post-CHAP groups, respectively. The incidence rate of suspected mild cognitive impairment was significantly lower in the post-CHAP group even after adjusted known factors associated with cognitive disorders. No cases of suspected severe cognitive impairment occurred in the post-CHAP group during the follow-up period. Estimated costs of JPY 1,628,450 (USD 11562.00 or EUR 10259.24, JPY 100 = USD 0.71 or EUR 0.63) and JPY 789,560 (USD 5605.88 or EUR 4974.23) per person per year were projected after 10 years with and without the CHAP, respectively. Conclusions: We demonstrated a reduction in the incidence rate of suspected mild cognitive impairment among residents who participated in the CHAP and a decrease in the medical and caregiving costs associated with suspected severe cognitive impairment. [ABSTRACT FROM AUTHOR]

Hippocampal dysfunction is associated with early clinical signs of Alzheimer's disease (AD). Due to the limited availability or invasiveness of current biomarkers, the AD diagnosis is usually based on cognitive assessment and structural brain imaging. The recent study by Lalive and colleagues examined the specificity of brain morphometry for the AD diagnosis in a memory clinic cohort with hippocampal-type amnestic syndrome. The results indicate that memory deficits and hippocampal atrophy are similar in AD and non-AD patients, highlighting their low diagnostic specificity. These findings challenge the traditional AD diagnosis and underscore the need for biomarkers to differentiate specific neuropathological entities. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is the most common neurodegenerative disorder which primarily involves memory and cognitive functions. It is increasingly recognized that motor involvement is also a common and significant aspect of AD, contributing to functional decline and profoundly impacting quality of life. Motor impairment, either at early or later stages of cognitive disorders, can be considered as a proxy measure of cognitive impairment, and technological devices can provide objective measures for both diagnosis and prognosis purposes. However, compared to other neurodegenerative disorders, the use of technological tools in neurocognitive disorders, including AD, is still in its infancy. Objective: This report aims to evaluate the role of technological devices in assessing motor involvement across the AD spectrum and in other dementing conditions, providing an overview of the existing devices that show promise in this area and exploring their clinical applications. Methods: The evaluation involves a review of the existing literature in the PubMed, Web of Science, Scopus, and Cochrane databases on the effectiveness of these technologies. 21 studies were identified and categorized as: wearable inertial sensors/IMU, console/kinect, gait analysis, tapping device, tablet/mobile, and computer. Results: We found several parameters, such as speed and stride length, that appear promising for detecting abnormal motor function in MCI or dementia. In addition, some studies have found correlations between these motor aspects and cognitive state. Conclusions: Clinical application of technological tools to assess motor function in people with cognitive impairments of a neurodegenerative nature, such as AD, may improve early detection and stratification of patients. [ABSTRACT FROM AUTHOR]

Background: Visuo-perceptual and visuo-attentional disorders, such as global processing deficit and simultanagnosia, are not routinely investigated in prodromal forms of typical Alzheimer's disease, as amnestic mild cognitive impairment (MCI). Objective: This study evaluated global processing abilities through Navon's classical paradigm in individuals with amnestic MCI and investigated the related visuo-perceptual and attentional components involved in simultanagnosia. Methods: Sixteen consecutive patients with amnestic MCI (6 single-domain, 10 multiple-domain) and 16 matched controls were requested to identify global and local elements of hierarchical Navon letters, and to name large and small solid letters. Results: While correctly identifying solid letters, patients with multiple-domain amnestic MCI were less accurate in processing the global level of hierarchical stimuli compared to controls. Single-case analyses suggested that global processing may also be impaired in single-domain amnestic MCI. In addition, patients with pathological performance in the Navon task showed perceptual and/or visual focal attention deficits. Conclusions: Early dysfunction of holistic processing can be detected in amnestic MCI. Visuo-perceptual and/or visual focal attention mechanisms, which have been shown to be damaged in Posterior Cortical Atrophy patients with simultanagnosia, may be impaired in individuals with amnestic MCI. Investigation and identification of global processing deficits in MCI could contribute to early diagnosis and longitudinal monitoring of the disease. [ABSTRACT FROM AUTHOR]

Background: Early detection of amyloid-β (Aβ) positivity is essential for an accurate diagnosis and treatment of Alzheimer's disease (AD), but it is currently costly and/or invasive. Objective: We aimed to classify Aβ positivity (Aβ+) using morphometric features from magnetic resonance imaging (MRI), a more accessible and non-invasive technique, in two clinical population scenarios: one containing AD, mild cognitive impairment (MCI) and cognitively normal (CN) subjects, and another only cognitively impaired subjects (AD and MCI). Methods: Demographic, cognitive (Mini-Mental State Examination [MMSE] scores), regional morphometry MRI (volumes, areas, and thicknesses), and derived morphometric graph theory (GT) features from all subjects (302 Aβ+, age: 73.3±7.2, 150 male; 246 Aβ–, age: 71.1±7.1, 131 male) were combined in different feature sets. We implemented a machine learning workflow to find the best Aβ+ classification model. Results: In an AD+MCI+CN population scenario, the best-performing model selected 120 features (107 GT features, 12 regional morphometric features and the MMSE total score) and achieved a negative predictive value (NPVadj) of 68.4%, and a balanced accuracy (BAC) of 66.9%. In a AD+MCI scenario, the best model obtained NPVadj of 71.6%, and BAC of 70.7%, using 180 regional morphometric features (98 volumes, 52 areas and 29 thicknesses from temporal, parietal, and frontal brain regions). Conclusions: Although with currently limited clinical applicability, regional MRI morphometric features have clinical usefulness potential for detecting Aβ status, which may be augmented by a combination with cognitive data when cognitively normal subjects make up a substantial part of the population presenting for diagnosis. [ABSTRACT FROM AUTHOR]

Background: Vascular cognitive impairment is frequent, in mild (mVCI) or severe forms (vascular dementia). Objective: To do a randomized controlled-trial to evaluate the impact of physical activity on cognition (primary outcome), neurocognitive measures, quality of life, functional status, and physical function (secondary outcomes), in patients with mVCI. Methods: A hundred and four patients with mVCI (mean age 71.2 years; 53 women) were randomized for a six-month intervention of moderate physical activity (60-minute sessions, 3 times/week) (n = 53) or best-practice "usual care" (n = 51). Comprehensive evaluations of primary and secondary outcomes included an objective measure of physical activity through accelerometry at baseline and after intervention. Results: Mean session attendance was 58%. Adverse events were negligible. After 6 months, no significant primary outcome change was observed, either in the intervention or 'usual care' group. The intervention group improved significantly in some secondary outcomes in physical function - aerobic capacity (U = 403; p = 0.000) and agility (U = 453; p = 0.005) after 6 months. Regardless of randomization arm, a post-hoc analysis based on fulfilling at least 21.5 minutes/day of moderate or 10.7 minutes/day of vigorous physical activity (World Health Organization-WHO standards) revealed improvements. These were not only in motor capacity but also on the global measure of cognition, executive functions and memory. Conclusions: Physical activity was safe and beneficial regarding domains of physical function. No significant cognitive decline was registered over 6-months, regardless of intervention allocation. Larger samples, longer follow-ups and focus on intervention adherence are needed to fully analyze the impact of WHO recommendations for physical activity in mVCI populations. [ABSTRACT FROM AUTHOR]

Background: Semantic intrusion errors (SIEs) are both sensitive and specific to PET amyloid-β (Aβ) burden in older adults with amnestic mild cognitive impairment (aMCI). Objective: Plasma Aβ biomarkers including the Aβ42/40 ratio using mass spectrometry are expected to become increasingly valuable in clinical settings. Plasma biomarkers are more clinically informative if linked to cognitive deficits that are salient to Alzheimer's disease (AD). Methods: This study included 119 older adults enrolled in the 1Florida Alzheimer's Disease Research Center (ADRC), 45 aMCI participants scored below the established Aβ42/40 ratio cut-off of 0.160 using the Quest AD-Detect™ assay indicating Aβ positivity (Aβ+), while 50 aMCI participants scored above this cut-off indicating Aβ negative status (Aβ–). Additionally, 24 cognitively unimpaired (CU) persons scored above the cut-off of 0.160 (Aβ–). Results: The aMCI plasma Aβ+ group evidenced the greatest percentage of SIEs, followed by the aMCI Aβ–. The CU Aβ– group exhibited the lowest percentage of SIEs. After adjustment for global cognitive impairment, aMCI plasma Aβ+ continued to demonstrate greater SIEs on tests tapping the failure to recover from proactive semantic interference (frPSI) as compared to the aMCI Aβ–group. Using pre-established cut-offs for frPSI impairment, 8.3% of CU Aβ– participants evidenced deficits, compared to 37.8% of aMCI Aβ–, and 74.0% of aMCI Aβ+. Conclusions: SIEs reflecting frPSI were associated with aMCI Aβ+ status based on the Aβ42/40 ratio. Results suggest the importance of SIEs as salient cognitive markers that map onto underlying AD pathology in the blood. [ABSTRACT FROM AUTHOR]

Background: Subjective cognitive decline (SCD) refers to self-reported cognitive decline in individuals with normal performance on standardized cognitive tests. Understanding the factors predicting progression from SCD to mild cognitive impairment (MCI) is crucial, as approximately 14% of SCD cases progress to dementia and about 27% develop MCI over four years. Objective: This study aims to identify neuropsychological predictors of progression from SCD to MCI, focusing on cognitive domains assessed through neuropsychological tests. Methods: This retrospective study at Seoul National University Bundang Hospital analyzed a cohort of 107 patients diagnosed with SCD through comprehensive assessment. Patients underwent annual neuropsychological testing, including the Digit Span Test, Boston Naming Test, Rey Complex Figure Test, Seoul Verbal Learning Test, and Stroop Test. Results: Annually, these patients underwent neuropsychological tests over a 5-year period; 24 progressed to MCI per NIA-AA criteria. Key predictors of MCI progression included age, ischemic heart disease, and scores from the forward digit span, delayed recall, and Boston naming tests. Lower scores in delayed recall and Boston naming tests significantly correlated with a higher risk of MCI (p < 0.001). Conclusions: These findings suggest a need for targeted management of memory and language functions to monitor disease progression effectively. [ABSTRACT FROM AUTHOR]

Aim: To explore the topological organization alterations of functional connectomes in type 2 diabetes (T2DM) patients with and without mild cognitive impairment (MCI), and compare these with structural connectomes changes. Methods: Twenty-six T2DM patients with MCI (DM-MCI), 26 without cognitive impairment (DM-NC), and 28 healthy controls were included. Diffusion tensor imaging (DTI) and resting-state functional MRI images were acquired. Networks were constructed and graph-theory based network measurements were calculated. The global network parameters and nodal efficiencies were compared across the three groups using one-way ANOVA and a false-discovery rate correction was applied for multiple comparisons. Partial correlation analyses were performed to investigate relationships between network parameters, cognitive performance and clinical variables. Results: In the structural connectome, the DM-MCI group exhibited significantly decreased global efficiency (Eglob) and local efficiency (Eloc) compared to the DM-NC and control groups. In the functional connectome, the DM-MCI group exhibited increased Eloc and clustering coefficient (Cp) compared to the controls. No significant differences were found in Eglob, Eloc, or Cp between the DM-NC and the control group, both in structural and functional connectomes. Nodal efficiencies decreased in some brain regions of structural and functional networks in the DM-MCI and DM-NC groups, but increased in five regions in functional network, some of which were involved in the default-mode network. Conclusion: Unlike the consistently decreased global properties and nodal efficiencies in the structural connectome of T2DM patients, increases in Eloc, Cp, and nodal efficiencies in the functional connectome may be viewed as a compensatory mechanism due to functional plasticity and reorganization. Altered nodal efficiency can hint at cognitive decrements at an early stage in T2DM patients. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusion Rapid eye movement sleep behavior disorder (RBD) is linked to the diffuse‐malignant subtype and higher cognitive burden in Lewy body disease (LBD).This study explores brain β‐amyloid deposition and its association with cognitive decline across the RBD–LBD continuum.Patients with isolated RBD (iRBD), Parkinson's disease with probable RBD (PDRBD), and dementia with Lewy bodies with probable RBD (DLBRBD) underwent 18F‐florbetaben positron emission tomography, 3T magnetic resonance imaging scans, and comprehensive neuropsychological assessments. Subjects were categorized as cognitively normal (NC), mild cognitive impairment (MCI), or dementia. Global and regional standardized uptake value ratios (SUVR) were estimated in predefined cognitive volumes of interest (VOI) derived from voxel‐wise comparison analysis among the cognitive groups, namely the prefrontal, parietal, precentral cortices, lingual gyrus, and supplementary motor area. Generalized linear models assessed the relationship between 18F‐florbetaben SUVRs and neuropsychological testing, adjusting for age and sex. Subgroup analysis focused on the polysomnography‐confirmed iRBD‐continuum subset (n = 41) encompassing phenoconverters and nonconverters in our prospective iRBD cohort.Eighty‐six subjects were classified as follows: 14 NC, 54 MCI, and 18 dementia. The proportion of positive β‐amyloid scans increased with advanced cognitive stages (P = 0.038). β‐Amyloid signals in cognitive VOIs were elevated in subgroups showing impairment in Trail‐Making Test B (TMT‐B). A linear association between TMT‐B z score and global cortical β‐amyloid levels was observed in the iRBD‐continuum subset (P = 0.013).Cortical β‐amyloid accumulates with declines in executive function within the RBD–LBD continuum. TMT‐B performance may be a useful marker associating with β‐amyloid load, particularly in the iRBD population. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

BackgroundAimsMethods & ProceduresOutcomes & ResultsConclusionsLanguage studies in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) have been primarily focused on lexicosemantic abilities, with a paucity of data regarding syntactic processing.We aimed to verify the sentence comprehension ability of older adults with amnestic MCI (aMCI), non-amnestic MCI (naMCI), and mild AD and compare it to the performance of cognitively healthy older adults.We evaluated 32 cognitively healthy older adults, 22 with aMCI, 43 with naMCI, and 12 with mild AD using the Test for Reception of Grammar Version 2 (TROG-2).There were significant differences between the control and MCI and control and AD groups in the total number of correct answers and among the four groups’ profiles according to the type of sentence (p < 0.05). Zero anaphor, pronoun gender/number, and centre-embedded sentences discriminated at least between two groups (p < 0.05).Poorer performance in sentences structurally more complex was in line with the severity of the cognitive decline, which may point to the effect of increased demands on working memory and executive functions on syntactic processing. [ABSTRACT FROM AUTHOR]

AbstractObjective: To determine the efficacy of a 12-week individual cognitive stimulation (iCS) intervention on global cognition, memory, and executive function of older adults with mild to moderate Alzheimer’s disease (AD). Method: Protocolized analysis using data from a multicenter, single-blind, randomized, parallel two-arm RCT of iCS for older adults with probable AD. A sample of 142 people with probable Alzheimer’s disease attending 13 Portuguese institutions providing care and support services for older adults were selected. Intervention group (n = 72) received 24 iCS sessions, twice a week for 12 weeks. Control group (n = 70) maintained their activities as usual. Outcomes included global cognitive function (Mini-Mental State Examination, and Alzheimer’s Disease Assessment Scale—Cognitive Subscale), memory (Memory Alteration Test, and Free and Cued Selective Reminding Test), and executive functioning (Frontal Assessment Battery). All participants were assessed at baseline (T0), after the intervention (T1), and 12 weeks follow-up (T2). Results: The results showed significant improvements in memory performance at follow-up for the intervention group and greater stability in global cognition in the intervention relative to the control group. Conclusion: The current iCS protocol shows effectiveness in cognitive functioning in older adults with probable AD, particularly for memory upon completion of the intervention and at follow-up, adding further support to previous iCS studies showing similar results and to the effectiveness of the current intervention. [ABSTRACT FROM AUTHOR]

Background: In Alzheimer's disease (AD), the associations between tau pathology and brain atrophy and cognitive decline are well established, but imperfect. We investigate whether cerebrospinal fluid (CSF) biomarkers of biological processes (vascular, synaptic, and axonal integrity, neuroinflammation, neurotrophic factors) explain the disconnection between tau pathology and brain atrophy (brain resilience), and tau pathology and cognitive decline (cognitive resilience). Methods: We included 428 amyloid positive participants (134 cognitively unimpaired (CU), 128 with mild cognitive impairment (MCI), 166 with AD dementia) from the BioFINDER-2 study. At baseline, participants underwent tau positron emission tomography (tau-PET), magnetic resonance imaging (MRI), cognitive testing, and lumbar puncture. Longitudinal data were available for MRI (mean (standard deviation) follow-up 26.4 (10.7) months) and cognition (25.2 (11.4) months). We analysed 18 pre-selected CSF proteins, reflecting vascular, synaptic, and axonal integrity, neuroinflammation, and neurotrophic factors. Stratifying by cognitive status, we performed linear mixed-effects models with cortical thickness (brain resilience) and global cognition (cognitive resilience) as dependent variables to assess whether the CSF biomarkers interacted with tau-PET levels in its effect on cortical atrophy and cognitive decline. Results: Regarding brain resilience, interaction effects were observed in AD dementia, with vascular integrity biomarkers (VEGF-A (βinteraction = -0.009, pFDR = 0.047) and VEGF-B (βinteraction = -0.010, pFDR = 0.037)) negatively moderating the association between tau-PET signal and atrophy. In MCI, higher NfL levels were associated with more longitudinal cortical atrophy (β = -0.109, pFDR = 0.033) and lower baseline cortical thickness (β = -0.708, pFDR = 0.033) controlling for tau-PET signal. Cognitive resilience analyses in CU revealed interactions with tau-PET signal for inflammatory (GFAP, IL-15; βinteraction -0.073–-0.069, pFDR 0.001–0.045), vascular (VEGF-A, VEGF-D, PGF; βinteraction -0.099–-0.063, pFDR < 0.001–0.046), synaptic (14–3-3ζ/δ; βinteraction = -0.092, pFDR = 0.041), axonal (NfL; βinteraction = -0.079, pFDR < 0.001), and neurotrophic (NGF; βinteraction = 0.091, pFDR < 0.001) biomarkers. In MCI higher NfL levels (βmain = -0.690, pFDR = 0.025) were associated with faster cognitive decline independent of tau-PET signal. Conclusions: Biomarkers of co-existing pathological processes, in particular vascular pathology and axonal degeneration, interact with levels of tau pathology on its association with the downstream effects of AD pathology (i.e. brain atrophy and cognitive decline). This indicates that vascular pathology and axonal degeneration could impact brain and cognitive resilience. [ABSTRACT FROM AUTHOR]

ABSTRACT Several studies show that Alzheimer's disease (AD) and other neurocognitive disorders have a negative impact on the self and identity formation. Most studies have included persons with mild to moderate dementia, but how AD patients in the earliest phases retrieve information about themselves has only been studied scarcely. The aim of this study was to investigate if persons with mild cognitive impairment (MCI) and mild AD would generate fewer self‐related statements than healthy controls. From a memory clinic, we included 17 aMCI patients, 17 patients with mild dementia (AD; MMSE ≥ 24), and 30 healthy controls. Three Events Test and Twenty Statements Test (TST) were applied to all participants. The persons with mild dementia gave significantly fewer statements compared to the controls (p < 0.001) and the aMCI patients (p < 0.01) on TST. Fewer statements were also produced by the aMCI patients compared to the control participants (p < 0.05). Persons from both patient groups produced significantly fewer contextual details compared to the controls on the Three Events Tests. There were significant associations to lexical fluency for both the TST and Three Events Test, but only a limited amount of variance was explained, and the results cannot be explained solely by a fluency effect. The results from this study are in accordance with findings from previous studies demonstrating that mild AD leads to a decline in both autobiographical memories and a diminished sense of self. Further, this study shows that changes in self‐concept may occur even in the earliest clinical stages of AD. [ABSTRACT FROM AUTHOR]

BackgroundMethodsResultsConclusionsThe burden of Alzheimer’s disease and related dementias (AD/ADRD) in Costa Rica is expected to become one of the highest in the region. Early detection will help optimize resources and improve primary care interventions. The Montreal Cognitive Assessment (MoCA) has shown good sensitivity for detecting mild cognitive impairment (MCI), but specificity varies depending on the population. This motivated the analysis of different cutoffs to minimize false-positive classifications in a Costa Rican sample for its use in clinical settings.Data was analyzed from 516 memory clinic outpatients (148 cognitively normal, 260 MCI, 108 mild AD/ADRD; mean age 66.3 ± 10.8 years) who underwent complete neurological and neuropsychological assessment and were diagnosed by consensus. Optimal MoCA cutoff scores were identified using a multiple cutoff approach.Overall, a cutoff score of ≥ 23 showed better accuracy to distinguish between normal cognition (NC) and MCI (sensitivity 73%, specificity 83%). When analyzed by educational levels, a cutoff score of ≥ 21 showed better accuracy for ≤ 6 years (sensitivity 80%, specificity 76%), ≥23 for 7–12 years (sensitivity 86%, specificity 76%) and ≥ 24 for > 12 years (sensitivity 70%, specificity 85%). For distinguishing MCI from mild AD/ADRD, the optimal overall cutoff score was ≥ 15 (sensitivity 66%, specificity 85%). When stratified by years of education, cutoff scores of ≥ 14 showed better accuracy for ≤ 6 years (sensitivity 70%, specificity 88%), ≥15 for 7–12 years (sensitivity 46%, specificity 95%) and ≥ 17 for > 12 years (sensitivity 67%, specificity 93%).A MoCA cutoff score of ≥ 23 in the Costa Rican population showed better diagnostic accuracy for detecting MCI and may reduce the false positive rate. Our findings may be helpful for primary care clinical settings and further referral criteria. [ABSTRACT FROM AUTHOR]

Background: In recent years, the problem of cognitive impairment in the elderly has become increasingly prominent. Understanding the research trend of influencing factors of mild cognitive impairment, and provide reference for medical staff to early screening of the elderly with mild cognitive impairment. Objective: Through the visual analysis of the influence factors of the elderly with mild cognitive impairment, the current research status was discussed. Methods: The relevant literature in the field of influencing factors of mild cognitive impairment in the elderly included in the Web of Science core collection database from 2013 to 2022 was searched. Using software such as Cite Space and VOS viewer to visually analyze literature citations, country, keywords, and development trends. Results: A total of 547 relevant literatures were included, and the number of publications showed an increasing trend in the past ten years. The United States ranked first in both the number of published papers (157) and centrality (0.34), and the United States and China had a greater influence on the influencing factors of mild cognitive impairment. Alzheimer's disease, cognitive decline, the elderly, risk factors, are the research hotspot in this field. Conclusion: Cognitive decline will affect the autonomy of the elderly. Cognitive frailty, MRI is the forefront of MCI research, to understand the research hotspots and frontiers in this field, to conduct early screening and intervention guidance for people with mild cognitive impairment, so as to delay the occurrence of Alzheimer's disease, and reduce the pressure on family caregivers and society. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a debilitating progressively neurodegenerative disease. The best-characterized hallmark of AD, which is marked by behavioral alterations and cognitive deficits, is the aggregation of deposition of amyloid-beta (Aß) and hyper-phosphorylated microtubule-associated protein Tau. Despite decades of experimental progress, the control rate of AD remains poor, and more precise deciphering is needed for potential therapeutic targets and signaling pathways involved. In recent years, phosphoinositide 3-kinase (PI3K) and Akt have been recognized for their role in the neuroprotective effect of various agents, and glycogen synthase kinase 3 (GSK3), a downstream enzyme, is also crucial in the tau phosphorylation and Aß deposition. An overview of the function of PI3K/Akt pathway in the pathophysiology of AD is provided in this review, along with a discussion of recent developments in the pharmaceuticals and herbal remedies that target the PI3K/Akt signaling pathway. In conclusion, despite the challenges and hurdles, cumulative findings of novel targets and agents in the PI3K/Akt signaling axis are expected to hold promise for advancing AD prevention and treatment. [ABSTRACT FROM AUTHOR]