Variance In Cognitive Performance Research Articles

Unique prediction of developmental psychopathology from genetic and familial risk.

Early detection is critical for easing the rising burden of psychiatric disorders. However, the specificity of psychopathological measurements and genetic predictors is unclear among youth. We measured associations between genetic risk for psychopathology (polygenic risk scores (PRS) and family history (FH) measures) and a wide range of behavioral measures in a large sample (n = 5,204) of early adolescent participants (9-11 years) from the Adolescent Brain and Cognitive Development StudySM . Associations were measured both with and without accounting for shared variance across measures of genetic risk. When controlling for genetic risk for other psychiatric disorders, polygenic risk for problematic opioid use (POU) is uniquely associated with lower behavioral inhibition. Attention deficit hyperactivity disorder (ADHD), depression (DEP), and attempted suicide (SUIC) PRS shared many significant associations with externalizing, internalizing, and psychosis-related behaviors. However, when accounting for all measures of genetic and familial risk, these PRS also showed clear, unique patterns of association. Polygenic risk for ASD, BIP, and SCZ, and attempted suicide uniquely predicted variability in cognitive performance. FH accounted for unique variability in behavior above and beyond PRS and vice versa, with FH measures explaining a greater proportion of unique variability compared to the PRS. Our results indicate that, among youth, many behaviors show shared genetic influences; however, there is also specificity in the profile of emerging psychopathologies for individuals with high genetic risk for particular disorders. This may be useful for quantifying early, differential risk for psychopathology in development.

Rich-Club Analysis of Structural Brain Network Alterations in HIV Positive Patients With Fully Suppressed Plasma Viral Loads

ObjectiveEven with successful combination antiretroviral therapy (cART), patients with human immunodeficiency virus positive (HIV+) continue to present structural alterations and neuropsychological impairments. The purpose of this study is to investigate structural brain connectivity alterations and identify the hub regions in HIV+ patients with fully suppressed plasma viral loads.MethodsIn this study, we compared the brain structural connectivity in 48 patients with HIV+ treated with a combination of antiretroviral therapy and 48 healthy controls, using diffusion tensor imaging. Further comparisons were made in 24 patients with asymptomatic neurocognitive impairment (ANI) and 24 individuals with non-HIV-associated neurocognitive disorders forming a subset of HIV+ patients. The graph theory model was used to establish the topological metrics. Rich-club analysis was used to identify hub nodes across groups and abnormal rich-club connections. Correlations of connectivity metrics with cognitive performance and clinical variables were investigated as well.ResultsAt the regional level, HIV+ patients demonstrated lower degree centrality (DC), betweenness centrality (BC), and nodal efficiency (NE) at the occipital lobe and the limbic cortex; and increased BC and nodal cluster coefficient (NCC) in the occipital lobe, the frontal lobe, the insula, and the thalamus. The ANI group demonstrated a significant reduction in the DC, NCC, and NE in widespread brain regions encompassing the occipital lobe, the frontal lobe, the temporal pole, and the limbic system. These results did not survive the Bonferroni correction. HIV+ patients and the ANI group had similar hub nodes that were mainly located in the occipital lobe and subcortical regions. The abnormal connections were mainly located in the occipital lobe in the HIV+ group and in the parietal lobe in the ANI group. The BC in the calcarine fissure was positively correlated with complex motor skills. The disease course was negatively correlated with NE in the middle occipital gyrus.ConclusionThe results suggest that the occipital lobe and the subcortical regions may be important in structural connectivity alterations and cognitive impairment. Rich-club analysis may contribute to our understanding of the neuropathology of HIV-associated neurocognitive disorders.

Cognitive, Sleep, and Autonomic Responses to Induction of a Ketogenic Diet in Military Personnel: A Pilot Study

BACKGROUND: This pilot study examined the effect of a 2-wk ketogenic diet (KD) compared with a carbohydrate (CHO) diet in military personnel on cognitive performance, mood, sleep, and heart rate variability (HRV).METHODS: A randomized-controlled, cross-over trial was conducted with eight male military personnel (age, 36 ± 7 yr; body mass, 83.7 ± 9.2 kg; BMI, 26.0 ± 2.3 kg · m-2). Subjects ingested their habitual diet for 7 d (baseline), then an iso-energetic KD (∼25 g CHO/d) or CHO diet (∼285 g CHO/d) for 14 d (adaptation), separated by a 12-d washout. HRV, fasting capillary blood D-βHB, and glucose concentration, mood, and sleep were measured daily. Cognitive performance was measured on the 7th day of baseline and the 7th and 14th days of adaptation. Data were analyzed using a series of linear mixed models.RESULTS: Mean weekly D-βHB was higher (95% CI, +0.34 to +2.38 mmol · L-1) and glucose was lower (-0.45 to -0.21 mmol · L-1) in the KD compared with the CHO diet. Cognitive performance (Psychomotor Vigilance Task, 2-choice reaction time, and running memory continuous performance test) and mean weekly fatigue, vigor, and sleep (sleep duration, sleep efficiency, and sleep onset latency) were similar between diets. A diet × week interaction for HRV approached significance, with exploratory analyses suggesting HRV was lower compared with baseline during week-2 adapt (-27 to +4 ms) in the KD.DISCUSSION: A 2-wk KD induction in military personnel does not appear to affect cognitive performance, mood, or sleep, but may lower HRV, indicating increased physiological stress.Shaw DM, Henderson L, van den Berg M. Cognitive, sleep, and autonomic responses to induction of a ketogenic diet in military personnel: a pilot study. Aerosp Med Hum Perform. 2022; 93(6):507-516.

The Matrix Matters: Beverage Carbonation Impacts the Timing of Caffeine Effects on Sustained Attention.

Both caffeine and the perception of refreshment delivered by cooling, tingling, and mouth-watering flavors have individually been shown to positively impact cognitive performance and mood, though presently there is limited evidence on their possible combined effects. This study explored the contribution of refreshing compounds in beverages, namely, carbon dioxide and citric acid, on the acute effects of caffeine on sustained attention and self-rated physical and mental energy. A randomized, controlled crossover trial was conducted by testing three products: a carbonated caffeinated beverage; a comparator caffeinated beverage; and a flavor-matched control beverage. Findings from 24 healthy adults revealed product-dependent variations in cognitive performance during a 60-min visual sustained-attention task, suggesting that the carbonated-caffeinated beverage led to faster, greater and more consistent levels of accuracy, compared to the control beverage. Specifically, significant differences were found between: (1) the carbonated-caffeinated beverage and the caffeinated beverage, and (2) between the caffeinated beverage and the control beverage for number of hits, reaction time and false alarm scores. Both caffeinated beverages led to higher physical and mental energy, and lower physical and mental fatigue 60-min post-consumption. These findings suggest beneficial effects on sustained attention through the combination of caffeine with refreshing compounds.

Combining MRI and cognitive evaluation to classify concussion in university athletes.

Current methods of concussion assessment lack the objectivity and reliability to detect neurological injury. This multi-site study uses combinations of neuroimaging (diffusion tensor imaging and resting state functional MRI) and cognitive measures to train algorithms to detect the presence of concussion in university athletes. Athletes (29 concussed, 48 controls) completed symptom reports, brief cognitive evaluation, and MRI within 72h of injury. Hierarchical linear regression compared groups on cognitive and neuroimaging measures while controlling for sex and data collection site. Logistic regression and support vector machine models were trained using cognitive and neuroimaging measures and evaluated for overall accuracy, sensitivity, and specificity. Concussed athletes reported greater symptoms than controls (∆R2 = 0.32, p < .001), and performed worse on tests of concentration (∆R2 = 0.07, p < .05) and delayed memory (∆R2 = 0.17, p < .001). Concussed athletes showed lower functional connectivity within the frontoparietal and primary visual networks (p < .05), but did not differ on mean diffusivity and fractional anisotropy. Of the cognitive measures, classifiers trained using delayed memory yielded the best performance with overall accuracy of 71%, though sensitivity was poor at 46%. Of the neuroimaging measures, classifiers trained using mean diffusivity yielded similar accuracy. Combining cognitive measures with mean diffusivity increased overall accuracy to 74% and sensitivity to 64%, comparable to the sensitivity of symptom report. Trained algorithms incorporating both MRI and cognitive performance variables can reliably detect common neurobiological sequelae of acute concussion. The integration of multi-modal data can serve as an objective, reliable tool in the assessment and diagnosis of concussion.

The prevalence and characteristics of MCCB cognitive impairment in unmedicated patients with bipolar II depression and major depressive disorder

BackgroundCognitive impairment has been acknowledged as a core clinical manifestation of bipolar disorder (BD) as well as major depressive disorder (MDD). Determining the prevalence and characteristics of cognitive impairment is important for clinical interventions. This study investigated the prevalence and characteristics of cognitive impairment based on the Measurement and Treatment Research to Improve Cognition Schizophrenia Consensus Cognitive Battery (MCCB) in both BD and MDD. MethodOne hundred and forty-nine BD II depression, 147 MDD, and 124 demographically matched healthy controls (HC) underwent MCCB cognitive assessment. The prevalence of MCCB cognitive impairment and group difference comparisons were performed. Additionally, association analysis was performed to investigate the relationship between cognitive performance and clinical variables. ResultsCompared to the HC group, both BD II depression and MDD groups had a significantly reduced performance for all MCCB cognitive domains (all p < 0.05). The numerical scores for visual learning were lower in the BD II depression group compared to the MDD group. 32.89% of the BD II depression patients had clinically significant impairment (>1.5 SD below the normal mean) in two or more MCCB domains compared to 23.13% for MDD patients. ConclusionsA high percent of patients in the BD II depression and MDD group exhibited MCCB cognitive impairments with clinical significance. Cognitive impairments were more common in BD II depression patients compared to MDD patients, particularly for visual learning. These findings suggest that clinicians should be aware of the severe cognitive impairment in mood disorders and establish effective cognitive screening and intervention strategies.

Variability in Cognitive Task Performance is Associated With Future Symptoms of Externalizing Psychopathology and Lower Functional Network Segregation

Intra-individual variability (IIV) during cognitive task performance is a key behavioral assay of attention. Across the lifespan, lower IIV is associated with higher anticorrelation between the dorsal attention network (DAN) and default mode network (DMN), which is thought to represent effective allocation of attention through functional network segregation. However, whether these behavioral and neural markers of sustained attention are (i) related to each other and (ii) can predict future attention-related deficits has not yet been investigated in a developmental, population-based cohort.

Effects of the physical and social environment on youth cognitive performance.

Individual differences in children's cognitive abilities impact life and health outcomes. What factors influence these individual differences during development? Here, we test whether children's environments predict cognitive performance, independent of well-characterized socioeconomic effects. We analyzed data from 9002 9- to 10-year olds from the Adolescent Brain Cognitive Development Study, an ongoing longitudinal study with community samples across the United States. Using youth- and caregiver-report questionnaires and national database registries (e.g., neighborhood crime, walkability), we defined principal components summarizing children's home, school, neighborhood, and cultural environments. In two independent samples (ns=3475, 5527), environmental components explained unique variance in children's general cognitive ability, executive functioning, and learning/memory abilities. Furthermore, increased neighborhood enrichment was associated with an attenuated relationship between sociodemographics and general cognitive abilities. Thus, the environment accounts for unique variance in cognitive performance in children and should be considered alongside sociodemographic factors to better understand brain functioning and behavior across development.

Resting-State Functional Connectivity in the Dorsal Attention Network Relates to Behavioral Performance in Spatial Attention Tasks and May Show Task-Related Adaptation.

Between-subject variability in cognitive performance has been related to inter-individual differences in functional brain networks. Targeting the dorsal attention network (DAN) we questioned (i) whether resting-state functional connectivity (FC) within the DAN can predict individual performance in spatial attention tasks and (ii) whether there is short-term adaptation of DAN-FC in response to task engagement. Twenty-seven participants first underwent resting-state fMRI (PRE run), they subsequently performed different tasks of spatial attention [including visual search (VS)] and immediately afterwards received another rs-fMRI (POST run). Intra- and inter-hemispheric FC between core hubs of the DAN, bilateral intraparietal sulcus (IPS) and frontal eye field (FEF), was analyzed and compared between PRE and POST. Furthermore, we investigated rs-fMRI-behavior correlations between the DAN-FC in PRE/POST and task performance parameters. The absolute DAN-FC did not change from PRE to POST. However, different significant rs-fMRI-behavior correlations were revealed for intra-/inter-hemispheric connections in the PRE and POST run. The stronger the FC between left FEF and IPS before task engagement, the better was the learning effect (improvement of reaction times) in VS (r = 0.521, p = 0.024). And the faster the VS (mean RT), the stronger was the FC between right FEF and IPS after task engagement (r = −0.502, p = 0.032). To conclude, DAN-FC relates to the individual performance in spatial attention tasks supporting the view of functional brain networks as priors for cognitive ability. Despite a high inter- and intra-individual stability of DAN-FC, the change of FC-behavior correlations after task performance possibly indicates task-related adaptation of the DAN, underlining that behavioral experiences may shape intrinsic brain activity. However, spontaneous state fluctuations of the DAN-FC over time cannot be fully ruled out as an alternative explanation.

Speech Perception in Noise Is Associated With Different Cognitive Abilities in Chinese-Speaking Older Adults With and Without Hearing Aids.

Chinese-speaking older adults usually do not perceive a hearing problem until audiometric thresholds exceed 45 dB HL, and the audiometric thresholds of the average hearing-aid (HA) user often exceed 60 dB HL. The purpose of this study was to examine the relationships between cognitive and hearing functions (measured as audiometric or speech reception thresholds) in older Chinese adults with HAs and with untreated hearing loss (HL). Participants were 49 Chinese older adults who used HAs and had moderate to severe HL (HA group), and 46 older Chinese who had mild to moderately severe HL but did not use HAs (untreated; or UT group). Multiple linear regression analysis was employed to evaluate how well age, education level, audiometric thresholds, and speech perception in noise were related to performance on general cognitive function, working memory, executive function, attention, and verbal learning tests. Results showed that speech perception in noise alone accounted for 13–25% of the variance in general cognitive function, working memory, and executive function in the UT group, and 9–21% of the variance in general cognitive function and verbal learning in the HA group (i.e., medium effect sizes). Audiometric thresholds did not explain any proportion of the variance in cognitive functioning in the HA or UT group. Thus, speech perception in noise accounts for more variance in cognitive performance than audiometric thresholds, and is significantly associated with different cognitive functions in older Chinese adults with HAs and with untreated HL.

Cognitive Benefits of Learning Additional Languages in Old Adulthood? Insights from an Intensive Longitudinal Intervention Study

Abstract Second language (L2) learning has been promoted as a promising intervention to stave off age-related cognitive decline. While previous studies based on mean trends showed inconclusive results, this study is the first to investigate nonlinear cognitive trajectories across a 30-week training period. German-speaking older participants (aged 64–75 years) enrolled for a Spanish course, strategy game training (active control) or movie screenings (passive control). We assessed cognitive performance in working memory, alertness, divided attention, and verbal fluency on a weekly basis. Trajectories were modeled using Generalized Additive Mixed Models to account for temporally limited transfer effects and intra-individual variation in cognitive performance. Our results provide no evidence of cognitive improvement differing between the Spanish and either of the control groups during any phase of the training period. We did, however, observe an effect of baseline cognition, such that individuals with low cognitive baselines increased their performance more in the L2 group than comparable individuals in the control groups. We discuss these findings against the backdrop of the cognitive training literature and Complex Dynamic Systems Theory.

Predicting quality of life with physical and cognitive functioning among older adults with cognitive impairment

Purpose: Older adults experience abnormal declines in physical and cognitive functioning that increase their risk of dependence, subsequently quality of life. This study aims to explore the relationship between physical and cognitive functioning, and to predict quality of life among older adults with mild cognitive impairment. Methods: Survey was conducted with older adults registered at dementia support centers. Seventy-four older adults signed the consent form and participated in the study. physical functioning consisted of grip strength, balance (OLS), Timed up and go, and activities of daily living. Cognitive functioning was measured by K-MOCA. SF-12 was used to assess quality of life. Results: The participants was 76 years old on average, more women (75.4%), and mostly elementary or less education level (60.9%). Physical functioning explained 22.1% of variance in cognitive functioning after controlling for age and gender (F change=4.789, p=.002). Balance (OLS: t=2.304, p=.024) and grip strength (t=2.207, p=.031) was significant predictors. Physical and cognitive functioning explained 36.7% of variance in quality of life after controlling for age and gender (F =5.466, p<.001). Indicators of physical functioning, TUG (t=-3.252) and grip strength (t=-2.633), were the most significant predictors of quality of life, while cognitive function explained additional 3.1% of variance in quality of life (F=3.216, p=.078). Conclusion: Physical functioning were significant predictors of cognitive functioning, subsequently to quality of life among older adults with cognitive impairment. Health promoting strategies should focus on improving physical functioning of this population to maintain or prevent cognitive declining, and to promote quality of life.

Education, Occupation, and the Cognitive Performance Distribution of South Korean Older Adults

Earlier research suggests that educational attainment up to early adulthood are crucial for the development of cognitive reserve, while intellectually stimulating activities later in the life course are of limited impact. We sought to explore the effects of educational attainment and occupational factors (occupation type and currently having work) across the distribution of cognitive performance for adults aged 45-65 years in South Korea. We analysed scores from the Korean Mini Mental State Exam (MMSE) provided in the 2006 wave of the Korean Longitudinal Study of Aging. We used quantile regressions to both investigate relationships across the distribution and to reduce bias for measures of the central tendency as the MMSE is known for its ceiling effects. The quantile function at the lowest conditional decile of MMSE scores suggested that education level was the dominant significant factor for adult performance on the MMSE (lowest MMSE decile, primary education: β = 6.11 points, p < 0.001; secondary education β = 9.56 points, p < 0.001). All occupational factors were non-significant. Further factors with a significant association with the MMSE were hearing loss, the log-transformed household income, and age squared. With the conditional median function, occupational factors became significant in the middle of the distribution but remained much less important than education levels. In summary, educational levels were more important to explain variation in cognitive functioning than occupational factors, echoing studies with Western samples. We discuss the findings with regard to the historically gender unequal educational and occupational opportunities in Korea.

Variability in Cognitive Performance on Mobile Devices Is Sensitive to Mild Cognitive Impairment: Results From the Einstein Aging Study.

Background and Objective: Within-person variability in cognitive performance has emerged as a promising indicator of cognitive health with potential to distinguish normative and pathological cognitive aging. We use a smartphone-based digital health approach with ecological momentary assessments (EMA) to examine differences in variability in performance among older adults with mild cognitive impairment (MCI) and those who were cognitively unimpaired (CU).Method: A sample of 311 systematically recruited, community-dwelling older adults from the Einstein Aging Study (Mean age = 77.46 years, SD = 4.86, Range = 70–90; 67% Female; 45% Non-Hispanic White, 40% Non-Hispanic Black) completed neuropsychological testing, neurological assessments, and self-reported questionnaires. One hundred individuals met Jak/Bondi criteria for MCI. All participants performed mobile cognitive tests of processing speed, visual short-term memory binding, and spatial working memory on a smartphone device up to six times daily for 16 days, yielding up to 96 assessments per person. We employed heterogeneous variance multilevel models using log-linear prediction of residual variance to simultaneously assess cognitive status differences in mean performance, within-day variability, and day-to-day variability. We further tested whether these differences were robust to the influence of environmental contexts under which assessments were performed.Results: Individuals with MCI exhibited greater within-day variability than those who were CU on ambulatory assessments that measure processing speed (p < 0.001) and visual short-term memory binding (p < 0.001) performance but not spatial working memory. Cognitive status differences in day-to-day variability were present only for the measure of processing speed. Associations between cognitive status and within-day variability in performance were robust to adjustment for sociodemographic and contextual variables.Conclusion: Our smartphone-based digital health approach facilitates the ambulatory assessment of cognitive performance in older adults and the capacity to differentiate individuals with MCI from those who were CU. Results suggest variability in mobile cognitive performance is sensitive to MCI and exhibits dissociative patterns by timescale and cognitive domain. Variability in processing speed and visual short-term memory binding performance may provide specific detection of MCI. The 16-day smartphone-based EMA measurement burst offers novel opportunity to leverage digital technology to measure performance variability across frequent assessments for studying cognitive health and identifying early clinical manifestations of cognitive impairment.

White matter tract integrity, but not amyloid burden, is related to cognition in cognitively normal older adults

AbstractBackgroundThe increased focus on preclinical Alzheimer’s disease (AD) necessitates an understanding of how general biomarkers of neuronal injury and AD‐specific biomarkers differentially contribute to the cognitive performance in cognitively normal individuals. It has been suggested that alterations in limbic white matter (WM) tracts may precede both gray matter atrophy and clinical impairment (Teipel et al., 2016). However, few studies have evaluated whether limbic tract alterations are associated with cognitive performance in individuals with normal cognition. To address this gap, this cross‐sectional, multi‐modal imaging study examined whether measures of WM tract integrity, using diffusion tensor imaging (DTI) (including fornix, hippocampal cingulum, and uncinate fasciculus), were related to cognitive performance, independent of cortical amyloid burden in cognitively normal individuals.MethodAnalyses included 130 cognitively normal participants from the BIOCARD Study (Table 1) who completed cognitive assessments, diffusion‐weighted MR and 11C‐PiB PET imaging during their annual visit. Cognitive performance was captured by cognitive composite scores reflecting verbal episodic memory, executive function, and visuospatial processing. WM tract integrity was measured by fractional anisotropy (FA) and radial diffusivity (RD) in the 3 above‐mentioned ROIs. PiB PET amyloid positivity was derived from cortical distribution volume ratios (cDVR) using cerebellar gray matter as the reference.Linear regressions (covarying age, sex, and education) were used to test 4 a priori cognition‐WM associations. The following relationships were examined: episodic memory and fornix and hippocampal cingulum integrity; executive function and uncinate fasciculus integrity; visuospatial processing and hippocampal cingulum integrity.ResultIn the linear regression models (Table 2), lower hippocampal cingulum FA and greater hippocampal cingulum RD were each associated with better episodic memory performance. Additionally, lower uncinate fasciculus RD (but not FA) was associated with better executive function performance. In contrast, amyloid positivity (i.e., cDVR &gt; 1.06) was unrelated to any of the cognitive composite scores (all ps &gt; .35).ConclusionMeasures of WM tract integrity account for variability in cognitive performance among cognitively normal individuals, and this association is independent of amyloid burden. Additional analyses are needed to determine whether these microstructural measures reflect general, age‐related markers of neuronal injury vs. alterations related to preclinical AD.

Neuropsychological correlates of plasma NfL in adults with Down syndrome

AbstractBackgroundThe diagnosis of symptomatic Alzheimer’s disease (AD) in Down syndrome (DS) is challenging, mainly because the variability in cognitive performance associated with the different levels of intellectual disability. Plasma NfL levels are a promising biomarker of axonal damage with good diagnostic and prognostic performance, but its impact on cognitive performance has not been assessed. We aimed to explore this association between NfL levels and both baseline cognitive performance and the longitudinal cognitive decline.MethodProspective longitudinal cohort study. We included adults with DS from the Down Alzheimer Barcelona Neuroimaging Initiative cohort with mild and moderate levels of intellectual disability (ID) who had available plasma and a neuropsychological evaluation (Cambridge Cognitive Examination for Older Adults with Down's syndrome [CAMCOG‐DS] and/or modified Cued Recall Test [mCRT]). Plasma NfL levels were determined by Simoa SR‐XTM. We performed correlation analysis between baseline NfL levels and cognitive scores and linear mixed models to account for longitudinal cognitive measures. Age, sex and cognitive status (asymptomatic, prodromal AD, AD dementia) were considered as co‐variables in the analysis. The analyses were stratified in mild and moderate ID separately.ResultWe selected 378 individuals (mean age: 43.1 [sd 10.9], 46.6% female): 287 had CAMCOG‐DS scores and 224 had mCRT scores. We observed a significant correlation between baseline NfL levels and both CAMCOG‐DS and mCRT (R2=0.18 and R2=0.30, respectively, both p&lt;0.001) (Figure). This correlation remained significant after stratification by ID (R2=0.17 and R2=0.19 for mild ID, R2=0.19 and R2=0.32 for moderate ID, all p&lt;0.001). There was a significant association between longitudinal cognitive scores and baseline NfL levels (β=‐0.0035, p=0.011 for CAMCOG‐DS; β=‐0.015, p&lt;0.001 for mCRT).ConclusionCognitive performance is inversely correlated to plasma NfL levels in adults with DS. This study supports the potential role of plasma NfL levels to identify and track AD‐related cognitive decline in DS.

Polygenic risk score for general cognitive function is associated with measures of cognition in South Asians from the LASI-DAD Study.

Genome wide association studies (GWAS) conducted primarily in European Ancestry (EA) have identified hundreds of single nucleotide polymorphisms (SNPs) that are associated with general cognitive function. The association between these SNPs and cognitive function has not yet been evaluated in South Asians yet, either individually or in polygenic risk scores (PRS) which aggregate the effects from many SNPs across the genome. The goal of this study was to investigate whether SNPs identified in EA GWAS, either individually or as a PRS, were associated with a general cognitive factor and the Hindi version of the Mini-Mental State Examination (HMSE) score in 932 South Asians from the Diagnostic Assessment of Dementia for the Longitudinal Aging Study of India (LASI-DAD). Participants were genotyped using the Illumina Global Screening Array and imputed to 1000G Phase 3v5. We used linear models to assess the association between 130 top SNPs from the EA GWAS (p<5e-08) and both measures of cognitive function after controlling for age, gender, and population structure. We also evaluated the association between PRSs using the top GWAS SNPs and the cognitive measures using the same models. Finally, we estimated the variation in cognitive function explained by the cognitive function PRS, Alzheimer's disease (AD) PRSs, and/or APOE e2 and e4 genotypes individually or simultaneously. Preliminary analyses showed that none of the GWAS SNPs were significantly associated either of the cognitive measures after multiple testing correction. The PRS, however, was significantly associated with the general cognitive factor and HMSE score (p<0.025). The PRS explained 0.40% and 0.59% of the variance in the general cognitive factor and HMSE score, and explained 1.50% and 1.85% of the variance when coupled with AD PRSs and APOE genotypes. SNPs identified for cognitive function in EA GWAS may not be as strongly associated in South Asians. However, the genetic risk score for both general cognitive function and AD contribute additively to cognitive function in LASI-DAD participants. Future large scale GWAS of general cognitive function and AD are needed to identify specific risk variants for cognition in South Asians.

Cognitive intraindividual variability as a biomarker for functional declines in the Texas Alzheimer’s Research and Care Consortium (TARCC) Longitudinal Hispanic Cohort

AbstractBackgroundWhile intraindividual variability (IIV) in cognitive performance has been associated with increased risk for cognitive decline, the relative predictive utility of IIV‐across versus IIV‐within different cognitive domains remains unknown. Given that cognitive IIV has also been linked to age‐related reductions in white matter integrity, the current study aimed to determine if IIV‐within a “frontal‐subcortical” domain may be a more robust predictor of functional declines over time than IIV‐across cognitive domains.MethodsParticipants included 651 controls, 211 MCI and 218 AD patients enrolled in the TARCC Hispanic Longitudinal Cohort. Mixed Linear Modeling was used to examine the fixed effects of static predictors (i.e., age, education, gender, ethnicity, APOE genotype, cognitive status) at baseline, and the fixed and random effects of time‐varying covariates (i.e., depression, pulse pressure, IIV‐across domains, and IIV‐within the frontal‐subcortical domain) on changes in functional independence over 5 years.ResultsAge, education and ethnicity moderated the relationship between APOE genotype, baseline cognitive status and declines in functional independence over time. Overall, greater pulse pressure, IIV‐across domains and IIV‐within the frontal‐subcortical domain were all associated with larger decrements in functional independence over time. Although increases in IIV‐across domains were primarily driven by increases in IIV‐within the frontal‐subcortical domain over time, the former emerged as a stronger predictor of functional independence than the latter. Gender and education significantly influenced individual differences in rates of change over time, while the effects of IIV‐across domains and IIV‐within the frontal‐subcortical domain on functional declines differed from person‐to‐person. The addition of cognitive IIV predictors significantly improved model fit with a 1498.3 reduction in ‐2LL (p &lt; 0.001). The final model accounted for 97.8% of the variance in functional independence over time.ConclusionsResults suggest that IIV‐across domains may be a robust biomarker of subsequent declines in functional independence and changes in this metric are primarily driven by increasing variability across tasks dependent on frontal‐subcortical circuitry. Findings also highlight important considerations for the development of future clinical trials aimed at early prevention and treatment, including the significance of demographic and clinical characteristics in moderating the risk of decline in functional independence over time.

Seasonality of cognitive function in the general population: the Rotterdam Study

Seasonal variation in cognitive function and underlying cerebral hemodynamics in humans has been suggested, but not consistently shown in previous studies. We assessed cognitive function in 10,276 participants from the population-based Rotterdam Study, aged 45 years and older without dementia, at baseline and at subsequent visits between 1999 and 2016. Seasonality of five cognitive test scores and of a summary measure of global cognition were determined, as well as of brain perfusion. Using linkage with medical records, we also examined whether a seasonal variation was present in clinical diagnoses of dementia. We found a seasonal variation of global cognition (0.05 standard deviations [95% confidence interval: 0.02–0.08]), the Stroop reading task, the Purdue Pegboard test, and of the delayed world learning test, with the best performance in summer months. In line with these findings, there were fewer dementia diagnoses of dementia in spring and summer than in winter and fall. We found no seasonal variation in brain perfusion. These findings support seasonality of cognition, albeit not explained by brain perfusion.

Lower cerebral oxygen utilization is associated with Alzheimer’s disease-related neurodegeneration and poorer cognitive performance among apolipoprotein E ε4 carriers

Oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) are markers of cerebral oxygen homeostasis and metabolism that may offer insights into abnormal changes in brain aging. The present study cross-sectionally related OEF and CMRO2 to cognitive performance and structural neuroimaging variables among older adults (n = 246, 74 ± 7 years, 37% female) and tested whether apolipoprotein E (APOE)-ε4 status modified these associations. Main effects of OEF and CMRO2 were null (p-values >0.06), and OEF interactions with APOE-ε4 status on cognitive and structural imaging outcomes were null (p-values >0.06). However, CMRO2 interacted with APOE-ε4 status on language (p = 0.002), executive function (p = 0.03), visuospatial (p = 0.005), and episodic memory performances (p = 0.03), and on hippocampal (p = 0.006) and inferior lateral ventricle volumes (p = 0.02). In stratified analyses, lower oxygen metabolism related to worse language (p = 0.02) and episodic memory performance (p = 0.03) among APOE-ε4 carriers only. Associations between CMRO2 and cognitive performance were primarily driven by APOE-ε4 carriers with existing cognitive impairment. Congruence across language and episodic memory results as well as hippocampal and inferior lateral ventricle volume findings suggest that APOE-ε4 may interact with cerebral oxygen metabolism in the pathogenesis of Alzheimer’s disease and related neurodegeneration.