Lothian Birth Cohort Research Articles

Lifecourse Activity Participation From Early, Mid, and Later Adulthood as Determinants of Cognitive Aging: The Lothian Birth Cohort 1921.

Objectives:To examine potential sensitive periods for activity participation across adulthood to reduce cognitive decline and to determine whether associations persist after accounting for the lifetime stability of cognitive ability.Method:The Lothian Birth Cohort 1921 is a longitudinal study of cognitive aging. Participants were born in 1921 and most completed a mental ability test at the age of 11 years. Cognitive assessments were completed at mean ages 79 (N = 550), 83 (N = 321), 87 (N = 235), and 90 years (N = 129). Participants provided retrospective details of their activity participation for young (20–35 years), mid (40–55 years), and later adulthood (60–75 years), and contemporaneously at age 79.Results:Associations between activity and the level of, and change in, cognitive ability in old age were examined with latent growth curve models. Accounting for demographics and childhood cognitive ability, engagement in leisure activities in midlife was positively associated with cognitive ability level (path coefficient = .32), whereas higher physical activity in later adulthood was associated with less cognitive decline (.27).Discussion:The findings support a lifecourse approach in identifying determinants of cognitive aging; leisure and physical activity during different periods of adulthood may enhance cognitive abilities or reduce decline.

Early life characteristics and late life burden of cerebral small vessel disease in the Lothian Birth Cohort 1936.

It is unknown whether relations between early-life factors and overall health in later life apply to burden of cerebral small vessel disease (cSVD), a major cause of stroke and dementia. We explored relations between early-life factors and cSVD in the Lothian Birth Cohort, a healthy aging cohort. Participants were recruited at age 70 (N = 1091); most had completed a test of cognitive ability at age 11 as part of the Scottish Mental Survey of 1947. Of those, 700 participants had brain MRI that could be rated for cSVD conducted at age 73. Presence of lacunes, white matter hyperintensities, microbleeds, and perivascular spaces were summed in a score of 0-4 representing all MRI cSVD features. We tested associations with early-life factors using multivariate logistic regression. Greater SVD score was significantly associated with lower age-11 IQ (OR higher SVD score per SD age-11 IQ = .78, 95%CI 0.65-.95, p=.01). The associations between SVD score and own job class (OR higher job class, .64 95%CI .43-.95, p=.03), age-11 deprivation index (OR per point deprivation score, 1.08, 95%CI 1.00-1.17, p=.04), and education (OR some qualifying education, .60 95%CI .37-.98, p=.04) trended towards significance (p<.05 for all) but did not meet thresholds for multiple testing. No early-life factor was significantly associated with any one individual score component. Early-life factors may contribute to age-73 burden of cSVD. These relations, and the potential for early social interventions to improve brain health, deserve further study.

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; β=−.518, p=0.025) and a trend effect for the Faux Pas task (a measure of complex theory of mind; ToM, β=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 (β=0.058, p=0.816), whereas the Simon task advantage remained (β=−.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.

Do white matter hyperintensities mediate the association between brain iron deposition and cognitive abilities in older people?

Background and purposeSeveral studies have reported associations between brain iron deposits (IDs), white matter hyperintensities (WMHs) and cognitive ability in older individuals. Whether the association between brain IDs and cognitive abilities in older people is mediated by or independent of total brain tissue damage represented by WMHs visible on structural magnetic resonance imaging (MRI) was examined.MethodsData from 676 community‐dwelling individuals from the Lothian Birth Cohort 1936, with Mini‐Mental State Examination scores >24, who underwent detailed cognitive testing and multimodal brain MRI at mean age 72.7 years were analysed. Brain IDs were assessed automatically following manual editing. WMHs were assessed semi‐automatically. Brain microbleeds were visually counted. Structural equation modelling was used to test for mediation.ResultsOverall, 72.8% of the sample had IDs with a median total volume of 0.040 ml (i.e. 0.004% of the total brain volume). The total volume of IDs, significantly and negatively associated with general cognitive function (standardized β = −0.17, P < 0.01), was significantly and positively associated with WMH volume (std β = 0.13, P = 0.03). WMH volume had a significant negative association with general cognitive function, independent of IDs (std β = −0.13, P < 0.01). The association between cognition and IDs in the brain stem (and minimally the total brain iron load) was partially and significantly mediated by WMH volume (P = 0.03).ConclusionsThe negative association between brain IDs and cognitive ability in the elderly is partially mediated by WMHs, with this mediation mainly arising from the iron deposition load in the brain stem. IDs might be an indicator of small vessel disease that predisposes to white matter damage, affecting the neuronal networks underlying higher cognitive functioning.

Cytomegalovirus infection is associated with an increase in systolic blood pressure in older individuals.

Background: Cytomegalovirus (CMV) is a chronic infection that is widely distributed in the population. CMV infects a range of tissues, including endothelium, and viral replication is suppressed by the host immune system. Infection is associated with increased risk of mortality from vascular disease in older people, but the mechanisms behind this have not been determined.Aim: We investigated the association between CMV infection and cardiovascular phenotype in a cohort of healthy elderly donors.Design: CMV serostatus and cardiovascular parameters were determined in the Lothian Birth cohort, which comprises 1091 individuals aged 70 years in whom many environmental, biochemical and radiological correlates of vascular function have been determined.Methods: CMV serostatus was determined by enzyme-linked immunosorbant assay and correlated with a range of biochemical and phenotypic measures.Results: Sixty-five percent of participants were CMV seropositive, which indicates chronic infection. The mean sitting systolic blood pressure (SBP) was 149.2 mmHg in CMV seropositive individuals compared with 146.2 mmHg in CMV seronegative subjects (SD 18.7 vs. 19.7; P < 0.017). This association between CMV infection and SBP was not attenuated after adjustment for a wide range of biological and socio-economic factors.Conclusions: These data show that CMV infection is associated with an increase in SBP in individuals at age 70 years. The magnitude is comparable to environmental variables such as obesity, diabetes or high salt intake. This is the first evidence to show that a chronic infection may be an important determinant of blood pressure and could have significant implications for the future management of hypertension.

Life review in advanced age: qualitative research on the 'start in life' of 90-year-olds in the Lothian Birth Cohort 1921.

BackgroundThis research report presents findings on ‘start in life’ from a qualitative study of 90-year-olds from the Lothian Birth Cohort 1921. The study aimed to contextualise the LBC1921 cohort in time and place, describe cohort members’ experiences of family and schooling and stimulate further inquiry into the relationships between ‘start in life’ and risk and resilience factors relating to longevity and healthy ageing. Scottish education and family life in the early 1930s are briefly described.MethodsLife review questionnaire: A qualitative Life Review Questionnaire was developed, requiring free-text handwritten responses. Its ‘Start in Life’ section focused on schooling and family support.Sample: Wave 4 of the Lothian Birth Cohort 1921 involved testing 129 members near to their 90th birthday. They reside largely in Edinburgh and its environs. The Life Review Questionnaire was administered to 126 participants, 54 % women.Qualitative analysis: Thematic analysis was the qualitative technique used to categorise, code and extract meaning from questionnaire text. Narratives were extracted from the data to present illustrative stories.ResultsNarratives of start in life gave contextual description. Thematic analysis showed LBC1921 members enjoying their schooling, highlighting teachers, academic achievement, school activities and school friendships. Personal qualities, family circumstances and aspects of schooling sometimes hindered educational performance. Family life was recalled mostly with warmth and parents were often portrayed as valuing education and supporting learning and development. Family adversity from poverty, parental illness and parental death was often mitigated by support from parents (or the remaining parent). Overall, most cohort members believed that they had got off to a good ‘start in life’.ConclusionsThis qualitative investigation of ‘start in life’ adds context and richness to quantitative investigations of the sizeable LBC1921 cohort, stimulating fresh insights and hypotheses into the relationship between child risk and resilience factors that may influence ageing. It demonstrates the utility and wider application of the Life Review Questionnaire. Although the surviving cohort is not representative of their childhood peers, their words provide insight into the processes of weaving experience and memory into a rich texture of meanings that may help create wellbeing across a lifetime.

Vascular risk factors and progression of white matter hyperintensities in the Lothian Birth Cohort 1936

We aimed to determine associations between multiple vascular risk factors (VRF) at ∼73 years and progression of white matter hyperintensities (WMH) from ∼73 years to ∼76 years. We calculated correlations and generalized estimating equation models of a comprehensive range of VRF at 73 years and change in WMH volume from 73 years to 76 years. Higher systolic (rho = 0.126, p = 0.009) and diastolic (rho = 0.120, p = 0.013) blood pressure at 73 years were significant predictors for greater WMH volume at 76 years in a simple correlation model. However, neither measured blood pressure nor self-reported hypertension at 73 years was significant predictors of WMH volume change in a fully adjusted model which accounted for initial WMH volume at 73 years. Lower high-density lipoprotein cholesterol (beta = −0.15 % intracranial, −1.80 mL; p < 0.05) and current smoking (beta = 0.43 % intracranial, 5.49 mL; p < 0.05) were the only significant VRF predictors of WMH volume change from 73 years to 76 years. A focus on smoking cessation and lipid lowering, not just antihypertensives, may lead to a reduction in WMH growth in the eighth decade of life.

DNA methylation levels at individual age-associated CpG sites can be indicative for life expectancy.

DNA-methylation (DNAm) levels at age-associated CpG sites can be combined into epigenetic aging signatures to estimate donor age. It has been demonstrated that the difference between such epigenetic age-predictions and chronological age is indicative for of all-cause mortality in later life. In this study, we tested alternative epigenetic signatures and followed the hypothesis that even individual age-associated CpG sites might be indicative for life-expectancy. Using a 99-CpG aging model, a five-year higher age-prediction was associated with 11% greater mortality risk in DNAm profiles of the Lothian Birth Cohort 1921 study. However, models based on three CpGs, or even individual CpGs, generally revealed very high offsets in age-predictions if applied to independent microarray datasets. On the other hand, we demonstrate that DNAm levels at several individual age-associated CpGs seem to be associated with life expectancy - e.g., at CpGs associated with the genesPDE4C and CLCN6. Our results support the notion that small aging signatures should rather be analysed by more quantitative methods, such as site-specific pyrosequencing, as the precision of age-predictions is rather low on independent microarray datasets. Nevertheless, the results hold the perspective that simple epigenetic biomarkers, based on few or individual age-associated CpGs, could assist the estimation of biological age.

Longitudinal telomere length shortening and cognitive and physical decline in later life: The Lothian Birth Cohorts 1936 and 1921

Telomere length is hypothesised to be a biological marker of both cognitive and physical ageing. Here we measure telomere length, and cognitive and physical abilities at mean ages 70, 73 and 76 years in the Lothian Birth Cohort 1936 (LBC1936), and at mean ages 79, 87, 90 and 92 years in the Lothian Birth Cohort 1921 (LBC1921). We investigate whether telomere length change predicts change in cognitive and physical abilities. In LBC1936 telomere length decreased by an average of 65 base pairs per year and in LBC1921 by 69 base pairs per year. However, change in telomere length did not predict change in cognitive or physical abilities. This study shows that, although cognitive ability, walking speed, lung function and grip strength all decline with age, they do so independently of telomere length shortening.

Polygenic risk for coronary artery disease is associated with cognitive ability in older adults.

Background: Coronary artery disease (CAD) is associated with cognitive decrements and risk of later dementia, but it is not known if shared genetic factors underlie this association. We tested whether polygenic risk for CAD was associated with cognitive ability in community-dwelling cohorts of middle-aged and older adults. Methods: Individuals from Generation Scotland: Scottish Family Health Study (GS:SFHS, N = 9865) and from the Lothian Birth Cohorts of 1921 (LBC1921, N = 517) and 1936 (LBC1936, N = 1005) provided cognitive data and genome-wide genotype data. Polygenic risk profile scores for CAD were calculated for all of the cohorts using the largest available genome-wide association studies (GWAS) data set, the CARDIoGRAM consortium (22 233 cases and 64 762 controls). Polygenic risk profile scores for CAD were then tested for their association with cognitive abilities in the presence and absence of manifest cardiovascular disease. Results: A meta-analysis of all three cohorts showed a negative association between CAD polygenic risk and fluid cognitive ability (β = −0.022, P = 0.016), verbal intelligence (β = −0.024, P = 0.011) and memory (β = −0.021, P = 0.028). Conclusions: Increased polygenic risk for CAD is associated with lower cognitive ability in older adults. Common genetic variants may underlie some of the association between age-related cognitive decrements and the risk for CAD.

Progression of White Matter Disease and Cortical Thinning Are Not Related in Older Community-Dwelling Subjects.

Background and Purpose—We assessed cross-sectional and longitudinal relationships between whole brain white matter hyperintensity (WMH) volume and regional cortical thickness.Methods—We measured WMH volume and regional cortical thickness on magnetic resonance imaging at ≈73 and ≈76 years in 351 community-dwelling subjects from the Lothian Birth Cohort 1936. We used multiple linear regression to calculate cross-sectional and longitudinal associations between regional cortical thickness and WMH volume controlling for age, sex, Mini Mental State Examination, education, intelligence quotient at age 11, and vascular risk factors.Results—We found cross-sectional associations between WMH volume and cortical thickness within and surrounding the Sylvian fissure at 73 and 76 years (rho=−0.276, Q=0.004). However, we found no significant longitudinal associations between (1) baseline WMH volume and change in cortical thickness; (2) baseline cortical thickness and change in WMH volume; or (3) change in WMH volume and change in cortical thickness.Conclusions—Our results show that WMH volume and cortical thinning both worsen with age and are associated cross-sectionally within and surrounding the Sylvian fissure. However, changes in WMH volume and cortical thinning from 73 to 76 years are not associated longitudinally in these relatively healthy older subjects. The underlying cause(s) of WMH growth and cortical thinning have yet to be fully determined.

Do Cognitive and Physical Functions Age in Concert from Age 70 to 76? Evidence from the Lothian Birth Cohort 1936.

The present study concerns the relation of mental and bodily characteristics to one another during ageing. The 'common cause' theory of ageing proposes that declines are shared across multiple, seemingly-disparate functions, including both physical and intellectual abilities. The concept of 'reserve' suggests that healthier cognitive (and perhaps bodily) functions from early in life are protective against the effects of senescence across multiple domains. In three waves of physical and cognitive testing data from the longitudinal Lothian Birth Cohort 1936 (n = 1,091 at age 70 years; n = 866 at 73; n = 697 at 76), we used multivariate growth curve modeling to test the 'common cause' and 'reserve' hypotheses. Support for both concepts was mixed: although levels of physical functions and cognitive functions were correlated with one another, physical functions did not decline together, and there was little evidence for shared declines in physical and mental functions. Early-life intelligence, a potential marker of system integrity, made a significant prediction of the levels, but not the slopes, of later life physical functions. These data suggest that common causes, which are likely present within cognitive functions, are not as far-reaching beyond the cognitive arena as has previously been suggested. They also imply that bodily reserve may be similar to cognitive reserve in that it affects the level, but not the slope, of ageing-related declines.

Intelligence and socioeconomic position in childhood in relation to frailty and cumulative allostatic load in later life: the Lothian Birth Cohort 1936

BackgroundInformation on childhood determinants of frailty or allostatic load in later life is sparse. We investigated whether lower intelligence and greater socioeconomic disadvantage in childhood increased the risk of frailty...

Polygenic risk of ischemic stroke is associated with cognitive ability.

Objectives:We investigated the correlation between polygenic risk of ischemic stroke (and its subtypes) and cognitive ability in 3 relatively healthy Scottish cohorts: the Lothian Birth Cohort 1936 (LBC1936), the Lothian Birth Cohort 1921 (LBC1921), and Generation Scotland: Scottish Family Health Study (GS).Methods:Polygenic risk scores for ischemic stroke were created in LBC1936 (n = 1005), LBC1921 (n = 517), and GS (n = 6,815) using genome-wide association study summary data from the METASTROKE collaboration. We investigated whether the polygenic risk scores correlate with cognitive ability in the 3 cohorts.Results:In the largest cohort, GS, polygenic risk of all ischemic stroke, small vessel disease stroke, and large vessel disease stroke, but not cardioembolic stroke, were correlated with both fluid and crystallized cognitive abilities. The highest correlation was between a polygenic risk score for all ischemic stroke and general cognitive ability (r = −0.070, p = 1.95 × 10−8). Few correlations were identified in LBC1936 and LBC1921, but a meta-analysis of all 3 cohorts supported the correlation between polygenic risk of ischemic stroke and cognitive ability.Conclusions:The findings from this study indicate that even in the absence of stroke, being at high polygenic risk of ischemic stroke is associated with lower cognitive ability.

Structural Brain MRI Trait Polygenic Score Prediction of Cognitive Abilities.

Structural brain magnetic resonance imaging (MRI) traits share part of their genetic variance with cognitive traits. Here, we use genetic association results from large meta-analytic studies of genome-wide association (GWA) for brain infarcts (BI), white matter hyperintensities, intracranial, hippocampal, and total brain volumes to estimate polygenic scores for these traits in three Scottish samples: Generation Scotland: Scottish Family Health Study (GS:SFHS), and the Lothian Birth Cohorts of 1936 (LBC1936) and 1921 (LBC1921). These five brain MRI trait polygenic scores were then used to: (1) predict corresponding MRI traits in the LBC1936 (numbers ranged 573 to 630 across traits), and (2) predict cognitive traits in all three cohorts (in 8,115-8,250 persons). In the LBC1936, all MRI phenotypic traits were correlated with at least one cognitive measure, and polygenic prediction of MRI traits was observed for intracranial volume. Meta-analysis of the correlations between MRI polygenic scores and cognitive traits revealed a significant negative correlation (maximal r = 0.08) between the HV polygenic score and measures of global cognitive ability collected in childhood and in old age in the Lothian Birth Cohorts. The lack of association to a related general cognitive measure when including the GS:SFHS points to either type 1 error or the importance of using prediction samples that closely match the demographics of the GWA samples from which prediction is based. Ideally, these analyses should be repeated in larger samples with data on both MRI and cognition, and using MRI GWA results from even larger meta-analysis studies.

Markers of Psychological Differences and Social and Health Inequalities: Possible Genetic and Phenotypic Overlaps.

Associations between markers of ostensible psychological characteristics and social and health inequalities are pervasive but difficult to explain. In some cases, there may be causal influence flowing from social and health inequalities to psychological differences, whereas sometimes it may be the other way around. Here, we focus on the possibility that some markers that we often consider as indexing different domains of individual differences may in fact reflect at least partially overlapping genetic and/or phenotypic bases. For example, individual differences in cognitive abilities and educational attainment appear to reflect largely overlapping genetic influences, whereas cognitive abilities and health literacy may be almost identical phenomena at the phenotypic, never mind genetic, level. We make the case for employing molecular genetic data and quantitative genetic techniques to better understand the associations of psychological individual differences with social and health inequalities. We illustrate these arguments by using published findings from the Lothian Birth Cohort and the Generation Scotland studies. We also present novel findings pertaining to longitudinal stability and change in older age personality traits and some correlates of the change, molecular genetic data-based heritability estimates of Neuroticism and Extraversion, and the genetic correlations of these personality traits with markers of social and health inequalities.

Dietary factors and biomarkers of systemic inflammation in older people: the Lothian Birth Cohort 1936

Epidemiological studies have reported inverse associations between various single healthy diet indices and lower levels of systemic inflammation, but rarely are they examined in the same sample. The aim of the present study was to investigate the potential relationships between biomarkers of systemic inflammation (C-reactive protein (CRP) and fibrinogen) and overall foods (dietary patterns), single foods (fruits and vegetables), and specific nutritive (antioxidants) and non-nutritive (flavonoids) food components in the same narrow-age cohort of older adults. The dietary intake of 792 participants aged 70 years from the Lothian Birth Cohort 1936 was assessed using a 168-item FFQ. Models were adjusted for age, sex, childhood cognitive ability, lifestyle factors and history of disease. Using logistic regression analyses, CRP (normal v. elevated) was favourably associated (at P<0·05) with the 'health-aware' (low-fat) dietary pattern (unstandardised β=(0·200, OR 0·82, 95% CI 0·68, 0·99) and fruit intake (unstandardised β=(0·100, OR 0·91, 95% CI 0·82, 0·99), including flavonoid-rich apples (unstandardised β=(0·456, OR 0·63, 95% CI 0·439, 0·946). Using linear regression analyses, fibrinogen (continuous) was inversely associated (at P<0·05) with the Mediterranean dietary pattern (standardised β=(0·100), fruit intake (standardised β=(0·083), and combined fruit and vegetable intake (standardised β=(0·084). We observed no association between food components (antioxidant nutrients or specific flavonoid subclasses) and inflammatory markers. In the present cross-sectional study, nutrient-dense dietary patterns were associated with lower levels of systemic inflammation in older people. The results are consistent with dietary guidelines that promote a balanced diet based on a variety of plant-based foods.

Post-mortem brain analyses of the Lothian Birth Cohort 1936: extending lifetime cognitive and brain phenotyping to the level of the synapse.

IntroductionNon-pathological, age-related cognitive decline varies markedly between individuals andplaces significant financial and emotional strain on people, their families and society as a whole.Understanding the differential age-related decline in brain function is critical not only for the development oftherapeutics to prolong cognitive health into old age, but also to gain insight into pathological ageing suchas Alzheimer’s disease. The Lothian Birth Cohort of 1936 (LBC1936) comprises a rare group of people forwhom there are childhood cognitive test scores and longitudinal cognitive data during older age, detailedstructural brain MRI, genome-wide genotyping, and a multitude of other biological, psycho-social, andepidemiological data. Synaptic integrity is a strong indicator of cognitive health in the human brain;however, until recently, it was prohibitively difficult to perform detailed analyses of synaptic and axonalstructure in human tissue sections. We have adapted a novel method of tissue preparation at autopsy toallow the study of human synapses from the LBC1936 cohort in unprecedented morphological andmolecular detail, using the high-resolution imaging techniques of array tomography and electronmicroscopy. This allows us to analyze the brain at sub-micron resolution to assess density, proteincomposition and health of synapses. Here we present data from the first donated LBC1936 brain andcompare our findings to Alzheimer’s diseased tissue to highlight the differences between healthy andpathological brain ageing.ResultsOur data indicates that compared to an Alzheimer’s disease patient, the cognitively normalLBC1936 participant had a remarkable degree of preservation of synaptic structures. However,morphological and molecular markers of degeneration in areas of the brain associated with cognition(prefrontal cortex, anterior cingulate cortex, and superior temporal gyrus) were observed.ConclusionsOur novel post-mortem protocol facilitates high-resolution neuropathological analysis of the well-characterized LBC1936 cohort, extending phenotyping beyond cognition and in vivo imaging to nowinclude neuropathological changes, at the level of single synapses. This approach offers an unprecedentedopportunity to study synaptic and axonal integrity during ageing and how it contributes to differences in agerelatedcognitive change.Electronic supplementary materialThe online version of this article (doi:10.1186/s40478-015-0232-0) contains supplementary material, which is available to authorized users.

From "aisle" to "labile": A hierarchical National Adult Reading Test scale revealed by Mokken scaling.

Decline in cognitive ability is a core diagnostic criterion for dementia. Knowing the extent of decline requires a baseline score from which change can be reckoned. In the absence of prior cognitive ability scores, vocabulary-based cognitive tests are used to estimate premorbid cognitive ability. It is important that such tests are short yet informative, to maximize information and practicability. The National Adult Reading Test (NART) is commonly used to estimate premorbid intelligence. People are asked to pronounce 50 words ranging from easy to difficult but whether its words conform to a hierarchy is unknown. Five hundred eighty-seven healthy community-dwelling older people with known age 11 IQ scores completed the NART as part of the Lothian Birth Cohort 1936 study. Mokken analysis was used to explore item responses for unidimensional, ordinal, and hierarchical scales. A strong hierarchical scale (“mini-NART”) of 23 of the 50 items was identified. These items are invariantly ordered across all ability levels. The validity of the interpretation of this briefer scale’s score as an estimate of premorbid ability was examined using the actual age 11 IQ score. The mini-NART accounted for a similar amount of the variance in age 11 IQ as the full NART (NART = 46.5%, mini-NART = 44.8%). The mini-NART is proposed as a useful short clinical tool to estimate prior cognitive ability. The mini-NART has clinical relevance, comprising highly discriminatory, invariantly ordered items allowing for sensitive measurement, and adaptive testing, reducing test administration time, and patient stress.

APOE/TOMM40 genetic loci, white matter hyperintensities, and cerebral microbleeds.

BackgroundTwo markers of cerebral small vessel disease are white matter hyperintensities and cerebral microbleeds, which commonly occur in people with Alzheimer's disease.Aim and/or hypothesisTo test for independent associations between two Alzheimer's disease‐susceptibility gene loci – APOE ε and the TOMM 40 ‘523’ poly‐T repeat – and white matter hyperintensities/cerebral microbleed burden in community‐dwelling older adults.MethodsParticipants in the Lothian Birth Cohort 1936 underwent genotyping for APOE ε and TOMM 40 523, and detailed structural brain magnetic resonance imaging at a mean age of 72·70 years (standard deviation = 0·7; range = 71–74).ResultsNo significant effects of APOE ε or TOMM 40 523 genotypes on white matter hyperintensities or cerebral microbleed burden were found amongst 624 participants.ConclusionsLack of association between two Alzheimer's disease susceptibility gene loci and markers of cerebral small vessel disease may reflect the relative health of this population compared with those in other studies in the literature.