Cognitive Trajectories Research Articles

Dynamic Features of Body Mass Index in Late Life Predict Cognitive Trajectories and Alzheimer's Disease: A Longitudinal Study.

The causal relationships of late-life body mass index (BMI) with Alzheimer's disease (AD) remains debated. We aimed to assess the associations of dynamic BMI features (ΔBMIs) with cognitive trajectories, AD biomarkers, and incident AD risk. We analyzed an 8-year cohort of 542 non-demented individuals who were aged ≥65 years at baseline and had BMI measurements over the first 4 years. ΔBMIs were defined as changing extent (change ≤ or >5%), variability (standard deviation), and trajectories over the first 4 years measured using latent class trajectory modeling. Linear mixed-effect models were utilized to examine the influence of ΔBMIs on changing rates of AD pathology biomarkers, hippocampus volume, and cognitive functions. Cox proportional hazards models were used to test the associations with AD risk. Stratified analyzes were conducted by the baseline BMI group and age. Over the 4-year period, compared to those with stable BMI, individuals who experienced BMI decreases demonstrated accelerated declined memory function (p = 0.006) and amyloid-β deposition (p = 0.034) while BMI increases were associated with accelerated hippocampal atrophy (p = 0.036). Three BMI dynamic features, including stable BMI, low BMI variability, and persistently high BMI, were associated with lower risk of incident AD (p < 0.005). The associations were validated over the 8-year period after excluding incident AD over the first 4 years. No stratified effects were revealed by the BMI group and age. High and stable BMI in late life could predict better cognitive trajectory and lower risk of AD.

Tracking cognitive trajectories in older survivors of COVID-19 up to 2.5 years post-infection.

Emerging evidence suggests that neurological and other post-acute sequelae of COVID-19 can persist beyond or develop following SARS-CoV-2 infection. However, the long-term trajectories of cognitive change after a COVID-19 infection remain unclear. Here we investigated cognitive changes over a period of 2.5 years among 1,245 individuals aged 60 years or older who survived infection with the original SARS-CoV-2 strain in Wuhan, China, and 358 uninfected spouses. We show that the overall incidence of cognitive impairment among older COVID-19 survivors was 19.1% at 2.5 years after infection and hospitalization, evaluated using the Telephone Interview for Cognitive Status-40. Cognitive decline primarily manifested in individuals with severe COVID-19 during the initial year of infection, after which the rate of decline decelerated. Severe COVID-19, cognitive impairment at 6 months and hypertension were associated with long-term cognitive decline. These findings reveal the long-term cognitive trajectory of the disease and underscore the importance of post-infection cognitive care for COVID-19 survivors.

Hemoglobin levels and cognitive trajectory: unveiling prognostic insights in post-stroke geriatric cohort

PurposeEvidence is scarce regarding the association between anemia and alterations in cognitive level among hospitalized older patients. We aimed to evaluate the associations between baseline hemoglobin (Hb) levels and changes in cognitive level in patients undergoing rehabilitation after stroke. MethodsA retrospective cohort study was conducted, encompassing consecutively hospitalized post-stroke patients. Data on serum Hb levels were extracted from medical records, specifically tests conducted within 24 hours of admission. Primary outcomes included discharge scores for cognitive function assessed by the cognitive domain of the Functional Independence Measure (FIM-cognition) and the corresponding change in FIM-cognition during hospitalization. Another outcome measure was the length of hospital stay. Multivariate linear regression analyses were employed to assess the association between Hb levels at admission and the designated outcomes, adjusting for potential confounding factors. ResultsData from 955 patients (mean age 73.2 years; 53.6% men) were included in the analysis. The median Hb level at admission was 13.3 [11.9, 14.5] g/dL. After fully adjusting for confounding factors, the baseline Hb level was significantly and positively associated with FIM-cognition at discharge (β = 0.045, p = 0.025) and its gain (β = 0.073, p = 0.025). Further, the baseline Hb level was independently and negatively associated with length of hospital stay (β = -0.013, p = 0.026). ConclusionElevated baseline Hb levels are correlated with preserved cognitive level and shorter hospital stays in post-stroke patients. Evaluating anemia at the outset serves as a crucial prognostic indicator.

Continuous β-Amyloid CSF/PET Imbalance Model to Capture Alzheimer Disease Heterogeneity.

Discordance between CSF and PET biomarkers of β-amyloid (Aβ) might reflect an imbalance between soluble and aggregated species, possibly reflecting disease heterogeneity. Previous studies generally used binary cutoffs to assess discrepancies in CSF/PET biomarkers, resulting in a loss of information on the extent of discordance. In this study, we (1) jointly modeled Aβ-CSF/PET data to derive a continuous measure of the imbalance between soluble and fibrillar pools of Aβ, (2) investigated factors contributing to this imbalance, and (3) examined associations with cognitive trajectories. Across 822 cognitively unimpaired (n = 261) and cognitively impaired (n = 561) Alzheimer's Disease Neuroimaging Initiative individuals (384 [46.7%] females, mean age 73.0 ± 7.4 years), we fitted baseline CSF-Aβ42 and global Aβ-PET to a hyperbolic regression model, deriving a participant-specific Aβ-aggregation score (standardized residuals); negative values represent more soluble relative to aggregated Aβ and positive values more aggregated relative to soluble Aβ. Using linear models, we investigated whether methodological factors, demographics, CSF biomarkers, and vascular burden contributed to Aβ-aggregation scores. With linear mixed models, we assessed whether Aβ-aggregation scores were predictive of cognitive functioning. Analyses were repeated in an early independent validation cohort of 383 Amyloid Imaging to Prevent Alzheimer's Disease Prognostic and Natural History Study individuals (224 [58.5%] females, mean age 65.2 ± 6.9 years). The imbalance model could be fit (pseudo-R2 = 0.94) in both cohorts, across CSF kits and PET tracers. Although no associations were observed with the main methodological factors, lower Aβ-aggregation scores were associated with larger ventricular volume (β = 0.13, p < 0.001), male sex (β = -0.18, p = 0.019), and homozygous APOE-ε4 carriership (β = -0.56, p < 0.001), whereas higher scores were associated with increased uncorrected CSF p-tau (β = 0.17, p < 0.001) and t-tau (β = 0.16, p < 0.001), better baseline executive functioning (β = 0.12, p < 0.001), and slower global cognitive decline (β = 0.14, p = 0.006). In the validation cohort, we replicated the associations with APOE-ε4, CSF t-tau, and, although modestly, with cognition. We propose a novel continuous model of Aβ CSF/PET biomarker imbalance, accurately describing heterogeneity in soluble vs aggregated Aβ pools in 2 independent cohorts across the full Aβ continuum. Aβ-aggregation scores were consistently associated with genetic and AD-associated CSF biomarkers, possibly reflecting disease heterogeneity beyond methodological influences.

Associations of Epigenetic Age Estimators With Cognitive Function Trajectories in the Women's Health Initiative Memory Study.

Epigenetic age estimators indicating faster/slower biological aging vs chronological age independently associate with several age-related outcomes; however, longitudinal associations with cognitive function are understudied. We examined associations of epigenetic age estimators with cognitive function measured annually. This longitudinal study consisted of older women enrolled in the Women's Health Initiative Memory Study with DNA methylation (DNAm) collected at baseline (1995-1998) from 3 ancillary studies and were followed up to 13 years. Global cognitive function was measured annually by Modified Mini-Mental State Examination (3MS; baseline-2007) and by modified Telephone Interview for Cognitive Status (TICS-m, 2008-2021). We calculated 5 epigenetic age estimators: extrinsic AgeAccel, intrinsic AgeAccel, AgeAccelPheno, AgeAccelGrim2, Dunedin Pace of Aging Calculated From the Epigenome (DunedinPACE), and AgeAccelGrim2 components (DNA-based plasma protein surrogates). We estimated longitudinal epigenetic age estimator-cognitive function associations using linear mixed-effects models containing age, education, race or ethnicity, and subsequently alcohol, smoking, body mass index, and comorbidities. We examined effect modification by APOE ε4 carriage. A total of 795 participants were enrolled. The mean baseline age was 70.8 ± 4 years (10.7% Black, 3.9% Hispanic or Latina, 85.4% White), A 1-SD (0.12) increment in DunedinPACE associated with faster annual declines in TICS-m scores in minimally adjusted (β = -0.118, 95% CI -0.202 to -0.034; p = 0.0006) and fully adjusted (β = -0.123, 95% CI -0.211 to -0.036; p = 0.006) models. AgeAccelPheno associated with faster annual declines in TICS-m with minimal adjustment (β = -0.091, 95% CI -0.176 to -0.006; p = 0.035) but not with full adjustment. No other epigenetic age estimators associated with changes in 3MS or TICS-m. Higher values of DNAm-based surrogates of growth differentiation factor 15, beta-2 microglobulin, Cystatin C, tissue inhibitor metalloproteinase 1, and adrenomedullin associated with faster annual declines in 3MS and TICS-m. Higher DNAm log A1c associated with faster annual declines in TICS-m only. DunedinPACE associated with faster annual declines in 3MS among APOE ε4 carriers but not among noncarriers (p-interaction = 0.020). Higher DunedinPACE associated with faster declines in TICS-m and 3MS scores among APOE ε4 carriers. DunedinPACE may help identify older women at risk of future cognitive decline. Limitations include the ancillary studies that collected epigenetic data not designed to study epigenetics and cognitive function. We examined epigenetic age estimators with global cognitive function and not specific cognitive domains. Findings may not generalize to men and more diverse populations.

Sex and gender differences in cognitive resilience to aging and Alzheimer's disease.

Sex and gender-biological and social constructs-significantly impact the prevalence of protective and risk factors, influencing the burden of Alzheimer's disease (AD; amyloid beta and tau) and other pathologies (e.g., cerebrovascular disease) which ultimately shape cognitive trajectories. Understanding the interplay of these factors is central to understanding resilienceand resistance mechanismsexplaining maintained cognitive function andreduced pathology accumulation in aging and AD.In this narrative review, the ADDRESS! Special Interest Group (Alzheimer's Association) adopted a multidisciplinary approach to provide the foundations and recommendations for future research into sex- and gender-specific drivers of resilience, including a sex/gender-oriented review of risk factors, genetics, AD and non-AD pathologies, brain structure and function, and animal research.We urge the field to adopt a sex/gender-aware approach to resilience to advance our understanding of the intricate interplay of biological and social determinants and consider sex/gender-specific resilience throughout disease stages. HIGHLIGHTS: Sex differences in resilience to cognitive decline vary by age and cognitive status. Initial evidence supports sex-specific distinctions in brain pathology. Findings suggest sex differences in the impact of pathology on cognition. There is a sex-specific change in resilience in the transition to clinical stages. Gender and sex factors warrant study: modifiable, immune, inflammatory, and vascular.

Association Between Plasma Levels of Vitamin B12 and Cognitive Trajectory: A Community-Based Cohort of Older Adults in China

Association Between Plasma Levels of Vitamin B12 and Cognitive Trajectory: A Community-Based Cohort of Older Adults in China

Associations Between Dietary Pattern and Global Cognitive Ability Trajectories Across the Life Course: Longitudinal Analysis of the 1946 British Birth Cohort

Associations Between Dietary Pattern and Global Cognitive Ability Trajectories Across the Life Course: Longitudinal Analysis of the 1946 British Birth Cohort

Historic Cognitive Function Trajectories as Predictors of Sedentary Behavior and Physical Activity in Older Adults.

We examined whether trajectories of cognitive function over 10 years predict later-life physical activity (PA), sedentary time (ST), and sleep. Participants were from the Adult Changes in Thought (ACT) cohort study. We included 611 ACT participants who wore accelerometers and had 3+ measures of cognition in the 10 years prior to accelerometer wear. The Cognitive Assessment Screening Instrument (CASI) measured cognition and was scored using item-response theory (IRT). activPAL and ActiGraph accelerometers worn over 7 days measured ST and PA outcomes. Self-reported time in bed and sleep quality measured sleep outcomes. Analyses used growth mixture modeling to classify CASI-IRT scores into latent groups and examine associations with PA, ST, and sleep including demographic and health covariates. Participants (Mean age = 80.3 (6.5) years, 90.3% White, 57.1% female, 29.3% had less than 16 years of education) fell into 3 latent trajectory groups: average stable CASI (56.1%), high stable CASI (34.0%), and declining CASI (9.8%). The declining group had 16 minutes less stepping time (95% confidence interval [95% CI]: 0.6, 31.4), 1517 fewer steps per day (95% CI: 138, 2896), and 16.3 minutes per day less moderate-to-vigorous PA (95% CI: 1.3, 31.3) compared to the average stable group. There were no associations between CASI trajectory and sedentary or sleep outcomes. Declining cognition predicted lower PA providing some evidence of a reverse relationship between PA and cognition in older adults. However, this conclusion is limited by having outcomes at only one time point, a nonrepresentative sample, self-reported sleep outcomes, and using a global cognition measure.

Risk and protective factors for cognitive decline in Brazilian lower educated older adults: A 15-year follow-up study using group-based trajectory modelling

BackgroundPatterns of cognitive change and modifiable factors for cognitive decline versus stable cognitive trajectories have rarely been described in lower-educated older adults. ObjectivesWe aimed to identify long-term trajectories of cognitive functioning and possible factors associated with cognitive decline. Design and participantsWe used data from 1,042 adults aged ≥ 60 participating in the Health, Welfare and Aging Study (SABE), São Paulo, Brazil, without cognitive impairment at baseline. Data were collected across four waves (2000–2015). Group-based trajectory modelling was used to identify cognitive trajectories. Associations with socioeconomic variables, childhood background, lifestyle, and cardiovascular risk factors were explored using weighted multinomial logistic regressions. MeasurementsThe abbreviated Mini-Mental State Examination was used to measure cognition. ResultsThree cognitive trajectories were identified: stable (n= 754, 68.6%), mild-decline (n= 183, 20.8%), and strong-decline (n= 105, 10.7%). At baseline, respondents in the strong-decline group were more likely to be older than those with stable and mild-decline trajectories. Furthermore, participants in both the mild and strong-decline groups were more likely to have no schooling, be divorced/separated, receive less than 4 monthly wages, and be underweight (BMI < 18.5) compared to the stable group. Finally, the mild-decline group was more likely to have lived in rural areas during childhood than participants located in a stable trajectory. ConclusionsOur findings suggest that interventions to reduce cognitive decline for low-educated older adults might include strategies addressing inequalities and improving modifiable risk factor burden.

Cognitive safety of focused ultrasound thalamotomy for tremor: 1-year follow-up results of the COGNIFUS part 2 study.

In the COGNitive in Focused UltraSound (COGNIFUS) study, we examined the 6-month cognitive outcomes of patients undergoing MRgFUS thalamotomy. This study endorsed the safety profile of the procedure in terms of cognitive functions that cannot be evaluated in real-time during the procedure unlike other aspects. The aim of the COGNIFUS Part 2 study was to investigate the cognitive trajectory of MRgFUS patients over a 1-year period, in order to confirm long-term safety and satisfaction. We prospectively evaluated the cognitive and neurobehavioral profile of patients with essential tremor (ET) or Parkinson's Disease (PD) related tremor undergoing MRgFUS thalamotomy at 1 year-follow-up following the treatment. The sample consists of 50 patients (male 76%; mean age ± SD 69.0 ± 8.56; mean disease duration ± SD 12.13 ± 12.59; ET 28, PD 22 patients). A significant improvement was detected at the 1 year-follow-up assessment in anxiety and mood feelings (Hamilton Anxiety rating scale 5.66 ± 5.02 vs. 2.69 ± 3.76, p ≤ <0.001; Beck depression Inventory II score 3.74 ± 3.80 vs. 1.80 ± 2.78, p = 0.001), memory domains (Rey Auditory Verbal Learning Test, immediate recall 31.76 ± 7.60 vs. 35.38 ± 7.72, p = 0.001 and delayed recall scores 5.57 ± 2 0.75 vs. 6.41 ± 2.48), frontal functions (Frontal Assessment Battery score 14.24 ± 3.04 vs. 15.16 ± 2.74) and in quality of life (Quality of life in Essential Tremor Questionnaire 35.00 ± 12.08 vs. 9.03 ± 10.64, p ≤ 0.001 and PD Questionnaire -8 7.86 ± 3.10 vs. 3.09 ± 2.29, p ≤ 0.001). Our study supports the long-term efficacy and cognitive safety of MRgFUS treatment for ET and PD.

Cerebrospinal fluid biomarkers and cognitive trajectories in patients with Alzheimer’s disease and a history of traumatic brain injury

Traumatic brain injury (TBI) and Alzheimer’s disease (AD) have overlapping mechanisms but it remains unknown if pathophysiological characteristics and cognitive trajectories in AD patients are influenced by TBI history. Here, we studied AD patients (stage MCI or dementia) with TBI history (ADTBI+, n=110), or without (ADTBI-, n=110) and compared baseline CSF concentrations of amyloid beta 1–42 (Aβ42), phosphorylated tau181 (pTau181), total tau, neurofilament light chain (NfL), synaptosomal associated protein-25kDa (SNAP25), neurogranin (Ng), neuronal pentraxin-2 (NPTX2) and glutamate receptor-4 (GluR4), as well as differences in cognitive trajectories using linear mixed models. Explorative, analyses were repeated within stratified TBI groups by TBI characteristics (timing, severity, number). We found no differences in baseline CSF biomarker concentrations nor in cognitive trajectories between ADTBI+ and ADTBI- patients. TBI >5 years ago was associated with higher NPTX2 and a tendency for higher SNAP25 concentrations compared to TBI ≤ 5 years ago, suggesting that TBI may be associated with long-term synaptic dysfunction only when occurring before onset or in a pre-clinical disease stage of AD.

CD4 nadir and neurocognitive trajectories in people living with HIV.

Human immunodeficiency virus-associated neurocognitive disorders persist in the combination antiretroviral therapy era. CD4 nadir is a well-established predictor of cognition cross-sectionally, but its impact on longitudinal neurocognitive (NC) trajectories is unclear. The few studies on this topic examined trajectories of global cognition, rather than specific NC domains. The current study examined CD4 nadir in relation to domain-specific NC decline. 132 HIV + adults from the Temple/Drexel Comprehensive NeuroHIV Center, Clinical and Translational Research Support Core Cohort were administered comprehensive NC assessments longitudinally, with last visit occurring an average of 12years after CD4 nadir. Linear mixed models were used to examine CD4 nadir in relation to longitudinal NC trajectories in three empirically identified NC domains: speed/executive function (S/EF), visuospatial memory (VM), and verbal fluency (VF). CD4 nadir was associated with change in VF (p = 0.020), but not with S/EF or VM. Specifically, those with CD4 nadir < 200 demonstrated increasing VF over time (p = .002), whereas those with CD4 nadir > 200 demonstrated stable VF (p = .568), though these differing trajectories may partly reflect regression to the mean or differential practice effect. CD4 dynamics over time were analyzed as potential mechanisms for the identified associations, with mixed findings. While low CD4 nadir has been associated with weaker neurocognition among people living with HIV, the results of this study suggest that low CD4 nadir is not associated with ongoing decline a decade later. Nadir-related deficits in VF may be stable or even improve over time, possibly reflecting the beneficial cognitive effects of long-term treatment and immune reconstitution.

Differences in Cognitive Trajectories of Dementia: Comparison of Alzheimer’s Disease Dementia and Dementia with Lewy Bodies in a Korean Patient Cohort

Introduction: Prediction of the dementia progression is important for patient management. We aimed to investigate the cognitive trajectories of Alzheimer’s disease dementia (ADD) and dementia with Lewy bodies (DLB) according to the initial structural change measured by comprehensive visual rating scales (CVRS). Methods: We retrospectively included the patients who initially visited the Dementia Clinic of Chonnam National University Hospital between 2010 and 2012. All patients underwent dementia workup including neuropsychological battery (Seoul Neuropsychological Screening Battery, SNSB). We recruited the participant who underwent SNSB annually for 3 years successively. A total of 136 patients of ADD and 63 patients of DLB were included for analysis. We analyzed the decline pattern of the cognitive profile according to the initial brain structural changes. Results: The general cognitive trajectories between ADD and DLB patients were not different. However, DLB patients showed more rapid decline of cognitive function in language and related function, visual memory function, and frontal executive function. The scores were lower in participants with DLB with the lesser atrophy group in attention, visuospatial function, and frontal executive function. In analysis of the cognitive trajectories, the visual memory domain declined rapidly in the DLB with lesser atrophy group compared with the ADD with lesser atrophy group. Conclusion: We founded that the differences in the visual cognitive profile in ADD and DLB patients in serial follow-up of neuropsychological tests. It is prominent in the mild structural change group of ADD and DLB.

Association Between Cognitive Trajectories and Subsequent Health Status, Depressive Symptoms, and Mortality Among Older Adults in the United States: Findings From a Nationally Representative Study

Abstract Background Cognitive decline may be an early indicator of major health issues in older adults, though research using population-based data is lacking. Researchers objective was to assess the relationships between distinct cognitive trajectories and subsequent health outcomes, including health status, depressive symptoms, and mortality, using a nationally representative cohort. Methods Data were drawn from the National Health and Aging Trends Study. Global cognition was assessed annually between 2011 and 2018. The health status of 4 413 people, depressive symptoms in 4 342 individuals, and deaths among 5 955 living respondents were measured in 2019. Distinct cognitive trajectory groups were identified using an innovative Bayesian group-based trajectory model. Ordinal logistic, Poisson, and logistic regression models were used to examine the associations between cognitive trajectories and subsequent health outcomes. Results Researchers identified five cognitive trajectory groups with distinct baseline values and subsequent changes in cognitive function. Compared with the group with stably high cognitive function, worse cognitive trajectories (ie, lower baseline values and sharper declines) were associated with higher risks of poor health status, depressive symptoms, and mortality, even after adjusting for relevant covariates. Conclusions Among older adults, worse cognitive trajectories are strongly associated with subsequent poor health status, high depressive symptoms, and high mortality risks. Regular screening of cognitive function may help to facilitate early identification and interventions for older adults susceptible to adverse health outcomes.

Examining behavioral settings and affordative space for the case of autism spectrum conditions in embodied cognition

ABSTRACT The aim of the paper is to deepen into a theoretical account on the role of behavioral settings and relational affordative space and how this perspective can be used to reconceptualize various human cognitive developmental trajectories and conditions. In the course of this theoretical work, we want to contribute in rethinking developmental trajectories based on the role of behavioral settings and relational affordances from an embodied perspective. Behavioral settings emerge from joint actions in conjunction with the affordances available. These affordances will have multiple levels and kinds of meanings for the organism which is why we need to distinguish between the general affordances for a form of life and the particular affordances for particular agents that are generated through sensorimotor interactions. We propose to apply this theoretical frame in different developmental conditions, taking as a leading example the Autistic Spectrum, extending it to other lived experiences of other groups marginalized by “normative behavioral settings” – and the ensuing ethical concerns.

Low testosterone levels relate to poorer cognitive function in women in an APOE-ε4-dependant manner

BackgroundPast research suggests that low testosterone levels relate to poorer cognitive function and higher Alzheimer’s disease (AD) risk; however, these findings are inconsistent and are mostly derived from male samples, despite similar age-related testosterone decline in females. Both animal and human studies demonstrate that testosterone’s effects on brain health may be moderated by apolipoprotein E ε4 allele (APOE-ε4) carrier status, which may explain some previous inconsistencies. We examined how testosterone relates to cognitive function in older women versus men across healthy aging and the AD continuum and the moderating role of APOE-ε4 genotype.MethodsFive hundred and sixty one participants aged 55–90 (155 cognitively normal (CN), 294 mild cognitive impairment (MCI), 112 AD dementia) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), who had baseline cognitive and plasma testosterone data, as measured by the Rules Based Medicine Human DiscoveryMAP Panel were included. There were 213 females and 348 males (self-reported sex assigned at birth), and 52% of the overall sample were APOE-ε4 carriers. We tested the relationship of plasma testosterone levels and its interaction with APOE-ε4 status on clinical diagnostic group (CN vs. MCI vs. AD), global, and domain-specific cognitive performance using ANOVAs and linear regression models in sex-stratified samples. Cognitive domains included verbal memory, executive function, processing speed, and language.ResultsWe did not observe a significant difference in testosterone levels between clinical diagnostic groups in either sex, regrardless of APOE-ε4 status. Across clinical diagnostic group, we found a significant testosterone by APOE-ε4 interaction in females, such that lower testosterone levels related to worse global cognition, processing speed, and verbal memory in APOE-ε4 carriers only. We did not find that testosterone, nor its interaction with APOE-ε4, related to cognitive outcomes in males.ConclusionsFindings suggest that low testosterone levels in older female APOE-ε4 carriers across the aging-MCI-AD continuum may have deleterious, domain-specific effects on cognitive performance. Although future studies including additional sex hormones and longitudinal cognitive trajectories are needed, our results highlight the importance of including both sexes and considering APOE-ε4 carrier status when examining testosterone’s role in cognitive health.

The progression of cognitive impairment and its influencing factors in older adults based on longitudinal item response theory.

Understanding the development of cognitive impairment and its influencing factors in older adults is crucial for formulating early intervention strategies. To identify the early dimensions of cognitive impairment and provide a comprehensive description of the trajectories of cognitive decline in older adults prior to death. Based on the data of 9883 older adults in the Chinese Longitudinal Healthy Longevity Survey from 2002 to 2018, a longitudinal item response theory (Longitudinal IRT) model including covariates was applied to estimate the following parameters. The items in which older adults encountered obstacles first had the least difficulty parameters (δ). The earlier the information curve of an item is lifted, the more information it provides in the early stages of cognitive impairment. Regression coefficient (β) represents the relative rate of cognitive decline. The cognitive impairment values estimated from the Longitudinal IRT were fitted to a mixed-effects model to examine cognitive impairment trajectories. 'Draw the figure on B Card' (δ = -0.816) was the most challenging item, followed by 'recalling 'clothes" (δ = 0.348) and 'recalling 'apples" (δ = 0.419), while 'name the 'pen" (δ = 4.402) was the simplest instruction for the old adults. The curves of the items in the recall dimension began to rise in the early stages of cognitive impairment. Cognitive impairment of older adults who were women (β = 0.061), elder (β = 0.111), smokers (β = 0.060), living in rural areas (β = 0.052), not participating in organised social activities (β = 0.092), suffering from hypertension (β = 0.022), hyperglycaemia (β = 0.035), dyslipidaemia (β = 0.314), low education levels (β = 0.128), manual labourers (β = 0.027), and eventual development of dementia (β = 0.212) exhibited a more accelerated progression. These individuals also had poorer cognitive trajectories. Recall is the earliest dimension of cognitive impairment. The subjects who were women, elder, smokers, living in rural areas, not participating in organised social activities, suffering from hypertension, hyperglycaemia, dyslipidaemia, low education, manual labourers, and eventually development of dementia, had a faster descending speed and poorer trajectories.

Beyond the heart: Cognitive and verbal outcomes in Arab children with congenital heart diseases.

This study investigates how congenital heart diseases (CHD) characteristics and interventions affect cognitive and verbal skills in Arab children, while also uncovering previously unexplored connections between these skills and the quality of life (QoL) scores as perceived by both children and parents. A cross-sectional study was conducted in Jordan, involving 62 children with CHD aged 6-16. Data were collected through standardized intelligence tests (namely The Raven's Progressive Matrices Test and The Wechsler Intelligence Scale for Children) and QoL assessments. Sex, disease severity, cyanosis, CHD defect status, conducted operations, and types of interventions did not significantly influence cognitive scores. However, a significant difference was observed in Wechsler's scores between cyanotic and non-cyanotic children (p < .01) and between severe and moderate cases (p = .01). Further, a significant positive correlation was identified between Wechsler's Scores and QoL reported by parents (r = 0.33, p < .01). This correlation was particularly pronounced in the social and school functioning dimensions of QoL. This study highlights the need for personalized care approaches for children with CHDs based on their individual characteristics. While cognitive abilities did not directly correlate with children's QoL reports, a significant positive correlation between verbal skills and QoL reported by parents underscores the importance of effective communication in assessing a child's overall well-being. Future research should further examine the cognitive development in this population, employing neurocognitive investigations and longitudinal studies to gain a deeper understanding of their cognitive profiles and trajectories.

Delineating the Heterogeneity of Alzheimer’s Disease and Mild Cognitive Impairment Using Normative Models of Dynamic Brain Functional Networks

BackgroundAlzheimer’s disease (AD), which has been identified as the most common type of dementia, presents considerable heterogeneity in its clinical manifestations. Early intervention at the stage of mild cognitive impairment (MCI) holds potential in AD prevention. However, characterizing the heterogeneity of neurobiological abnormalities and identifying MCI subtypes pose significant challenges. MethodsWe constructed sex-specific normative age models of dynamic brain functional networks and mapped the deviations of the brain characteristics for individuals from multiple datasets, including 295 patients with AD, 441 patients with MCI, and 1160 normal control participants. Then, based on these individual deviation patterns, subtypes for both AD and MCI were identified using the clustering method, and their similarities and differences were comprehensively assessed. ResultsIndividuals with AD and MCI were clustered into 2 subtypes, and these subtypes exhibited significant differences in their intrinsic brain functional phenotypes and spatial atrophy patterns, as well as in disease progression and cognitive decline trajectories. The subtypes with positive deviations in AD and MCI shared similar deviation patterns, as did those with negative deviations. There was a potential transformation of MCI with negative deviation patterns into AD, and participants with MCI had a more severe cognitive decline rate. ConclusionsIn this study, we quantified neurophysiological heterogeneity by analyzing deviation patterns from the dynamic functional connectome normative model and identified disease subtypes of AD and MCI using a comprehensive resting-state functional magnetic resonance imaging multicenter dataset. The findings provide new insights for developing early prevention and personalized treatment strategies for AD.