Cognitive Syndrome Research Articles

Apathy as a Predictor of Motoric Cognitive Risk Syndrome

AbstractBackgroundApathy is a psychological syndrome, characterized by lack of motivation and interest, flattening of affect, and social withdrawal; that predicts cognitive decline including dementia. Current literature highlights apathy as a separate entity from depression, which is uniquely correlated to cognitive and functional decline in neurologic diseases like stroke and Parkinson’s Disease as well as in community dwelling‐older adults. Further, apathy may mediate the previously described association between depression and cognitive/functional decline. Our objectives were to 1) investigate the association between apathy at baseline and incident predementia syndromes including mild cognitive impairment (MCI) and motoric cognitive risk syndrome (MCR) and 2) explore the direct and indirect relationships of apathy and motoric cognitive outcomes.MethodWe prospectively studied the association between apathy (3‐item subscale of the Geriatric Depression Scale) and incident predementia syndromes in 542 community‐dwelling older adults enrolled in the Central Control of Mobility in Aging study, using Cox proportional hazard models. Associations were reported as hazard ratio (HR) with 95% confidence intervals (CIs), adjusting for age, education, baseline cognitive performance, and dysphoria. In a subset of 347 participants, we examined the mediating role of cytokines on the association between apathy and gait velocity in linear regression models at cross section. We also looked at the mediating role of apathy on the association between dysphoria and multimorbidity and gait velocity.ResultApathy was associated with incident MCR (HR 2.39, 95% CI: 1.10‐5.20), but not MCI. Linear regression models showed that Interleukin‐6 (Il‐6), but not C‐Reactive Protein was significantly associated with apathy adjusted for age, gender, and years of education (B = 0.037, 95% CI: 0.002–0.072, p = 0.04). Apathy was associated with a slower gait velocity (B = 14.45, 95% CI: 24.89–4.01, p = 0.01), cross sectionally. Mediation analyses demonstrated that IL‐6 modestly mediates the relationship between apathy and gait velocity. Additionally, apathy mediated the relationships between dysphoria and multimorbidity and gait velocity.ConclusionOverall, our findings indicate that apathy may be an early predictor of motoric cognitive decline, which precedes predementia syndromes. Inflammation plays a modest role, but the underlying biology of apathy warrants further investigation.

Trajectories of Motoric Cognitive Risk and Incident Dementia in Scotland

AbstractBackgroundMotoric cognitive risk syndrome (MCR) ‐ objective slow gait and subjective cognitive complaints ‐ is quick and easy to measure, making it a potentially useful clinical tool for identifying those at high risk of developing dementia. This is the first exploration of MCR syndrome’s predictive ability for incident dementia in a Scottish cohort (Lothian Birth Cohort 1936) and the first examination of the various trajectories of MCR.MethodWe classified a total of 680 community‐dwelling participants (mean [SD] age 76.3 [0.8] years) free from dementia into non‐MCR or MCR groups. We used cox proportional hazard methods to evaluate the risk of developing all‐cause dementia in the years following MCR diagnosis. Our final model adjusted for age, sex, comorbidity index, apolipoprotein E status, physical activity level, and years of education. We analysed the trajectories for everyone with MCR by tracking their outcomes over 9 years. All analyses were performed in R version 4.0.2.ResultThe prevalence of MCR at baseline was 5.6% (n = 38/680). After 9 years of follow‐up, 11.6% (n = 79/680) of the total cohort developed dementia. The presence of MCR increased the risk of dementia (adjusted hazard ratio 2.37 [95%CI 1.06‐5.32; p = 0.0359]). The trajectories of those with MCR at baseline were: i) reverted to healthy (n = 6/38), ii) ongoing MCR (n = 13/38), iii) progressed to dementia (n = 9/38), or iv) died (n = 10/38).ConclusionMCR showed similar prognostic ability for dementia in a Scottish cohort as for other populations. MCR could identify a target group for early interventions of modifiable risk factors to prevent incident dementia. Individuals with MCR follow similar trajectories to the related predementia syndrome, Mild Cognitive Impairment.

A cross‐national comparison of the risk factors associated with the Motoric Cognitive Risk syndrome in high and middle‐income countries

AbstractBackgroundThe Motoric Cognitive Risk (MCR) syndrome is associated with increased risk of Alzheimer’s disease and vascular dementia. MCR does not require cognitive or lab tests to diagnose, increasing its utility in resource‐poor settings. The specific risk factors associated with MCR in different high‐ and middle‐income countries are not established.MethodsWe examined the epidemiology of MCR in harmonized cross‐sectional data from 17,050 adults aged ≥ 65 years enrolled in the U.S. Health and Retirement Study (HRS; n = 3,748), English Longitudinal Study of Ageing (ELSA; n = 4,110), Mexican Health and Aging Study (MHAS; n = 738), the China Health and Retirement Study (CHARLES; n = 3,275), the Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI‐DAD; n = 1,276) and the Survey of Health, Ageing and Retirement in Europe (SHARE; n = 3,973). MCR was defined as the presence of cognitive complaints and slow gait in the absence of mobility disability and dementia. Risk factors included demographics [age, sex, education], medical [hypertension, diabetes, Parkinson’s, heart disease, stroke, obesity], sensorimotor [grip strength, hearing], psychological [depression], behavioral factors [smoking, sedentariness, sleep quality] and falls (see Table 1 for definitions). Logistic regression was used to examine factors associated with prevalent MCR.ResultsParticipants’ mean age in different cohorts ranged between 71.3 and 80.2 years. Proportion of females ranged between 45.3% and 60.9%. MCR prevalence was 3.6%, 2.1%, 8.9% 6.1%, 5.8% and 6.8% in HRS, ELSA, MHAS, CHARLES, LASI‐DAD and SHARE, respectively. Tables 2 and 3 show risk factors associated with each cohort in univariate and multivariable models. Despite some overlaps, specific risk factors were associated with each cohort with relative risk ratios ranging as follows: 0.4‐2.8 for education and multiple falls in HRS, 2.3‐7.1 for poor hearing and sedentariness in ELSA, 2.3‐2.6 for weak grip strength and diabetes in MHAS, 1.9‐2.2 for depression and sedentariness in CHARLES, 0.5‐5.3 for education and stroke in LASI‐DAD and 0.3‐2.4 for education and depression in SHARE.ConclusionIn community‐dwelling older adults from twenty countries (high‐ and middle‐income), specific risk factors were associated with MCR in each cohort – laying the foundation for preventing MCR and subsequently dementia in ethnically, culturally, and socioeconomically diverse populations.

Combining speech biomarkers for cognition and mood improves diagnostic accuracy between MCI and subjective cognitive decliners in a memory clinic sample

AbstractIntroductionDepressive symptoms are a common comorbidity in an old age memory clinic population. Cognitive and affective syndromes coexist, and supposedly modulate each other. While, there have been separate research streams on analysing speech to infer cognitive performance, as well as mood related symptoms, they are seldom investigated side‐by‐side. We present results from a small sub sample of a larger MCI and dementia cohort indicating that modelling both depressive symptoms and cognitive problems from speech can improve the diagnostic accuracy for MCI above speech biomarkers for cognition alone.MethodsThe ki:e Speech Biomarker for cognition (ki:e SB‐C; Tröger et al., 2022) and a free speech task were collected from 35 memory clinic participants (12F) with 10 of them having an MCI diagnosis (compare Table 1). From the free speech tasks (“Tell me about your upcoming vacation plans.”) we extracted speech features using ki:elements proprietary speech analysis engine SIGMA. Free speech features were corrected for cognitive performance, sex and age and then combined into a mood speech biomarker. To benchmark the diagnostic utility of both cognitive and mood speech biomarker side by side, we trained two groups of simple classifiers (tree based classifiers with leave one participant out cross validation) once with SB‐C alone and once with both SB‐C and the newly‐composed mood speech biomarker.ResultsBy combining the speech biomarker for cognition and mood diagnostic performance was significantly improved (AUC of 88%) as compared to classification with the SB‐C alone (AUC of 74%). The mood biomarker correlates significantly with the Geriatric Depression Scale (r = 0.39, p < 0.05). Most important free speech features were jitter, number or pauses, mean pause duration or pronoun rate.ConclusionOverall we present rare evidences that combining speech‐based digital biomarkers tapping both into cognition but also mood‐related symptoms helps to improve diagnostic accuracy in MCI patients. Though just a small feasibility study, the results are clearly encouraging and point towards potential application in both clinical practice as well as clinical research.

Decline in cognitive trajectories in the neuropathological spectrum of Lewy Body disease

AbstractBackgroundPathological Lewy body disease (LBD) may commonly present clinically as Parkinson’s disease dementia (PDD), Dementia with Lewy bodies (DLB) or Alzheimer’s disease dementia (ADD). Neuropathological definitions also include a group in which ADD is present, but the postmortem Lewy pathology does not meet threshold density and distribution levels for the neuropathological diagnosis of DLB (ADLB). Little is known about the cognitive profiles of patients with ADLB and despite common underlying pathology, studies delineating neuropsychological profiles in LBD are fraught with inconsistencies. We characterized the longitudinal cognitive trajectories defined by neuropsychological profiles in cases along the pathological spectrum of LBD.MethodCases from the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND) with a cognitive diagnosis of dementia at death and who at minimum, had two neuropsychological evaluations were included. Final neuropathological diagnosis was determined as LBD (neocortical or limbic LB ± AD), ADLB, and AD pathology only. LBD cases were categorized by their cognitive clinical syndromes as PDD and DLB. Global cognition was evaluated using MMSE. Neuropsychological domains of Memory, Executive function, language, attention, and visuospatial were evaluated. Mixed linear methods were used to predict longitudinal change for a given baseline MMSE.Result287 participants and 1874 participant‐years of data were included in this study. LBD (n = 115), and ADLB (52) groups were predominantly male, while AD (n = 114) group was primarily female. Baseline MMSE was similar across all pathologic groups. Linear mixed modelling methods showed faster decrease in memory domain scores (decreasing 0.22 units/year – 0.42 units/year faster, p = 0.01) in ADLB group compared to other groups. Significantly faster decline was noted in LBD and ADLB group in clock drawing (p<0.001), fluency scores (declining 1.02 unit/year faster p<0.001) compared to AD group. There was no difference between PDD and DLB clinical subgroups.ConclusionIn autopsy confirmed cases, ADLB had an accelerated trajectory of decline in memory tasks, while AD, and LBD appeared to have similar trajectories. In contrast, all groups with Lewy bodies progressed faster and showed accelerated decline compared to AD in measures of frontal‐subcortical functions. These results may inform antemortem classification of patients and diagnostic accuracy in these groups.

P177: Motoric cognitive risk syndrome is associated with MRI-derived brain age: the Arakawa Geriatric Cohort Study

Objective:Motoric cognitive risk (MCR) syndrome is characterized by slow gait speed and subjective cognitive decline, which could predict future dementia. Previous research reported the associations between MCR and gray matter volume reduction in total and specific cortical regions and increased white matter hyperintensities in the brain. However, knowledge is scarce on the relationship between MCR and neuroimaging-derived brain age. The present study explored the association between MCR and brain-predicted age differences.Methods:The present study is a cross-sectional study that involved 1,099 community- dwelling older adults in the Arakawa Ward, Tokyo, Japan, who were between 65 to 84 years old in 2016. In defining MCR, subjective cognitive decline was deemed positive for those who answered “Yes” to the question, “Do you feel that you have more problems with memory than most?” in the Geriatric Depression Scale. Slower gait speed was defined as walking slower than the -1 standard deviation of the age- and sex- stratified gait speed. Brain age was predicted on the 1,021 participants with brain magnetic resonance imaging without severe artifacts or lesions. We used the support vector regression algorithm using MATLAB's “fitrsvm” function, applying ten-fold cross-validation to the results of primary component analysis of the spatially normalized gray-matter images. We calculated the brain-predicted age difference (Brain-PAD) by subtracting the chronological age from the predicted brain age. After excluding the participants with dementia (N=23), the difference in the mean Brain-PAD between MCR+ and MCR- was compared with the Student's t-test. The association between MCR and Brain PAD was examined with multiple regression analyses, adjusting for clinical-demographical data.Results:The median ages were 72 for both MCR+ (N=96) and MCR- (N=902). The mean Brain-PAD was 3.29 for MCR+ and -0.19 for MCR- (p < .001, Hedges' g = -0.504). Multiple regression analysis showed a significant association between Brain- PAD and MCR (standardized β = 0.159, p < .001) after adjusting for covariates.Conclusion:The present findings suggest that MCR reflects accelerated brain aging, which may increase the risk of neurodegeneration. Future studies should examine the longitudinal trajectories of brain age and incident dementia in participants with MCR.

Motor alterations associated with cognitive impairment in a third‐level hospital

AbstractBackgroundCognition and motor function declines have been shown to precede cognitive impairments, and motor changes have been proposed as potential clinical biomarkers to help predict dementia syndromes; there are reports that gait speed declined a decade before the diagnosis of MCI and preceded declines in cognitive function tests. The slow gait speed associated with cognitive complaint, motor cognitive risk syndrome is a clinical biomarker for high risk of neurologic degeneration.MethodThis report is a secondary analysis from a transversal study, the inclusion criteria include adults from 60 or older, who complete evaluations at the baseline in a from a dementia clinic at a tertiary care center in Mexico. Gait performance were evaluated in all the participants which had to walk 10 meter distance and timed, slow gait were considered as those more than 1 meter/second. Variables such as sex, age, education, marital status, occupation, depression, anxiety, frailty, cognitive impairments and geriatric syndromes were considered for the analysis. The outcome was the description of the characteristics of gait disturbance in the follow‐up evaluation and their relationships with the variables discussed.ResultFinally, 222 patients were studied, highlighting a prevalence of 73% (n = 158) being female and 28% (n = 64) being male. A total of 72% (n = 160) of patients presented a speed <1m/s and 28% (n = 62) with a speed >1m/s. Polypharmacy, intestinal habit disorder, sensory deprivation, and housewife occupation were associated with a decrease in gait speed. The group with mild cognitive impairment, 32% (n = 72), predominantly had a gait speed of less than 1 m/s. Regarding functionality, we found that the moderate dependence group, 31% (n = 71), and pre‐frail patients, 32% (n = 72), had a greater association with a decrease in gait speed. A significant association was found between MMSE and gait speed (p = 0.003).ConclusionIt was found that female patients have a prevalence of slow walking speed <1m/sec. In addition, patients with mild cognitive impairment have a higher prevalence, which suggests that walking speed may be a prodromal sign for mild cognitive impairment. Only was significative sex, polypharmacy, and fraility.

Alzheimer´s Disease initial cognitive profile in an Argentinian cohort of individuals with Down Syndrome

AbstractBackgroundDown Syndrome [DS] is the most frequent cause of genetic developmental and intellectual disability. The lifetime risk of Alzheimer’s Disease [AD] in people with DS is more than 90%, with an earlier age of onset than the general population. There is ongoing debate whether there are significant differences in dementia presentation in the specific context of DS, with some studies suggesting a predominantly frontal phenotype with behavioural symptoms and others suggesting a more frequent amnestic presentation.The aim of this study was to characterize the initial cognitive profile of AD in a cohort of Argentinian adults with DS.MethodAdults with DS and prodromal or established AD dementia who were part of the IASDA (Argentinian initiative for the study of DS and AD) cohort or spontaneusly attended our Memory Clinic were included. Initial cognitive profile was determined by a semi‐structured interview conducted by a cognitive neurologist with the subject, their family and caregivers.ResultSixteen adults with DS were included. Fifty‐six percent (n = 9) were males. Mean age was 51 yo (42‐59 yo). Sixty‐two percent (n = 10) had premorbid moderate intellectual disability [DI], 25% (n = 4) had severe DI and 13% (n = 2) had mild DI.Fifty‐six percent (n = 9) had a clinical diagnosis of prodromal AD, and the remaining individuals had clinically established AD dementia. Fifty percent (n = 8) had positive amiloid biomarkers (determined by cerebral PiB‐PET or cerebrospinal fluid levels of Aβ42, phosphorylated‐tau and total‐tau), while the remaining subjects did not undergo amiloid biomarker assessment. Due to cognitive impairment, premorbid language impairment and/or premorbid severe DI, only 25% (n = 4) of individuals completed neuropsychological testing (CAMDEX‐DS, Cued Recall Task).Initial cognitive profile was charactirized as amnestic (single‐domain amnestic or multiple‐domain amnestic) in 81% percent (n = 13) of the cohort. Only 13% (n = 2) of the subjects had initial non‐amnestic syndromes, and in one case (6%) the initial cognitive syndrome was uncertain.ConclusionAmnestic cognitive impariment was the most frequent presentation of AD in this small cohort of Latin American adults with DS.

Distracted and unfocused driving in supervised and unsupervised teen drivers: Associations with sleep, inattention, and cognitive disengagement syndrome symptoms

Road crashes are a leading cause of death and disability in adolescence. Various factors can contribute to these crashes including overt risk-taking but also distracted, inattentive, and unfocused driving. Adolescent drivers are likely to be more susceptible to these issues if they experience sleep issues or have symptoms associated with inattention (e.g., ADHD) or cognitive disengagement syndrome (CDS; formerly termed sluggish cognitive tempo). In this study we surveyed 365 teenage drivers aged 16–18 years living in New Zealand. The survey included measures of distracted and unfocused driving, self-reported sleep issues, inattention and CDS. Smartphone use while driving was significantly associated with sleep issues, inattention and CDS symptoms among teens who drive unsupervised, but not those who only drive under supervision (i.e., Learners), whereas unfocused driving was correlated with inattention, CDS and to a lesser extent sleep issues in both groups. Modelling revealed that daytime sleepiness mediated the association between sleep issues and distracted driving for unsupervised drivers, but not supervised learners. In contrast, both inattention and CDS mediated the association between sleep issues and unfocused driving, and these effects were not moderated by unsupervised driving status. However, unsupervised teen drivers reported significantly higher rates of all forms of aberrant driving behaviour than supervised teens. These results highlight that sleep issues are a key risk factor for distracted and inattentive driving among young drivers, and that inattention and CDS symptoms influence unfocused driving.

Associations of sarcopenia, sarcopenia parameters and motoric cognitive risk syndrome in Chinese older adults

Associations of sarcopenia, sarcopenia parameters and motoric cognitive risk syndrome in Chinese older adults

Effect of acupuncture on mild cognitive impairment in the elderly: A randomized controlled trial

Background and objectiveMild cognitive impairment (MCI) is a cognitive dysfunction syndrome defined mostly by memory or other cognitive impairments, and may serve as a precursor to Alzheimer's disease (AD). In recent years, acupuncture has gained recognition as a potential intervention for MCI, attracting significant attention as a promising and well-established therapy. In this study, we critically evaluate the clinical efficacy and safety of an innovative acupuncture approach, termed “Kidney Nourishment and Spirit Regulation”, as a therapeutic modality for MCI in geriatric populations. MethodsA prospective, randomized, single-blind, placebo-controlled, single-center clinical trial design where patients will be allocated in acupuncture, placebo (sham acupuncture sessions), or blank for eight weeks. The blank group will receive health education over the same eight-week period and will be offered compensatory acupuncture therapy after this period. The selected acupoints for this investigation include GV20, EX-HN1, GV24, GV29, CV6, CV4, PC6, KI3, LI4, LR3, HT7 and SP6. The primary outcome measure will be the Montreal Cognitive Assessment (MoCA), while secondary outcomes include the Mini Mental State Examination (MMSE), Activity of Daily Living (ADL), and Electroencephalogram (EEG). DiscussionThis study seeks to provide an optimum regimen for acupuncture therapy in elderly MCI patients and to provide considerable theoretical evidence for its popularization and future broad adoption. We thus postulate that the current trial data might enlighten and potentially guide future research in terms of study design refinement.

Prodromal Motoric Cognitive Risk Syndrome and Everyday Function.

Motoric cognitive risk syndrome (MCR), a pre-dementia syndrome characterized by subjective cognitive complaints and slow gait, is associated with disability in instrumental activities of daily living. It is unknown whether these functional limitations occur even before this pre-dementia syndrome is diagnosed. To assess profiles of complex and instrumental activities of daily living in the prodromal stages of MCR. We examined functional profiles in 46 older adults (mean age 79 years, 59% women) living in the community with normal cognition at baseline who developed MCR over follow-up ('pre-MCR') with 264 older adults (mean age 75 years, 57% women) who remained cognitively intact over the follow-up period. Pre-MCR individuals had more limitations on complex everyday function at baseline compared to normal controls in multivariable logistic regression models (odds ratio 1.21). Pre-MCR cases at baseline had limitations in handling finances (odds ratio 3.0) and performing hobbies (odds ratio 5.5) as compared to normal controls. Pre-MCR cases had a greater difference in the number of complex functional limitations from baseline to MCR compared to the difference from baseline to final visit for the controls (1.2±3.0 versus 0.5±2.2, p < 0.001). Limitations in complex everyday tasks arise in the prodromal stages of MCR and can assist in risk prognostication.

Cognitive Disengagement Syndrome Symptoms from Early Childhood to Adolescence in a Nationally Representative Spanish Sample

ABSTRACT Objective The identification of a common set of symptoms for assessing cognitive disengagement syndrome (CDS, formerly sluggish cognitive tempo) for early childhood (ages 5–8), middle childhood (ages 9–12), and adolescence (ages 13–16) is needed to advance research on the developmental psychopathology of CDS (i.e. a common symptom set with comparable internal and external validity for each age group). Method Parents of a nationally representative sample of 5,525 Spanish children and adolescents (ages 5 to 16, 56.1% boys) completed measures of CDS, attention-deficit/hyperactivity disorder-inattention (ADHD-IN), and other measures. Results First, the 15 CDS symptoms showed convergent and discriminant validity relative to the ADHD-IN symptoms within each age group. Second, CDS showed stronger first-order and unique associations than ADHD-IN with anxiety, depression, somatization, daytime sleep-related impairment, and nighttime sleep disturbance, whereas ADHD-IN showed stronger first-order and unique associations than CDS with ADHD-hyperactivity/impulsivity, oppositional defiant disorder, and academic impairment. Third, CDS showed stronger first-order and unique associations than ADHD-IN with a history of having an anxiety, depression, or bipolar disorder diagnosis, whereas ADHD-IN showed stronger first-order and unique associations with having an ADHD diagnosis. Conclusions The identification of a common set of CDS symptoms spanning early childhood to adolescence allows for the advancement of research on CDS, with a particular need now for longitudinal studies and examination of CDS with other functional outcomes and across other cultural contexts.

Association of multimorbidity patterns with motoric cognitive risk syndrome among older adults: Evidence from a China longitudinal study.

Motoric cognitive risk syndrome (MCR), a pre-dementia syndrome, is characterized by slow gait and subjective cognitive complaints among older adults. This study assessed the relationship between multimorbidity, its patterns, and MCR. Data for this study were obtained from three waves (2011, 2013, and 2015) of the China Health and Retirement Longitudinal Study. Participants who were aged 60years and older and had complete data at baseline as well as complete data about MCR at follow-up were selected. Patients without MCR at baseline were selected for further analyses. Longitudinal associations between multimorbidity, its patterns, and MCR were examined using a Cox proportional hazards model. Multimorbidity patterns were classified using latent class analysis. A total of 4923 respondents were included at baseline, 43.47% of whom had multimorbidity. Additionally, the prevalence of MCR at baseline was 12.61%. After adjusting for covariates, multimorbidity was positively associated with MCR (hazard ratio [HR]=1.33, 95% confidence interval [CI]=1.06-1.68). A higher number of multimorbidity was also significantly associated with an increased risk of developing MCR (HR=1.10, 95% CI=1.02-1.19). Three multimorbidity patterns were selected: relatively healthy pattern, respiratory pattern, and cardiovascular pattern. Older adults with the cardiovascular pattern were 1.57 times more likely to develop MCR than those with the relatively healthy pattern (HR=1.57, 95% CI=1.16-2.13). There was no significant difference between the relatively healthy pattern and the respiratory pattern (HR=1.31, 95% CI=0.91-1.92). MCR is highly prevalent among older Chinese adults. MCR may be exacerbated by multimorbidity. For older adults with multimorbidity (especially cardiovascular multimorbidity), attention should be paid to MCR to achieve early detection, diagnosis, and treatment.

Intraindividual difference in estimated GFR by creatinine and cystatin C, cognitive trajectories and motoric cognitive risk syndrome.

Intraindividual differences between estimated glomerular filtration rate (eGFR) based on cystatin C (eGFRcys) and creatinine (eGFRcr) can convey important clinical information regarding health status. However, the clinical implications of these differences (eGFRdiff) for risk of cognitive decline and motoric cognitive risk (MCR) syndrome remains unclear. We aimed to investigate the longitudinal associations of eGFRdiff with cognitive trajectories and incident MCR. Based on the China Health and Retirement Longitudinal Study, we identified two study subcohorts: one for cognitive trajectory follow-up (6423 participants, 2011-2018) and another for incident MCR follow-up (2477 participants, 2011-2015). The eGFRdiff was defined as eGFRcys-eGFRcr. Adjusted ordinal and binary logistic regression models were separately used to assess the associations of eGFRdiff with cognitive trajectories and incident MCR. We also performed discordance analyses for eGFRdiff versus eGFRcys, eGFRcr or eGFR based on both creatinine and cystatin C (eGFRcys-cr). In the first subcohort, four distinct 7-year cognitive trajectories were identified. Each 1 standard deviation (SD) higher eGFRdiff (value for eGFRcys-eGFRcr) was associated with a lower risk of poorer cognitive trajectories {odds ratio 0.909 [95% confidence interval (CI) 0.877-0.942]}. In the second subcohort, 121 participants developed incident MCR after a 4-year follow-up. Each 1-SD higher eGFRdiff (value for eGFRcys-eGFRcr) was linked with a 25.3% (95% CI 16.6-33.2) decreased risk for MCR. The above associations persisted in individuals with normal kidney function. Additionally, the risk for cognitive decline and incident MCR was more strongly associated with eGFRcys than eGFRcr and eGFRcys-cr. For the discordance analyses, the 'discordantly high eGFRdiff/low eGFR' group but not the 'discordantly low eGFRdiff/high eGFR' exhibited a significantly lower risk of poorer cognitive trajectories and MCR compared with the concordant group. A large negative difference between eGFRcys and eGFRcr (eGFRcys < eGFRcr) was associated with a higher risk of cognitive decline and incident MCR. The eGFRdiff could capture additional valuable risk information beyond eGFRcys, eGFRcr and eGFRcys-cr.

37 Cognitive Disengagement Syndrome (CDS; Sluggish Cognitive Tempo) in Pediatric Epilepsy

Objective:Cognitive disengagement syndrome (CDS; previously known as “sluggish cognitive tempo” or SCT) refers to a set of behavioral symptoms characterized by slowed thinking/behavior, daydreaming, and mental fogginess or confusion. It has been described as related to, yet separate from, symptoms associated with Attention-deficit Hyperactivity Disorder (ADHD) inattention. There is a paucity of research on CDS within pediatric epilepsy populations despite substantial risk factors inherent to the disorder and a large proportion of patients with comorbid ADHD. This study therefore describes CDS as reported by parents for a large sample of children with epilepsy. Relationship between epilepsy variables (e.g., number of antiepileptic drugs [AEDs], seizure frequency, seizure type) and CDS symptoms was explored. Additionally, considering the negative association between CDS and academic performance in other populations, the relationship between parentrated CDS and academic risk factors was examined.Participants and Methods:Participants included 151 children with epilepsy (mean age = 11y, range 6-18y; 55% male; IQ&gt;70), referred for outpatient neuropsychological assessment. As part of routine clinical care, parents completed the Penny Sluggish Cognitive Tempo Scale (SCT) and the Colorado Learning Difficulties Questionnaire (CLDQ). Scores and basic demographic information were extracted from an IRB approved clinical database; the IRB granted approval for retrospective chart review to extract additional medical variables. Parent report of CDS included total CDS score and three subdomains: Sleepy/Sluggish, Low Initiation, and Daydreamy. Higher scores represent greater parent-reported difficulties. Independent samples t-tests compared the participants’ means on total CDS and each subdomain to the normative sample. Analysis of variance was conducted to determine differential impact of seizure type (Generalized, Focal, or Multifocal) on total CDS and each subdomain. Correlations between other medical variables, scores on the CLDQ, and parent ratings on the SCT were examined.Results:Parents of children with epilepsy rated overall CDS total and subdomain scores as significantly higher compared to the normative means with highest elevation in symptoms of Low Initiation (p = &lt;.001). Total CDS was associated with increased parent-reported academic difficulties; however, of the three subdomains, only Low Initiation was significantly associated with concerns for academic functioning. Number of AEDs was associated with increased symptoms on the Sleepy/Sluggish subdomain only. Seizure frequency was associated with total CDS and Sleepy/Sluggish symptoms, though this finding is likely mediated by increased number of AEDs for those with more frequent seizures. Seizure type was not associated with significant differences in Total CDS or CDS subdomains.Conclusions:Children with epilepsy are at increased risk for experiencing slowed thinking and cognitive disengagement. Low initiation is particularly elevated in pediatric epilepsy populations, which may lead to increased academic difficulties. Potential interventions targeting low initiation may therefore have benefit in the academic setting for children with epilepsy, regardless of epilepsy type.

89 The Effect of Personality Traits on the Development of Predementia Cognitive States: Results from the Einstein Aging Study

Objective:Recent research has found associations between the Five Factor Model (FFM) personality traits (Openness to Experience, Conscientiousness, Extraversion, Agreeableness, and Neuroticism) and risk of developing subjective cognitive decline (SCD), mild cognitive impairment (MCI), and/or dementia. It has therefore been proposed that personality should be incorporated into conceptual models of dementia risk, as personality assessments have utility as readily available, low-cost measures to predict who is at greater risk for developing pathological cognitive decline. The objective of the present study was to explore the relationship between FFM personality traits and predementia cognitive syndromes including SCD, amnestic MCI (aMCI), and non-amnestic MCI (naMCI). The first aim was to compare baseline personality traits between participants who transitioned from healthy cognition or SCD to aMCI vs. naMCI. The second aim was to determine the relationship between FFM personality traits and risk of transition between predementia cognitive states. The third aim was to explore relationships between levels of FFM personality traits and performance on a comprehensive cognitive battery.Participants and Methods:The participants for this study were 562 (Aim 3; Mean Age = 78.90) older adults from the Einstein Aging Study, 378 of which had at least one follow-up assessment (Aims 1 &amp; 2; Mean Age = 78.60). Baseline levels of FFM personality traits were measured in the EAS using the 50-item International Personality Item Pool (IPIP) version of the NEO-Personality Inventory. Baseline levels of anxiety and depressive symptoms, medical history, performance on a cognitive battery and age sex, and years of education were also collected. A multistate Markov approach was used to model the risk of transition across the four predementia states (cognitively healthy, SCD, aMCI, and naMCI) with each FFM personality trait as covariates.Results:Regarding Aim 1, Mann-Whitney U tests revealed no differences in levels of FFM personality traits between participants who developed aMCI compared to those who developed naMCI. Regarding Aim 2, the multistate Markov model revealed that higher levels of conscientiousness were protective against developing SCD while higher levels of neuroticism resulted in an increased risk of developing SCD. Further, the model revealed that higher levels of extraversion were protective against developing naMCI. Finally, regarding Aim 3, exploratory correlations revealed many positive associations between levels of openness to experience and performance on neuropsychological tests. Few associations were found for the other FFM personality traits.Conclusions:Results from this study suggest that premorbid personality traits may play a predictive role in the risk for or protection against specific predementia syndromes. Thus, FFM personality traits may be useful in improving predictions of who is at greatest risk for developing specific predementia syndromes. These personality measures could be used (in addition to other established risk factors for cognitive decline) to enrich clinical trials by targeting individuals who are at greatest risk for developing specific forms of cognitive decline. Such measures may also be useful in diagnostic prediction models for predementia syndromes. These results should be replicated in future studies with larger sample sizes and younger participants.

4 Neurophenotypes and recovery trajectories following laboratory-confirmed SARS-CoV-2 infection

Objective:Cognitive sequelae are reported in 20-25% of patients following SARS-CoV-2 infection. It remains unclear whether post-infection sequelae cluster into a uniform cognitive syndrome. In this cohort study, we characterized post-COVID neuropsychological outcome clusters, identified factors associated with cluster membership, and examined 6-month recovery trajectories by cluster.Participants and Methods:The Mayo Clinic Institutional Review Board approved study protocols. Informed consent was obtained from all participants. Participants (&gt; 18 years old) were recruited from a hospital-wide registry of Mayo Clinic Florida patients who tested positive for SARS-CoV-2 infection from July 2020 to Feb 2022. We abstracted participant health history and COVID-19 disease severity (NIAID score) from the electronic health record and retrieved Area Deprivation Index (ADI) scores as a measure of neighborhood socioeconomic disadvantage. We assessed objective cognitive performance with the CNS Vital-Signs (CNSVS) and subjective neuropsychological symptoms with the Neuropsych Questionnaire-45 (NPQ-45). Results were used as input features in a K-means clustering analysis to derive neurophenotypes. Chi-square and analysis of variance (AnOvA) tests were used to identify clinical and sociodemographic factors associated with cluster membership. Participants repeated the CNS Vital Signs, NPQ-45, as well as the Medical Outcomes Survey (MOS SF-36) and a posttraumatic stress disorder (PTSD) checklist (PCL-C 17) 6 months following initial testing. Repeated-measures ANOVA was used to assess change in neurocognitive performance over time by cluster. Significance was set at P &lt; 0.05.Results:Our cohort consisted of 205 participants (171 ambulatory, 34 hospitalized) who completed post-acute outcome assessment a mean of 5.7 (± 3.8) weeks following testing positive for SARS-CoV-2. K-means clustering with elbow method fitting identified three subgroups (see figure). The first cluster (N = 31) is characterized by executive dysfunction, greater socioeconomic disadvantage, and higher rates of obesity. The second cluster (N = 32) is characterized by memory and speed impairment, higher COVID severity, prevalent anosmia (70%), and greater severity of memory complaints, depression, anxiety, and fatigue. The third and largest cluster (N = 142) is absent cognitive impairment. Approximately 39% of participants completed the 6-month outcome assessment (N=79). Regardless of cluster membership, verbal memory, psychomotor speed, and reaction time scores improved over time. Regardless of timepoint, cluster 1 (dysexecutive) showed lower scores on cognitive flexibility and complex attention and cluster 2 (memory-speed impaired) showed lower scores on verbal memory, psychomotor speed, and reaction time. Modeling of cluster by timepoint interactions showed a steeper slope of improvement in complex attention and cognitive flexibility in cluster 1 (dysexecutive). Cluster 3 (normal) showed significant improvement in fatigue while cluster 2 (memory-speed impaired) continued to report moderate-severe fatigue, worse medical outcomes, and higher PTSD symptom severity scores at six months.Conclusions:Most participants were cognitively normal or experienced cognitive recovery following SARS-CoV-2 infection. The 25-30% of participants who showed cognitive impairment cluster into two different neurophenotypes. The dysexecutive phenotype was associated with socioeconomic factors and medical comorbidities that are non-specific to COVID-19, while the amnestic phenotype was associated with COVID-19 severity and anosmia. These results suggest that cognitive sequelae following SARS-CoV-2 infection are not uniform. Deficits may be influenced by distinct patient- and disease-specific factors, necessitating differentiated treatment approaches.

Cognitive Disengagement Syndrome But Not ADHD Symptoms Increases Risk for Child Body Mass Index: Examination in a Sample of Clinically Referred Youth.

Given the substantial increase in pediatric obesity rates in recent decades, its long-term stability, and its pervasive negative outcomes, continuous efforts to identify factors that may place children at increased risk for overweight or obesity (OW/OB) are essential. As such, the primary aim of the present investigation was to examine the extent to which symptoms of Cognitive Disengagement Syndrome (CDS; i.e., Sluggish Cognitive Tempo) relates to child body mass index (BMI) independent of Attention-Deficit/Hyperactivity Disorder (ADHD). The study is the first to examine whether CDS subdomains of slowed thinking, hypoarousal, and daydreamy is associated with BMI. Analyses included data from 72 clinically-referred children (46 males, 26 females) aged 4-12years old (M = 8.41, SD = 2.48). CDS and ADHD were assessed using standardized parent-report rating scales, and children's BMI was collected at the time of encounter. Bayesian hierarchical regression models revealed no evidence that overall CDS symptoms or ADHD symptoms (overall and subdomain) predicted child BMI. However, models did provide moderate evidence that hypoarousal and daydream subdomains jointly predicted BMI independent of ADHD (BF10 = 19.28-21.87). The present study suggests that CDS is a risk factor for obesity in young children and future research is needed to inform clinical interventions and to provide further understanding of the relatively nuanced association between CDS symptoms and obesity.

Multi-method examination of cognitive disengagement syndrome and ADHD inattentive symptoms in relation to early adolescents' academic functioning.

Cognitive disengagement syndrome (CDS), previously referred to as sluggish cognitive tempo, is a set of symptoms characterized by excessive daydreaming, mental fogginess, and slowed behavior/thinking. Studies examining the association between CDS and academic functioning have reported mixed findings and have relied upon limited measures of CDS, broad ratings of academic impairment, and/or focused only on elementary-aged children. The current study examined the relationship between CDS and academic functioning in adolescents using a comprehensive, multi-informant, multi-method design. Participants were 302 adolescents (Mage = 13.17years; 44.7% female; 81.8% White; 52% with ADHD) recruited in the fall of their 8th grade. Above and beyond ADHD inattentive symptoms, CDS symptoms were related to poorer homework performance, lower math fluency, and lower daily academic motivation across multiple informants, and teacher-reported CDS symptoms were related to lower grades. Findings were not moderated by ADHD diagnosis, suggesting that associations between CDS and academic outcomes do not differ for adolescents with and without ADHD. Findings demonstrate that CDS symptoms are uniquely associated with daily academic difficulties as well as global indices of academic performance. These findings have implications for assessing and monitoring CDS symptoms in interventions aiming to improve the academic functioning in adolescents with and without ADHD.