Cognitive Reserve Proxies Do Not Differentially Account for Cognitive Performance in Patients with Focal Frontal and Non-Frontal Lesions.

OBJECTIVE: Cognitive reserve (CR) suggests that premorbid efficacy, aptitude, and flexibility of cognitive processing can aid the brain's ability to cope with change or damage. Our previous work has shown that age and literacy attainment predict the cognitive performance of frontal patients on frontal-executive tests. However, it remains unknown whether CR also predicts the cognitive performance of non-frontal patients. METHOD: We investigated the independent effect of a CR proxy, National Adult Reading Test (NART) IQ, as well as age and lesion group (frontal vs. non-frontal) on measures of executive function, intelligence, processing speed, and naming in 166 patients with focal, unilateral frontal lesions; 91 patients with focal, unilateral non-frontal lesions; and 136 healthy controls. RESULTS: Fitting multiple linear regression models for each cognitive measure revealed that NART IQ predicted executive, intelligence, and naming performance. Age also significantly predicted performance on the executive and processing speed tests. Finally, belonging to the frontal group predicted executive and naming performance, while membership of the non-frontal group predicted intelligence. CONCLUSIONS: These findings suggest that age, lesion group, and literacy attainment play independent roles in predicting cognitive performance following stroke or brain tumour. However, the relationship between CR and focal brain damage does not differ in the context of frontal and non-frontal lesions.

Individual differences in cognitive processes underlying Trail Making Test-B performance in old age: The Lothian Birth Cohort 1936.

The Trail Making Test Part B (TMT-B) is commonly used as a brief and simple neuropsychological assessment of executive dysfunction. The TMT-B is thought to rely on a number of distinct cognitive processes that predict individual differences in performance. The current study examined the unique and shared contributions of latent component variables in a large cohort of older people. Five hundred and eighty-seven healthy, community-dwelling older adults who were all born in 1936 were assessed on the TMT-B and multiple tasks tapping cognitive domains of visuospatial ability, processing speed, memory and reading ability. Firstly, a first-order measurement model examining independent contributions of the four cognitive domains was fitted; a significant relationship between TMT-B completion times and processing speed was found (ß = -0.610, p < .001). Secondly, a bifactor model examined the unique influence of each cognitive ability when controlling for a general cognitive factor. Importantly, both a general cognitive factor (g; ß = -0.561, p < .001) and additional g-independent variance from processing speed (ß = -0.464, p < .001) contributed to successful TMT-B performance. These findings suggest that older adults' TMT-B performance is influenced by both general intelligence and processing speed, which may help understand poor performance on such tasks in clinical populations.

Does bilingualism influence cognitive aging?

Recent evidence suggests a positive impact of bilingualism on cognition, including later onset of dementia. However, monolinguals and bilinguals might have different baseline cognitive ability. We present the first study examining the effect of bilingualism on later-life cognition controlling for childhood intelligence. We studied 853 participants, first tested in 1947 (age = 11 years), and retested in 2008-2010. Bilinguals performed significantly better than predicted from their baseline cognitive abilities, with strongest effects on general intelligence and reading. Our results suggest a positive effect of bilingualism on later-life cognition, including in those who acquired their second language in adulthood.

Genetic diversity is a predictor of mortality in humans.

BACKGROUND: It has been well-established, both by population genetics theory and direct observation in many organisms, that increased genetic diversity provides a survival advantage. However, given the limitations of both sample size and genome-wide metrics, this hypothesis has not been comprehensively tested in human populations. Moreover, the presence of numerous segregating small effect alleles that influence traits that directly impact health directly raises the question as to whether global measures of genomic variation are themselves associated with human health and disease. RESULTS: We performed a meta-analysis of 17 cohorts followed prospectively, with a combined sample size of 46,716 individuals, including a total of 15,234 deaths. We find a significant association between increased heterozygosity and survival (P = 0.03). We estimate that within a single population, every standard deviation of heterozygosity an individual has over the mean decreases that person's risk of death by 1.57%. CONCLUSIONS: This effect was consistent between European and African ancestry cohorts, men and women, and major causes of death (cancer and cardiovascular disease), demonstrating the broad positive impact of genomic diversity on human survival.

Prevalence of impaired awareness of hypoglycemia and identification of predictive symptoms in children and adolescents with type 1 diabetes.

BACKGROUND: In children with type 1 diabetes mellitus (T1DM) the prevalence of impaired awareness of hypoglycemia (IAH) is uncertain. This study aimed to ascertain this with greater precision. Secondary aims were to assess symptoms of hypoglycemia and which of these best predict awareness of hypoglycemia in children. METHODS: Questionnaires were completed by 98 children with T1DM (mean age 10.6 yr) and their parent(s); hospital admission data for the previous year were collected. Awareness of hypoglycemia was assessed using two questionnaire-based methods that have been validated in adults. For 4 wk, participants performed routine blood glucose measurements and completed questionnaires after each episode of hypoglycemia. Principal components analysis determined how symptoms correlate; multinomial logistic regression models identified which symptom aggregate best predicted awareness status. RESULTS: The 'Gold' questionnaire classified a greater proportion of the participants as having IAH than the 'Clarke' questionnaire (68.4 vs. 22.4%). Using the 'Clarke' method, but not the 'Gold' method, children with IAH were younger and more likely to require external assistance or hospital admission. Most aged ≥9 yr (98.6%) were able to self-assess awareness status accurately. Puberty and increasing age, augmented symptom scores; duration of diabetes and glycemic control had no effect. In contrast to adults, behavioral symptoms were the best predictors of awareness status. CONCLUSIONS: IAH affects a substantial minority of children and impending hypoglycemia may be heralded by behavioral symptoms. The 'Clarke' method was more effective at identifying those at increased risk and could be used as a screening tool.

Mood and Anxiety Symptom Questionnaire anxiety items in an adult british clinical sample: one scale or two?

In seeking to establish British clinical normative data for the two anxiety scales (anxious symptoms and anxious arousal) of the Mood and Anxiety Symptom Questionnaire (MASQ), the responses of 237 British National Health Service outpatients were examined. Factor analyses (exploratory and confirmatory) failed to confirm the expected structure. Data were presented and discussed, considering the 28 anxiety item pool in terms of being either two highly correlated scales of somatic anxiety versus psychological anxiety, or as a single general anxiety scale. As neither of these outcomes accorded with the test constructors' assumptions, it was concluded that the MASQ is not a suitable measure for assessing the tripartite model of adverse mood states in British clinical samples.

The structure of the Hospital Anxiety and Depression Scale in four cohorts of community-based, healthy older people: the HALCyon program.

BACKGROUND: The Hospital Anxiety and Depression Scale (HADS) is widely used but evaluation of its psychometric properties has produced equivocal results. Little is known about its structure in non-clinical samples of older people. METHODS: We used data from four cohorts in the HALCyon collaborative research program into healthy aging: the Caerphilly Prospective Study, the Hertfordshire Ageing Study, the Hertfordshire Cohort Study, and the Lothian Birth Cohort 1921. We used exploratory factor analysis and confirmatory factor analysis with multi-group comparisons to establish the structure of the HADS and test for factorial invariance between samples. RESULTS: Exploratory factor analysis showed a bi-dimensional structure (anxiety and depression) of the scale in men and women in each cohort. We tested a hypothesized three-factor model but high correlations between two of the factors made a two-factor model more psychologically plausible. Multi-group confirmatory factor analysis revealed that the sizes of the respective item loadings on the two factors were effectively identical in men and women from the same cohort. There was more variation between cohorts, particularly those from different parts of the U.K. and in whom the HADS was administered differently. Differences in social-class distribution accounted for part of this variation. CONCLUSIONS: Scoring the HADS as two subscales of anxiety and depression is appropriate in non-clinical populations of older men and women. However, there were differences between cohorts in the way that individual items were linked with the constructs of anxiety and depression, perhaps due to differences in sociocultural factors and/or in the administration of the scale.

Five Factor Model personality traits and all-cause mortality in the Edinburgh Artery Study cohort.

OBJECTIVE: To examine whether personality traits are related to all-cause mortality in a general adult population in Scotland. METHODS: The Edinburgh Artery Study began in 1987 to 1988 by recruiting 1592 men and women aged 55 to 74 years to be followed-up for atherosclerotic diseases. The NEO Five-Factor Inventory (NEO-FFI) was completed by 1035 surviving participants in 1995 to 1996. Deaths from all causes were examined in relation to personality traits and social and physical risk factors for mortality. RESULTS: During follow-up, 242 (37.1%) men and 165 (24.6%) women died. For the whole sample, there was a 28% lower rate of all-cause mortality for each 1 SD increase in NEO-FFI openness (95% CI, 0.61-0.84) and a 18% lower rate of all-cause mortality for each 1 SD increase in NEO-FFI conscientiousness (95% CI, 0.70-0.97). In men, the risk of all-cause mortality was 0.63 (95% CI, 0.5-10.78) for a 1 SD increase in openness and 0.75 (95% CI, 0.61-0.91) for a 1 SD increase in conscientiousness. In women, none of the personality domains were significantly associated with all-cause mortality. Well fitting structural equation models in men (n = 652) showed that the relationships between conscientiousness and openness and all-cause mortality were not substantially explained by smoking, or other variables in the models. CONCLUSION: High conscientiousness and openness may be protective against all-cause mortality in men. Further investigations are needed on the mechanisms of these associations, and the influence of personality traits on specific causes of death.

Smarter in middle age, faster in old age: a cross-lagged panel analysis of reaction time and cognitive ability over 13 years in the West of Scotland Twenty-07 Study.

Participants in the West of Scotland Twenty-07 Study performed reaction time tasks and took the Alice Heim 4 Part 1 test (AH4) of intelligence twice, 13 years apart. Cross-lagged associations between speed of processing and AH4 were examined using latent variables in structural equation modeling. The stability coefficients of the latent traits of processing speed and of AH4 score across 13 years were .49 and .89, respectively. There was a significant association (-.21) between AH4 score at age 56 and speed of processing at age 69 but not vice versa. The results fail to support the theory that processing speed is a foundation for successful cognitive aging but support a hypothesis that suggests that higher general intelligence might be associated with lifestyle and other factors that preserve processing speed.

Longitudinal associations between hearing loss and general cognitive ability: The Lothian Birth Cohort 1936.

Hearing impairment is associated with poorer cognitive function in later life. We tested for the potential contribution of childhood cognitive ability to this relationship. Childhood cognitive ability is strongly related to cognitive function in older age, and may be related to auditory function through its association with hearing impairment risk factors. Using data from the Lothian Birth Cohort, 1936, we tested whether childhood cognitive ability predicted later-life hearing ability then whether this association was mediated by demographic or health differences. We found that childhood cognitive ability was negatively associated with hearing impairment risk at age 76 (odds ratio = .834, p = .042). However, this association was nonsignificant after subsequent adjustment for potentially mediating demographic and health factors. Next, we tested whether associations observed in older age between hearing impairment and general cognitive ability level or change were accounted for by childhood cognitive ability. At age 76, in the minimally adjusted model, hearing impairment was associated with poorer general cognitive ability level (ß = -.119, p = .030) but was not related to decline in general cognitive ability. The former association became nonsignificant after additional adjustment for childhood cognitive ability (ß = -.068, p = .426) suggesting that childhood cognitive ability contributes (potentially via demographic and health differences) to the association between levels of hearing and cognitive function in older age. Further work is needed to test whether early life cognitive ability also contributes to the association (documented in previous studies) between older-age hearing impairment and cognitive decline. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Cognitive function trajectories and their determinants in older people: 8 years of follow-up in the English Longitudinal Study of Ageing.

BACKGROUND: Maintaining cognitive function is an important aspect of healthy ageing. In this study, we examined age trajectories of cognitive decline in a large nationally representative sample of older people in England. We explored the factors that influence such decline and whether these differed by gender. METHODS: Latent growth curve modelling was used to explore age-specific changes, and influences on them, in an 8-year period in memory, executive function, processing speed and global cognitive function among 10 626 participants in the English Longitudinal Study of Ageing. We run gender-specific models with the following exposures: age, education, wealth, childhood socioeconomic status, cardiovascular disease, diabetes, physical function, body mass index, physical activity, alcohol, smoking, depression and dementia. RESULTS: After adjustment, women had significantly less decline than men in memory (0.011, SE 0.006), executive function (0.012, SE 0.006) and global cognitive function (0.016, SE 0.004). Increasing age and dementia predicted faster rates of decline in all cognitive function domains. Depression and alcohol consumption predicted decline in some cognitive function domains in men only. Poor physical function, physical inactivity and smoking were associated with faster rates of decline in specific cognitive domains in both men and women. For example, relative to study members who were physically active, the sedentary experienced greater declines in memory (women -0.018, SE 0.009) and global cognitive function (men -0.015, SE 0.007 and women -0.016, SE 0.007). CONCLUSIONS: The potential determinants of cognitive decline identified in this study, in particular modifiable risk factors, should be tested in the context of randomised controlled trials.

Carotid disease at age 73 and cognitive change from age 70 to 76 years: A longitudinal cohort study.

Cognitive decline and carotid artery atheroma are common at older ages. In community-dwelling subjects, we assessed cognition at ages 70, 73 and 76 and carotid Doppler ultrasound at age 73, to determine whether carotid stenosis was related to cognitive decline. We used latent growth curve models to examine associations between four carotid measures (internal carotid artery stenosis, velocity, pulsatility and resistivity indices) and four cognitive ability domains (memory, visuospatial function, crystallised intelligence, processing speed) adjusted for cognitive ability at age 11, current age, gender and vascular risk factors. Amongst 866 participants, carotid stenosis (median 12.96%) was not associated with cognitive abilities at age 70 or cognitive decline from age 70 to 76. Increased ICA pulsatility and resistivity indices were associated with slower processing speed (both P < 0.001) and worse visuospatial function ( P = 0.036, 0.031, respectively) at age 70, and declining crystallised intelligence from ages 70 to 76 ( P = 0.008, 0.006, respectively). The findings suggest that vascular stiffening, rather than carotid luminal narrowing, adversely influences cognitive ageing and provides a potential target for ameliorating age-related cognitive decline.

Cognitive reserve and cognitive performance of patients with focal frontal lesions.

The Cognitive reserve (CR) hypothesis was put forward to account for the variability in cognitive performance of patients with similar degrees of brain pathology. Compensatory neural activity within the frontal lobes has often been associated with CR. For the first time we investigated the independent effects of two CR proxies, education and NART IQ, on measures of executive function, fluid intelligence, speed of information processing, verbal short term memory (vSTM), naming, and perception in a sample of 86 patients with focal, unilateral frontal lesions and 142 healthy controls. We fitted multiple linear regression models for each of the cognitive measures and found that only NART IQ predicted executive and naming performance. Neither education nor NART IQ predicted performance on fluid intelligence, processing speed, vSTM or perceptual abilities. Education and NART IQ did not modify the effect of lesion severity on cognitive impairment. We also found that age significantly predicted performance on executive tests and the majority of our other cognitive measures, except vSTM and GNT. Age was the only predictor for fluid intelligence. This latter finding suggests that age plays a role in executive performance over and above the contribution of CR proxies in patients with focal frontal lesions. Overall, our results suggest that the CR proxies do not appear to modify the relationship between cognitive impairment and frontal lesions.

Bilingualism, social cognition and executive functions: A tale of chickens and eggs.

The influence of bilingualism on cognitive functioning is currently a topic of intense scientific debate. The strongest evidence for a cognitive benefit of bilingualism has been demonstrated in executive functions. However, the causal direction of the relationship remains unclear: does learning other languages improve executive functions or are people with better executive abilities more likely to become bilingual? To address this, we examined 90 male participants of the Lothian Birth Cohort 1936; 26 were bilingual, 64 monolingual. All participants underwent an intelligence test at age 11 years and were assessed on a wide range of executive and social cognition tasks at age 74. The only notable differences between both groups were found for the Simon Effect (which indexes stimulus-response conflict resolution; ß=-.518, p=0.025) and a trend effect for the Faux Pas task (a measure of complex theory of mind; ToM, ß=0.432, p=0.060). Controlling for the influence of childhood intelligence, parental and own social class significantly attenuated the bilingual advantage on the Faux Pas test (ß=0.058, p=0.816), whereas the Simon task advantage remained (ß=-.589, p=0.049). We find some weak evidence that the relationship between bilingualism and cognitive functions may be selective and bi-directional. Pre-existing cognitive and social class differences from childhood may influence both ToM ability in older age and the likelihood of learning another language; yet, bilingualism does not appear to independently contribute to Faux Pas score. Conversely, learning a second language is related to better conflict processing, irrespective of initial childhood ability or social class.

The dynamic relationship between cognitive function and walking speed: the English Longitudinal Study of Ageing.

Cross-sectional studies show that older people with better cognition tend to walk faster. Whether this association reflects an influence of fluid cognition upon walking speed, vice versa, a bidirectional relationship or the effect of common causes is unclear. We used linear mixed effects models to examine the dynamic relationship between usual walking speed and fluid cognition, as measured by executive function, verbal memory and processing speed, in 2,654 men and women aged 60 to over 90 years from the English Longitudinal Study of Ageing. There was a bidirectional relationship between walking speed and fluid cognition. After adjusting for age and sex, better performance on executive function, memory and processing speed was associated with less yearly decline in walking speed over the 6-year follow-up period; faster walking speed was associated with less yearly decline in each cognitive domain; and less yearly decline in each cognitive domain was associated with less yearly decline in walking speed. Effect sizes were small. After further adjustment for other covariates, effect sizes were attenuated but most remained statistically significant. We found some evidence that walking speed and the fluid cognitive domains of executive function and processing speed may change in parallel with increasing age. Investigation of the association between walking speed and cognition earlier in life is needed to better understand the origins of this relation and inform the development and timing of interventions.

Vascular risk factors, large-artery atheroma, and brain white matter hyperintensities.

OBJECTIVE: To determine the magnitude of potentially causal relationships among vascular risk factors (VRFs), large-artery atheromatous disease (LAD), and cerebral white matter hyperintensities (WMH) in 2 prospective cohorts. METHODS: We assessed VRFs (history and measured variables), LAD (in carotid, coronary, and leg arteries), and WMH (on structural MRI, visual scores and volume) in: (a) community-dwelling older subjects of the Lothian Birth Cohort 1936, and (b) patients with recent nondisabling stroke. We analyzed correlations, developed structural equation models, and performed mediation analysis to test interrelationships among VRFs, LAD, and WMH. RESULTS: In subjects of the Lothian Birth Cohort 1936 (n = 881, mean age 72.5 years [SD ±0.7 years], 49% with hypertension, 33% with moderate/severe WMH), VRFs explained 70% of the LAD variance but only 1.4% to 2% of WMH variance, of which hypertension explained the most. In stroke patients (n = 257, mean age 74 years [SD ±11.6 years], 61% hypertensive, 43% moderate/severe WMH), VRFs explained only 0.1% of WMH variance. There was no direct association between LAD and WMH in either sample. The results were the same for all WMH measures used. CONCLUSIONS: The small effect of VRFs and LAD on WMH suggests that WMH have a large "nonvascular," nonatheromatous etiology. VRF modification, although important, may be limited in preventing WMH and their stroke and dementia consequences. Investigation of, and interventions against, other suspected small-vessel disease mechanisms should be addressed.

Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function.

BACKGROUND: Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function. METHODS: We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis. RESULTS: The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P  =  5.71 × 10(-7)). In addition, meta-analysis using the five cohorts with ≥3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P  =  2.18 × 10(-8)) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively. CONCLUSIONS: In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function.

Modeling the effects of hypoglycemia on a two-choice task in adult humans.

OBJECTIVE: Previous research has demonstrated that hypoglycemia causes reaction times to be slower and more variable. Reaction time tests, however, use multiple cognitive and noncognitive processes. This study is the first to use a validated sequential sampling model (diffusion model) applied to results obtained from a simple 2-choice task in adult humans to assess the effects of hypoglycemia on the basic parameters of decision making. METHOD: Fourteen adult volunteers were tested on a numerosity discrimination task with and without reduced blood glucose concentrations. The results were analyzed with a model that dissects the components of processing that underlie decisions: the quality of the information on which a decision is based (drift rate), the critical amount of evidence that must be accumulated before a decision is made (boundary separation), and the time taken by nondecision processes. RESULTS: Hypoglycemia resulted in a reduction of mean drift rate from 0.290 to 0.211, t(13) = 4.10, p < .05. No effect of experimental state was observed on the amount of evidence required to make a decision or peripheral and motor processes. CONCLUSION: This study locates the precise processing deficit associated with hypoglycemia and provides further understanding of the precise cognitive effect of hypoglycemia. Further research into the amelioration of these effects is required.

Dual task during encoding, maintenance, and retrieval in Alzheimer's disease.

Previous dual task studies have demonstrated minimal costs when healthy individuals simultaneously perform two tasks at their own individual ability levels. Conversely, Alzheimer's disease (AD) patients show dual task decrements, but it is unclear whether the problem arises at the encoding, maintenance, and/or retrieval phases of memory. Two experiments combined digit recall and visuo-motor tracking to investigate dual task effects during encoding, maintenance, and/or retrieval for AD patients compared with healthy adults. The demands of each single task were titrated for the ability of each participant. In Experiment 1, the dual task requirement was present throughout both encoding and retrieval of digit recall and the differential dual task effects on a secondary tracking task were examined post-hoc. In Experiment 2, the impact of dual task during encoding only, during maintenance only, and during retrieval only was examined systematically. The findings suggest that the specific AD deficit reflects impairment of a cognitive function that supports the simultaneous performance of two tasks in the healthy brain, particularly during the encoding and retrieval phases of the memory task.