Multiple Cognitive Domains Research Articles

Sleep, Mental Health, and Cognition Across Diverse Adult Populations

Abstract Sleep is often impaired in late life, raising concerns about the effect of poor sleep on mental and cognitive health in aging individuals. This symposium brings together five rigorous studies that show how poor sleep may be an under-recognized risk factor for mental health and cognitive outcomes in the second half of life. Specifically, this symposium showcases data from a variety of study cohorts (including Midlife in the United Study, Einstein Aging Study, and Study of Muscle, Mobility, and Aging), using diverse indicators of subjective and objective sleep. Paper 1 focuses on healthcare workers (HCWs), a group critical for the delivery of quality patient care, and examines both individual and joint associations of poor sleep and pain with mental health in HCWs vs. non-HCWs. Paper 2 investigates the association between EEG-measured sleep and depressive symptoms in older adults. Paper 3 explores the relationship between intra-individual variability of sleep and mild cognitive impairment (MCI) and identifies gender differences in these associations. Paper 4 establishes the associations of actigraphy-measured sleep and circadian rest-activity rhythms with multiple domains of cognition in older adults. Paper 5 examines the effect of latent dose/duration patterns of common sleep medications on development of Alzheimer’s disease and related dementias. The discussant, Dr. Adam Spira, will integrate key findings from these studies, discuss their contributions to the literature, and consider opportunities for future research. This is a Sleep, Circadian Rhythms and Aging Interest Group Sponsored Symposium. This is a collaborative symposium between the Alzheimer’s Disease and Related Dementias, Geroscience, and Health Behavior Change Interest Groups.

COGNITION ON THE GO: UNIQUE INSIGHTS INTO BRAIN HEALTH FROM HIGH-FREQUENCY COGNITIVE APPROACHES

Abstract High-frequency ambulatory cognitive assessments offer the opportunity to examine cognitive change at multiple timescales. When deployed multiple times per day via pervasive mobile technology (e.g., smartphones), ambulatory cognitive assessments allow us to conduct semi-continuous monitoring of cognitive changes while individuals go about their daily lives. Variation in performance that occurs over these short timescales may be associated with a wide range of contextual factors (e.g., our thoughts, emotions, and behaviors) including the way we respond to challenges presented by our everyday environments. Short-term change and variation may also reveal information about overall brain health and risk for cognitive decline over longer timescales. This symposium focuses on how high-frequency, ambulatory cognitive assessments can generate new insights into cognitive aging, psychological processes, and risk for neurocognitive decline by revealing detailed patterns of cognitive change and variation over short timescales (hours to weeks). The talk by Sliwinski et al. gives an overview of high-frequency cognitive assessment approaches. The talk by Harrington et al. will show how dimensions of experienced affect may influence short-term changes in multiple domains of cognition. The talk by Hakun et al. will show how short-term cognitive variation may predict how we respond to everyday stressful experiences. The talk by Oravecz et al. will show how to extract substantively meaningful predictors of long-term cognitive change from short-term processes such as retest learning.

OBJECTIVE SLEEP AND CIRCADIAN REST–ACTIVITY RHYTHMS AND MULTIPLE DOMAINS OF COGNITIVE FUNCTION IN OLDER ADULTS

Abstract Evidence suggests that sleep and circadian rest-activity rhythms (RAR) play a key role in dementia and Alzheimer Disease (AD) pathology. Studies with objective measures of sleep and RAR and multiple domains of cognition remain limited. We studied 820 older adults enrolled in the Study of Muscle, Mobility and Aging (SOMMA). Actigraphs were worn for one week, and processed for sleep-wake measures including total sleep time (TST) and sleep efficiency (SE); and parametric (acrophase, pseudo-F) and non-parametric (interdaily stability [IS], intradaily variability [IV], and relative amplitude [RA]) 24-hour RAR variables. Cognitive assessments included global cognition (the Montreal Cognitive Assessment), executive function (Trails B test), memory (California Verbal Learning Test-short form; and psychomotor performance (Digit-Symbol Coding Test). Adjusting for age, sex, clinic site and education, we examined adjusted mean cognitive test scores by categories of sleep and RAR exposures. Mean age was 76 years, 58% were female, and 15% were non-white. Higher RA, reflecting a more robust 24-hour RAR, was associated with better cognition on all tests (p for trend <0.05). Reduced SE was related to lower cognitive function (psychomotor performance, global cognition, memory; p<.05). There were no associations with TST and any cognitive measures examined. SE and RAR were variably associated with both global and specific domains of cognition in older men and women. The RA in particular was strongly related to multiple domains of cognition related to AD, and may be useful in identifying individuals at risk. Additional analyses will explore sex differences and longitudinal associations.

Intra- and inter-individual cognitive variability in schizophrenia and bipolar spectrum disorder: an investigation across multiple cognitive domains

There is substantial cognitive heterogeneity among patients with schizophrenia (SZ) and bipolar disorders (BD). More knowledge about the magnitude and clinical correlates of performance variability could improve our understanding of cognitive impairments. Using double generalized linear models (DGLMs) we investigated cognitive mean and variability differences between patients with SZ (n = 905) and BD spectrum disorders (n = 522), and healthy controls (HC, n = 1170) on twenty-two variables. The analysis revealed significant case-control differences on 90% of the variables. Compared to HC, patients showed larger intra-individual (within subject) variability across tests and larger inter-individual (between subject) variability in measures of fine-motor speed, mental processing speed, and inhibitory control (SZ and BD), and in verbal learning and memory and intellectual functioning (SZ). In SZ, we found that lager intra -and inter (on inhibitory control and speed functions) individual variability, was associated with lower functioning and more negative symptoms. Inter-individual variability on single measures of memory and intellectual function was additionally associated with disorganized and positive symptoms, and use of antidepressants. In BD, there were no within-subject associations with symptom severity. However, greater inter-individual variability (primarily on inhibitory control and speeded functions) was associated with lower functioning, more negative -and disorganized symptoms, earlier age at onset, longer duration of illness, and increased medication use. These results highlight larger individual differences in patients compared to controls on various cognitive domains. Further investigations of the causes and correlates of individual differences in cognitive function are warranted.

The role of visual working memory in capacity-limited cross-modal ensemble coding

Ensemble coding refers to the brain's ability to rapidly extract summary statistics, such as average size and average cost, from a large set of visual stimuli. Although ensemble coding is thought to circumvent a capacity limit of visual working memory, we recently observed a VWM-like capacity limit in an ensemble task where observers extracted the average sweetness of groups of food pictures (i.e., they could only integrate information from four out of six available items), thus suggesting the involvement of VWM in this novel form of cross-modal ensemble coding. Therefore, across two experiments we investigated if this cross-modal ensemble capacity limit could be explained by individual differences in VWM processing. To test this, observers performed both an ensemble task and a VWM task, and we determined 1) how much information they integrated into their ensemble percepts, and 2) how much information they remembered from those displays. Interestingly, we found that individual differences in VWM capacity did not explain differences in performance on the ensemble coding task (i.e., high-capacity individuals did not have significantly higher “ensemble abilities” than low-capacity individuals). While our data cannot definitively state whether or not VWM is necessary to perform the ensemble task, we conclude that it is certainly not sufficient to support this cognitive process. We speculate that the capacity limit may be explained by 1) a bottleneck at the perceptual stage (i.e., a failure to process multiple visual features across multiple items, as there are no singular features that convey taste), or 2) the interaction of multiple cognitive systems (e.g., VWM, gustatory working memory, long term memory). Our results highlight the importance of examining ensemble perception across multiple sensory and cognitive domains to provide a clearer picture of the mechanisms underlying everyday behavior.

Case study of invalid to valid shift in cognitive performance following successful treatment of psychogenic nonepileptic seizure events

ABSTRACT Patients with psychogenic nonepileptic seizure (PNES) who fail performance validity testing (PVT) may appear to produce non-valid cognitive profiles. Consequently, they may not get referred to treatment and events persist, with worsening disability and high resource utilization. As a result, we report pre- and post-treatment neuropsychological evaluation findings in a 59-year-old woman with a confirmed diagnosis of PNES established using video-EEG monitoring. At pre-treatment baseline neuropsychological evaluation, PNES events occurred weekly to daily. Performance was impaired across PVTs and across multiple cognitive domains. After behavioral intervention specific to PNES, these events substantially reduced in frequency to rare stress-induced flares. Post-treatment neuropsychological evaluation revealed marked improvement of most cognitive and behavioral scores from baseline, and valid PVT scores. We review predisposing, precipitating, and perpetuating factors for PNES and cognitive impairment in this case and discuss the patient’s outcome from treatment. Effectively managing PNES events and dissociative tendencies while reducing unnecessary pharmacological interventions appears to have allowed this patient to function closer to her optimal state. This case illustrates the complexity of Functional Neurologic Disorder (FND) clinical presentation and challenges the assumption that suboptimal neuropsychological performance predicts poor treatment engagement and outcome. We showcase the reversibility of PNES and cognitive manifestations of FND using targeted psychotherapeutic interventions, which resulted in reduced disability and associated healthcare costs, as well as re-engagement in life.

Effect of cocoa extract supplementation on cognitive function: results from the clinic subcohort of the COSMOS trial

BackgroundSome prior randomized clinical trials (RCTs) that tested the effects of cocoa extract (CE), a source of flavanols, on late-life cognition have yielded promising findings. A long-term RCT using in-person neuropsychological tests covering multiple cognitive domains may clarify the cognitive effects of CE. ObjectivesTo test whether daily supplementation with CE, compared with placebo, produces better cognitive change over 2 y. MethodsThe COcoa Supplement and Multivitamin Outcomes Study (COSMOS) is a 2 × 2 factorial RCT of CE [500 mg flavanols/d, including 80 mg (–)-epicatechin] and/or a daily multivitamin-mineral supplement for cardiovascular disease and cancer prevention among 21,442 United States adults aged ≥60 y. There were 573 participants in the clinic subcohort of COSMOS (that is, COSMOS-Clinic) who completed all cognitive tests at baseline; of these, 492 completed 2-y follow-up assessments. The primary outcome was global cognition (averaging z-scores across 11 tests). Secondary outcomes were episodic memory and executive function/attention. Repeated measures models were used to compare randomized groups. ResultsParticipants' mean age (standard deviation) was 69.6 (5.3); 49.2% were females. Daily supplementation with CE, compared with placebo, had no significant effect on 2-y change in global cognition {mean difference [95% confidence interval (CI)]: −0.01 (−0.08, 0.05) standard deviation units (SU)}. CE, compared with placebo, had no significant effects on 2-y change in episodic memory [mean difference (95% CI): −0.01 (−0.13, 0.10) SU] or executive function/attention [mean difference (95% CI): 0.003 (−0.07, 0.08) SU]. Subgroup analyses uncorrected for multiple-testing suggested cognitive benefits of CE supplementation, compared with placebo among those with poorer baseline diet quality. ConclusionsAmong 573 older adults who underwent repeat in-person, detailed neuropsychological assessments over 2 y, daily CE supplementation, compared with placebo, showed no overall benefits for global or domain-specific cognitive function. Possible cognitive benefits of CE among those with poorer diet quality warrant further study. Trial registrationThis trial was registered at clinicaltrials.gov with identifier – NCT02422745.

High-density transcranial direct current stimulation to improve upper limb motor function following stroke: study protocol for a double-blind randomized clinical trial targeting prefrontal and/or cerebellar cognitive contributions to voluntary motion

BackgroundFocal brain lesions following a stroke of the middle cerebral artery induce large-scale network disarray with a potential to impact multiple cognitive and behavioral domains. Over the last 20 years, non-invasive brain neuromodulation via electrical (tCS) stimulation has shown promise to modulate motor deficits and contribute to recovery. However, weak, inconsistent, or at times heterogeneous outcomes using these techniques have also highlighted the need for novel strategies and the assessment of their efficacy in ad hoc controlled clinical trials.MethodsWe here present a double-blind, sham-controlled, single-center, randomized pilot clinical trial involving participants having suffered a unilateral middle cerebral artery (MCA) stroke resulting in motor paralysis of the contralateral upper limb. Patients will undergo a 10-day regime (5 days a week for 2 consecutive weeks) of a newly designed high-definition transcranial direct current stimulation (HD-tDCS) protocol. Clinical evaluations (e.g., Fugl Meyer, NIHSS), computer-based cognitive assessments (visuo-motor adaptation and AX-CPT attention tasks), and electroencephalography (resting-state and task-evoked EEG) will be carried out at 3 time points: (I) Baseline, (II) Post-tDCS, and (III) Follow-up. The study consists of a four-arm trial comparing the impact on motor recovery of three active anodal tDCS conditions: ipsilesional DLPFC tDCS, contralesional cerebellar tDCS or combined DLPFC + contralesional cerebellar tDCS, and a sham tDCS intervention. The Fugl-Meyer Assessment for the upper extremity (FMA-UE) is selected as the primary outcome measure to quantify motor recovery. In every stimulation session, participants will receive 20 min of high-density tDCS stimulation (HD-tDCS) (up to 0.63 mA/cm2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\\mathrm{cm}}^{2}$$\\end{document}) with πcm2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\\mathrm{\\pi cm}}^{2}$$\\end{document} electrodes. Electrode scalp positioning relative to the cortical surface (anodes and cathodes) and intensities are based on a biophysical optimization model of current distribution ensuring a 0.25 V/m impact at each of the chosen targets.DiscussionOur trial will gauge the therapeutic potential of accumulative sessions of HD-tDCS to improve upper limb motor and cognitive dysfunctions presented by middle cerebral artery stroke patients. In parallel, we aim at characterizing changes in electroencephalographic (EEG) activity as biomarkers of clinical effects and at identifying potential interactions between tDCS impact and motor performance outcomes. Our work will enrich our mechanistic understanding on prefrontal and cerebellar contributions to motor function and its rehabilitation following brain damage.Trial registrationClinicalTrials.gov NCT05329818. April 15, 2022.

Objective Sleep and Circadian Rest‐Activity Rhythms and Multiple Domains of Cognitive Function in Older Men and Women

AbstractBackgroundEmerging evidence from experimental and epidemiologic studies suggests that sleep and circadian rest‐activity rhythms (RAR) play a key role in dementia and Alzheimer Disease (AD) pathology. Studies with objective measures of sleep and RAR and multiple domains of cognition in older adults remain limited.MethodWe studied 820 older men and women enrolled in the Study of Muscle, Mobility, and Aging (SOMMA), a unique cohort designed to study the cellular biology of aging and related loss of mobility. In this initial cross‐sectional analysis, participants wore wrist actigraphs for a mean of 8.0 consecutive days; recordings were processed for traditional sleep‐wake measures including total sleep time (TST) and sleep efficiency (SE); as well as parametric (acrophase, pseudo‐F) and non‐parametric (interdaily stability [IS], intradaily variability [IV], and relative amplitude [RA]) 24‐hour RAR variables. Measures of cognitive function included global cognition (the Montreal Cognitive Assessment), executive function (Trails B test), memory (California Verbal Learning Test‐short form; and psychomotor performance (Digit‐Symbol Coding Test). In models adjusted for age, sex, clinic site and education, we examined adjusted mean cognitive test scores by quartiles or categories of sleep and RAR exposures.ResultMean age of the cohort was 76 years, 58% were female, and 15% were non‐white. Mean TST and SE were 6.9 hours and 85%, respectively. Higher RA, reflecting a more robust 24‐hour RAR, was associated with better cognition on all tests (p for trend <0.05). The association of higher pseudo‐F, a parametric measure or robustness of RAR, to cognition was limited to psychomotor performance (p<0.03). Better psychomotor performance was also related to higher IS (consistency of RAR across days); whereas those with delayed timing (acrophase) had worse psychomotor performance (p<.0006). Lower SE was related to worse cognitive function (psychomotor performance, global cognition, memory; p<.05). There were no associations between TST and any cognitive measures.ConclusionSE and RAR were variably associated with both global and specific domains of cognition in older men and women. The RA in particular was strongly related to multiple domains of cognition related to AD, and may be useful in identifying individuals at risk. Additional analyses will explore gender differences and longitudinal associations.

Domain‐specific cognitive decline associates with differential regional tau burden in the Alzheimer’s disease spectrum

AbstractBackgroundPatients presenting with distinct clinical variants of Alzheimer’s disease (AD) present differential patterns of tau pathology measured with positron emission tomography (PET). Yet, a single set of brain regions like a temporal meta‐ROI is often chosen to study the association between cognition and tau. Instead, we aimed to map the associations between regional tau and multiple cognitive domains, and to test whether using whole brain information yields stronger associations with cognition compared to a singular composite region.MethodWe included 372 amyloid‐positive ADNI participants that had at least one tau‐PET scan (163 cognitively unimpaired [CU], 132 with mild cognitive impairment [MCI], 77 with AD dementia). Composite cognitive scores for memory, executive functioning, visuospatial and language were used for cross‐sectional (closest score to tau‐PET) and longitudinal analyses. Individual rate of cognitive decline was computed using linear mixed effect models, leveraging all visits available for each participant. We did region‐wise analyses, relating tau in the 64 regions of the Desikan‐Killiany atlas plus the amygdalae with cognitive performance and rate of cognitive decline. We also derived a “spatial extent index” where we computed the number of abnormal tau regions and compared the performance of this index to detect cognitive impairment to what would have been found with a classical temporal meta‐ROI SUVR value.ResultNo regional association between tau and cognition survived FDR correction in CU participants. Cross‐sectionally and longitudinally, participants with MCI and with AD dementia, associations between tau and memory were predominant in the temporal lobe, associations with language were restricted mostly to the left hemisphere and associations with executive functioning spanned the entire cortex. (Fig 1) Comparing the sum of tau positive regions (spatial extent index) to tau SUVR in the temporal meta‐ROI, both measures were similarly associated with cognition, except for executive functioning at baseline where the spatial extent index was more strongly associated with cognition than the meta‐ROI. (Fig 2)ConclusionWhile temporal meta‐ROI tau SUVR may be sufficient to track non‐executive cognitive performance in individual with cognitive impairments, a whole brain measure may provide additional information regarding executive impairment occurring in AD.

Inter‐ and intra‐individual variation in brain structural‐cognition relationships in aging

AbstractBackgroundThe sources of inter‐ and intra‐individual variability in age‐related cognitive decline remain poorly understood. We examined the association between 20‐year trajectories of cognitive decline and multimodal brain structure and morphology in older age.MethodWe used the Whitehall II Study, an extensively characterised cohort with 3T brain magnetic resonance images acquired at older age (mean age = 69.52 ± 4.9) and 5 repeated cognitive performance assessments between mid‐life (mean age = 53.2 ±4.9 years) and late‐life (mean age = 67.7 ± 4.9). Using non‐negative matrix factorisation, we identified 10 brain components integrating cortical thickness, surface area, fractional anisotropy, and mean and radial diffusivities (Figure 1).ResultWe observed two latent variables describing distinct brain‐cognition associations. The first describes variations in 5 structural components associated with low mid‐life performance across multiple cognitive domains, decline in reasoning, but maintenance of fluency abilities. The second describes variations in 6 structural components associated with low mid‐life performance in fluency and memory, but retention of multiple abilities (Figure 2). Expression of latent variables predicts future cognition 3.2 years later (mean age = 70.87 ± 4.9) (Figure 3).ConclusionLongitudinal cognitive decline and maintenance across diverse cognitive functions are both positively and negatively associated with distinct markers of cortical structure. Latent brain‐behaviour relationships predict future cognitive performance.

Dementia Associated Diseases, Driving Status, and Cognitive Function: Perception Does Not Match Performance – Truth and Consequence for Driving Shared Decision Making

AbstractBackgroundDementia associated diseases (DAD) refer to a group of disorders clinically characterized by progressive cognitive impairment (CI). CI may reflect abnormalities across multiple cognitive domains (CD) to varying degrees and combinations and interfere with the ability to carry out activities of daily living (ADL). Determination of driving ability in routine care relies on patient, family, and clinician shared‐decision making, as availability of routine on‐road driving assessment might be limited. Incorporation of patient reported outcomes (PRO) in routine care has increased, becoming more important for patient care and treatment decisions. Neuro‐QoL Cognitive Function Questionnaire (CF) provides an opportunity to assess self‐reported cognition routinely. The relationship of CF to objective computerized multi‐domain cognitive testing and self‐reported driving has not been explored. Providing easily available objective screening might be of great value for all involved in the decision to continue or stop driving in view of the profound impact loss of driving has on independence.MethodA retrospective review of PwDAD who provided self‐reported driving status and completed both objective and subjective cognitive function (CF) measures. Subjective CF was measured by CF score which pertaining to comprehension, cognition, attention, and learning. The validated computerized cognitive assessment battery (CAB‐NT), includes 7 cognitive domains: memory(Mem), executive function(Exe), attention(Att), information processing speed(Inf), visual‐spatial(Vis), verbal function(Ver), motor skills(Mot) and a global cognitive summary score(GCS). T‐tests and regression analysis was utilized for analysis assuming both equal and unequal variances, with significance (p< 0.05).Results496 PwDAD, average age 73.4±8.9, 61.2% female. T‐test showed significant differences between driving status yes/no for both CF and all CAB‐NT domains. However, regression analysis showed a small effect size between CF and CAB‐NT cognitive domains scores.ConclusionSelf‐reported driving status in PwDAD corresponds to both perceived/subjective CF and objective measures of cognitive function. However, the relationship between subjective and objective cognitive function measures is problematic. With various CDs involved in the safe effective operation of a motor vehicle, it is necessary to objectively assess this risk with objective measures. Evidence of incongruent relationship between objective and subjective cognitive function enhances the importance of incorporating objective measures of cognitive ability to safely maintain an active driving status.

Enhanced Insight into Factors Impacting Driving Ability Across Manual Dexterity, Satisfaction with Managing Daily Activities and Select Cognitive Domains in People with Dementia Associated Disease

AbstractBackgroundDementia associated diseases (DAD) refers to a group of disorders characterized by progressive cognitive impairment (CI) that adversely influences ability to function independently in real world activities. CI may reflect abnormalities across multiple cognitive domains (CD) to varying degrees. Successful completion of activities of daily living (ADL) is progressively impaired DAD. Symptom recognition by family and clinicians typically present following irreversible damage, highlighting a demand for effective methods of early DAD diagnosis and treatment. Neurocognitive screening tools combined with patient reported outcomes (PRO) might provide deeper insight into the patterns and progression of DAD. Comparison of PRO across Upper Extremity Function Score (UEF), Self‐Efficacy for Managing Daily Activities (SEMDA), and cognitive performance measures with driving status in PwDAD might enhance understanding of disability across a continuum and identify the medical necessity of transportation assistance for PwDAD.MethodRetrospective review of examiner independent information collected in the course of routine care of a population of PwDAD including demographics, driving status, UEF, SEMDA, executive function (NT‐EF), and motor function, reflecting time to move and accuracy, (NT‐MF) of a multi‐domain computerized cognitive test (CTB). T‐tests were utilized for analysis with significance (p<0.05).Result529 PwDAD (59% female, average age 74.4 +/‐ 8.8 years) provided the data collected to compare patient driving status with UEF, SEMDA, NT‐MF, NT‐EF scores. Statistically significant (p<0.01) relationships were identified between driving status and PRO score for all domains: UEF, SEMDA, NT‐MF, and NT‐EF.ConclusionActive driving status in PwDAD is associated with better scores on a self‐reported upper extremity ability profile, self‐efficacy for managing daily activities as well as better executive function and cognitively defined motor function planning. While effective collaboration across a cognitive network provides for driving, simultaneous monitoring of UEF and SEMDA in conjunction with both NT‐MF, and NT‐EF might provide enhanced insight into driving impairment along a continuum. Improved awareness of the multiple potential paths of impairment and real‐world impact can offer proactive opportunities for intervention as well as novel important endpoints to measure therapy efficacy.

Dementia Associated Disorders and Cognitive Impairment – The Relationship of Quantitative Multi‐Domain Computerized Cognitive Testing to Patient Centric Perception of Health Literacy

AbstractBackgroundDementia associated diseases (DAD) refers to clinical conditions characterized by progressive cognitive impairment (CI) that interferes with ability to function independently. However, cognitive impairments can vary in degree and combination of cognitive deficits across multiple cognitive domains. Traditional history and cognitive assessments in clinic are insufficient to identify these varied combinations. Therefore, a clinician may be unaware of these variations and impact on patient QOL and decision‐making. Effective quantitative analysis of cognitive function can be obtained in routine care by a validated, examiner‐independent, sensitive, and reliable computerized cognitive assessment battery (CAB‐NT). Patient reported outcomes (PRO) provide information regarding patient perception of ability across clinically relevant concerns. The BRIEF Health Literacy survey (BHL) PRO is used to find the degree to which one can read, understand, exchange, and use health information and resources. Comparison to computerized cognitive testing has not been explored in this population.MethodRetrospective cross‐sectional analysis of patients with DAD (PwDAD) who completed both PRO BHL and CAB in routine care on the same day. CAB‐NT included 7 cognitive domains: memory (Mem), executive function (Exe), attention (Att), information processing speed (Inf), visual‐spatial (Vis), verbal function (Ver), motor skills (Mot) and global cognitive summary score (GCS). Linear regression analysis was explored with significance (p<0.05).Result329 PwDaD, average age of 70±13 years, 63.2% female. Linear regression was used to analyze trends between BHL and CAB. Significant correlations (p = 0.05) were found for CAB‐NT vs: BHL: GCS‐r = 0.42, Vis‐r = 0.36, Mem‐r = 0.31, Exe‐r = 0.39, Ver‐r = 0.25, Mot‐r = 0.22, Inf‐r = 0.32, and Att‐r = 0.28. One‐way ANOVA was performed between BHL (inadequate, marginal, and adequate) and the cognitive domains of the CAB‐NT. Significant differenced (p = 0.05) were found between the three BHL groups within each cognitive domain.ConclusionPatient centric DAD performances on CAB‐NT is related to patient‐reported health literacy. The more impaired the CAB‐NT scores, the poorer patient‐perceived health literacy reported. Patient centric recognition of CI can enhance clinician’s recognition of those people who may require additional information for health‐care decisions or incorporate health‐care proxy for effective shared decision making in routine care. Incorporation of this patient centric information can potentially lead to improved outcomes and satisfaction.

Domain‐specific cognitive decline associates with differential regional tau burden in the Alzheimer’s disease spectrum

AbstractBackgroundPatients presenting with distinct clinical variants of Alzheimer’s disease (AD) present differential patterns of tau pathology measured with positron emission tomography (PET). Yet, a single set of brain regions like a temporal meta‐ROI is often chosen to study the association between cognition and tau. Instead, we aimed to map the associations between regional tau and multiple cognitive domains, and to test whether using whole brain information yields stronger associations with cognition compared to a singular composite region.MethodWe included 372 amyloid‐positive ADNI participants that had at least one tau‐PET scan (163 cognitively unimpaired [CU], 132 with mild cognitive impairment [MCI], 77 with AD dementia). Composite cognitive scores for memory, executive functioning, visuospatial and language were used for cross‐sectional (closest score to tau‐PET) and longitudinal analyses. Individual rate of cognitive decline was computed using linear mixed effect models, leveraging all visits available for each participant. We did region‐wise analyses, relating tau in the 64 regions of the Desikan‐Killiany atlas plus the amygdalae with cognitive performance and rate of cognitive decline. We also derived a “spatial extent index” where we computed the number of abnormal tau regions and compared the performance of this index to detect cognitive impairment to what would have been found with a classical temporal meta‐ROI SUVR value.ResultNo regional association between tau and cognition survived FDR correction in CU participants. Cross‐sectionally and longitudinally, participants with MCI and with AD dementia, associations between tau and memory were predominant in the temporal lobe, associations with language were restricted mostly to the left hemisphere and associations with executive functioning spanned the entire cortex. (Fig 1) Comparing the sum of tau positive regions (spatial extent index) to tau SUVR in the temporal meta‐ROI, both measures were similarly associated with cognition, except for executive functioning at baseline where the spatial extent index was more strongly associated with cognition than the meta‐ROI. (Fig 2)ConclusionWhile temporal meta‐ROI tau SUVR may be sufficient to track non‐executive cognitive performance in individual with cognitive impairments, a whole brain measure may provide additional information regarding executive impairment occurring in AD.

Relationships between excessive daytime sleepiness and arterial stiffness with cognitive function in a racially diverse high‐risk cohort

AbstractBackgroundAs pathologic processes leading to Alzheimer’s disease (AD) begin many years before clinical diagnosis, assessment of pre‐clinical AD risk factors in high‐risk individuals is needed. Excessive daytime sleepiness (EDS) is associated with increased cardiovascular dysfunction, neuroinflammation, and neurodegeneration, leading to cognitive impairment. We tested the hypothesis that EDS and increased arterial stiffness are related to worse cognitive function in a cohort of Black or African American (B/AA) and non‐Hispanic White (NHW) participants.MethodA community‐based racially diverse sample of cognitively unimpaired adults (47‐83 years), most (87%) with a family history of AD, were enrolled. Cognitive testing took one hour and included domains of executive function, working memory, and verbal and visuospatial ability and language. Daytime sleepiness was measured with Epworth Sleepiness Scale (ESS); EDS was defined as ESS≥10. Arterial stiffness was measured using pulse wave velocity (PWV).ResultParticipants (N = 85) were 64±8 years of age, 75% female, 48% B/AA, and highly educated (81% ≥college). Mean central blood pressures were 126±18 mmHg (systolic) and 80±10 mmHg (diastolic), with no differences by race or sex. Scores were lower among B/AA versus NHW participants for Judgement of Line of Orientation (17.71±6.0 versus 23.53±6.0, p<.001, Cohen’s d = .083) and Multilingual Naming Test (28.25±2.7 versus 30.57±2.0, p = .005, d = .950). EDS was present among 15% of participants and associated with lower scores on Digit Symbol (p = .004, d = .917), and Multilingual Naming Test (p = .006, d = 1.455). Total time on Trails A was higher among those with EDS (36s versus 30s, p = .040, d = .575). Higher PWV values were associated with lower scores on Digit Symbol Substitution (r = ‐.259, p = .029), Buschke Selective Reminding Test (‐.298, p = .012), CERAD Word List (‐.306, p = .009), F‐A‐S (r = ‐.253, p = .033), and Animal Fluency (r = ‐.326, p = .006).ConclusionIn a racially diverse cohort at risk for AD, we found that excessive self‐reported daytime sleepiness and increased arterial stiffness were associated with worse scores across multiple cognitive domains. Poor sleep and vascular dysfunction are known contributors to AD pathology, providing potential modifiable targets of intervention to reduce or delay the development of AD in cognitively normal, but high‐risk individuals. Further work is needed for a better understanding of modifiable AD risk factors in diverse populations

Analysis of multi‐dimensional cognitive function of different sexes in the middle‐aged and elderly people at high altitude

AbstractBackgroundTo explore the overall and multi‐dimensional cognitive function of middle‐aged and elderly people and gender difference analysis of its influencing factors under hypoxia environment.MethodFrom January 2018 to December 2021, using cross‐sectional study design, all participants from Xining, Qinghai Province (with an average altitude of 2,500m) who have lived for more than 20 years were selected.General data questionnaire survey, laboratory collection, overall and multi‐dimensional cognitive function assessment were conducted.ResultA total of 500 middle‐aged and elderly people were included in this study, 299 males and 201 females, with an average age of 64.17 ± 10.58 years. Compared with women, there were more men working in civil service, earning more than 5000 months, smoking and drinking, accompanied by hypertension and diabetes (P<0.01, P<0.001), but Geriatric Depression Scale(GDS)and Pittsburgh sleep quality index (PSQI) scores were significantly lower (P<0.01).Compared with women’s multiple cognitive domains, scores of Mini mental state examination(MMSE), Complex Figure Test Delay Recall(CFT‐DR), Digit Span Forward(DSF) and Digit Span Backward(DSB) in men were higher (P<0.05, P<0.01), while scores of Trail Making Test (TMT‐A and TMT‐B) were significantly lower (P<0.01, P<0.001).The neutrophil lymphocyte ratio (NLR) and homocysteine (HCY) in peripheral blood were higher than those in women (P<0.05, P<0.01). Covariance analysis showed after adjusting for education level that scores of MMSE and situational memory (CFT‐DR) of men in different age groups were higher than those of women, while scores of attention (TMT‐A) and executive ability (TMT‐B) were lower than those of women (P<0.05, P<0.01). After adjusting for age, scores of MMSE and CFT‐DR of men in primary school, middle school and high school were higher than those of women (P<0.05, P<0.01). With the influence of education level, men’s TMT‐A scores showed a trend of lower (P<0.05, P<0.01), while women’s TMT‐A scores changed little.TMT‐B score of men was lower than that of women in the four education stages (P<0.05), but there was no trend for men and women to optimize with the increase of education level.ConclusionMiddle‐aged and elderly people of different sexes living in high altitude hypoxic environment may have different multidimensional cognitive decline.

P133: Impairment of Executive Functions in Dialysis Patients. Necessity of Evaluation Cognitive State in Advanced Chronic Kidney Disease

Introduction:Cognitive impairment is common and underdiagnosed in patients in hemodialysis (HD) can be moderate and severe. About 38% of patients in Dialysis has serious deficits in executive function and this affects patients of all ages.Material and methods:Based on the case of an 82-year-old patient in a HD program who enters from Nephrology to the Convalescence Unit for miscontrol of pain due to ganglion and liver recidivism after years of cystectomy by bladder neoplasia and having acute confusional syndrome (ACS) subsequently presented after treatmet with morphine MST and Tramadol. We performed an integral geriatric evaluation that showed a deterioration of the executive functions. Through medical literature we analyze this find of atypical pattern and its possible relationship to renal disease.Results:BI 100/100. No known history of cognitive impairment. Despite optimal pain control with fentanyl patch, pregabalin, paracetamol, metamizol and dexamethasone, without new episodes of ACS, we saw high difficulties in comprehension time schedule, spatial location, bad understanding of medical treatment, etc. Neuropsychological study showed MMSE 24/30; SKT subtest of immediate memory 1/12, null recognition without understanding the task. Memory Imparily Screen 5/8, Test clock 3/7. In summary there were deficits in executive functions such as complex attention, mental control, fluency and reasoning. Fluctuating memory abilities. Mild multiple cognitive impairment executive domain. Atypical Profile.Conclusions:There is a strong correlation between the decrease in GF and the degree of cognitive impairment. This worsens with the Dialysis due to hemodynamic changes. It is essential to evaluate the cognitive situation in all patients with CKD. Being the most affected cognitive domain, the function executive,it can avoid in these patients the correct assesment of established medications and dietary restrictions that are so important in the control of potassium, phosphorus and liquids that cause greater complications and even more mortality.

Association between social networking and cognition among middle aged and older adults in rural India

AbstractBackgroundEmerging evidence suggests that better social networking is associated with better cognitive performance among older adults. However, most of the prior studies have used global cognitive measures to study the above relationship. In this study, we aim to investigate the role of social networking on distinct cognitive domains, among dementia‐free middle‐aged and older‐age adults from a rural Indian population.MethodBaseline assessment data of 2403 participants (≥45 years), who are part of an ongoing, prospective, aging cohort study in rural India (Srinivaspura Aging, NeuroSenescence, and COGnition, SANSCOG) and having a Clinical Dementia Rating (CDR) of ‘0’ who are cognitively healthy was utilized for this study. Social networking was assessed using Cohen’s Social Network Index (SNI), wherein three dimensions were examined – network diversity, number of people in social network and number of embedded networks. Cognitive functions were assessed using episodic memory, geometric figure spatial recognition, verbal fluency, semantic association, word comprehension, reading comprehension and visuospatial span subtests of a culturally validated, computerized, neurocognitive test battery. Linear regression models, adjusted with age and gender were used for statistical analysis.ResultIn the linear regression model, adjusted for age and gender, higher network diversity was significantly associated with better cognitive performance in episodic memory (β = 0.16, p = 0.001), attention function (β = 0.07, p = 0.004), geometric figure spatial recognition (β = 0.13, p = 0.001), verbal fluency phonemic cue (β = 0.11, p = 0.001), reading comprehension (β = 0.09, p = 0.001) and semantic language association function (β = 0.08, p = 0.001). Further, higher dimension of number of people in social network was significantly associated with better cognitive performances in semantic language association function (β = 0.002, p = 0.04). Furthermore, in the third dimension of SNI, higher dimension of number of embedded networks was significantly associated with better cognitive performances in visuospatial span (β = 0.05, p = 0.046) and verbal fluency phonemic cue (β = 0.103, p = 0.001).ConclusionThe findings suggest that better social networking in all three dimensions was associated with better cognitive functions in multiple distinct cognitive domains. It is important to follow‐up these participants longitudinally with serial cognitive monitoring to understand if social networking can potentially delay cognitive decline and thereby, serve as a protective factor for dementia.

Sex‐specific genetic architecture of multiple domains of cognition among older adults

AbstractBackgroundGenetic analyses of cognitive endophenotypes have led to discoveries of novel loci contributing to Alzheimer’s disease (AD) risk. Sex differences are present in cognitive trajectories in aging and AD, and these may vary across cognitive domain. However, genetic drivers that may contribute to sex differences in cognitive trajectories have yet to be explored. Thus, we sought to investigate the sex‐specific genetic architecture of cognition.MethodWe leveraged 10 cohorts of cognitive aging and AD to complete this sex‐aware genetic study (N = 31,800; mean age = 73 yrs.; 55% female). Harmonized cognitive scores for memory, executive functioning, and language were derived using confirmatory factor analysis models. We calculated change in cognitive scores over time using a mixed effects model, to facilitate analysis on cognitive decline. We performed GWAS of baseline score and of estimated rate of decline in each domain and in each cohort separately among non‐Hispanic white (NHW) individuals, adjusting for baseline age and genetic principal components. Then we meta‐analyzed the results.ResultIn addition to the well‐characterized APOE locus, we identified a genome‐wide significant chromosome 2 locus that was associated with language decline among NHW women (rs13387871: MAF = 0.20; βwomen = 2.97×10−3; Pwomen = 2.65×10−9), but not among male counterparts (βmen = ‐3.14×10−4, Pmen = 0.60). This locus contains multiple eQTLs for VRK2, a serine/threonine kinase that has been previously linked to neuropsychiatric disorders, including schizophrenia. Furthermore, the top variant in this locus (rs13387871) was nominally significant for memory decline (βwomen = 1.74×10−3, Pwomen = 0.01) and for executive functioning decline (βwomen = 7.58×10−4, Pwomen = 0.02) in meta‐analyses among NHW women.ConclusionOur genetic analysis suggests that there may be some genetic drivers of language performance that differ by sex, and that these drivers may be shared to an extent across domains. Our future sex‐aware meta‐analyses will also include 1) non‐Hispanic black (NHB) within ancestry (N = 4,200), 2) cross‐ancestry (NHW + NHB), 3) diagnosis‐stratified, and 4) analysis of X‐chromosome. Planned follow‐up analyses will include gene‐set analyses, heritability tests, and genetic correlation tests. Through our preliminary analysis, we identified a promising locus for further exploration, and this is the first of many steps in elucidating the sex‐specific genetic architecture of cognition across ancestry groups.