Cognitive Assessment Research Articles

Reversibility of Cognitive Deficits and Functional Connectivity With Transfusion in Children With Sickle Cell Disease.

People with sickle cell disease (SCD) are at risk of cognitive dysfunction independent of stroke. Diminished functional connectivity in select large-scale networks and white matter integrity reflect the neurologic consequences of SCD. Because chronic transfusion therapy is neuroprotective in preventing stroke and strengthening executive function abilities in people with SCD, we hypothesized that red blood cell (RBC) transfusion facilitates the acute reversal of disruptions in functional connectivity while white matter integrity remains unaffected. Children with SCD receiving chronic transfusion therapy underwent a brain MRI measuring white matter integrity with diffusion tensor imaging and resting-state functional connectivity within 3 days before and after transfusion of RBCs. Cognitive assessments with the NIH Toolbox were acquired after transfusion and then immediately before the following transfusion cycle. Sixteen children with a median age of 12.5 years were included. Global assessments of functional connectivity using homotopy (p = 0.234) or modularity (p = 0.796) did not differ with transfusion. Functional connectivity within the frontoparietal network significantly strengthened after transfusion (median intranetwork Z-score 0.21 [0.17-0.30] before transfusion, 0.29 [0.20-0.36] after transfusion, p < 0.001), while there was not a significant change seen within the sensory motor, visual, auditory, default mode, dorsal attention, or cingulo-opercular networks. Corresponding to the change within the frontoparietal network, there was a significant improvement in executive function abilities after transfusion (median executive function composite score 87.7 [81.3-90.7] before transfusion, 90.3 [84.3-93.7] after transfusion, p = 0.021). Participants with stronger connectivity in the frontoparietal network before transfusion had a significantly greater improvement in the executive function composite score with transfusion (r = 0.565, 95% CI 0.020-0.851, p = 0.044). While functional connectivity and executive abilities strengthened with transfusion, there was not a significant change in white matter integrity as assessed by fractional anisotropy and mean diffusivity within 16 white matter tracts or globally with tract-based spatial statistics. Strengthening of functional connectivity with concomitant improvement in executive function abilities with transfusion suggests that functional connectivity MRI could be used as a biomarker for acutely reversible neurocognitive injury as novel therapeutics are developed for people with SCD.

Effect of Endovascular Thrombectomy for Acute Ischemic Stroke on Cognitive Outcomes: A Secondary Analysis of the ESCAPE Trial.

The effect of endovascular therapy (EVT) for large vessel occlusion stroke on cognitive outcomes is not well understood. We evaluated the effect of EVT on cognitive function in the Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial. Patient data from the ESCAPE randomized trial were analyzed. Cognitive assessments completed at 90 days after stroke were the Montreal Cognitive Assessment (MoCA), the Sunnybrook Neglect Assessment Procedure (SNAP), the Boston Naming Test (BNT), Trail-making test A (Trails A), and Trail-making test B (Trails B). We used logistic regression to evaluate the association between EVT and favorable cognitive outcome on the 5 separate tests, adjusting for demographic and clinical factors. We used generalized estimating equations and ordinal regression to determine the odds of favorable outcome with EVT on global cognition incorporating the 5 tests. We added final infarct volume (FIV) to the models to assess the relationship of FIV with cognitive outcome. The ESCAPE trial included 315 patients, 165 randomized to EVT and 150 randomized to control. There was higher odds of favorable outcome with EVT for MoCA (adjusted odds ratio [aOR] 2.32, 95% CI 1.30-4.16), SNAP (aOR 3.85, 95% CI 2.00-7.45), BNT (aOR 2.33, 95% CI 1.30-4.17), trails A (aOR 3.50, 95% CI 1.93-6.36), and trails B (aOR 2.56, 95% CI 1.46-4.48). There was higher odds of favorable outcome with EVT on global binary (aOR 2.57, 95% CI 1.67-3.94) and ordinal analyses (aOR 2.83, 95% CI 1.68-4.76) of cognitive function. After adding FIV to the models, both FIV and EVT were significantly associated with cognitive outcome. There was a significant correlation between global cognitive performance and mRS at day 90 (r = -0.78, p < 0.001), with the largest reductions in favorable cognitive outcome from mRS score 4 to 5 and from mRS 2 to 3. In this secondary analysis of the ESCAPE trial, EVT was associated with favorable outcome on 5 separate cognitive tests and in global analyses of cognitive benefit. These results provide novel evidence for the effect of EVT on cognition and support the global benefit of treatment with EVT. This study provides Class II evidence that in patients with acute ischemic stroke due to intracranial internal carotid artery (ICA) or M1 segment MCA occlusion, including tandem extracranial ICA occlusions, EVT compared with best medical therapy increased odds of favorable cognitive outcome.

Mediation of White Matter Alterations in the Association Between Ventricular Dilation and Cognitive Decline in Hydrocephalus Patients: An MRI Study.

Cognitive impairment is commonly observed in hydrocephalus patients. Ventricular enlargement compresses brain parenchyma, especially the white matter (WM). To investigate whether the relationship between ventricular dilation and cognitive decline in hydrocephalus patients is mediated by WM alterations. Retrospective. 51 communicating hydrocephalus patients (median age, 54 years), 50 obstructive hydrocephalus patients (median age, 49 years), and 53 control subjects (median age, 50 years). Diffusion tensors imaging, 3D T1 BRAVO, 3D FIESTA, CUBE T2, and FLAIR sequences at 3T. DTI parameters (skeletonized fractional anisotropy (FA), skeletonized mean diffusivity (MD), and peak width of skeletonized mean diffusivity p(PSMD)) were extracted using FSL software. Global, periventricular, and deep white matter hyperintensity (WMH) volumes, degree of ventricular enlargement (Evans index), and other conventional imaging markers (number of lacunes and perivascular spaces, intracranial and brain volume) were extracted using united imaging intelligence. Cognitive tests included Montreal cognitive assessment (MoCA), clock drawing test (CDT), and vocabulary fluency test (VFT). Multivariable linear regression analysis, mediation analyses, and dominance analysis. P-value <0.05 was considered significant. The degree of ventricular dilation, DTI parameters, and cognitive function scores were interrelated. The skeletonized FA values (β = -0.0917, 95% confidence interval (CI): -0.205, -0.024) and normalized global WMH volume (β = -0.0635, 95% CI: -0.13, -0.0005) together mediated 37.2% of the association between Evans index and MoCA. A comparable causal pathway was found for periventricular WMHs but not for deep WMHs. Dominance analysis indicated skeletonized FA values had a greater impact on cognition than WMH volume. The skeletonized FA values also mediated the association between Evans index and CDT (β = -0.0897, 95% CI: -0.165, -0.026) and VFT (β = -0.1589, 95% CI: -0.27, -0.083). WM alterations were causal mediators between ventricular dilation and cognitive decline in hydrocephalus patients. 3. Stage 3.

Distinctive subgingival microbial signatures in older adults with different levels of cognitive function.

To examine association between subgingival microbial signatures and levels of cognitive impairment in older adults. We analysed subgingival plaque samples and 16S ribosomal RNA sequences for microbiota among 165 participants (normal controls [NCs]: 40, subjective cognitive decline [SCD]: 40, mild cognitive impairment [MCI]: 49 and dementia: 36). The bacterial richness was lower among individuals with worse cognitive function, and subgingival microbial communities differed significantly among the four groups. Declining cognitive function was associated with decreasing relative abundance of genera Capnocytophaga, Saccharibacteria_genera_incertae_sedis, Lautropia and Granulicatella, and increasing abundance of genus Porphyromonas. Moreover, there were differentially abundant genera among the groups. Random forest model based on subgingival microbiota could distinguish between cognitive impairment and NC (AUC = 0.933, 95% confidence interval 0.873-0.992). Significant correlations were observed between oral microbiota and sex, Montreal Cognitive Assessment (MoCA) score and Mini-Mental State Examination score. Partial correlation analysis showed that Leptotrichia and Burkholderia were closely negatively associated with the MoCA score after adjusting for multiple covariates. Gene function was not significantly different between SCD and NC groups, whereas three homozygous genes were altered in MCI patients and two in dementia patients. This is the first study to demonstrate an association between the composition, function and metabolic pathways of subgingival microbiota and different levels of cognitive function among older individuals. Future cohort studies should assess its diagnostic usefulness for cognitive impairment.

Effect of Sleep Restriction on Adolescent Cognition by Adiposity: A Randomized Crossover Trial.

Pediatric obesity is associated with impaired cognitive function; however, the mechanisms underlying this association demand assessment. Sleep may be a relevant moderator, as poor sleep predicts both increased adiposity and impaired cognitive function. To determine the effects of adiposity and sleep on adolescent cognitive function. This single-blind randomized crossover trial was conducted from September 2020 to October 2022. Parents or caregivers provided demographic information for adolescent participants. Body mass index percentile and bioelectrical impedance analysis assessed adiposity. Adolescents completed 2 actigraphy-confirmed sleep conditions, adequate and restricted, followed by in-person cognitive assessment. No additional follow-up was provided. Data collection for this population-based study took place in a behavioral medicine clinic in Birmingham, Alabama. A total of 323 participants were assessed for eligibility (ages 14-19 years and healthy). Of the 244 eligible adolescents, 157 declined participation. Eighty-seven were randomized and 26 dropped out postenrollment. The final sample included 61 adolescents, 31 with healthy weight and 30 with overweight or obesity. Data were analyzed from April to October 2023. Following a 2-day washout period of adequate sleep, adolescents completed 2 sleep conditions: adequate (mean [SD] duration, 8 hours, 54 minutes [58.0 minutes]) and restricted (mean [SD] duration, 4 hours, 12 minutes [50.7 minutes]). The National Institutes of Health Cognitive Toolbox assessed global and fluid cognition, cognitive flexibility, working and episodic memory, attention, and processing speed. The Stroop Task assessed inhibition. The final sample included 61 adolescents (mean [SD] age, 16.3 [1.6] years; 35 [57.4%] female). Restricted sleep predicted poorer global cognition scores (restricted mean [SD], 98.0 [2.8]; adequate mean [SD], 103.2 [2.9]), fluid cognition scores (restricted mean [SD], 94.5 [3.2]; adequate mean [SD], 102.0 [3.6]), and cognitive flexibility scores (restricted mean [SD], 84.8 [3.0]; adequate mean [SD], 92.8 [3.0]) for adolescents with overweight or obesity. No differences emerged for adolescents with healthy weight. Adolescents with overweight or obesity also had poorer attention scores (mean [SD], 80.0 [2.3]) compared to adolescents with healthy weight (mean [SD], 88.4 [SD, 2.3]) following restricted sleep. No differences emerged following adequate sleep. Findings were similar for total body fat percentage (TBF%); however, for adolescents with TBF% above 42, restricted sleep also predicted poorer processing speed, and the association between sleep and attention did not vary based on TBF%. Adolescents with overweight or obesity may be more vulnerable to negative cognitive effects following sleep restriction. Improved sleep hygiene and duration in this group may positively impact their cognitive health. ClinicalTrials.gov Identifier: NCT04346433.

Systemic immune-inflammation index upon admission correlates to post-stroke cognitive impairment in patients with acute ischemic stroke.

The purpose of this prospective study was to evaluate the association of systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI), with PSCI in patients with acute ischemic stroke (AIS). First-onset AIS patients were consecutively included from January 1, 2022 to March 1, 2023. The baseline information was collected at admission. Fasting blood was drawn the next morning. Cognitive function was assessed by the Montreal Cognitive Assessment (MoCA) 3 months after onset. Logistic regression analysis was performed to explore the correlation between SII, SIRI, and PSCI. Receiver operating characteristic (ROC) was conducted to evaluate the predictive ability of SII. 332 participants were recruited, and 193 developed PSCI. Compared with patients without PSCI, the patients with PSCI had higher SII (587.75 (337.42, 988.95) vs. 345.66 (248.44, 572.89), P<0.001) and SIRI (1.59 (0.95, 2.84) vs. 1.02 (0.63, 1.55), P=0.007). SII and SIRI negatively correlated with MoCA scores (both P<0.05). The multivariable logistic regression analysis indicated that SII was independently associated with PSCI (P<0.001), while SIRI was not. The optimal cutoff for SII to predict PSCI was 676.83×109/L. A higher level of SII upon admission was independently correlated to PSCI three months later in AIS patients.

The circulating proteome and brain health: Mendelian randomisation and cross-sectional analyses

Decline in cognitive function is the most feared aspect of ageing. Poorer midlife cognitive function is associated with increased dementia and stroke risk. The mechanisms underlying variation in cognitive function are uncertain. Here, we assessed associations between 1160 proteins’ plasma levels and two measures of cognitive function, the digit symbol substitution test (DSST) and the Montreal Cognitive Assessment in 1198 PURE-MIND participants. We identified five DSST performance-associated proteins (NCAN, BCAN, CA14, MOG, CDCP1), with NCAN and CDCP1 showing replicated association in an independent cohort, GS (N = 1053). MRI-assessed structural brain phenotypes partially mediated (8–19%) associations between NCAN, BCAN, and MOG, and DSST performance. Mendelian randomisation analyses suggested higher CA14 levels might cause larger hippocampal volume and increased stroke risk, whilst higher CDCP1 levels might increase intracranial aneurysm risk. Our findings highlight candidates for further study and the potential for drug repurposing to reduce the risk of stroke and cognitive decline.

Principal Component Analysis of Cognitive Executive Function: A Predictive Model of Academic Performance of Students in Mathematics in Secondary Schools

There is a growing interest from instructional scientists in using parameters of brain executive functions to unfold cognitive disorders, Mathematical Learning Difficulties (MLD), and assessment of learners’ academic performance. Thus, it is imperative to investigates, extracts and classify the major principal components of learners’ cognitive executive functions that predict academic performance of students in Mathematics and science related courses in secondary schools. An ex post facto quasi-experimental design was adopted for the study. Students’ cognitive profile was measured using a validated and reliable cognitive assessment Battery (CAB) application. There were significant positive correlations between cognitive executive functions and academic performance of students in Mathematics. The major components of the executive functions that accounted for substantial effects on academic performance of students in Mathematics include working memory, conceptual memory, short-term memory, inhibition, updating, focus attention, divided attention, auditory perception, and visual perception. Also, processing speed, shifting, planning, hand-eye coordination and response time accounted for moderate effects on academic performance of students in Mathematics. Consequently, instructors should reinforce learners’ cognitive processes using cognitive retraining programmes, personalized learning, differentiated instructional strategies for exceptional students, and offer therapeutic interventions on the identified cognitive parameters that could reduce extraneous cognitive loads. These could facilitate mental internalization of external perception during instructional delivery and learning.

A systematic review of the biomarkers associated with cognition and mood state in bipolar disorder

BackgroundBipolar disorder (BD) is a severe psychiatric disorder characterized by changes in mood that alternate between (hypo) mania or depression and mixed states, often associated with functional impairment and cognitive dysfunction. But little is known about biomarkers that contribute to the development and sustainment of cognitive deficits. The aim of this study was to review the association between neurocognition and biomarkers across different mood states.MethodSearch databases were Web of Science, Scopus and PubMed. A systematic review was carried out following the PRISMA guidelines. Risk of bias was assessed with the Newcastle–Ottawa Scale. Studies were selected that focused on the correlation between neuroimaging, physiological, genetic or peripheral biomarkers and cognition in at least two phases of BD: depression, (hypo)mania, euthymia or mixed. PROSPERO Registration No.: CRD42023410782.ResultsA total of 1824 references were screened, identifying 1023 published articles, of which 336 were considered eligible. Only 16 provided information on the association between biomarkers and cognition in the different affective states of BD. The included studies found: (i) Differences in levels of total cholesterol and C reactive protein depending on mood state; (ii) There is no association found between cognition and peripheral biomarkers; (iii) Neuroimaging biomarkers highlighted hypoactivation of frontal areas as distinctive of acute state of BD; (iv) A deactivation failure has been reported in the ventromedial prefrontal cortex (vmPFC), potentially serving as a trait marker of BD.ConclusionOnly a few recent articles have investigated biomarker-cognition associations in BD mood phases. Our findings underline that there appear to be central regions involved in BD that are observed in all mood states. However, there appear to be underlying mechanisms of cognitive dysfunction that may vary across different mood states in BD. This review highlights the importance of standardizing the data and the assessment of cognition, as well as the need for biomarkers to help prevent acute symptomatic phases of the disease, and the associated functional and cognitive impairment.

Cognitive Processing Speed and Loneliness in Stroke Survivors: Insights from a Large-Scale Cohort Study.

Loneliness, when prolonged, is associated with many deleterious effects and has been shown to be highly prevalent in those with a history of stroke, yet the cognitive mechanisms underpinning this phenomenon remain unclear. Therefore, the current study aims to investigate the extent to which cognitive factors, with specific focus on processing speed, are associated with loneliness in those with a history of stroke. Utilizing data from the British Cohort Study, a nationally representative dataset, we conducted secondary data analysis. A total of 7,752 participants completed relevant questions related to health, social interactions, demographics, loneliness, and cognitive assessments. Among them, 47 had experienced a stroke ("stroke," n = 47), 5,545 reported other health conditions ("ill," n = 5,545), and 2,857 were deemed healthy ("healthy," n = 2,857). Consistent with previous research, our findings confirmed a positive correlation between stroke history and heightened loneliness. However, inferential analysis revealed that processing speed, alongside other cognitive factors, had a minimal impact on loneliness, with correlations too small to draw definitive conclusions. This study suggests that cognitive processing speed alone is not a robust predictor of loneliness in stroke survivors. Consequently, when developing interventions to combat loneliness in this population, it is crucial to consider a broader spectrum of factors, such as social engagement, emotional wellbeing, and interpersonal relationships. This underscores the imperative need for comprehensive assessments to better comprehend the multifaceted nature of loneliness and inform more effective intervention strategies.

The Impact of Virtual Reality Training Combined with Traditional Chinese Medicine Health Preservation Therapy on Cognitive Function, Neurological Function, and Physical Function of Stroke Patients.

The aim of this study was to investigate the effects of virtual reality training combined with traditional Chinese medicine health preservation therapy on cognitive function, neurological function, and physical function of stroke patients. The patients were randomly divided into an experimental group (receiving virtual reality training combined with traditional Chinese medicine health preservation therapy) and a control group (receiving conventional rehabilitation treatment combined with traditional Chinese medicine health preservation therapy). A series of cognitive, neurological, and physical function assessments were conducted to collect and analyze data from both groups before treatment, after treatment, and during follow-up. The application of traditional Chinese medicine health preservation concepts was also explored. After treatment, the experimental group had significantly higher scores in the Mini-Mental State Examination (MMSE) compared to the control group. The overall effective rate of neurological function in the experimental group was higher than that in the control group. The Fugl-Meyer Assessment (FMA) scores for upper limb function in the experimental group were significantly higher than those in the control group. The degree of improvement in the Modified Barthel Index scores after treatment was significantly better in the experimental group compared to the control group (all P < 0.05). The results of this study demonstrate that virtual reality training combined with traditional Chinese medicine health preservation therapy significantly improves cognitive function, neurological function, and physical function in stroke patients. This approach provides new insights and methods for stroke rehabilitation therapy and is worthy of promotion.

Effect of motor, non-motor clinical features including sleep quality, and prescription pattern on adherence to antiparkinsonian medications in Parkinson’s disease

Objectives: Adherence to antiparkinsonian medications (APMs) may significantly influence Parkinson’s disease (PD) outcome. The present study assesses the role of motor and non-motor features, and prescription patterns on adherence. Materials and Methods: This observational and cross-sectional study included 50 PD patients taking APMs for ≥24 months. Demographic data, PD characteristics, treatment, and follow-up history were collected. Patients following up at least once in six months were considered as regular, else were labeled irregular. Montreal cognitive assessment, patient health questionnaire-4, Pittsburgh sleep quality (SQ) index, Epworth sleepiness scale, global quality of life (GQOL) scale, and Morisky Green Levine medication adherence scale (MGL-MAS) were used to evaluate cognition, depressive and anxiety features, SQ, excessive daytime sleepiness (EDS), quality of life (QOL), and APMs adherence, respectively. Results: Nearly half (46%) of the PD patients reported high adherence (MGL-MAS = 0). Most of the clinical characteristics were comparable between those with medium/low and high adherence, except for a larger proportion of patients in the medium/low adherence group belonging to Hoehn–Yahr stage &gt;2 (P = 0.02). A comparable proportion of patients in both groups reported poor SQ (P = 0.52) and EDS (P = 0.32). In comparison to the high adherence group, a significantly lower median GQOL score was observed in the medium/low adherence group (median [interquartile range] = 65 [50–70] vs. 80 [70–85]; P &lt; 0.001). The APMs prescription and follow-up patterns were comparable between both groups. Conclusion: More than half the PD patients reported medium-to-low adherence. While motor severity and depressive symptoms were associated with medium-to-low adherence, poor SQ was comparable in both groups. Those with medium-to-low adherence reported poor QOL.

Effectiveness of a Dual-Task Intervention Involving Exercise and Vocalized Cognitive Tasks

Background/Objectives: Population aging is rapidly increasing, and the importance of preventive medicine has been stressed. Health checkups, diet, and exercise are of paramount importance. This study aimed to evaluate the effectiveness of a personalized dual-task intervention that combined exercise with cognitive tasks in improving physical and cognitive functions among independently living older individuals. Methods: Participants aged &gt;65 years who were mostly independent in their activities of daily living were divided into two groups. The group receiving the 20 min robot-assisted session was compared with the group receiving traditional functional restoration training. This randomized trial assessed the impact of this intervention on the 30 s chair stand test score and Montreal Cognitive Assessment—Japanese version score of the participants. Results: Both scores significantly improved in the intervention group, indicating enhanced lower-limb function and cognitive capabilities. Conclusions: These findings suggest that integrating cognitive tasks with physical exercise can stand as an effective strategy to improve overall well-being in older people, offering valuable insights for designing comprehensive preventive health programs tailored to this demographic.

Development and first-stage validation of a digital version of the Digit Symbol Substitution test for use in assessing cognitive function in older people with diabetes.

To describe the development and report the first-stage validation of a digital version of the digit symbol substitution test (DSST), for assessment of cognitive function in older people with diabetes. A multidisciplinary team of experts was convened to conceptualize and build a digital version of the DSST and develop a machine-learning (ML) algorithm to analyse the inputs. One hundred individuals with type 2 diabetes (aged ≥ 60 years) were invited to participate in a one-time meeting in which both the digital and the pencil-and-paper (P&P) versions of the DSST were administered. Information pertaining to demographics, laboratory measurements, and diabetes indices was collected. The correlation between the digital and P&P versions of the test was determined. Additionally, as part of the validation process, the performance of the digital version in people with and without known risk factors for cognitive impairment was analysed. The ML model yielded an overall accuracy of 89.1%. A strong correlation was found between the P&P and digital versions (r = 0.76, p < 0.001) of the DSST, as well as between the ML model and the manual reading of the digital DSST (r = 0.99, p < 0.001). This study describes the development of and provides first-stage validation data for a newly developed digital cognitive assessment tool that may be used for screening and surveillance of cognitive function in older people with diabetes. More studies are needed to further validate this tool, especially when self-administered and in different clinical settings.

Neurofilament Light Chain as a Biomarker of Global Cognition in Individuals With Possible Vascular Mild Cognitive Impairment.

Neurofilament Light Chain (NfL) is a biomarker of axonal injury elevated in mild cognitive impairment (MCI) and Alzheimer's disease dementia. Blood NfL also inversely correlates with cognitive performance in those conditions. However, few studies have assessed NfL as a biomarker of global cognition in individuals demonstrating mild cognitive deficits who are at risk for vascular-related cognitive decline. To assess the relationship between blood NfL and global cognition in individuals with possible vascular MCI (vMCI) throughout cardiac rehabilitation (CR). Additionally, NfL levels were compared to age/sex-matched cognitively unimpaired (CU) controls. Participants with coronary artery disease (vMCI or CU) were recruited at entry to a 24-week CR program. Global cognition was measured using the Montreal Cognitive Assessment (MoCA) and plasma NfL level (pg/ml) was quantified using a highly sensitive enzyme-linked immunosorbent assay. Higher plasma NfL was correlated with worse MoCA scores at baseline (β = -.352, P = .029) in 43 individuals with vMCI after adjusting for age, sex, and education. An increase in NfL was associated with worse global cognition (b[SE] = -4.81[2.06], P = .023) over time, however baseline NfL did not predict a decline in global cognition. NfL levels did not differ between the vMCI (n = 39) and CU (n = 39) groups (F(1, 76) = 1.37, P = .245). Plasma NfL correlates with global cognition at baseline in individuals with vMCI, and is associated with decline in global cognition during CR. Our findings increase understanding of NfL and neurobiological mechanisms associated with cognitive decline in vMCI.

Predictors of cognitive aging profiles over 15 years: A longitudinal population-based study.

The present study aimed to characterize profiles of cognitive aging and how these can be predicted from interindividual differences in demographic, lifestyle, health, and genetic factors. The participants were 1,966 older adults (mean baseline age = 71.6 years; 62.9% female), free from dementia at baseline and with at least two cognitive assessments over the 15-year follow-up, from the population-based Swedish National Study on Aging and Care in Kungsholmen. The cognitive assessment comprised tests of semantic and episodic memory, letter and category fluency, perceptual speed, and executive function. First, we estimated the level and change within each of the cognitive domains with linear mixed effect models, based on which we grouped our sample into participants with "maintained high cognition," "moderate cognitive decline," or "accelerated cognitive decline." Second, we analyzed determinants of group membership within each cognitive domain with multinomial logistic regression. Third, group memberships within each cognitive domain were used to derive general cognitive aging profiles with latent class analysis. Fourth, the determinants of these profile memberships were analyzed with multinomial logistic regression. Follow-up analyses targeted profiles and predictors specifically related to the rate of cognitive change. We identified three latent profiles of overall cognitive performance during the follow-up period with 31.6% of the sample having maintained high cognition, 50.6% having moderate cognitive decline, and 17.8% having accelerated cognitive decline. In multiadjusted analyses, maintained high cognition was predicted by female sex, higher education, and faster walking speed. Smoking, loneliness, and being an ε4 carrier were associated with a lower likelihood of maintained high cognition. Higher age, diagnosis of diabetes, depression, and carrying the apolipoprotein E ε4 allele increased the likelihood of accelerated cognitive decline. Factors at baseline that could significantly predict profile membership within the specific cognitive domains included age, sex, years of education, walking speed, diabetes, and the ε4 allele. Of note, these factors differed across cognitive domains. In sum, we identified demographic, lifestyle, health, and genetic factors of interindividual differences in domain-specific and general cognitive aging profiles, some of which are modifiable. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Do we all do the same things? Applicability of daily activities at the intersection of demographics.

To evaluate the extent to which demographic factors-and their intersections-influence the applicability of items assessing activities of daily living (ADLs) in a sample of older adults. Participants' (n = 44,713) Functional Activities Questionnaire (FAQ) scores from a multicenter database were evaluated to see how participant and collateral demographics, contextual, and clinical characteristics impacted ADL nonapplicability (NA). Collateral, contextual, and clinical characteristics were matched in those with and without NA. The effect of participant demographics and their interactions on NA responses were modeled with logistic regression. At least one FAQ item (most commonly bill payment, taxes, playing games, and meal preparation) was rated as NA in up to one third of participants across ethnoracial groups. Dementia staging had the largest impact on NA, followed by participant demographics. In a matched sample, logistic models revealed that participant demographics, in particular sex, best predicted NA. However, meaningful interactions with ethnoracial group were noted for bill payment, taxes, meal preparation, and game engagement, suggesting that demographic intersections (e.g., younger vs. older Latinxs) meaningfully predict whether a given ADL was applicable to an individual participant. Neuropsychology is predicated on accurate assessments of both cognition and daily functioning and, in an increasingly diverse aging population, there should be careful consideration of demographic factors, their interactions, and historical contexts that drive day-to-day demands. This study establishes limitations of existing measures and paths forward for creating fair measures of functioning in older adults. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

PINK1 knockout rats show premotor cognitive deficits measured through a complex maze

Cognitive decline in Parkinson’s disease (PD) is a critical premotor sign that may occur in approximately 40% of PD patients up to 10 years prior to clinical recognition and diagnosis. Delineating the mechanisms and specific behavioral signs of cognitive decline associated with PD prior to motor impairment is a critical unmet need. Rodent PD models that have an impairment in a cognitive phenotype for a time period sufficiently long enough prior to motor decline can be useful to establish viable candidate mechanisms. Arguably, the methods used to evaluate cognitive decline in rodent models should emulate methods used in the assessment of humans to optimize translation. Premotor cognitive decline in human PD can potentially be examined in the genetically altered PINK1−/− rat model, which exhibits a protracted onset of motor decline in most studies. To increase translation to cognitive assessment in human PD, we used a modified non-water multiple T-maze, which assesses attention, cognitive flexibility, and working memory similarly to the Trail Making Test (TMT) in humans. Similar to the deficiencies revealed in TMT test outcomes in human PD, 4-month-old PINK1−/− rats made more errors and took longer to complete the maze, despite a hyperkinetic phenotype, compared to wild-type rats. Thus, we have identified a potential methodological tool with cross-species translation to evaluate executive functioning in an established PD rat model.

Prediabetes Increases the Risk of Frailty in Older Adults With Prefrail Hypertension: Beneficial Effects of Metformin.

Prediabetes has garnered increasing attention due to its association with cardiovascular conditions, especially hypertension, which heightens the risk of prefrailty and frailty among older individuals. We screened elders with prefrail hypertension from March 2021 to January 2023. We assessed the correlation linking cognitive dysfunction (Montreal Cognitive Assessment score), insulin resistance (triglyceride-to-glucose index), and physical impairment (5-meter gait speed). Then, we measured the risk of developing frailty after a 1-year follow-up period, adjusting the outcome using multivariable Cox regression analysis. We also investigated the impact of administering 500 mg of metformin once daily to a subset of frail subjects for an additional 6 months. We assessed the relationship between the triglyceride-to-glucose index and the Montreal Cognitive Assessment score, observing a significant correlation (r, 0.880; P<0.0001). Similarly, we analyzed the association between the triglyceride-to-glucose index and 5-meter gait speed, uncovering a significant link between insulin resistance and physical impairment (r, 0.809; P<0.0001). Prediabetes was found to significantly (P<0.0001) elevate the risk of frailty development compared with individuals without prediabetes by the end of the 1-year follow-up, a finding confirmed via multivariable analysis with Cox regression. Furthermore, among the subgroup of subjects who developed frailty, those who received metformin exhibited a significant decrease in frailty levels (P<0.0001). Insulin resistance and prediabetes play substantial roles in the development of cognitive and physical impairments, highlighting their importance in managing hypertension, even before the onset of frank diabetes. Metformin, a well-established drug for the treatment of diabetes, has shown favorable effects in mitigating frailty.

Association of plasma biomarkers of Alzheimer's disease and related disorders with cognition and cognitive decline: The MYHAT population-based study.

Plasma biomarkers of Alzheimer's disease and related dementias predict global cognitive performance and decline over time; it remains unclear how they associate with changes in different dementia syndromes affecting distinct cognitive domains. In a prospective study with repeated assessments of a randomly selected population-based cohort (n=787, median age 73), we evaluated performance and decline in different cognitive domains over up to 8 years in relation to plasma concentrations of amyloid beta 42/40 (Aβ42/40) ratio, phosphorylated tau181 (p-tau181), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP). Cross-sectionally, memory showed the strongest associations with p-tau181, and attention, executive, and visuospatial functions with NfL.Longitudinally, memory decline was distinguishable with all biomarker profiles dichotomized according to data-driven cutoffs, most efficiently with Aβ42/40. GFAP and Aβ42/40 were the best discriminators of decline patterns in language and visuospatial functions, respectively. These relatively non-invasive tests may be beneficial for clinical screening after replication in other populations and validation through neuroimaging or cerebrospinal fluid analysis. We performed a prospective study with up to 8 years of repeated domain-specific cognitive assessments and baseline plasma Alzheimer's disease and related dementias biomarker measurements in a randomly selected population-based cohort. We considered distinct growth curves of trajectories of different cognitive domains and survival bias induced by missing data by adding quadratic time and applying joint modeling technique. Cross-sectionally, memory showed the strongest associations with plasma phosphorylated tau181, while attention, executive, and visuospatial functions were most strongly associated with neurofilament light chain. Longitudinally, memory and visuospatial declines were most efficiently distinguished by dichotomized amyloid beta 42/40 profile among all plasma biomarkers, while language was by dichotomized glial fibrillary acidic protein. These relatively non-invasive tests may be beneficial for clinical screening; however, they will need replication in other populations and validation through neuroimaging and/or cerebrospinal fluid assessments.