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Background The number of people diagnosed with dementia worldwide is set to increase significantly. While patients with dementia often have comorbidities, particularly diabetes, patients with type 2 diabetes mellitus (T2DM) have a high risk of cognitive decline. This study aimed to determine whether older people with T2DM exhibit specificity in cognitive function. Methods The Montreal Cognitive Assessment (MoCA) is a well-known tool for examining mild cognitive impairment. The modified Japanese version (MoCA-J) has been confirmed as effective. We conducted an investigative survey to assess the cognitive function of Japanese individuals aged ≥75 years with and without T2DM, using the MoCA-J, and analyzed the results. Results Thirty-three patients with T2DM and 23 non-DM patients completed the examination. Between both groups, a significant difference in the MoCA-J total scores was found. (T2DM mean, 21.4 ± 3.5; non-DM mean, 23.5 ± 3.6). Only 9% of patients with T2DM and 39% of those with non-DM showed scores ≥26, which is the cutoff point for mild cognitive impairment, whereas all patients had the ability of self-care. Additionally, older patients with T2DM had significantly lower delayed recall scores than the non-DM group. Conclusions Patients aged ≥75 years with T2DM might have lower cognition than those without T2DM; the inability to perform delayed recall in T2DM patients might denote a cognitive function decline.Therefore, compared with other patients, patients aged ≥75 years with T2DM need to receive individually tailored explanations about their care, based on their cognition.

Background: Poor social health is likely associated with cognitive decline and risk of dementia; however, studies show inconsistent results. Additionally, few studies separate social health components or control for mental health. Objective: To investigate whether loneliness and social support are independently associated with cognitive decline and risk of dementia, and whether depressive symptoms confound the association. Methods: We included 4,514 participants from the population-based Rotterdam Study (RS; aged 71±7SD years) followed up to 14 years (median 10.8, interquartile range 7.4–11.6), and 2,112 participants from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K; aged 72±10SD years) followed up to 10 years (mean 5.9±1.6SD). At baseline, participants were free of major depression and scored on the Mini-Mental State Examination (MMSE) ≥26 for RS and ≥25 for SNAC-K. We investigated loneliness, perceived social support, and structural social support (specifically marital status and number of children). In both cohorts, dementia was diagnosed and cognitive function was repeatedly assessed with MMSE and a global cognitive factor (g-factor). Results: Loneliness was prospectively associated with a decline in the MMSE in both cohorts. Consistently, persons who were lonely had an increased risk of developing dementia (RS: HR 1.34, 95%CI 1.08–1.67; SNAC-K: HR 2.16, 95%CI 1.12–4.17). Adjustment for depressive symptoms and exclusion of the first 5 years of follow-up did not alter results. Neither perceived or structural social support was associated with cognitive decline or dementia risk. Conclusion: Loneliness, not social support, predicted cognitive decline and incident dementia independently of depressive symptoms.

Background: Superficial white matter (SWM) alterations correlated with cognitive decline have been described in Alzheimer’s disease (AD). Objective: The study aims to extend the investigation of the SWM alterations to AD and non-AD neurodegenerative dementia (ND) and explore the relationship with cerebrospinal fluid (CSF) biomarkers and clinical data. Methods: From a database of 323 suspected dementia cases, we retrospectively recruited 55 ND with abnormal amyloid-β42 (AD) and 38 ND with normal amyloid-β42 (non-AD) and collected clinical data, CSF biomarkers, and magnetic resonance images. Ten healthy controls (HC) were recruited for imaging and Mini-Mental State Examination (MMSE). Diffusion tensor imaging (DTI) measurements were performed in the lobar SWM regions and Kruskal Wallis tests were used for among-group comparison. Spearman’s correlation tests were performed between DTI measures, CSF biomarkers, and clinical data. Results: AD and non-AD showed significant differences in the DTI measures across the SWM compared to HC. Significant differences between AD and non-AD were detected in the left parietal lobe. DTI measures correlated with amyloid-β42 and MMSE diffusely in the SWM, less extensively with total-tau and phosphorylated tau, and with disease duration in the parietal lobe bilaterally. Conclusion: Widespread SWM alterations occur in both AD and non-AD ND and AD shows appreciably more severe alterations in the parietal SWM. Notably, the alterations in the SWM are strongly linked not only to the cognitive decline but also to the diagnostic CSF biomarkers. Further studies are encouraged to evaluate the DTI measures in the SWM as in vivo non-invasive biomarkers in the preclinical phase.

Introduction and objectives: The Mini-Cog is a very brief, widely used cognitive test that includes a memory task and a simplified assessment of the Clock Drawing Test (CDT). There is not a formal evaluation of the Mini-Cog test in Spanish. This study aims to analyse the diagnostic usefulness of the Mini-Cog and CDT for detecting cognitive impairment (CI). Methods: We performed a cross-sectional study, systematically including all patients who consulted at our neurology clinic over a 6-month period. We assessed diagnostic usefulness for detecting CI (defined according to the National Institute on Aging-Alzheimer’s Association criteria for mild cognitive impairment and dementia) according to the area under the receiver operating characteristic curve (AUC). Sensitivity, specificity, and positive and negative likelihood ratios were calculated for each cut-off point. Results: The study included 581 individuals (315 with CI); 55.1% were women and 27.7% had not completed primary studies. The Mini-Cog showed greater diagnostic usefulness than the CDT (AUC ± sensitivity: 0.88 ± 0.01 vs 0.84 ± 0.01; P

Alzheimer disease (AD) is a leading cause of dementia that has gained prominence in our aging society. Yet, the complexity of diagnosing AD and measuring its invasiveness poses an obstacle. To this end, blood-based biomarkers could mitigate the inconveniences that impede an accurate diagnosis. We developed models to diagnose AD and measure the severity of neurocognitive impairment using blood protein biomarkers. Multiple reaction monitoring–mass spectrometry, a highly selective and sensitive approach for quantifying targeted proteins in samples, was used to analyze blood samples from 4 AD groups: cognitive normal control, asymptomatic AD, prodromal AD), and AD dementia. Multimarker models were developed using 10 protein biomarkers and apolipoprotein E genotypes for amyloid beta and 10 biomarkers with Korean Mini-Mental Status Examination (K-MMSE) score for predicting Alzheimer disease progression. The accuracies for the AD classification model and AD progression monitoring model were 84.9% (95% CI 82.8 to 87.0) and 79.1% (95% CI 77.8 to 80.5), respectively. The models were more accurate in diagnosing AD, compared with single APOE genotypes and the K-MMSE score. Our study demonstrates the possibility of predicting AD with high accuracy by blood biomarker analysis as an alternative method of screening for AD.

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

INTRODUCTION Resting heart rate (RHR) predicts future risk for cardiovascular disease (CVD). However, longitudinal studies investigating the relationship of RHR with cognitive decline are scarce. METHODS This population-based cohort study included 2147 participants (age≥60) in SNAC-K who were free of dementia and regularly followed from 2001-2004 to 2013-2016. RHR was assessed with electrocardiogram. Dementia was diagnosed following the Diagnostic and Statistical Manual of Mental Disorders 4th Revision criteria. Global cognitive function was assessed using Mini-Mental State Examination (MMSE). Data were analyzed using Cox and linear mixed-effects models. RESULTS RHR≥80 (vs. 60-69) bpm was associated with a multi-adjusted hazard ratio of 1.55 (95% confidence interval 1.06-2.27) for dementia. The association remained significant after excluding participants with prevalent and incident CVDs. Similarly, RHR≥80 bpm was associated with a multi-adjusted β-coefficient of -0.13 (-0.21 to -0.04) for MMSE score. DISCUSSION Higher RHR is associated with increased risk for dementia and faster cognitive decline independent of CVDs in a general population of elderly people.

This study presents a systematic review on existing cognitive screening tools for mild cognitive impairment and dementia in populations with low education and literacy levels. Cochrane Library, PubMed and LILACS databases were examined for studies including adults aged 50 years old or older with low educational level. 61 articles were included. Despite its frequent use, studies on Mini-Mental State Examination (MMSE) revealed that educational level biased the score obtained, regardless of other factors. Separately, the Informant Questionnaire on Cognitive Decline in the Elderly, the Fototest, or the Eurotest, appear to minimize the effect of education and literacy. MMSE is unreliable for individuals with low literacy. Tasks involving reading, writing, arithmetics, drawing, praxis, visuospatial, and visuoconstructive skills have a greater educational bias than naming, orientation, or memory. An adequate determination of educational level and validation of instruments in populations with heterogeneous levels of literacy requires further research.

Background: The Memory Alteration Test (M@T) is a verbal episodic and semantic memory screening test able to detect subjective cognitive decline (SCD) and Mild Cognitive Impairment (MCI). Objective: To adapt M@T, creating a Greek version of the Memory Alteration Test (M@T-GR), and to validate M@T-GR compared to the Mini-Mental State Examination (MMSE), and Subjective Cognitive Decline- Questionnaire (SCD-Q) MyCog and TheirCog. Methods: 232 people over 55 years old participated in the study and they were classified as healthy controls (HC, n = 65), SCD (n = 78), or MCI (n = 89). Results: The ANCOVA showed that the M@T-GR’s total score was significantly different in HC and SCD (I-J = 2.26, p = 0.032), HC and MCI (I-J = 6.16, p

Mild cognitive impairment (MCI) is a clinical syndrome of mild memory or other cognitive impairment without dementia and is a clinical transition state between normal aging and dementia. Careful and meticulous nursing intervention can improve the clinical symptoms of MCI and delay the progression of the disease.This research aimed to evaluate the efficacy of cognitive function training interventions in elderly patients with MCI.106 patients were randomized into the intervention group or the control group. They received conventional nursing intervention and those in the intervention group received additional cognitive training program for 6 weeks. The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), activities of daily living (ADL) scales, and Barthel index (BI) were evaluated before and 6 weeks after the intervention, as well as the serum levels of S100β and neuron-specific enolase (NSE) at two time points.After intervention, the MMSE scores and MoCA scores in both groups were significantly increased and the score in the intervention group was significantly higher. In the intervention group, the performance of conventional nursing intervention and cognitive training program significantly increased the scores of ADL and BI (p 0.001). The serum levels of NSE and S100β in the intervention group were significantly lower.The performance of cognitive training program alleviated the brain tissue damage in elderly patients with MCI.The performance of cognitive training program in elderly patients with MCI improved their cognitive ability and daily living ability.

Background: Cognitive impairment (CI) has been reported to negatively impact rehabilitation outcomes. Knowledge about differences in rehabilitation received in dependence of CI as a potential mediating factor is limited. Objective: To analyze whether CI affects amount and frequency of rehabilitation received and if associations between CI and rehabilitation outcome are mediated by the provided amount of therapy. Methods: Observational cohort study in ward-based geriatric rehabilitation consecutively including 373 patients (mean age 82.0±6.69 years, mean MMSE 23.66±5.31). Outcome measures were amount, frequency, and type of multi-professional therapy sessions and rehabilitation outcome assessed with the Barthel Index (BI). Cognitive status was measured with the Mini-Mental-State Examination (MMSE) classifying three patient subgroups according to cognitive status. Results: Patients with more severe CI received least total therapy hours (TTH) (MMSE 26, 17.79±8.88 h, p = 0.014) and were less often included in occupational therapy (MMSE 26, 71.4%, p = 0.019) and group-based physiotherapy (MMSE 26, 81.2%, p = 0.027). Regression models showed that CI negatively impacted TTH (β= 0.24, p = 0.003) and rehabilitation outcome (β= 0.41, p = 0.008). In the mediation model, TTH accounted for 23.18%(p

Background: Serum levels of inflammatory factors, such as C3, C4, C-reactive protein (CRP), immunoglobulin (Ig) G, IgA, and IgM, in patients with Alzheimer’s disease (AD) and their correlation with cognitive function remain unexplored. Objective: To investigate the expression of serum inflammatory factors in patients with AD and its correlation with cognitive function. Methods: Serum levels of C3, C4, CRP, IgG, IgA, and IgM in 200 patients with AD (mild, moderate, and severe) and those in 174 normal controls were assessed. Spearman’s rank correlation analysis was used to explore the relationships among biomarker levels, cognitive function, and activities of daily living (ADL). Results: Among these inflammatory factors, C3 and CRP levels were significantly lower, and IgG and IgA levels were significantly higher in the AD group than in the control group (p 0.05). In all participants, CRP level was positively correlated with the Mini-Mental State Examination and Montreal Cognitive Assessment scores (p 0.05). Conclusion: Inflammatory factors C3, CRP, IgG, and IgA have the potential to serve as biomarkers for AD. Furthermore, serum IgA was not only correlated with AD but also with ADL. These results support the hypothesis that inflammation is involved in the occurrence and development of AD.

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

Deciding on the smallest change in an outcome that constitutes a clinically meaningful treatment effect (ie, the minimum clinically important difference [MCID]) is fundamental to interpreting clinical trial outcomes, making clinical decisions, and designing studies with sufficient statistical power to detect any such effect. There is no consensus on MCIDs for outcomes in Alzheimer's disease trials, but the US Food and Drug Administration's consideration of aducanumab clinical trials data has exposed the uncertainty of the clinical meaning of statistically significant but small improvements. Although MCIDs for outcomes, including Clinical Dementia Rating-Sum of Boxes and Mini-Mental State Examination in Alzheimer's disease have been reported, the Food and Drug Administration's guidelines, drafted in 1989 to facilitate regulatory approval of substantially effective antidementia drugs, do not specify quantified minimum differences. Although it is important that regulatory requirements encourage drug development and approval, without MCIDs, sponsors are motivated to power trials to detect statistical significance for only small and potentially inconsequential effects on clinical outcomes. MCIDs benefit patients, family members, caregivers, and health-care systems and should be incorporated into clinical trials and drug development guidance for Alzheimer's disease.

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

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

Background: Amnestic mild cognitive impairment (aMCI) is the transitional stage between normal aging and Alzheimer’s disease (AD). Some aMCI patients will progress into AD eventually, whereas others will not. If the trajectory of aMCI can be predicted, it would enable early diagnosis and early therapy of AD. Objective: To explore the development trajectory of aMCI patients, we used diffusion tensor imaging to analyze the white matter microstructure changes of patients with different trajectories of aMCI. Methods: We included three groups of subjects:1) aMCI patients who convert to AD (MCI-P); 2) aMCI patients who remain in MCI status (MCI-S); 3) normal controls (NC). We analyzed the fractional anisotropy and mean diffusion rate of brain regions, and we adopted logistic binomial regression model to predicate the development trajectory of aMCI. Results: The fraction anisotropy value is significantly reduced, the mean diffusivity value is significantly increased in the two aMCI patient groups, and the MCI-P patients presented greater changes. Significant changes are mainly located in the cingulum, fornix, hippocampus, and uncinate fasciculus. These changed brain regions significantly correlated with the patient’s Mini-Mental State Examination scores. Conclusion: The study predicted the disease trajectory of different types of aMCI patients based on the characteristic values of the above-mentioned brain regions. The prediction accuracy rate can reach 90.2%, and the microstructure characteristics of the right cingulate band and the right hippocampus may have potential clinical application value to predict the disease trajectory.

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

OBJECTIVES Electroconvulsive therapy (ECT) is an effective treatment for depressive disorders and approved for use in adolescents and adults, but it is unclear whether efficacy or cognitive side effect burden differs with age or if effectiveness in usual clinical practice matches that in prospective studies. We examined the effects of ECT on depression and cognition in a large clinical cohort. METHODS A retrospective cohort study of patients ages 16 and older receiving ECT between 2011 and 2020 and who were evaluated with the Quick Inventory of Depressive Symptomatology (QIDS), the Behavior and Symptom Identification Scale-24 (BASIS-24), and the Montreal Cognitive Assessment (MoCA) at baseline and after treatment #10. RESULTS Among 1698 patients, ECT was associated with a decrease in depression symptoms (QIDS reduction from 17.1 ± 4.9 to 10.1 ± 5.2) and improvement in self-reported mental health (BASIS-24 scores improved from 1.92 ± 0.55 to 1.17 ± 0.60). There was a reduction in MoCA scores from 25.8 ± 3.1 to 25.4 ± 3.1. In multivariate models, age was not associated with a differential QIDS or BASIS-24 response, but older age was associated with a lesser reduction in MoCA. CONCLUSION Among 1698 patients aged 16 and older, ECT was associated with improvement in depression and overall self-reported mental health, with a slight decrease in cognition. Age was not associated with changes in efficacy, but older age was associated with a lesser cognitive change as measured by the MoCA. These results provide normative data of real-world effectiveness of ECT, and add further support to its utility in patients with severe psychiatric illness.

Introduction Neurocognitive tests are an integral component of sport-related concussion (SRC) workup. A history of psychiatric illness (HPI) is common among young athletes. Investigations of factors that influence athletes’ baseline neurocognitive function are crucial for an accurate assessment of SRC. Objective In this study, we aim to elucidate the effect of HPI and selective-serotonin reuptake inhibitor (SSRI) medication use on baseline neurocognitive performance in young athletes. Methods We conducted a retrospective cross-sectional study of Immediate Post-Concussion Assessment and Cognitive Testing assessments. A total of 268 athletes with HPI and a control group of 6,364 athletes were included. The outcomes were total symptom score based on post-concussion symptom scale, verbal memory, visual memory, visual motor, reaction time, and impulse control scores with self-reported HPI status and SSRI use. Results Athletes with HPI had an elevated symptom score in both univariate analysis (p Conclusions Clinicians should consider the impact of HPI on baseline neurocognitive performance during the assessment of a suspected SRC. Additional research is required to bolster our findings on SSRI use and ascertain the effects of other drug classes on baseline neurocognitive performance.

Aim Executive dysfunction is pathognomonic for dementia and impedes the activities of daily living (ADL). This study aimed to examine the relationship of dementia severity with executive dysfunction and ADL in mild cognitive impairment and dementia. Methods This single-center study enrolled 86 patients (men, 40; women, 46; mean age, 76.1 ± 7.5 years) referred for cognitive and physical rehabilitation between October 2015 and September 2020. The Clinical Dementia Rating (CDR) was 0.5, 1, and ≥2 in 45, 30, and 11 patients, respectively. The presence and severity of executive dysfunction were assessed using the Behavioral Assessment of the Dysexecutive Syndrome-Japanese version (BADS). The ADL and instrumental ADL (IADL) were assessed using the Barthel Index and Frenchay Activities Index (FAI), respectively. We examined the relationship between CDR severity and overall BADS profile score and its sub-items, and that between the overall BADS profile score and IADL. Results The cognitive and executive functional assessment scores differed significantly depending on the CDR severity. The CDR severity and overall BADS profile score exhibited significant correlations. The BADS found cognitive impairment in 31%, 70%, and 100% of patients with CDR0.5, CDR1, and CDR≥2, respectively. The FAI score differed according to the CDR severity in women but not in men. The overall profile and age-adjusted BADS scores were strongly correlated with the IADL in women but not in men. Conclusions The greater the severity of executive dysfunction, the greater the difficulty in performing ADL. This effect was more pronounced in women and may predict dementia progression. Geriatr Gerontol Int 2021; ••: ••-••.

Previous studies report hippocampal volume loss can help predict conversion from normative aging to mild cognitive impairment to dementia. Additionally, a growing literature indicates that stress-related allostatic load may increase disease vulnerability. The current study examined the relationship between stress-related cytokines (ie, interleukin-6 [IL-6]), cognition as measured by Mini-Mental State Examination (MMSE) scores, and hippocampal volume. Mixed models were employed to examine both within- (across time) and between-subject effects of IL-6 and hippocampal volume on MMSE score among 566 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The within-subject analysis found left hippocampal volume significantly (p = .009) predicted MMSE score. Between-subject analysis found the effect of IL-6 on MMSE was moderated by right hippocampal volume (p = .001). These results replicate previous findings and also extend prior work demonstrating stress-related cytokines may play a role in Alzheimer’s disease progression.

Background: Motor complications are a consequence of the chronic dopaminergic treatment of Parkinson’s disease (PD) and include levodopa-induced dyskinesia (LIDs) and motor fluctuations (MF). Currently, evidence is on lacking whether patients with GBA-associated PD differ in their risk of developing motor complications compared to the general PD population. Objective: To evaluate the association of GBA carrier status with the development of LIDS and MFs from early PD. Methods: Motor complications were recorded prospectively in 884 patients with PD from four longitudinal cohorts using part IV of the UPDRS or MDS-UPDRS. Subjects were followed for up to 11 years and the associations of GBA mutations with the development of motor complications were assessed using parametric accelerated failure time models. Results: In 439 patients from Europe, GBA mutations were detected in 53 (12.1%) patients and a total of 168 cases of LIDs and 258 cases of MF were observed. GBA carrier status was not associated with the time to develop LIDs (HR 0.78, 95%CI 0.47 to 1.26, p = 0.30) or MF (HR 1.19, 95%CI 0.84 to 1.70, p = 0.33). In the American cohorts, GBA mutations were detected in 36 (8.1%) patients and GBA carrier status was also not associated with the progression to LIDs (HR 1.08, 95%CI 0.55 to 2.14, p = 0.82) or MF (HR 1.22, 95%CI 0.74 to 2.04, p = 0.43). Conclusion: This study does not provide evidence that GBA-carrier status is associated with a higher risk of developing motor complications. Publication of studies with null results is vital to develop an accurate summary of the clinical features that impact patients with GBA-associated PD. publishedVersion

Background: Epigenetic changes may contribute importantly to cognitive decline in late life including Alzheimer’s disease (AD) and vascular dementia (VaD). Bromodomain and extra-terminal (BET) proteins are epigenetic “readers” that may distort normal gene expression and contribute to chronic disorders. Objective: To assess the effects of apabetalone, a small molecule BET protein inhibitor, on cognitive performance of patients 70 years or older participating in a randomized trial of patients at high risk for major cardiovascular events (MACE). Methods: The Montreal Cognitive Assessment (MoCA) was performed on all patients 70 years or older at the time of randomization. 464 participants were randomized to apabetalone or placebo in the cognition sub-study. In a prespecified analysis, participants were assigned to one of three groups: MoCA score≥26 (normal performance), MoCA score 25–22 (mild cognitive impairment), and MoCA score≤21 (dementia). Exposure to apabetalone was equivalent in the treatment groups in each MoCA-defined group. Results: Apabetalone was associated with an increased total MoCA score in participants with baseline MoCA score of≤21 (p = 0.02). There was no significant difference in change from baseline in the treatment groups with higher MoCA scores. In the cognition study, more patients randomized to apabetalone discontinued study drug for adverse effects (11.3% versus 7.9%). Conclusion: In this randomized controlled study, apabetalone was associated with improved cognition as measured by MoCA scores in those with baseline scores of 21 or less. BET protein inhibitors warrant further investigation for late life cognitive disorders.

OBJECTIVE: Assess cognitive impairment (global cognition and executive functioning) in older incarcerated males overall, and according to education and race. DESIGN: Cross-sectional PARTICIPANTS: The sample included 239 racially diverse (37.7% White, 41.4% Black, 20.9% Hispanic/Other) incarcerated males age ≥50 (mean age = 56.4±6.1; range 50–79 years). MEASUREMENTS: Global cognitive impairment assessed using the Montreal Cognitive Assessment (MoCA) – standard MoCA scoring (1-point adjustment for ≤12 years education, and score

Background and Purpose The aim of this study was to describe the variations in the speech range profile (SRP) of patients affected by cognitive decline. Methods We collected the data of patients managed for suspected voice and speech disorders, and suspected cognitive impairment. Patients underwent an Ear Nose and Throat evaluation and Mini-Mental State Examination (MMSE). To obtain SRP, we asked the patients to read 18 sentences twice, at their most comfortable pitch and loudness as they would do in daily conversation, and recorded their voice on to computer software. Results The study included 61 patients. The relationship between the MMSE score and SRP parameters was established. Increased severity of the MMSE score resulted in a statistically significant reduction in the average values of the semitones to the phonetogram, and the medium and maximum sound pressure levels (p

Psychological, emotional, and behavioral domains could be altered in COVID-19 patients and measurement of variables within these domains seems to be mandatory. Neuropsychological assessment could detect possible cognitive impairment caused by COVID-19 and the choice of appropriate tools is an important question. Aim of this exploratory study was to verify the effectiveness of an assessment model for patients with COVID-19. Twelve patients were enrolled and tested with Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Anxiety and Depression Short Scale (AD-R), and the Neuropsychiatry Inventory (NPI), at the time of their entrance (T0) and discharge (T1) from a rehabilitative unit. Moreover, a follow-up evaluation after 3 months (T2) has been conducted on eight patients. Results showed that at baseline (T0), 58.3% of the patients reported a score below cut-off at MMSE and 50% at MoCA. Although a significant amelioration was found only in NPI scores, a qualitative improvement has been detected at all tests, except for MoCA scores, in the T0-T1 trend analysis. A one-way repeated measures analysis of variance showed a significant variation in AD-R depression score, considering the three-assessment time (T0, T1, and T2). The evaluation and tracking over time of the impact of COVID-19 on cognitive, psychological, and behavioral domains has relevant implications for rehabilitation and long-term assistance needs planning. The choice of assessment tools should consider patients vulnerability and match the best compromise among briefness, sensitivity, and specificity.

Background: Studies have suggested a connection between a decrease in the levels of polyunsaturated fatty acids (PUFAs) and Alzheimer’s disease (AD). We aimed to assess the effect of supplementation with omega-3 fatty acids (n-3 FAs) on biomarkers analyzed in the cerebrospinal fluid (CSF) of patients diagnosed with AD. Objective: To investigate the effects of daily supplementation with 2.3 g of PUFAs in AD patients on the biomarkers in CSF described below. We also explored the possible correlation between these biomarkers and the performance in the cognitive test Mini-Mental State Examination (MMSE). Methods: Thirty-three patients diagnosed with AD were randomized to either treatment with a daily intake of 2.3 g of n-3 FAs (n = 18) or placebo (n = 15). CSF samples were collected at baseline and after six months of treatment, and the following biomarkers were analyzed: Aβ 38, Aβ 40, Aβ 42, t-tau, p-tau, neurofilament light (NfL), chitinase-3-like protein 1 (YKL-40), acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), soluble IL-1 receptor type II (sIL-1RII), and IL-6. Results: There were no significant differences between the groups concerning the level of the different biomarkers in the CSF at baseline. Within the treatment group, there was a small but significant increase in both YKL-40 (p = 0.04) and NfL (p = 0.03), while the other CSF biomarkers remained stable. Conclusion: Supplementation with n-3 FAs had a statistically significant effect on NfL and YKL-40, resulting in an increase of both biomarkers, indicating a possible increase of inflammatory response and axonal damage. This increase in biomarkers did not correlate with MMSE score.

Background: Differences exist regarding post-stroke cognitive outcomes. Objective: The aim of this study investigates the potential factors associated with post-stroke cognitive performance and trajectories. Methods: We performed a prospective cohort study using serial monitoring of cognitive function over a 1-year period after a first-ever ischemic stroke. Small vessel disease (SVD) burden and hippocampal atrophy (HA) were evaluated using the modified cerebral small vessel disease scores (mCSVD) and medial temporal atrophy score (MTA) scores. A generalized estimating equation (GEE) model and a group-based trajectory model (GBTM) was used to analyze the potential factors associated with post-stroke cognitive outcomes. Results: A total of 112 patients were enrolled. The GEE model showed that all patients, regardless of initial cognitive performance, had a tendency to show an increase in the Montreal Cognitive Assessment over time. The cognitive performance was better in male patients with higher education levels (p = 0.046 and p

Background: A key challenge in studies that model outcomes, disease progression, and cost-effectiveness of existing and emerging dementia treatments is the lack of conversion criteria to translate, or ‘crosswalk’, scores on multiple measurement scales. Clinical status in dementia is commonly characterized in the cognitive, functional, and behavioral domains. Objective: We conducted a systematic review of peer-reviewed dementia measure crosswalks in the three domains. Methods: We systematically reviewed published literature for crosswalks between scales used to measure cognitive, functional, or behavioral outcomes in Alzheimer’s and related dementias. The search was conducted in PubMed, and additional crosswalks were identified through snowballing and expert input from dementia modelers. Results: Of the reviewed articles, 2,334 were identified through a PubMed search, 842 articles were sourced from backward and forward citation snowballing, and 8 additional articles were recommended through expert input. 31 papers were eligible for inclusion, listing 74 unique crosswalks. Of those, 62 (83.8%) were between endpoints of the cognitive domain and 12 (16.2%) were either between endpoints of the functional domain or were hybrid in nature. Among crosswalks exclusively in the cognitive domain, a majority involved the Mini-Mental State Examination (MMSE) (37 crosswalks) or the Montreal Cognitive Assessment (MoCA) and its variants (25 crosswalks). MMSE was directly compared to MoCA or MoCA variants in 16 crosswalks. Conclusion: Existing crosswalks between measures of dementia focus largely on a limited selection of outcome measures, particularly MMSE and MoCA. Few crosswalks exist in the functional domain, and no crosswalks were identified for solely behavioral measures.

Introduction The prevalence of subtle cognitive decline in the early stages of Parkinson's Disease (PD) is common and is thought to be even greater in patients carrying genetic mutations in the GBA gene. Current cognitive tests often lack sensitivity to identify subtle impairments. Technological advancements may offer greater precision. We explored the utility of a digitized cognitive clock-drawing test to assess cognition in patients with PD compared to healthy controls (HC) and its sensitivity compared to that of standardized neuropsychological tests. Further, we investigated the existence of a cognitive profile based on genotype. Methods The study included 75 early stage PD patients (24 with GBA-PD, 23 LRRK2-PD, 28 idiopathic PD cases) and 59 HC. Participants underwent a cognitive assessment which included the Montreal Cognitive Assessment (MoCA), the Color Trails Test (CTT) and a digital clock drawing test (DCTclock). Results Patients with PD presented lower scores than HC on all cognitive tests. The DCTclock best discriminated PD from HC (AUC: 0.807) compared to the MoCA (0.590) and CTT (0.636 and 0.717 for CTT-1 and CTT-2 respectively). In-depth quantitative analysis of the DCTclock revealed that LRRK2-PD showed better performance than other PD sub-groups. Conclusion The use of quantitative digital cognitive assessment showed greater sensitivity in identifying subtle cognitive decline than the current standardized tests. Differences in cognitive profiles were observed based on genotype. The identification of early cognitive decline may improve the clinical management of PD patients and be useful for cognitive related clinical trials.

Impaired olfaction and reduced cholinergic nucleus 4 (Ch4) volume both predict greater cognitive decline in Parkinson's disease (PD). We examined the relationship between olfaction, longitudinal change in cholinergic basal forebrain nuclei and their target regions, and cognition in early PD.We analyzed a cohort of 97 PD participants from the Parkinson's Progression Markers Initiative with brain MRIs at baseline, 1 year, 2 years, and 4 years. Using probabilistic maps, regional grey matter density (GMD) was calculated for Ch4, cholinergic nuclei 1, 2, and 3 (Ch123), and their target regions.Baseline University of Pennsylvania Smell Identification Test score correlated with change in GMD of all regions of interest (all p 0.05). Rate of change of Ch4 GMD was correlated with rate of change of Ch123 (p = 0.034), cortex (p = 0.001), and amygdala GMD (p 0.001), but not hippocampus GMD (p = 0.38). Rate of change of Ch123 GMD was correlated with rate of change of cortex (p = 0.001) and hippocampus (p 0.001), but not amygdala GMD (p = 0.133). In a linear regression model including change in GMD of all regions of interest and age as predictors, change in cortex GMD (βˆImpaired olfaction is associated with degeneration of the cholinergic basal forebrain and bilateral cortex, amygdala, and hippocampus in PD. The relationship between impaired olfaction and cognitive decline may be mediated by greater atrophy of the cortex and hippocampus.

Serum neurofilament light chain (NfL) levels are associated with disease severity in early Parkinson's disease (PD). We assessed the association of serum NfL with motor and cognitive function and decline in advanced PD patients.NfL concentrations were analyzed with single molecule array (Simoa) assay in serum of 289 PD patients with advanced disease from the single-center prospective observational biobank study Biomarkers in Parkinson's disease (MARK-PD). Motor and cognitive symptoms were assessed with MDS-UPDRS III, HoehnYahr stages and Montreal Cognitive Assessment (MoCA) at baseline and during 520 [364, 674] days of follow-up.Serum NfL concentrations were associated with HoehnYahr stages. During follow-up, baseline NfL levels were associated with time to cognitive decline in adjusted Cox regression models (hazard ratio: 3.23; 95% CI [1.16, 9.00], P 0.025). Serum NfL was associated with NT-proBNP in adjusted models linking neuronal and cardiac damage in advanced PD patients.In advanced PD patients, serum NfL concentrations are associated with motor function, cognitive decline and subclinical cardiac damage.

Background Comprehensive testing of cognitive functioning is standard practice in studies of Alzheimer disease (AD). Short-form tests like the Montreal Cognitive Assessment (MoCA) use a “sampling” of measures, administering key items in a shortened format to efficiently assess cognition while reducing time requirements, participant burden, and administrative costs. We compared the MoCA to a commonly used long-form cognitive battery in predicting AD symptom onset and sensitivity to AD neuroimaging biomarkers. Methods Survival, area under the receiver operating characteristic (ROC) curve (AUC), and multiple regression analyses compared the MoCA and long-form measures in predicting time to symptom onset in cognitively normal older adults (n = 6230) from the National Alzheimer’s Coordinating Center (NACC) cohort who had, on average, 2.3 ± 1.2 annual assessments. Multiple regression models in a separate sample (n = 416) from the Charles F. and Joanne Knight Alzheimer Disease Research Center (Knight ADRC) compared the sensitivity of the MoCA and long-form measures to neuroimaging biomarkers including amyloid PET, tau PET, and cortical thickness. Results Hazard ratios suggested that both the MoCA and the long-form measures are similarly and modestly efficacious in predicting symptomatic conversion, although model comparison analyses indicated that the long-form measures slightly outperformed the MoCA (HRs > 1.57). AUC analyses indicated no difference between the measures in predicting conversion (DeLong’s test, Z = 1.48, p = 0.13). Sensitivity to AD neuroimaging biomarkers was similar for the two measures though there were only modest associations with tau PET (rs = − 0.13, ps < 0.02) and cortical thickness in cognitively normal participants (rs = 0.15–0.16, ps < 0.007). Conclusions Both test formats showed weak associations with symptom onset, AUC analyses indicated low diagnostic accuracy, and biomarker correlations were modest in cognitively normal participants. Alternative assessment approaches are needed to improve how clinicians and researchers monitor cognitive changes and disease progression prior to symptom onset.

Aims of the study: We aimed to define the cognitive burden of the largest pseudotumor cerebri syndrome (PTCS) population to date, compare objective to subjective cognitive dysfunction, and determine clinical predictors of cognitive dysfunction amongst an array of previously unstudied factors. Clinical rationale: Patients with PTCS commonly report cognitive dysfunction, a factor associated with poor quality of life. It is not definitively known whether cognitive impairment is present in these patients, and what features of the syndrome predict impairment. Materials and methods: We administered a cognitive battery consisting of the National Adult Reading Test, Mini-Mental Status Exam, Digit Span, Boston Naming Test, Rey Auditory Verbal Learning Test, Clock Drawing, Trail Making Test, Controlled Oral Word Association, and Category Fluency. Cognitive impairment was defined as mild-single domain with one test score, and mild-multiple domain with two scores, more than two standard deviations below the mean for age-, gender-, and education-adjusted norms. Results: One-hundred and one prospectively recruited PTCS patients were enrolled. The objective testing showed 30 patients had mild-single domain impairment, and 25 had mild-multi domain impairment. More patients without objective cognitive impairment had transverse venous sinus stenosis, but otherwise the groups did not differ. Two measures of headache severity, the Headache Impact Test and pain on the Numeric Rating Scale, were negatively associated with the composite cognitive score, as was ocular pain, vision-related disability, and mental health. Opening pressure and visual function were not associated with objective cognitive impairment. We found no association between subjective and objective cognitive impairment. Conclusions and clinical implications: Patients with PTCS may be cognitively impaired, and this correlates with measures of headache burden. Studies evaluating cognitive impairment before and after remission of the headache disorder would have to be performed to investigate this relationship further. Patients with self-perception of cognitive burden are no more likely to be cognitively impaired.

Objectives:Cognitive impairment is common in individuals with substance use disorders (SUDs), yet no evidence-based guidelines exist regarding the most appropriate screening measure for use in this population. This systematic review aimed to (1) describe different cognitive screening measures used in adults with SUDs, (2) identify substance use populations and contexts these tools are utilised in, (3) review diagnostic accuracy of these screening measures versus an accepted objective reference standard, and (4) evaluate methodology of included studies for risk of bias.Methods:Online databases (PsycINFO, MEDLINE, Embase, and CINAHL) were searched for relevant studies according to pre-determined criteria, and risk of bias and applicability was assessed using the Quality Assessment of Diagnostic Accuracy Studies–2 (QUADAS–2). At each review phase, dual screening, extraction, and quality ratings were performed.Results:Fourteen studies met inclusion, identifying 10 unique cognitive screening tools. The Montreal Cognitive Assessment (MoCA) was the most common, and two novel screening tools (Brief Evaluation of Alcohol-Related Neuropsychological Impairments [BEARNI] and Brief Executive Function Assessment Tool [BEAT]) were specifically developed for use within SUD populations. Twelve studies reported on classification accuracy and relevant psychometric parameters (e.g., sensitivity and specificity). While several tools yielded acceptable to outstanding classification accuracy, there was poor adherence to the Standards for Reporting Diagnostic Accuracy Studies (STARD) across all studies, with high or unclear risk of methodological bias.Conclusions:While some screening tools exhibit promise for use within SUD populations, further evaluation with stronger methodological design and reporting is required. Clinical recommendations and future directions for research are discussed.

Objectives In Alzheimer's Disease (AD) research, choosing appropriate method for measuring change in cognitive function over time can be challenging. The aim for this study was to examine the sensitivity of four neuropsychological tests used to measure cognition during the transition from mild cognitive impairment (MCI) to AD, and the impacts of associated covariates. Methods We enrolled 223 patients with MCI who progressed to AD and had completed multiple follow-up assessments in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We constructed nonlinear mixed model for multivariate longitudinal data assuming that multiple neuropsychological tests would exhibit nonlinear transformation of a common factor in the latent cognitive process underlying the progression from MCI to AD. Results The Clinical Dementia Rating-Sum of the Boxes (CDR-SB) and Alzheimer's Disease Assessment Scale (11 items; ADAS-11) were more sensitive to cognitive changes in individuals with higher cognitive function, the Functional Activities Questionnaire (FAQ) was more sensitive to cognitive changes in individuals with middle cognitive function, and the Mini-Mental State Examination (MMSE) was more sensitive to cognitive changes in individuals with lower cognitive function. Gender (p = 0.0139) and educational level (p = 0.0094) had varying effects on different tests, such that men performed better on the FAQ and CDR-SB, and individuals with higher educational level tended to perform better on the FAQ and MMSE. Conclusions When choosing appropriate neuropsychological tests in cognitive measurements, the cognitive functional level of the patient as well as the impacts of covariates should be considered.