Lower Cognitive Scores Research Articles

Antenatal diagnosis, neonatal brain volumes, and neurodevelopment in transposition of the great arteries.

To examine whether antenatal diagnosis modifies relationships between neonatal brain volumes and 18-month neurodevelopmental outcomes in children with transposition of the great arteries (TGA). In a retrospective cohort of 139 children with TGA (77 antenatally diagnosed), we obtained total brain volumes (TBVs) on pre- (n = 102) and postoperative (n = 112) magnetic resonance imaging. Eighteen-month neurodevelopmental outcomes were assessed using the Bayley Scales of Infant and Toddler Development, Third Edition. Generalized estimating equations with interaction terms were used to determine whether antenatal diagnosis modified associations between TBVs and neurodevelopmental outcomes accounting for postmenstrual age at scan, brain injury, and ventricular septal defect. Infants with postnatal diagnosis had more preoperative hypotension (35% vs 14%, p = 0.004). The interactions between antenatal diagnosis and TBVs were significantly related to cognitive (p = 0.003) outcomes. Specifically, smaller TBVs were associated with lower cognitive scores in infants diagnosed postnatally; this association was attenuated in those diagnosed antenatally. Antenatal diagnosis modifies associations between neonatal brain volume and 18-month cognitive outcome in infants with TGA. These findings suggest that antenatal diagnosis may be neuroprotective, possibly through improved preoperative clinical status. These data highlight the need to improve antenatal diagnosis rates. Antenatal diagnosis of transposition of the great arteries modified relationships between neonatal brain volume and neurodevelopment. Smaller brain volumes related to poorer cognitive scores with postnatal diagnosis only. There was more preoperative hypotension in the postnatal diagnosis group.

Parental and child genetic burden of glycaemic dysregulation and early-life cognitive development: an Asian and European prospective cohort study

Insulin resistance and glucose metabolism have been associated with neurodevelopmental disorders. However, in the metabolically more susceptible Asian populations, it is not clear whether the genetic burden of glycaemic dysregulation influences early-life neurodevelopment. In a multi-ethnic Asian prospective cohort study in Singapore (Growing Up in Singapore Towards healthy Outcomes (GUSTO)), we constructed child and parental polygenic risk scores (PRS) for glycaemic dysregulation based on the largest genome-wide association studies of type 2 diabetes and fasting glucose among Asians. We found that child PRS for HOMA-IR was associated with a lower perceptual reasoning score at ~7 years (β = −0. 141, p-value = 0.024, 95% CI −0. 264 to −0. 018) and a lower WIAT-III mean score at ~9 years (β = −0.222, p-value = 0.001, 95% CI −0.357 to −0.087). This association were consistent in direction among boys and girls. These inverse associations were not influenced by parental PRS and were likely mediated via insulin resistance rather than mediators such as birth weight and childhood body mass index. Higher paternal PRS for HOMA-IR was suggestively associated with lower child perceptual reasoning at ~7 years (β = −0.172, p-value = 0.002, 95% CI −0.280 to −0.064). Replication analysis in a European cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort, showed that higher child PRS for fasting glucose was associated with lower verbal IQ score while higher maternal PRS for insulin resistance was associated with lower performance IQ score in their children at ~8.5 years. In summary, our findings suggest that higher child PRS for HOMA-IR was associated with lower cognitive scores in both Asian and European replication cohorts. Differential findings between cohorts may be attributed to genetic and environmental factors. Further investigation of the functions of the genetic structure and ancestry-specific PRS and a more comprehensive investigation of behavioural mediators may help to understand these findings better.

The relationship between performance validity testing, external incentives, and cognitive functioning in long COVID

ABSTRACT Introduction Performance validity test (PVT) failures occur in clinical practice and at higher rates with external incentives. However, little PVT research has been applied to the Long COVID population. This study aims to address this gap. Methods Participants were 247 consecutive individuals with Long COVID seen for neuropsychological evaluation who completed 4 PVTs and a standardized neuropsychological battery. The sample was 84.2% White and 66% female. The mean age was 51.16 years and mean education was 14.75 years. Medical records were searched for external incentive (e.g., disability claims). Three groups were created based on PVT failures (Pass [no failures], Intermediate [1 failure], and Fail [2+ failures]). Results A total of 8.9% participants failed 2+ PVTs, 6.4% failed one PVT, and 85% passed PVTs. From the full sample, 25.1% were identified with external incentive. However, there was a significant difference between the rates of external incentives in the Fail group (54.5%) compared to the Pass (22.1%) and Intermediate (20%) groups. Further, the Fail group had lower cognitive scores and higher frequency of impaired range scores, consistent with PVT research in other populations. External incentives were uncorrelated with cognitive performance. Conclusions Consistent with other populations, results suggest Long COVID cases are not immune to PVT failure and external incentives are associated with PVT failure. Results indicated that individuals in the Pass and Intermediate groups showed no evidence for significant cognitive deficits, but the Fail group had significantly poorer cognitive performance. Thus, PVTs should be routinely administered in Long COVID cases and research.

Association of Multi-Domain Factors with Cognition in the UK Biobank Study.

Dementia is a multifactorial syndrome attributable to a combination of vascular risk factors, lifestyle factors and neurodegeneration. However, little is known about the relative contribution of all these factors and their combined effects on cognition among the older population. To examine the association of four domains of risk factors (sociodemographic, vascular risk factors, neuroimaging markers, lifestyle and psychosocial factors) with cognition in older adults. A cross-sectional study. Data was obtained from a large-scale population-based study, UK Biobank study, at the first imaging visit assessment. Participants are citizen or permanent residents of UK, aged 60 years old and above. Cognitive function was assessed using the general cognitive ability score (g-factor score) derived from principal components analysis estimates of six cognitive tests. Associations with cognition were examined using multivariable linear regression for each domain and in combination. The study included 19,773 participants (mean age 68.5 ± 5.3 years SD, 9,726 (49%) male). Participants with lower cognitive scores (poorer cognition) were older, female, non-whites individuals, less educated and more socially deprived than participants with better cognitive scores. Participants with lower cognitive scores also tended to have higher vascular risk factors, lower brain volumes and more adverse lifestyle behaviours. The multivariable analysis found associations between adverse lifestyle and psychosocial factors with poorer cognition, i.e., being obese by measure of body fat percentage, having diabetes, higher white matter hyperintensity volume, increased sedentary screen time watching TV, being socially isolated and having depression were independently associated with poorer cognition. While larger hippocampal volume, having optimal sleep duration, adherence to a heathy diet, current and former alcohol drinking, increased wine consumption and sedentary screen time using a computer were associated with better cognition. A combination of adverse lifestyle and psychosocial factors were independently associated with poorer cognition in older adults. Findings in this study can potentially support public health communications to promote cognitive function and independence among older adults. This research has been conducted using the UK Biobank Resource under Application Number 71022.

Night Screen Time is Associated with Cognitive Function in Healthy Young Adults: A Cross-Sectional Study.

In recent years, a significant shift toward remote work, virtual education, and social distancing measures was witnessed, thereby leading people to increasingly depend on digital devices for communication, work, and entertainment. This increased exposure to screens has raised concerns regarding its potential impact on cognitive function. This study investigated the relationship between screen time and cognitive function among healthy young adults. One hundred forty-five healthy individuals (mean age 21.55 ± 2.84 years) participated in this cross-sectional study. Sociodemographic information including age, sex, height, weight, and level of education were obtained. Participants reported screen time using a screen time questionnaire. Cognitive function tests including, Paced Auditory Serial Addition Task (PASAT), Montreal Cognitive Assessment (MoCA) and Symbol Digit Modalities Test (SDMT) were conducted. Multilinear regression analyses were used to examine the associations between age, sex, level of education, screen time, and cognitive function. One hundred thirty-nine participants (76 women) completed the study. Increased night screen time, bachelor's educational level, and women were associated with lower PASAT scores (R2=0.258; p≤0.047). Moreover, increased night screen time was associated with lower MoCA scores (R2=0.029; p=0.035). However, no associations were found between night screen time and SDMT scores. Participants who had higher night screen exposure had lower cognitive scores in the information speed processing, working memory, calculation, and attention domains. Considering these findings, this study emphasizes on the importance of setting a future recommended screen time guidelines for young adults as well as to promote healthy cognitive habits in order to preserve cognitive function and reduce the risk of developing neurodegenerative disease in the future. Future prospective cohort studies involving a more diverse age range is needed.

Occupation, Retirement Age, and 20-Year Cognitive Decline: The Atherosclerosis Risk in Communities Neurocognitive Study

Introduction: We examined the association of both midlife occupation and age at retirement with cognitive decline in the Atherosclerosis Risk in Communities (ARIC) biracial community-based cohort. Methods: Current or most recent occupation at ARIC baseline (1987–1989; aged 45–64 years) was categorized based on 1980 US Census major occupation groups and tertiles of the Nam-Powers-Boyd occupational status score (n = 14,090). Retirement status via annual follow-up questionnaires administered ascertained in 1999–2007 was classified as occurring before or after age 70 (n = 7,503). Generalized estimating equation models were used to examine associations of occupation and age at retirement with trajectories of global cognitive factor scores, assessed from visit 2 (1990–1992) to visit 5 (2011–2013). Models were a priori stratified by race and sex and adjusted for demographics and comorbidities. Results: Low occupational status and blue-collar occupations were associated with low baseline cognitive scores in all race-sex strata. Low occupational status and homemaker status were associated with faster decline in white women but slower decline in black women compared to high occupational status. Retirement before age 70 was associated with slower cognitive decline in white men and women and in black men. Results did not change substantially after accounting for attrition. Conclusion: Low occupational status was associated with cognitive decline in women but not in men. Earlier retirement was associated with a slower cognitive decline in white participants and in black men. Further research should explore reasons for the observed associations and race-sex differences.

Adaptive behavior of school-aged children with Autism Spectrum Disorder

Children with Autism Spectrum Disorder (ASD) face challenges related to their functioning, also known as adaptive behavior. Studies in recent literature explore the association between adaptive behavior and cognitive ability in children with ASD. Aim: The present study investigates adaptive behavior and adaptive skills in children with ASD in relation to their cognitive ability. Methods: In the present study, the sample consisted of 54 children with ASD, with a minimum Intelligence Quotient-IQ of “70”, who were admitted to a Child Psychiatric Hospital Clinic. Screening of functional and cognitive difficulties was performed by administering the Vineland Adaptive Behavior Scales (VABS) and Wechsler's Intelligence Scale for children-III (WISC-III), respectively. Results: Children with ASD exhibited deviations in adaptive behavior, with a pattern of deficits in adaptive skills (p<0.001). The group with high general cognitive score showed higher performance in the areas of Communication and Socialization, compared to the group with low general cognitive score. Both groups showed significant deficits in Daily Living Skills. The relationship between adaptive behavior/adaptive skills was investigated in relation to general, verbal and performance IQ (VIQ-PIQ). The general cognitive score was found to predict the performance of adaptive behavior. In the high cognitive ability group, the verbal and performance cognitive score predicted performance in Communication and Activities of Daily Living, respectively. Conclusions: The functioning of children with ASD is reflected in adaptive behavior, where a pattern of deficits is presented in relation to the cognitive ability.

Neuropsychiatric symptoms in Alzheimer's continuum and their association with plasma biomarkers

BackgroundLittle is known about association between neuropsychiatric symptoms and plasma biomarkers across the entire Alzheimer's continuum. MethodsA total of 305 individuals with amyloid-β (Aβ) deposition (determined by 18F-florbetapir PET) participated in this study, including cognitively normal controls (n = 53), subjective cognitive decline (SCD, n = 75), mild cognitive impairment (MCI, n = 74), and dementia (n = 103). Plasma biomarkers (Aβ1-42, Aβ1-40, total tau [t-tau], phosphorylated tau 181 [p-tau181], and neurofilament light [NfL]), apolipoprotein E (APOE) genotyping and Neuropsychiatric Inventory Questionnaire (NPI-Q) were completed. Neuropsychiatric symptoms were classified into four subsymdromes (hyperactivity, psychosis, affective, and apathy). Logistic regression analysis was conducted to investigate relationships between neuropsychiatric symptoms and plasma biomarkers. ResultsAbout one-third of cognitively unimpaired individuals (normal controls: 34.0 %, SCD: 28.0 %) reported one or more neuropsychiatric symptoms, and more in symptomatic stages such as MCI (40.5 %) and dementia (81.0 %). Plasma NfL significantly increased in dementia group compared to SCD and healthy controls, relating to a higher risk of aberrant motor behavior, anxiety, sleep disturbance, disinhibition, and euphoria. Older age (odds ratio [OR] = 1.079, 95 % confidence interval [CI] = 1.022–1.140, p = 0.006), lower cognitive score (OR = 0.846, 95%CI = 0.791–0.905, p < 0.001) and increased plasma NfL (OR = 1.021, 95%CI = 1.00–1.042, p = 0.041) could predict psychosis. No significant differences were found in plasma Aβ1-42/Aβ1-40, t-tau or p-tau181 across all groups, and none correlated with neuropsychiatric symptoms. LimitationsThe cross-sectional design, small sample size and use of NPI-Q. ConclusionsThis study supported neuropsychiatric symptoms as early manifestations of preclinical Alzheimer's disease, and suggested plasma NfL to be a potential biomarker for detecting neuropsychiatric symptoms in Alzheimer's continuum.

THE DIFFERENCE BETWEEN CYSTATIN C- AND CREATININE-BASED EGFR AND ASSOCIATIONS WITH COGNITION IN THE CHS

Abstract The difference (eGFRDiff) between cystatin C-based estimated glomerular filtration rate (eGFRcys) and creatinine based eGFR (eGFRcr) has been shown to be associated with frailty and mortality, but its association with cognition is unclear. Among 4,764 adults aged ≥ 65 from the Cardiovascular Health Study, we analyzed eGFRDiff per 1-SD lower (18.6 mL/min/1.73m2). Cognitive function was evaluated annually using the Modified Mini Mental State Exam (3MS; range 0-100), and the Digit Symbol Substitution Test (DSST; range 0-90); higher scores mean better performance. We used linear regression for cross-sectional analyses, and mixed models for longitudinal analyses adjusted for demographic and clinical variables. The mean age was 72.2 ±, the mean eGFRDiff was 0.64, and mean follow-up was 4.4 ± years. eGFRDiff was not associated with 3MS at baseline. Each SD lower eGFRDiff at baseline was associated with a 0.82 [95% CI: -1.22, -0.42] lower DSST score. In longitudinal analyses each SD lower eGFRDiff was associated with a significant 0.06 [95% CI: -0.11, -0.01] faster decline in 3MS scores and a 0.04 [95% CI: -0.08, -0.01] faster decline in DSST scores over time. In older adults, we found that lower eGFRDiff was associated with lower cognitive scores at baseline, and associated with more rapid decline over time. This suggests that eGFRDiff could be used clinically as a laboratory-based screen to identify older adults in need for cognitive assessment.

ASSOCIATION OF CHILDHOOD EXPOSURE TO SCHOOL RACIAL SEGREGATION WITH LATE-LIFE COGNITION AMONG AMERICAN ADULTS

Abstract Racial segregation may contribute to enduringly worse health outcomes and aging. Prior research mainly focuses on residential segregation, yet the long-term effects of school segregation and the effects for different racial/ethnic groups are largely unknown. Linking measures of primary school segregation using administrative data with a nationally representative population survey in the US, we examine how childhood exposure to school racial segregation shapes the late-life cognitive function. 23,752 non-Hispanic White (White), 6,364 non-Hispanic Black (Black) American adults aged 50 and older were identified from the Health and Retirement Study; and state-level school dissimilarity indexes in late 1960s were linked to participants’ latest wave of cognitive assessment using childhood residence. Multivariate regression analyses demonstrated that exposure to White-Black school segregation had strong, negative effects on cognitive outcomes for both White and Black participants. One standard deviation increase in dissimilarity index was associated with lower cognitive score (White: = -0.16 [95%CI, -0.22, -0.11]; Black: = -0.42 [95%CI, -0.53, -0.30]) and more cognitive impairment (White: Odds Ratio (OR) = 1.10 [95%CI, 1.06, 1.13]; Black: OR = 1.21 [95%CI, 1.14, 1.27]) adjusting for age and sex. Educational attainment and other socioeconomic characteristics explained most associations (40-70%), and the effects remained significant even after accounting for a rich set of late-life factors. Overall, these findings suggest that childhood exposure to school segregation has long-lasting effects on late-life cognition for both White and Black Americans. Educational policy and reform should be promoted to reduce school racial segregation within and between school districts to address health inequities.

TOBACCO USE AND COGNITIVE FUNCTION AMONG OLDER ADULTS IN MEXICO AND BRAZIL

Abstract Older adults in Brazil and Mexico have high lifetime tobacco exposure, which is an important modifiable dementia risk factor. They also have lower levels of education, which is associated with lower cognitive reserve. This study examines how tobacco use is associated with cognition and how this association differs by education among older adults in Brazil and Mexico. Data included adults 50 and older in the 2015 waves of the Mexican Health and Aging Study (MHAS, n=14,018) and the Brazilian Longitudinal Study of Aging (ELSI, n=9,409). The outcome was a global cognitive score, calculated with standardized cognitive tasks. Tobacco use was defined as current, former, and never smoker. Linear regression models were used to test differences in cognitive function by tobacco use, adjusted by sex, educational level, rural/urban area, chronic disease and included the interaction between smoking and education. Current and former smokers represented 17% and 37% of the sample in Brazil and 13.4% and 27.4% in Mexico, respectively. Current smokers in both countries were more likely to be men and be younger. However, current smokers in Brazil were more likely to have lower educational levels whereas those in Mexico were more likely to have 8+ years of education. In Brazil, current smokers had lower cognitive scores than never smokers (B= -0.06; 95%CI: -0.11; -0.01). In Mexico, current and former smokers had higher cognitive scores than never smokers (B=0.09 ; 95%CI: [0.05; 0.13] and B=0.10 [0.07;0.13], respectively). Cognitive scores for current smokers were significantly lower as education increased in Mexico.

The Reduced Gray Matter Volume and Functional Connectivity of the Cerebellum in Type 2 Diabetes Mellitus with High Insulin Resistance

Introduction: Insulin resistance is widely thought to be a critical feature in type 2 diabetes mellitus (T2DM), and there is significant evidence indicating a higher abundance of insulin receptors in the human cerebellum than cerebrum. However, the specific structural or functional changes in the cerebellum related to T2DM remain unclear, and the association between cerebellar alterations, insulin resistance, cognition, and emotion is yet to be determined. Methods: We investigated neuropsychological performance, and structural and functional changes in specific cerebellar subregions in 43 T2DM patients with high insulin resistance (T2DM-highIR), 72 T2DM patients with low insulin resistance (T2DM-lowIR), and 50 controls. Furthermore, the correlation and stepwise multiple linear regression analysis were performed. Results: Compared to the controls, T2DM exhibited lower cognitive scores and higher depressive/anxious scores. Furthermore, T2DM-highIR patients showed reduced gray matter volume (GMV) in the right cerebellar lobules VIIb, Crus I/II, and T2DM showed reduced GMV in left lobules I–IV compared to controls. Additionally, functional connectivity decrease was observed between the right lobules I–V and orbital part of the superior frontal gyrus in T2DM-highIR compared to both T2DM-lowIR and controls. Notably, there were negative correlations between the GMV of the lobules VIIb, Crus I/II, and updated homeostatic model assessment of insulin resistance, and positive correlation with executive/visuospatial performance in T2DM patients. Conclusions: These results suggest that the cerebellar lobules VIIb, Crus I/II, represent vulnerable brain regions in the context of insulin resistance. Overall, this study offers new insights into the neuropathophysiological mechanisms of brain impairment in patients with T2DM.

Association of obstructive sleep apnea and sleep quality with cognitive function: a study of middle-aged and elderly persons in India.

Symptoms of obstructive sleep apnea (OSA) and poor sleep quality affect around one in ten people in India. We aimed to determine if OSA symptoms and poor sleep quality are independently associated with cognition in middle-aged and elderly urban Indian populations. We studied the cross-sectional association between OSA symptoms (by Berlin Questionnaire), poor sleep quality (by Pittsburgh Sleep Quality Index), and cognitive function in adults ≥ 50years. Using a standard neuropsychological battery for cognitive function, a G-factor was derived as the first rotated principal component assessing domains of information processing, memory, and executive function. The associations of exposures with cognitive measures were modeled using linear regression, adjusted for metabolic risk factors, lifestyle factors, and psychosocial problems, followed by stratified analysis by decadal age group. A total of 7505 adults were enrolled.Excluding those with MMSE < 26 (n 710), of 6795 individuals (49.2% women), mean (SD) age 64.2 (9.0) years, 38.3% had high risk of OSA symptoms, and 15.9% had poor sleep quality. OSA symptoms were negatively associated with cognitive domains of information processing (adjusted beta coefficient of z-score - 0.02, p-value 0.006), memory (- 0.03, 0.014), and G-factor (- 0.11, 0.014) in full-model. Stratified analysis by age group showed significant adverse effects of OSA symptoms on cognition for middle-aged people (50-60years) (- 0.26, 0.001), but not in later age groups. Poor sleep quality was also associated with lower cognitive scores for G-factor (- 0.48, < 0.001), memory (- 0.08, 0.005), and executive domains (- 0.12, < 0.001), but not with information domain. The findings suggest that both symptoms of OSA and poor sleep quality have a direct adverse impact on cognition in an Indian setting. A modest effect of age on the relationship of OSA and cognition was also observed.

The association of blood‐based biomarkers of neuropathology with cognitive performance and dementia in a diverse, population‐based sample of US adults

AbstractBackgroundThe association of blood‐based biomarkers of neuropathology with cognition and dementia, including potential variation by race/ethnicity (whites, blacks and Hispanics), has not been examined in large, diverse, population‐based samples of adults.MethodThe sample included Health and Retirement Study (HRS) respondents over age 50 with blood‐based neuropathology biomarker, demographic, and cognitive data (n = 4,214). A𝛃‐40, A𝛃‐42, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were measured in plasma (Quanterix Neurology 4‐Plex E kit), and phosphorylated tau (pTau‐181) was measured in serum (Quanterix Advantage V2.0 kit). Cognitive tests included immediate and delayed word recall, serial 7s, and backward counting (total score 0‐27). Dementia classification relied on a diagnostic algorithm previously validated in HRS. Linear and unconditional logistic regressions were weighted to account for sample design and used to model associations between the biomarkers and the cognitive score/dementia classification after controlling for age, sex, and batch effects.ResultAbout 80% of the sample was white, 10% black, and 10% Hispanic. Correlations were modest among pTau‐181, NfL, and GFAP (r = 0.29‐0.46).When the biomarkers were analyzed individually, higher A𝛃‐42/A𝛃‐40 ratio was associated with higher cognitive score among whites. Higher NfL was associated with lower cognitive score in the total sample and in each race/ethnic group (whites, blacks and Hispanics). Higher pTau‐181 was associated with lower cognitive score in the total and white sample. Higher GFAP was related to lower cognitive score in the total, white, and Hispanic samples. In a model that included all four biomarkers, GFAP remained significantly related to cognitive performance in the total sample, and NfL remained significantly related to cognitive performance in the total sample and in each race/ethnic group.When the biomarkers were analyzed individually, higher NfL was associated with higher likelihood of dementia in the total sample. Higher pTau‐181 was associated with higher likelihood of dementia among whites. Higher GFAP was associated with dementia in the total and white samples, alone and in the fully adjusted model with all four biomarkers.ConclusionThese results show the importance of examining blood‐based biomarkers of neuropathology as predictors of cognitive performance and dementia in diverse, population‐based samples.

Single‐cell Transcriptomes Reveal Cell‐type Specific Roles of VEGF Family Genes in the Pathogenesis of Alzheimer’s Disease

AbstractBackgroundThe role of the vascular endothelial growth factors (VEGFs) in the pathogenesis of Alzheimer’s disease (AD) has been recently described, including notable changes along the VEGFB/FLT1 signaling pathway. Yet, cell‐specific alterations are not well characterized. To disentangle VEGFs’ cell‐specific effect on AD‐related traits, we performed association analyses of mRNA expression from 10 VEGF genes with cognitive performance and AD pathology in eight brain cell types using a large single nucleus RNA sequencing dataset from human brain.MethodThis project utilized recently published single‐cell transcriptomes derived from dorsolateral prefrontal cortex tissues of 424 donors collected at Rush Alzheimer’s Disease Center. Processed single cell RNA sequencing data were acquired from AD Knowledge Portal (syn2580853). Mean age at death was 89 years, 68% were females, and 37% were AD cases. Negative binomial lognormal mixed models implemented in the NEBULA R package were used to detect differential expression between AD cases and cognitively normal controls, and to analyze the associations with immunohistochemical amyloid and tangles, and finally to assess cross‐sectional and longitudinal global cognitive scores. Correction for multiple comparisons was completed using the false discovery rate procedure (Pfdr&lt;0.05).ResultPrefrontal cortical FLT1 expression was upregulated in AD participants compared to cognitively normal controls in both endothelial (endo) and microglial (micro) cells. Higher micro‐FLT1, endo‐FLT4, and oligodendrocyte (oligo) VEGFB expression was associated with greater β‐amyloid burden in AD samples, whereas higher VEGFB expression in inhibitory neurons was associated with lower β‐amyloid burden. Higher expression of micro‐FLT1 and oligo‐VEGFB associated with worse cognitive trajectories. Higher micro‐ and endo‐ expression of FLT1 associated with lower cognition scores at the last clinic visit before death. Lastly, higher astrocyte‐expressed NRP1 was associated with lower tangle burden.ConclusionConsistent with our previously reported bulk tissue results, prefrontal cortical expression of FLT1 and FLT4 were associated with global cognition, longitudinal cognitive trajectories, and AD neuropathology, and these associations appear to be limited to endothelial and microglial cells. In contrast, VEGFB expression seems to have opposite effects on amyloid burden depending on the cell types, suggesting its more dynamic role in AD physiopathology.

Effect modification of the association between BMI and cognition in India

AbstractBackgroundHigh body‐mass index in midlife is an established risk factor for poor cognition and dementia. While most evidence supporting the association between high BMI and dementia comes from high‐income countries, 60% of global dementia cases are expected to be in low‐ and middle‐income countries by 2050. Existing evidence from India suggests higher BMI is associated with better cognition and lower odds of dementia. We sought to replicate these findings and investigate effect modification by age, rurality, and education to better contextualize results.MethodWe used cross‐sectional data from the Longitudinal Aging Study in India (N = 57,164). We used weighted linear regression models to assess associations between latent cognitive functioning, estimated from confirmatory factor analysis models, and BMI category. We compared unadjusted models to models controlling for age, sex, rurality, state, literacy, education, per capita consumption quintile, parental education, smoking, and depressive symptoms. We investigated effect modification by age, rurality, and education.ResultCompared to unadjusted models, estimated associations from multivariable models were substantially attenuated but remained statistically significant. Underweight BMI was associated with lower cognitive scores and overweight and obesity were associated with higher cognitive scores (underweight = ‐0.16 SD units [‐0.18‐ ‐0.14]; overweight = 0.10 [0.09‐0.12]; obese = 0.13 [0.11‐0.16]). For participants in urban settings or with higher educational attainment, associations between cognition and overweight and obesity were smaller and not statistically significant for those with tertiary education. A global ANOVA test for effect modification was statistically significant for rurality (p&lt;0.01), trending towards significance for education (p = 0.09), but not significant for age category (p = 0.31).ConclusionCounter to findings in high‐income settings, but consistent with prior findings in India, high BMI was associated with higher cognitive performance. Lack of evidence for effect modification by age and the association between low BMI (underweight) and lower cognition, indicate reverse causation due to weight loss in early disease stages is unlikely to explain results. Instead, strong attenuation of effects with confounder control and effect modification by rurality and education indicate that associations could be due to the clustering of access to fat‐enriched foods with other factors that are beneficial for health, such as higher education and access to healthcare.

Traumatic Brain Injury and Cognitive Aging Among Older Veteran Men – A Twin Study Accounting for Genetics and Medical Conditions

AbstractBackgroundTraumatic brain injury (TBI) is associated with increased risk of dementia, but whether TBI influences cognitive trajectories in later life is less clear. Identifying those at high‐risk of cognitive decline creates intervention opportunities to delay dementia. Since twins share many genes and environmental factors, we capitalize on the twin‐study design to investigate the association between lifetime TBI and cognitive decline.MethodParticipants (n = 8,662) members of the National Academy of Sciences‐National Research Council’s Twins Registry of World‐War‐II Male Veterans born between 1917‐1927 with self or proxy‐reported history of TBI and from one to four assessments over 12 years using the modified‐Telephone Interview for Cognitive Status (TICS‐m). We used linear random‐effects‐mixed models to examine the association between TBI and TICS‐m in the full sample and among co‐twins discordant for TBI. Additional TBI predictor variables included: number and severity (with/without loss‐of‐consciousness[LOC]) of TBI; and age of first TBI (age &lt;25 vs 25+). Models were adjusted for age (centered‐at‐70‐years), age‐squared, education, wave, twin pairs and for lifestyle behaviors and medical conditions. In a subset, we assessed the impact of APOE on TICS‐m.ResultHistory of any TBI, TBI with LOC, and older age of TBI were associated with lower TICS‐m scores at 70‐years (p‐values&lt;0.001). TBI with LOC, more than one TBI, and older age of TBI were associated with faster cognitive decline (p‐values&lt;0.05). Among monozygotic twin pairs discordant for TBI (589 pairs), a history of TBI and having TBI at older age was associated with lower TICS‐m scores (p‐values&lt;0.01); those with more than one TBI and TBI at older age showed greater cognitive decline (p‐values&lt;0.05) compared to their cotwin without TBI. Across all twins, APOE‐e4 carriers with TBI, more than one TBI, TBI with LOC, and older age of TBI had lower TICS‐m scores and greater cognitive decline compared to APOE‐e4 non‐carriers.ConclusionThese findings support an association between TBI and lower cognitive score and more rapid cognitive decline in later life. The results in the monozygotic pairs, who share all genes and many exposures particularly in early life, provide evidence of a causal relationship between TBI and poorer late life cognitive outcomes.

The technological reserve hypothesis: A meta‐analysis

AbstractBackgroundOlder adults are increasingly crossing the digital divide, regularly engaging with technologies such as the internet, smartphones, and personal computers. Two distinct theories of the cognitive impact of this digital engagement have been raised. According to the digital distraction hypothesis, regular engagement with technology acutely negatively effects cognition by increasing distractions and decreases cognitive skills over the long‐term by regularly offloading tasks such as recall of facts, directions, and other daily memory tasks into digital technologies. By contrast, according to the technological reserve hypothesis, regular engagement with technology acutely benefits functioning via use of assistive technologies and can reduce long‐term risk for cognitive disorders with age by promoting complex cognitive engagement, sustained connection, and acquisition of digital based compensatory skills.MethodRandom effects meta‐analysis was used to pool effect sizes, with primary effect sizes reported as odds ratios (odds of developing a cognitive diagnosis or odds of having lower cognitive scores as appropriate to each study). We conducted systematic evaluations of study quality and to determine the influence of socioeconomic, education, age, and type of technology.ResultOf 6,183 records identified, 26 studies met inclusion criteria and were included in the final analysis. Engagement with smartphones, computers, and/or the internet was associated with decreased risk of cognitive decline, mild cognitive impairment, and dementia (pooled OR = 0.45, 95% CI 0.318‐0.637, p&lt;.0001; I2 = 99.2%; Figure 1). Potential confounding variables, such as adjustment for socioeconomic factors and education or type of technology measured did not moderate this relationship (Figure 2). Study quality was generally good (Figure 3), though all studies assessed technology use by self‐report and few measured intraindividual changes in technology use over time.ConclusionEngagement with everyday digital technologies is associated with decreased risk of cognitive decline and dementia, consistent with the technological reserve hypothesis. While these studies do not prove causality of this relationship, they do highlight the potential for digital health approaches to promote cognitive health and well being with age. Limitations, particularly with regard to understanding digital disparities and incorporating objective digital use metrics in future studies are discussed in detail.

Evaluation of 'Normal' Cognitive Functions and Correlation With MRI Volumetry: Towards a Definition of Vascular Cognitive Impairment.

Introduction It is important to establish criteria to define vascular cognitive impairment (VCI) in India as VCI is an image-based diagnosis and magnetic resonance imaging (MRI) changes resulting from age with prevalent vascular risk factors may confound MRI interpretation. The objective of this study was to establish normative community data for MRI volumetryincluding white matter hyperintensity volume (WMHV), correlated with age-stratified cognitive scores and vascular risk factors (VRFs), in adults aged 40 years and above. Methods We screened 2651 individuals without known neurological morbidity, living in Mumbai and nearby rural areas, using validated Marathi translations of Kolkata Cognitive Battery (KCB) and geriatric depression score (GDS). We stratified 1961 persons with GDS ≤9 by age and cognitive score, and randomly selected 10% from each subgroup for MRI brain volumetry. Crude volumes were standardized to reflect percentage of intracranial volume. Results MRI volumetry studies were done in 199 individuals (F/M = 90/109; 73 with body mass index (BMI) ≥25; 44 hypertensives; 29 diabetics; mean cognitive score 76.3). Both grey and white matter volumes decreased with increasing age. WMHV increased with age and hypertension. Grey matter volume (GMV) decreased with increasing WMHV. Positive predictors of cognition included standardized hippocampal volume (HCV), urban living, education, and BMI, while WMHV and age were negative predictors. Urban dwellers had higher cognitive scores than rural, and, paradoxically, smaller HCV. Conclusion In this study of MRI volumetry correlated with age, cognitive scores and VRFs, increasing age and WMHV predicted lower cognitive scores, whereas urban living and hippocampal volume predicted higher scores. Age and WMHV also correlated with decreasing GMV. Further study is warranted into sociodemographic and biological factors that mutually influence cognition and brain volumes, including nutritional and endocrine factors, especially at lower cognitive score bands. In this study, at the lower KCB score bins, the lack of laboratory data pertaining to nutritional and endocrine deficiencies is a drawback that reflects the logistical limitations of screening large populations at the community level.Our volumetric data which is age and cognition stratified, and takes into account the vascular risk factors associated, nevertheless constitutesimportant baseline data for the Indian population. Our findings couldpossibly contribute to the formulation of baseline criteria for defining VCI inIndia and could help in early diagnosis and control of cognitive decline and its key risk factors.

Impact of tramadol and heroin abuse on electroencephalography structure and cognitive functions

BackgroundOpioids, defined as medicines that stimulate opioid receptors, are primarily used in the treatment of moderate to severe pain. They induce central nervous system (CNS) adverse effects. This study aimed to assess the effect of opioids on brain electrical activity, the effect of opioids on cognitive functions, and corroborate whether there was any correlation between changes in brain electrical activity and cognitive functions that may do in opioid addicts.MethodsThis cross-sectional case–control study was performed on 80 cases (divided into two groups 40 cases with tramadol use disorders and 40 cases with heroin use disorders) and 40 age-/sex-matched healthy control. All subjects were subordinated to neuropsychiatric evaluation, assessment of opioid use complaint through history from the case and his relatives, substance monitoring in urine, medicine abuse screening test (DAST), electroencephalography (EEG), and cognitive assessment by Montreal Cognitive Assessment (MOCA).ResultsOpioid dependence convinced global cognitive function impairment, specific cognitive disciplines impairment that included visual-conceptual, visual-motor tracking, visual-constructional skills, language function, attention, memory, and orientation. Additionally, affection of the brain’s electrical activities with significant changes compared with control. Comparison of cognitive impairment substantiated by lower cognitive scores in relation to abnormal EEG changes among studied case groups revealed significant differences.ConclusionsOpioid abusers had a significant impairment of cognitive functions and EEG changes with a significant correlation between changes in brain electrical activity and impairment of cognitive functions.