Fluid Intelligence Scores Research Articles

Relationship between hearing impairment and dementia and cognitive function: a Mendelian randomization study

BackgroundThere is a substantial body of observational research indicating an association between hearing impairment and dementia, yet the causal relationship and underlying mechanisms remain uncertain. This study aims to investigate the causal relationship between hearing impairment and its subtypes with dementia and cognitive function using two-sample Mendelian randomization (MR) analysis.MethodsWe performed two-sample MR analysis to examine the causal effects of hearing impairment and its subtypes, including conductive and sensorineural hearing loss (CSHL), conductive hearing loss (CHL), sensorineural hearing loss (SHL), and sudden sensorineural hearing loss (SIHL), on six dementia phenotypes (overall dementia, Alzheimer’s disease [AD], Lewy body dementia [DLB], frontotemporal dementia [FTD], Parkinson’s disease dementia, and vascular dementia) and four cognitive functions. Additionally, multivariable MR (MVMR) analysis was employed to investigate potential mediating mechanisms.ResultsGenetically determined CSHL was associated with an elevated risk of DLB (odds ratio [OR] 1.69; 95% CI 1.08 to 2.63; P = 0.021) and FTD (OR 1.66; 1.04 to 2.67; P = 0.035), but not AD (P = 0.958). Genetic predisposition to CHL was found to link with increased risks of AD (OR 1.07; 1.01 to 1.14; P = 0.031). Genetically determined SHL was causally associated with an elevated risk of semantic dementia (OR 3.81; 1.09 to 13.37; P = 0.037). Genetically predicted CHL and SIHL were both causally associated with lower general cognitive performance (β -0.015 and − 0.043; P = 0.007 and 0.013) and fluid intelligence score (β -0.045 and − 0.095; P = 0.037 and 0.040). In MVMR analysis, the causal relationship between hearing impairment and dementia was mediated by loneliness, depressed mood, and brain cortical volume, particularly the medial temporal lobe, but not by aging or ischemic stroke.ConclusionOverall, the study provides evidence supporting a causal relationship between hearing impairment and increased risks of different types of dementia (including AD, FTD, and DLB), as well as poorer general cognitive function. These findings underscore the importance of addressing hearing impairment as a modifiable risk factor for dementia.

Genetic and vascular risk factors for ischemic stroke and cortical morphometry in individuals without a history of stroke: A UK Biobank observational cohort study

BackgroundStroke risk factors may contribute to cognitive decline and dementia by altering brain tissue integrity. If their effects on brain are nonnegligible, the target regions for stroke rehabilitation with brain stimulation identified by cross-sectional case-control studies may be biased due to the pre-existing brain differences caused by these risk factors. Here, we investigated the effects of stroke risk factors on cortical thickness (CT) and surface area (SA) in individuals without a history of stroke. MethodsIn this observational study, we used data from the UK Biobank cohort to explore the effects of polygenic risk score for ischemic stroke (PRSIS), systolic blood pressure (SBP), diastolic blood pressure (DBP), glycated hemoglobin (HbA1c), triglycerides (TG), and low-density lipoprotein (LDL) on CT and SA of 62 cerebral regions. We excluded non-Caucasian participants and participants with missing data, unqualified brain images, or a history of stroke or any other brain diseases. We constructed a multivariate linear regression model for each phenotype to simultaneously test the effect of each factor and interaction between factors. The results were verified by sensitivity analyses of SDP or DBP input and adjusting for body-mass index, high-density lipoprotein cholesterol, or smoking and alcohol intake. By excluding participants with abnormal blood pressure, glucose, or lipid, we tested whether vascular risk factor within normal range also affected cortical phenotypes. To determine clinical relevance of our findings, we also investigated the effects of stroke risk factors and cortical phenotypes on cognitive decline assessed by fluid intelligence score (FIQ) and the mediation of cortical phenotype for the association between stroke risk factor and FIQ. ResultsThe study consisted of 27 120 eligible participants. Stroke risk factors were associated with 16 CT and two SA phenotypes in both main and sensitivity analyses (all p < 0.0004, Bonferroni corrected), which could explain portions of variances (partial R2, median 0.62 % [IQR 0.44–0.75 %] in main analyses) in these phenotypes. Among the 18 cortical phenotypes associated with stroke risk factors, we identified 26 specific predictor-phenotype associations (all p < 0.0026), including the positive associations between PRSIS and SA and between HbA1c and CT, negative associations of SBP and TG with CT, and mixed associations of PRSIS and DBP with CT. Neither LDL nor interactions between risk factors affected cortical phenotypes. Of the 16 associations between vascular risk factors and cortical phenotypes, ten were still significant after excluding participants with abnormal vascular risk assessments and diagnoses. Stroke risk factors were associated with FIQ in all analyses (p < 0.0004; partial R2, range 0.22–0.3 %), of which the associations of PRSIS and SBP with cognitive decline were mediated by CT phenotypes. ConclusionsStroke risk factors have substantial effects on cortical morphometry and cognitive decline in middle-aged and older people, which should be considered in the prevention of dementia and in the identification of target regions for stroke rehabilitation with brain stimulation.

Polygenic scores stratify neurodevelopmental copy number variant carrier cognitive outcomes in the UK Biobank

Rare copy-number variants associated with neurodevelopmental conditions (ND-CNVs) exhibit variable expressivity of clinical, physical, behavioural outcomes. Findings from clinically ascertained cohorts suggest this variability may be partly due to additional genetic variation. Here, we assessed the impact of polygenic scores (PGS) and rare variants on ND-CNV carrier fluid intelligence (FI) scores in the UK Biobank. Greater PGS for cognition (PSCog) and educational attainment (PSEA) is associated with increased FI scores in all ND-CNVs (n = 1317), 15q11.2 del. (n = 543), and 16p13.11 dup. carriers (n = 275). No association of rare variants associated with intellectual disability, autism, or putatively loss-of-function, brain-expressed genes was found. Positive predictive values in the first deciles of PScog and PSEA showed a two- to five-fold increase in the rate of low FI scores compared to baseline rates. These findings demonstrate that PGS can stratify ND-CNV carrier cognitive outcomes in a population-based cohort.

Identifying potential causal effects of Parkinson’s disease: A polygenic risk score-based phenome-wide association and mendelian randomization study in UK Biobank

There is considerable uncertainty regarding the associations between various risk factors and Parkinson’s Disease (PD). This study systematically screened and validated a wide range of potential PD risk factors from 502,364 participants in the UK Biobank. Baseline data for 1851 factors across 11 categories were analyzed through a phenome-wide association study (PheWAS). Polygenic risk scores (PRS) for PD were used to diagnose Parkinson’s Disease and identify factors associated with PD diagnosis through PheWAS. Two-sample Mendelian randomization (MR) analysis was employed to assess causal relationships. PheWAS results revealed 267 risk factors significantly associated with PD-PRS among the 1851 factors, and of these, 27 factors showed causal evidence from MR analysis. Compelling evidence suggests that fluid intelligence score, age at first sexual intercourse, cereal intake, dried fruit intake, and average total household income before tax have emerged as newly identified risk factors for PD. Conversely, maternal smoking around birth, playing computer games, salt added to food, and time spent watching television have been identified as novel protective factors against PD. The integration of phenotypic and genomic data may help to identify risk factors and prevention targets for PD.

Association between surgical admissions, cognition, and neurodegeneration in older people: a population-based study from the UK Biobank

Previous studies have shown that major surgical and medical hospital admissions are associated with cognitive decline in older people (aged 40-69years at recruitment), which is concerning for patients and caregivers. We aimed to validate these findings in a large cohort and investigate associations with neurodegeneration using MRI. For this population-based study, we analysed data from the UK Biobank collected from March 13, 2006, to July 16, 2023, linked to the National Health Service Hospital Episode Statistics database, excluding participants with dementia diagnoses. We constructed fully adjusted models that included age, time, sex, Lancet Commission dementia risk factors, stroke, and hospital admissions with a participant random effect. Primary outcomes were hippocampal volume and white matter hyperintensities, both of which are established markers of neurodegeneration, and exploratory analyses investigated the cortical thickness of Desikan-Killiany-Tourville atlas regions. The main cognitive outcomes were reaction time, fluid intelligence, and prospective and numeric memory. Surgeries were calculated cumulatively starting from 8years before the baseline evaluation. Of 502 412participants in the UK Biobank study, 492 802participants were eligible for inclusion in this study, of whom 46 706underwent MRI. Small adverse associations with cognition were found per surgery: reaction time increased by 0·273ms, fluid intelligence score decreased by 0·057correct responses, prospective memory (scored as correct at first attempt) decreased (odds ratio 0·96 [95% CI 0·95to 0·97]), and numeric memory maximum correct matches decreased by 0·025in fully adjusted models. Surgeries were associated with smaller hippocampal volume (β=-5·76mm³ [-7·89to-3·64]) and greater white matter hyperintensities volume (β=100·02 mm³ [66·17to 133·87]) in fully adjusted models. Surgeries were also associated with neurodegeneration of the insula and superior temporal cortex. This population-based study corroborates that surgeries are generally safe but cumulatively are associated with cognitive decline and neurodegeneration. Perioperative brain health should be prioritised for older and vulnerable patients, particularly those who have multiple surgical procedures. The Australian and New Zealand College of Anaesthetists (ANZCA) Foundation and the University of Sydney.

Evaluating the associations between intelligence quotient and multi-tissue proteome from the brain, CSF and plasma.

Intelligence quotient is a vital index to evaluate the ability of an individual to think rationally, learn from experience and deal with the environment effectively. However, limited efforts have been paid to explore the potential associations of intelligence quotient traits with the tissue proteins from the brain, CSF and plasma. The information of protein quantitative trait loci was collected from a recently released genome-wide association study conducted on quantification data of proteins from the tissues including the brain, CSF and plasma. Using the individual-level genotypic data from the UK Biobank cohort, we calculated the polygenic risk scores for each protein based on the protein quantitative trait locus data sets above. Then, Pearson correlation analysis was applied to evaluate the relationships between intelligence quotient traits (including 120 330 subjects for 'fluid intelligence score' and 38 949 subjects for 'maximum digits remembered correctly') and polygenic risk scores of each protein in the brain (17 protein polygenic risk scores), CSF (116 protein polygenic risk scores) and plasma (59 protein polygenic risk scores). The Bonferroni corrected P-value threshold was P < 1.30 × 10-4 (0.05/384). Finally, Mendelian randomization analysis was conducted to test the causal relationships between 'fluid intelligence score' and pre-specific proteins from correlation analysis results. Pearson correlation analysis identified significant association signals between the protein of macrophage-stimulating protein and fluid intelligence in brain and CSF tissues (P brain = 1.21 × 10-8, P CSF = 1.10 × 10-7), as well as between B-cell lymphoma 6 protein and fluid intelligence in CSF (P CSF = 1.23 × 10-4). Other proteins showed close-to-significant associations with the trait of 'fluid intelligence score', such as plasma protease C1 inhibitor (P CSF = 4.19 × 10-4, P plasma = 6.97 × 10-4), and with the trait of 'maximum digits remembered correctly', such as tenascin (P plasma = 3.42 × 10-4). Additionally, Mendelian randomization analysis results suggested that macrophage-stimulating protein (Mendelian randomization-Egger: β = 0.54, P = 1.64 × 10-61 in the brain; β = 0.09, P = 1.60 × 10-12 in CSF) had causal effects on fluid intelligence score. We observed functional relevance of specific tissue proteins to intelligence quotient and identified several candidate proteins, such as macrophage-stimulating protein. This study provided a novel insight to the relationship between tissue proteins and intelligence quotient traits.

Prediction of Adolescents' Fluid Intelligence Scores based on Deep Learning with Reconstruction Regularization.

The aim of this study was to develop a predictive model for uncorrected/actual fluid intelligence scores in 9-10 year old children using magnetic resonance T1-weighted imaging. Explore the predictive performance of an autoencoder model based on reconstruction regularization for fluid intelligence in adolescents. We collected actual fluid intelligence scores and T1-weighted MRIs of 11,534 adolescents who completed baseline tasks from ABCD Data Release 3.0. A total of 148 ROIs were selected and 604 features were proposed by FreeSurfer segmentation. The training and testing sets were divided in a ratio of 7:3. To predict fluid intelligence scores, we used AE, MLP and classic machine learning models, and compared their performance on the test set. In addition, we explored their performance across gender subpopulations. Moreover, we evaluated the importance of features using the SHapley Additive Explain method. Results: The proposed model achieves optimal performance on the test set for predicting actual fluid intelligence scores (PCC = 0.209 ± 0.02, MSE = 105.212 ± 2.53). Results show that autoencoders with refactoring regularization are significantly more effective than MLPs and classical machine learning models. In addition, all models performed better on female adolescents than on male adolescents. Further analysis of relevant characteristics in different populations revealed that this may be related to gender differences in underlying fluid intelligence mechanisms. We construct a weak but stable correlation between brain structural features and raw fluid intelligence using autoencoders. Future research may need to explore ensemble regression strategies utilizing multiple machine learning algorithms on multimodal data in order to improve the predictive performance of fluid intelligence based on neuroimaging features.

The causal effects of intelligence and fluid intelligence on Parkinson’s disease: a Mendelian randomization study

BackgroundParkinson’s disease (PD) is a chronic neurodegenerative disease that affects the central nervous system, primarily the motor nervous system, and occurs most often in older adults. A large number of studies have shown that high intelligence leads to an increased risk of PD. However, whether there is a causal relationship between intelligence on PD has not yet been reported.MethodsIn this study, Mendelian randomization (MR) analysis was performed with intelligence (ebi-a-GCST006250) and fluid intelligence score (ukb-b-5238) as exposure factors and PD (ieu-b-7) as an outcome, which the datasets were mined from the IEU OpenGWAS database. MR analysis was performed through 3 methods [MR Egger, weighted median, inverse variance weighted (IVW)], of which IVW was the primary method. In addition, the reliability of the results of the MR analysis was assessed via the heterogeneity test, the horizontal polytropy test, and Leave-One-Out (LOO). Finally, based on gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, the genes corresponding to intelligence and fluid intelligence score related to SNPs were enriched for functional features and pathways.ResultsThe results of MR analysis suggested that elevated intelligence indicators can increase the risk of PD [p = 0.015, Odd Ratio (OR) = 1.316]. Meanwhile, fluid intelligence score was causally associated with the PD (p = 0.035), which was a risk factor (OR = 1.142). The reliability of the results of MR analysis was demonstrated by sensitivity analysis. Finally, the results of GO enrichment analysis for 87 genes corresponding to intelligence related SNPs mainly included regulation of synapse organization, developmental cell growth, etc. These genes were enriched in the synaptic vessel cycle, polycomb expressive complex in KEGG. Similarly, 44 genes corresponding to SNPs associated with fluid intelligence score were used for enrichment analysis. Based on the GO database, these genes were mainly enriched in regulation of developmental growth, negative regulation of neuron projection development, etc. In KEGG, 44 genes corresponding to SNPs associated with fluid intelligence score were enriched in signaling pathways including Alzheimer’s disease, the cellular senescence, etc.ConclusionThe causal relationships between intelligence and fluid intelligence scores, and PD were demonstrated through MR analysis, providing an important reference and evidence for the study of PD.

No genetic causal associations between periodontitis and brain atrophy or cognitive impairment: evidence from a comprehensive bidirectional Mendelian randomization study

BackgroundObservational studies have explored the relationships of periodontitis with brain atrophy and cognitive impairment, but these findings are limited by reverse causation, confounders and have reported conflicting results. Our study aimed to investigate the causal associations of periodontitis with brain atrophy and cognitive impairment through a comprehensive bidirectional Mendelian randomization (MR) research.MethodsWe incorporated two distinct genome-wide association study (GWAS) summary datasets as an exploration cohort and a replication cohort for periodontitis. Four and eight metrics were selected for the insightful evaluation of brain atrophy and cognitive impairment, respectively. The former involved cortical thickness and surface area, left and right hippocampal volumes, with the latter covering assessments of cognitive performance, fluid intelligence scores, prospective memory, and reaction time for mild cognitive impairment to Alzheimer's disease (AD), Lewy body dementia, vascular dementia and frontotemporal dementia for severe situations. Furthermore, supplementary analyses were conducted to examine the associations between the longitudinal rates of change in brain atrophy and cognitive function metrics with periodontitis. The main analysis utilized the inverse variance weighting (IVW) method and evaluated the robustness of the results through a series of sensitivity analyses. For multiple tests, associations with p-values < 0.0021 were considered statistically significant, while p-values ≥ 0.0021 and < 0.05 were regarded as suggestive of significance.ResultsIn the exploration cohort, forward and reverse MR results revealed no causal associations between periodontitis and brain atrophy or cognitive impairment, and only a potential causal association was found between AD and periodontitis (IVW: OR = 0.917, 95% CI from 0.845 to 0.995, P = 0.038). Results from the replication cohort similarly corroborated the absence of a causal relationship. In the supplementary analyses, the longitudinal rates of change in brain atrophy and cognitive function were also not found to have causal relationships with periodontitis.ConclusionsThe MR analyses indicated a lack of substantial evidence for a causal connection between periodontitis and both brain atrophy and cognitive impairment.

Effects of saturated and monounsaturated fatty acids on cognitive impairment: evidence from Mendelian randomization study.

Prior observational studies have suggested correlations between saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) with cognitive function. However, causal relationships remains unclear. We assessed the causal impact of two SFAs (palmitic acid [PA] and stearic acid [SA]) and two MUFAs (oleic acid [OA] and palmitoleic acid [POA]) on cognitive function-related traits, and dementia-related traits by univariable Mendelian randomization (UVMR) and multivariable Mendelian randomization (MVMR) analyses. UVMR indicated β of 0.060 (P = 4.05E-06) for cognitive performance score and 0.066 (P = 4.21E-04) for fluid intelligence per standard deviation (SD) increase in OA level. MVMR indicated: (i) β of -0.608 (P = 8.37E-05) for fluid intelligence score per SD increase in POA; (ii) β of 0.074 (P = 0.018) for fluid intelligence score per SD increase in OA; (iii) β of 0.029 (P = 0.033) for number of incorrect matches in round per SD increase in PA; and (iv) β of 0.039 (P = 0.032) for number of incorrect matches in round per SD increase in SA. In addition, a secondary MVMR analysis after excluding the effect of polyunsaturated fatty acids suggested that: (i) β of -0.043 (P = 1.97E-02) for cognitive performance score per SD increase in PA and (ii) β of -0.079 (P = 1.79E-03) for cognitive performance score per SD increase in SA. Overall, UVMR and MVMR suggest that OA may be beneficial for cognitive function, while POA, PA, and SA may have detrimental effects on cognitive function.

C-reactive protein and cognitive impairment: A bidirectional Mendelian randomization study

ObjectivesWhile C-reactive protein (CRP) has been solidly linked as a risk factor for cognitive impairment, observational research alone cannot definitively demonstrate a causal relationship. This study therefore sought to determine whether there was an association between CRP and the development of cognitive impairment. MethodsThis study employed bidirectional Mendelian randomization (MR) to investigate the genetic association between CRP and cognitive impairment. genome-wide association studies (GWAS) summary statistics for both were sourced from IEU Open GWAS or prior reports. Cognitive GWAS's used were on tests designed to assess cognitive performance, fluid intelligence, prospective memory, and reaction time. The MR analysis applied several methods, including inverse variance-weighted (IVW), MR Egger, weighted median, simple mode, and weighted mode approaches, then use of MR sensitivity analyses to interrogate findings. ResultsForward MR analysis showed that genetically proxied CRP was associated with prospective memory (P = 0.009), whereas there is little evidence to support an association between CRP and other cognitive tests. Reverse MR analysis indicated a potential association between genetic proxy cognitive performance (P = 0.002) and fluid intelligence score (P = 0.019) with CRP levels. For genetically proxied CRP on prospective memory, the level of pleiotropy (P > 0.05) and no genetic variant heterogeneity (P > 0.05) made bias unlikely, and leave-one-out tests also confirmed robust associations. ConclusionsThe effect of genetically proxied CRP on prospective memory, with little evidence on other cognitive tests. The reverse MR shows some evidence of genetically proxied cognition (cognitive performance and fluid intelligence) on CRP levels.

Polyphenol intake beneficially associates with inflammation and cognitive performance, and is mediated by MRI‐derived features

AbstractBackgroundEarly changes to cognitive performance and neurophysiological biomarkers offer insights into one’s future risk of developing Alzheimer’s disease or other dementias. Evidence suggests a link between polyphenol intake and reduced incidence of age‐associated cognitive decline and neurodegeneration. These relationships may be driven by the effect of dietary polyphenols on inflammation and degeneration of critical neurological structures and systems. These relationships are challenging to assess, as few cohorts allow cohesive assessment of polyphenol intake, systemic inflammation, neurophysiological measures and cognition.MethodPolyphenol intake was assessed in two UK cohorts: The Airwave Health Monitoring Study and UK Biobank (UKB). Diet diary and questionnaire data were integrated with polyphenol composition data from Phenol‐Explorer to allow for testing of associations between polyphenol intake, blood biomarkers of inflammation, and cognitive performance. 9008 Airwave participants and 209,163 UKB participants were included in a cross‐sectional analysis. C‐reactive protein (CRP) and fibrinogen were used as blood biomarkers of inflammation, and cognitive assessments included reaction time (milliseconds) and fluid intelligence (score /13). Neuroimaging assessments included grey matter volumes and white matter integrity, and were considered individually and using PCA.ResultLinear regressions showed inverse associations between total polyphenol intake and CRP: ß ‐0.00702 (Airwave) and ß = ‐0.00672 (UKB), both P &lt;0.001, as well as fibrinogen: ß ‐0.00221; P = 0.038 (Airwave only), in addition to biomarker associations with polyphenols at the compound group level. Regarding cognition, linear regressions revealed beneficial associations between total intake and performance in fluid intelligence tests: ß 0.00657; P = 0.009 (Airwave) and ß 0.00715, P &lt;0.001 (UKB), and reaction time ß ‐0.0000977; P = 0.020 (UKB). Mediations of the polyphenol‐fluid intelligence relationship were detected for IDPs including grey matter volumes of hippocampal‐associated regions, and white matter integrity measured using ISOVF.ConclusionWe described polyphenol intake in two large, contemporary UK cohorts, and discovered associations between higher intake and improved inflammatory markers and cognitive performance, as well as mediations of the polyphenol‐cognition relationship by physical neurological markers. This contributes to evidence supporting the health benefits of dietary polyphenols, clarifies the physiological pathways through which they may act, and highlights their relevance when considering preventative interventions for neurodegeneration.

Polyphenol intake beneficially associates with inflammation and cognitive performance, and is mediated by MRI‐derived features

AbstractBackgroundEarly changes to cognitive performance and neurophysiological biomarkers offer insights into one’s future risk of developing Alzheimer’s disease or other dementias. Evidence suggests a link between polyphenol intake and reduced incidence of age‐associated cognitive decline and neurodegeneration. These relationships may be driven by the effect of dietary polyphenols on inflammation and degeneration of critical neurological structures and systems. These relationships are challenging to assess, as few cohorts allow cohesive assessment of polyphenol intake, systemic inflammation, neurophysiological measures and cognition.MethodPolyphenol intake was assessed in two UK cohorts: The Airwave Health Monitoring Study and UK Biobank (UKB). Diet diary and questionnaire data were integrated with polyphenol composition data from Phenol‐Explorer to allow for testing of associations between polyphenol intake, blood biomarkers of inflammation, and cognitive performance. 9008 Airwave participants and 209,163 UKB participants were included in a cross‐sectional analysis. C‐reactive protein (CRP) and fibrinogen were used as blood biomarkers of inflammation, and cognitive assessments included reaction time (milliseconds) and fluid intelligence (score /13). Neuroimaging assessments included grey matter volumes and white matter integrity, and were considered individually and using PCA.ResultLinear regressions showed inverse associations between total polyphenol intake and CRP: β ‐0.00702 (Airwave) and β = ‐0.00672 (UKB), both P &lt;0.001, as well as fibrinogen: β ‐0.00221; P = 0.038 (Airwave only), in addition to biomarker associations with polyphenols at the compound group level. Regarding cognition, linear regressions revealed beneficial associations between total intake and performance in fluid intelligence tests: β 0.00657; P = 0.009 (Airwave) and β 0.00715, P &lt;0.001 (UKB), and reaction time β ‐0.0000977; P = 0.020 (UKB). Mediations of the polyphenol‐fluid intelligence relationship were detected for IDPs including grey matter volumes of hippocampal‐associated regions, and white matter integrity measured using ISOVF.ConclusionWe described polyphenol intake in two large, contemporary UK cohorts, and discovered associations between higher intake and improved inflammatory markers and cognitive performance, as well as mediations of the polyphenol‐cognition relationship by physical neurological markers. This contributes to evidence supporting the health benefits of dietary polyphenols, clarifies the physiological pathways through which they may act, and highlights their relevance when considering preventative interventions for neurodegeneration.

A brain‐wide risk score of Alzheimer’s disease based on multimodal neuroimaging predicts cognition in large N&gt;37000 population data

AbstractBackgroundAlzheimer’s disease (AD) is the most frequent age‐related dementia impairing memory, thinking, and social skills. Much research has been conducted in recent years to investigate the genetic risk of AD, but little effort has been made to find a brain imaging‐based AD risk evaluation. Here, we proposed a multimodal neuroimaging‐based measure of AD risk, called brain‐wide risk score (BRS).MethodFunctional network connectivity (FNC) and voxelwise gray matter (GM) from the Open Access Series of Imaging Studies (OASIS)‐3 (N = 1302 samples) cohort was used as a reference dataset to define mild cognitive impairment (MCI) and control (CN)group to evaluate individuals in the UK Biobank (N = 37,784) dataset. We calculated the mean of FNC and GM of MCI and CN. Next, we removed the mean FNC and GM from each sample FNC and GM of the target dataset. Then, we calculated the distance between the target dataset and CN (i.e., dist_CN) and MCI (i.e., dist_MCI) of the reference dataset using Euclidian distance. Finally, we calculated Δdiff = dist_CN‐dist_MCI as a BRS of AD, where the positive values are associated with higher AD BRS. Using two BRSs estimated based on FNC and GM for target dataset, we identified four AD biotypes. Samples with two negative Δdist represent low AD risk (Biotype1), samples with two positive Δdist represent high AD risk (Biotype4), and samples with one negative and one positive Δdist represent moderate AD risk (Biotype2/3). Next, we compared cognitive scores including fluid intelligence (FI) and reaction time (RT) across four biotypes.ResultFig.1 shows the 2D histogram of two BRS estimated from FNC and GM. We identified 11704 participants as biotype1, 10910 as biotype2, 7804 as biotype3 and 7366 as biotype4. We also found that Biotype1, with lower AD BRS, significantly shows a higher FI score than Biotype3 and Biotype4 (Fig.2, FI panel). Additionally, Biotype 4, with the highest BRS, had the most increased RT among all four AD biotypes (Fig.2, RT panel).ConclusionWe develop a new multimodal neuroimaging‐based BRS based which we identified four AD biotypes. We found that BRS predict cognitive scores in the identified biotypes.

41 The Role of Physical Activity, Social Support and Genetic Risk in Age-Related Cognitive Decline Over Time: A UK Biobank Study

Objective:This study aimed to determine how modifiable risk factors, such as physical exercise and social support, and non-modifiable risk factors, such as genetic risk may affect cognitive function over time in older adults. As well, the study explored how changes in modifiable risk factors (i.e., increase in exercise) may affect cognitive function over time. This research question was shaped with the help of a patient partner team.Participants and Methods:The study used UK Biobank data, and patient partners were involved in shaping research questions/goals. The UK Biobank study had participants complete comprehensive baseline assessments (2006-2010), with subgroups also completing repeat assessments (2012-2013), imaging assessments (2014-ongoing) and/or repeat imaging assessments (2019-ongoing; i.e., 2-4 data points per participant). Age, sex, education, ethnicity, and apolipoprotein E (APOE) e4 status (at least one e4 allele present) data were collected at baseline. Employment, physical activity, social support, and recent depressive symptom data were collected across timepoints. A Fluid intelligence score was obtained at each timepoint via a series of thirteen 1-pt. reasoning tasks (range: 0-13). Participants who did not complete cognitive testing at baseline and at least one other time point, and those with neurological conditions or events (e.g., stroke, epilepsy, dementia) were excluded (final N=17,409).Multi-Level Modeling (with Maximum Likelihood) was utilized, with fluid intelligence as the primary outcome measure. We ran Model 1: fully unconditioned, Model 2: with time predictor in years (baseline= 0), and Model 3: with baseline physical activity, social support and APOE e-4 predictors and covariates (mean-centered as appropriate), time-varying physical activity and social support predictors, and interaction terms. Nonsignificant interaction terms were trimmed from Model 3 to facilitate interpretation.Results:Model 1 was significant (p&lt;.001) with an intraclass correlation (ICC) of 0.64, suggesting that 64% of the total variance in fluid intelligence in this sample is due to interindividual differences. Model 2 revealed that the average fluid intelligence score at baseline mean age (55.85) was 6.79 and significantly decreased with each year increase since baseline. Results from Model 3 (trimmed) revealed that being male, white, and having at least a university degree were associated with higher score at baseline, while being older and having more recent depressive symptoms were associated with lower scores. Higher social support quality was associated with higher scores while higher social support quantity was associated with lower scores at baseline; however, higher social support quantity at baseline was associated with less decline in scores over time. Surprisingly, having at least one e4 allele was associated with higher scores. Engaging in more moderate physical activity was associated with lower scores at baseline, however, individuals who increased the length of their moderate physical activity sessions over time showed higher timepoint-specific fluid intelligence scores. Additional significant interactions will be elaborated.Conclusions:Results suggest that increases in the length of moderate physical activity exercise sessions were associated with better cognitive function over time. Having better social support quality was also associated with better cognitive function, while higher social support quantity was associated with less cognitive decline over time. These findings suggest that positive lifestyle changes in older adulthood may slow cognitive decline.

Getting it right takes time: response time and performance in secondary school students

The relation between response time and performance in cognitive tasks is increasingly evident. In the present study, we analyzed the effect of participants’ spontaneous speed when responding to a mental rotation task. We carried out a data reanalysis from a previous study where a training of 3 practice sessions of 100 trials each was applied. The procedure was applied to a sample of 21 high school students (11 boys, 10 girls). The relation between response time and performance (hits) across the training trials was analyzed. In addition, we carried out a regression analysis of performance on the learning task as a function of response time on that same task, as well as with the score on two previously applied tests of spatial intelligence and fluid intelligence. Results showed, (a) a significant relationship (r = 0.624) between response time and hits, (b) that the group of participants with longer response times performed better; (c) that participants’ response time explained most of the variance of their score on the training task in the regression analysis, although spatial and fluid intelligence scores improved the prediction of performance. Our results suggest that the reflective style achieves greater performance in solving spatial tasks, which could have important practical implications to promote a slower and more reflective style when solving school tasks with spatial components.

Effects of adult education on cognitive function and risk of dementia in older adults: a longitudinal analysis.

Mid/late-life cognitive activities are associated with a lower rate of subsequent cognitive decline and lower subsequent dementia risk over time. In this study, we investigated the association between adult education class participation and subsequent cognitive decline and dementia risk over time after adjusting for baseline cognitive function and genetic risk of dementia, correcting for several potential confounding variables, using a large prospective cohort data of participants from the UK Biobank study followed from 2006 to 2010. The results revealed that participation in adult education classes at baseline was associated with greater subsequent retention of fluid intelligence score. Cox proportional hazard models revealed that subjects who participated in adult education classes showed a significantly lower risk of incident dementia 5 years after baseline compared with those that did not at baseline. In this study, we show that participation in adult education classes preceded greater retention of subsequent fluid intelligence and a lower risk of developing dementia after 5 years: this association did not change after adjusting for cognitive function at baseline or genetic predisposition to dementia. Accordingly, participation in such classes could reduce the risk of developing dementia.

Genetically Predicted Blood Pressure and Cognition in Midlife: A UK Biobank Study.

This UK Biobank study uses a mendelian randomization approach to mitigate the variability and confounding that has affected previous analyses of the relationship between measured blood pressure (BP) and cognition and thus delineate the true association between the two. Systolic BP (SBP) and diastolic BP polygenic risk scores (PRSs) were calculated using summary statistics from the International Consortium of Blood Pressure-Genome Wide Association Study (n=299 024). Adjusted nonlinear mixed-effects regression models were used, including a natural splines term for BP-PRS with outcomes of fluid intelligence, reaction time (RT), and composite attention score. Moderating effects of age, sex, and antihypertensive use were assessed in separate models. There were 448 575 participants (mean age, 56.3 years; age range, 37-72 years) included in the analysis after genetic and neurological disease exclusions. Genetic propensity for high SBP had an approximately linear association with worsened fluid intelligence (P=0.0018). This relationship was significantly moderated by age (P<0.0001). By contrast, genetic propensity for high and low SBP and diastolic BP predicted worse attention function (P=0.0099 and P=0.0019), with high PRSs predicting worse function than low PRSs. Genetic propensity for low SBP and diastolic BP was associated with considerably worse RTs, while for high SBP-PRSs, the RT plateaued (P<0.0001). The relationships between RT and the PRSs were significantly moderated by sex (P<0.0001) and antihypertensive use (P<0.0001). Genetic propensity for high and low BP impacts on midlife cognition in subtle ways and differentially affects cognitive domains. While a genetic propensity to low BP may preserve nontimed tests in midlife, it may come at a trade-off with worsened attention scores and RT.

Olfactory training effects in children after mild traumatic brain injury

ABSTRACT Objective Mild traumatic brain injury (mTBI) might impair the sense of smell and cognitive functioning. Repeated, systematic exposure to odors, i.e., olfactory training (OT) has been proposed for treatment of olfactory dysfunctions, including post-traumatic smell loss. Additionally, OT has been shown to mitigate cognitive deterioration in older population and enhance selected cognitive functions in adults. We aimed to investigate olfactory and cognitive effects of OT in the pediatric population after mTBI, likely to exhibit cognitive and olfactory deficits. Methods Our study comprised 159 children after mTBI and healthy controls aged 6–16 years (M = 9.68 ± 2.78 years, 107 males), who performed 6-months-long OT with a set of 4 either high- or low-concentrated odors. Before and after OT we assessed olfactory functions, fluid intelligence, and executive functions. Results OT with low-concentrated odors increased olfactory sensitivity in children after mTBI. Regardless of health status, children who underwent OT with low-concentrated odors had higher fluid intelligence scores at post-training measurement, whereas scores of children performing OT with high-concentrated odors did not change. Conclusion Our study suggests that OT with low-concentrated odors might accelerate rehabilitation of olfactory sensitivity in children after mTBI and support cognitive functions in the area of fluid intelligence regardless of head trauma.

“Life's Essential 8” Cardiovascular Health and Dementia Risk, Cognition, and Neuroimaging Markers of Brain Health

ObjectiveTo evaluate associations of Life's Essential 8 (LE8) score, the recently updated metric for promoting cardiovascular health (CVH), with the risk of incident dementia and its subtypes, cognition, and neuroimaging outcomes and to determine whether these associations differ among apolipoprotein E (APOE)-ε4 genotypes. DesignProspective cohort study. Setting and ParticipantsA total of 316,669 participants [mean (SD) age, 56.3 (8.1) years] without prior cardiovascular disease or dementia from the UK Biobank study at baseline survey (2006–2010) were enrolled. MethodsA modified version of the LE8 score was created (range: 0–100) and categorized into poor (0–49), intermediate (50–79), and optimal (80–100) CVH. Cox proportional hazard and multivariable linear regression models were used. ResultsDuring a median 12.6 years of follow-up, 4238 all-cause dementia cases including 1797 Alzheimer's disease and 939 vascular dementia (VaD) occurred. Individuals with optimal CVH had 44% (95% CI, 0.48–0.64) lower incident all-cause dementia risk and 71% (95% CI, 0.22–0.38) lower VaD risk compared with those who had poor CVH. A 10-point increment in LE8 was associated with higher fluid intelligence scores (β, 0.088; 95% CI, 0.073–0.102) and numeric memory scores (β, 0.054; 95% CI, 0.043–0.065), and was also associated with lower white matter hyperintensity volume (β, −0.673; 95% CI, −0.751 to −0.596), larger total brain volume (β, 77.93; 95% CI, 62.03–93.84), and hippocampal volume (β, 0.197; 95% CI, 0.106–0.288). In addition, the association between LE8 profiles and dementia diagnosis differed by APOE genotype (all P for interaction ≤ .001), and was more evident among APOE-ε4 noncarriers. Conclusions and ImplicationsIndividuals with a higher LE8 score experienced fewer dementia events (driven especially by incident VaD) and were associated with better neurocognitive brain health profiles. CVH optimization may be beneficial to the maintenance of brain health.