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An active lifestyle has been associated with better cognitive performance in many studies. However, most studies have focused on leisure activities or paid work, with less consideration of the kind of prosocial activities, many people engage in, including volunteering, grandparenting, and family care. In the present study, based on four waves of the German Ageing Survey ( N = 6,915, aged 40-85 at baseline), we used parallel growth curves to investigate the longitudinal association of level and change in volunteering, grandparenting, and family care with level and change in processing speed. Given the gendered nature of engagement in these activities over the life span, we tested for gender differences in the associations. Only volunteering was reliably associated with higher speed of processing at baseline, no consistent longitudinal associations were found. Our results show that although prosocial activities are of great societal importance, expectations of large rewards in terms of cognitive health may be exaggerated. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

A growing body of literature suggests that higher engagement in a range of activities can be beneficial for cognitive health in old age. Such studies typically rely on self-report questionnaires to assess level of engagement. These questionnaires are highly heterogeneous across studies, limiting generalisability. In particular, the most appropriate domains of activity engagement remain unclear. The Victoria Longitudinal Study-Activity Lifestyle Questionnaire comprises one of the broadest and most diverse collections of activity items, but different studies report different domain structures. This study aimed to help establish a generalisable domain structure of the Victoria Longitudinal Study-Activity Lifestyle Questionnaire. The questionnaire was adapted for use in a sample of UK-based older adults (336 community-dwelling adults aged 65-92 with no diagnosed cognitive impairment). An exploratory factor analysis was conducted on 29 items. The final model retained 22 of these items in a six-factor structure. Activity domains were: Manual (e.g., household repairs), Intellectual (e.g., attending a public lecture), Games (e.g., card games), Religious (e.g., attending religious services), Exercise (e.g., aerobics) and Social (e.g., going out with friends). Given that beneficial activities have the potential to be adapted into interventions, it is essential that future studies consider the most appropriate measurement of activity engagement across domains. The factor structure reported here offers a parsimonious and potentially useful way for future studies to assess engagement in different kinds of activities., Competing Interests: The authors have declared that no competing interests exist.

Objective: Mean speed of responding is the most commonly used measure in the assessment of reaction time (RT). An alternative measure is intraindividual variability (IIV): the inconsistency of responding across multiple trials of a test. IIV has been suggested as an important indicator of central nervous system functioning, and as such, there has been increasing interest in the associations between IIV and brain imaging metrics. Results however, have been inconsistent. The present seeks to provide a comprehensive evaluation of the associations between a variety of measures of brain white matter integrity and individual differences in choice RT (CRT) IIV., Method: MRI brain scans of members of the Lothian Birth Cohort 1936 were assessed to obtain measures of the volume and severity of white matter hyperintensities, and the integrity of brain white matter tracts. CRT was assessed with a 4 CRT task on a separate occasion. Data were analyzed using multiple regression (N range = 358-670)., Results: Greater volume of hyperintensities and more severe hyperintensities in frontal regions were associated with higher CRT IIV. White matter tract integrity, as assessed by both fractional anisotropy and mean diffusivity, showed the smallest effect sizes in associations with CRT IIV. Associations with hyperintensities were attenuated and no longer significant after controlling for M CRT., Conclusions: Taken together, the results of the present study suggested that IIV was not incrementally predictive of white matter integrity over mean speed. This is in contrast to previous reports, and highlights the need for further study. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Objective: We conducted a U.K.-wide survey to collect information on people's beliefs, fears, perceptions, and attitudes to cognitive aging., Methods: This community-based aging survey included 3,146 adults aged 40 years and over., Results: Respondents believed memory might be the earliest cognitive skill to decline (mean: 59.4 years), followed by speed of thinking (mean: 64.9). Those in their 40s were more pessimistic, because they estimated cognitive changes would start up to 15 years earlier than respondents aged over 70. Having a purpose in life, healthy eating, challenging the mind, sleep, and physical activity ranked higher in terms of perceived importance for maintaining or improving cognitive skills. However, less than 50% engaged in any of these activities. Although 91% believed there are things people can do to maintain or improve their cognitive skills, more than 40% were unsure or did not know how to do so. Respondents who strongly agreed that changes in cognitive skills might be a sign of something more serious were significantly more likely to do various activities to benefit their cognitive skills., Conclusion: Results suggest that people are less aware of the potential cognitive benefits of certain activities, such as exercise and diet. It is important to build awareness about the benefits of lifestyles and activities for cognitive health., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Fully characterizing age differences in the brain is a key task for combating aging-related cognitive decline. Using propensity score matching on 2 independent, narrow-age cohorts, we used data on childhood cognitive ability, socioeconomic background, and intracranial volume to match participants at mean age of 92 years (n = 42) to very similar participants at mean age of 73 years (n = 126). Examining a variety of global and regional structural neuroimaging variables, there were large differences in gray and white matter volumes, cortical surface area, cortical thickness, and white matter hyperintensity volume and spatial extent. In a mediation analysis, the total volume of white matter hyperintensities and total cortical surface area jointly mediated 24.9% of the relation between age and general cognitive ability (tissue volumes and cortical thickness were not significant mediators in this analysis). These findings provide an unusual and valuable perspective on neurostructural aging, in which brains from the 8th and 10th decades of life differ widely despite the same cognitive, socioeconomic, and brain-volumetric starting points., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

We aimed to assess whether and how changes in brain volume and increases in white matter hyperintensity (WMH) volume over three years predict gait speed and its change independently of demographics, vascular risk factors and physical status. We analyzed 443 individuals from the Lothian Birth Cohort 1936, at mean age 73 and 76 years. Gait speed at age 76 was predicted by age, grip strength and body mass index at mean age 73, three-year brain volume decrease and WMH volume increase, explaining 26.1% of variance. Decline in gait speed to age 76 was predicted by the same five variables explaining 40.9% of variance. In both analyses, grip strength and body mass index explained the most variance. A clinically significant decline in gait speed (≥ 0.1 m/s per year) occurred in 24.4%. These individuals had more structural brain changes. Brain volume and WMH changes were independent predictors of gait dysfunction and its three-year change, but the impact of malleable physical factors such as grip strength or body mass index was greater.

Introduction: The hippocampus plays an important role in cognitive abilities which often decline with advancing age., Methods: In a longitudinal study of community-dwelling adults, we investigated whether there were coupled changes in hippocampal structure and verbal memory, working memory, and processing speed between the ages of 73 ( N  = 655) and 76 years ( N  = 469). Hippocampal structure was indexed by hippocampal volume, hippocampal volume as a percentage of intracranial volume (H_ICV), fractional anisotropy (FA), mean diffusivity (MD), and longitudinal relaxation time (T1)., Results: Mean levels of hippocampal volume, H_ICV, FA, T1, and all three cognitive abilities domains decreased, whereas MD increased, from age 73 to 76. At baseline, higher hippocampal volume was associated with better working memory and verbal memory, but none of these correlations survived correction for multiple comparisons. Higher FA, lower MD, and lower T1 at baseline were associated with better cognitive abilities in all three domains; only the correlation between baseline hippocampal MD and T1, and change in the three cognitive domains, survived correction for multiple comparisons. Individuals with higher hippocampal MD at age 73 experienced a greater decline in all three cognitive abilities between ages 73 and 76. However, no significant associations with changes in cognitive abilities were found with hippocampal volume, FA, and T1 measures at baseline. Similarly, no significant associations were found between cognitive abilities at age 73 and changes in the hippocampal MRI biomarkers between ages 73 and 76., Conclusion: Our results provide evidence to better understand how the hippocampus ages in healthy adults in relation to the cognitive domains in which it is involved, suggesting that better hippocampal MD at age 73 predicts less relative decline in three important cognitive domains across the next 3 years. It can potentially assist in diagnosing early stages of aging-related neuropathologies, because in some cases, accelerated decline could predict pathologies.

Individuals differ markedly in brain structure, and in how this structure degenerates during ageing. In a large sample of human participants (baseline n = 731 at age 73 years; follow-up n = 488 at age 76 years), we estimated the magnitude of mean change and variability in changes in MRI measures of brain macrostructure (grey matter, white matter, and white matter hyperintensity volumes) and microstructure (fractional anisotropy and mean diffusivity from diffusion tensor MRI). All indices showed significant average change with age, with considerable heterogeneity in those changes. We then tested eleven socioeconomic, physical, health, cognitive, allostatic (inflammatory and metabolic), and genetic variables for their value in predicting these differences in changes. Many of these variables were significantly correlated with baseline brain structure, but few could account for significant portions of the heterogeneity in subsequent brain change. Physical fitness was an exception, being correlated both with brain level and changes. The results suggest that only a subset of correlates of brain structure are also predictive of differences in brain ageing.

Both aging and chronic inflammation produce complex structural and biochemical alterations to the lung known to impact work of breathing. Mice deficient in surfactant protein D (Sftpd) develop progressive age-related lung pathology characterized by tissue destruction/remodeling, accumulation of foamy macrophages and alteration in surfactant composition. This study proposes to relate changes in tissue structure seen in normal aging and in chronic inflammation to altered lung mechanics using a computational model. Alterations in lung function in aging and Sftpd -/- mice have been inferred from fitting simple mechanical models to respiratory impedance data (Zrs), however interpretation has been confounded by the simultaneous presence of multiple coexisting pathophysiologic processes. In contrast to the inverse modeling approach, this study uses simulation from experimental measurements to recapitulate how aging and inflammation alter Zrs. Histologic and mechanical measurements were made in C57BL6/J mice and congenic Sftpd-/- mice at 8, 27 and 80 weeks of age (n = 8/group). An anatomic computational model based on published airway morphometry was developed and Zrs was simulated between 0.5 and 20 Hz. End expiratory pressure dependent changes in airway caliber and recruitment were estimated from mechanical measurements. Tissue elements were simulated using the constant phase model of viscoelasticity. Baseline elastance distribution was estimated in 8-week-old wild type mice, and stochastically varied for each condition based on experimentally measured alteration in elastic fiber composition, alveolar geometry and surfactant composition. Weighing reduction in model error against increasing model complexity allowed for identification of essential features underlying mechanical pathology and their contribution to Zrs. Using a maximum likelihood approach, alteration in lung recruitment and diminished elastic fiber density were shown predictive of mechanical alteration at airway opening, to a greater extent than overt acinar wall destruction. Model-predicted deficits in PEEP-dependent lung recruitment correlate with altered lung lining fluid composition independent of age or genotype.

We examined whether apolipoprotein E (APOE) status interacts with vascular risk factors (VRFs) to predict the progression of white matter hyperintensities (WMHs) on brain MRI scans over a specific period of life in older age when the risk of dementia increases. At age 73 years, baseline VRFs were assessed via self-reported history of diabetes, hypertension, smoking, and hypercholesterolemia, and via objective measures of blood HbA1c, body mass index, diastolic and systolic blood pressure, and blood high-density lipoprotein to total cholesterol (HDL) ratio. APOE e4 allele was coded as either present or absent. WMH progression was measured on MRI over 3 years in 434 older adults, in a same-year-of-birth cohort. APOE e4 carriers with either a self-reported diagnosis of diabetes (β = 0.160, p = 0.002) or higher glycated hemoglobin levels (β = 0.114, p = 0.014) exhibited greater WMH progression, and the former survived correction for multiple testing. All other APOE-VRF interactions were nonsignificant (β interaction < 0.056, p > 0.228). The results suggest that carrying the APOE "risk" e4 allele increases the risk of greater age-related WMH progression over the early part of the eighth decade of life, when combined with poorer glycemic control. The interaction effect was robust to co-occurring VRFs, suggesting a possible target for mitigating brain and cognitive aging at this age., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Structural measures of the hippocampus have been linked to a variety of memory processes and also to broader cognitive abilities. Gross volumetry has been widely used, yet the hippocampus has a complex formation, comprising distinct subfields which may be differentially sensitive to the deleterious effects of age, and to different aspects of cognitive performance. However, a comprehensive analysis of multidomain cognitive associations with hippocampal deformations among a large group of cognitively normal older adults is currently lacking. In 654 participants of the Lothian Birth Cohort 1936 (mean age = 72.5, SD = 0.71 years), we examined associations between the morphology of the hippocampus and a variety of memory tests (spatial span, letter-number sequencing, verbal recall, and digit backwards), as well as broader cognitive domains (latent measures of speed, fluid intelligence, and memory). Following correction for age, sex, and vascular risk factors, analysis of memory subtests revealed that only right hippocampal associations in relation to spatial memory survived type 1 error correction in subiculum and in CA1 at the head (β = 0.201, p = 5.843 × 10 -4 , outward), and in the ventral tail section of CA1 (β = -0.272, p = 1.347 × 10 -5 , inward). With respect to latent measures of cognitive domains, only deformations associated with processing speed survived type 1 error correction in bilateral subiculum (β absolute ≤ 0.247, p < 1.369 × 10 -4 , outward), bilaterally in the ventral tail section of CA1 (β absolute ≤ 0.242, p < 3.451 × 10 -6 , inward), and a cluster at the left anterior-to-dorsal region of the head (β = 0.199, p = 5.220 × 10 -6 , outward). Overall, our results indicate that a complex pattern of both inward and outward hippocampal deformations are associated with better processing speed and spatial memory in older age, suggesting that complex shape-based hippocampal analyses may provide valuable information beyond gross volumetry., (Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Cerebral small vessel disease (SVD) may cause cognitive dysfunction. We tested the association between the combined presence of magnetic resonance imaging (MRI) features of SVD and cognitive ability in older age. Cognitive testing and brain MRI were performed in 680 older participants. MRI presence of lacunes, white matter hyperintensities, microbleeds, and perivascular spaces were summed in a score of 0-4 representing all SVD features combined. We also applied latent variable modeling to test whether the 4 MRI features form a unitary SVD construct. The SVD score showed significant associations with general cognitive ability. Latent variable modeling indicated that the 4 MRI markers formed a unitary construct, which showed consistent associations with cognitive ability compared with the SVD score. Total MRI load of SVD is associated with lower general cognitive ability in older age. The total SVD score performed consistently with the more complex latent variable model, suggesting validity and potential utility in future research for determining total SVD load., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Several studies have reported associations between brain iron deposits and cognitive status, and cardiovascular and neurodegenerative diseases in older individuals, but the mechanisms underlying these associations remain unclear. We explored the associations between regional brain iron deposits and different factors of cognitive ability (fluid intelligence, speed and memory) in a large sample (n = 662) of individuals with a mean age of 73 years. Brain iron deposits in the corpus striatum were extracted automatically. Iron deposits in other parts of the brain (i.e., white matter, thalamus, brainstem and cortex), brain tissue volume and white matter hyperintensities (WMH) were assessed separately and semi-automatically. Overall, 72.8 % of the sample had iron deposits. The total volume of iron deposits had a small but significant negative association with all three cognitive ability factors in later life (mean r = -0.165), but no relation to intelligence in childhood (r = 0.043, p = 0.282). Regression models showed that these iron deposit associations were still present after control for a variety of vascular health factors, and were separable from the association of WMH with cognitive ability. Iron deposits were also associated with cognition across the lifespan, indicating that they are relevant for cognitive ability only at older ages. Iron deposits might be an indicator of small vessel disease that affects the neuronal networks underlying higher cognitive functioning.

Background: while sexual behaviours are potentially important for quality of life in older adults, they are under-researched. The current study examined associations between frequency and importance of sexual behaviours and quality of life in older adults., Method: one hundred and thirty-three participants (mean 74 years, SD = 7.1) provided information about the frequency with which they participated in six sexual behaviours and the perceived importance of these: touching/holding hands, embracing/hugging, kissing, mutual stroking, masturbating and intercourse. Participants also completed the WHO Quality of Life scale, providing an overall quality of life score, in addition to the domains of physical health, psychological health, social relationships and environment. Participants provided information on their marital status, living arrangements and self-reported health., Results: both the frequency and importance of sexual behaviours were moderately positively correlated with quality of life (r = 0.52 and 0.47, respectively, both P < 0.001). In separate regression analyses, the frequency of sexual behaviours was a significant predictor of quality of life in the social relationships domain (β = 0.225, P < 0.05), and the importance of sexual behaviours was associated with the psychological domain (β = 0.151, P < 0.05), independent of the presence of a spouse/partner and self-reported health., Conclusions: with ageing trends, a broader understanding of the factors that influence quality of life in older adults is increasingly important. The current findings suggest that aspects of sexual behaviour and quality of life were positively associated. Researchers are encouraged to consider aspects of sex and sexuality when exploring determinants of well-being in later life., (© The Author 2015. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Memory performance in older persons can reflect genetic influences on cognitive function and dementing processes. We aimed to identify genetic contributions to verbal declarative memory in a community setting., Methods: We conducted genome-wide association studies for paragraph or word list delayed recall in 19 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, comprising 29,076 dementia- and stroke-free individuals of European descent, aged ≥45 years. Replication of suggestive associations (p < 5 × 10(-6)) was sought in 10,617 participants of European descent, 3811 African-Americans, and 1561 young adults., Results: rs4420638, near APOE, was associated with poorer delayed recall performance in discovery (p = 5.57 × 10(-10)) and replication cohorts (p = 5.65 × 10(-8)). This association was stronger for paragraph than word list delayed recall and in the oldest persons. Two associations with specific tests, in subsets of the total sample, reached genome-wide significance in combined analyses of discovery and replication (rs11074779 [HS3ST4], p = 3.11 × 10(-8), and rs6813517 [SPOCK3], p = 2.58 × 10(-8)) near genes involved in immune response. A genetic score combining 58 independent suggestive memory risk variants was associated with increasing Alzheimer disease pathology in 725 autopsy samples. Association of memory risk loci with gene expression in 138 human hippocampus samples showed cis-associations with WDR48 and CLDN5, both related to ubiquitin metabolism., Conclusions: This largest study to date exploring the genetics of memory function in ~40,000 older individuals revealed genome-wide associations and suggested an involvement of immune and ubiquitin pathways., (Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Allostatic load (AL) has been proposed as a general framework for understanding the cumulative effects of life stress on individuals. Despite growing interest in AL, limited research has been conducted on aging samples. We consider the association of AL (operationalized by a range of inflammatory, cardiovascular, and metabolic measures) with a range of brain volume measurements and cognitive ability in a large cohort sample of older adults (n = 658, mean age = 72.5 years, standard deviation = 0.7) using structural equation modeling. AL was significantly inversely associated with total brain volume (range of standardized β = -0.16 to -0.20) and white-matter volume (-0.35 to -0.36) and positively with hippocampal volume (0.10-0.15) but not gray-matter volume (0.04). AL was also significantly inversely associated with general cognitive ability (range β = -0.13 to -0.20), processing speed (-0.20 to -0.22), and knowledge (-0.18 to -0.20) but not memory or nonverbal reasoning. The associations of AL with cognitive abilities were not mediated by these brain volume measures. AL did not predict cognitive change from age 11 to approximately age 73. The findings suggest a link between AL and later life brain health and cognitive functioning., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

White matter hyperintensities (WMH) of presumed vascular origin are a common finding in brain magnetic resonance imaging of older individuals and contribute to cognitive and functional decline. It is unknown how WMH form, although white matter degeneration is characterized pathologically by demyelination, axonal loss, and rarefaction, often attributed to ischemia. Changes within normal-appearing white matter (NAWM) in subjects with WMH have also been reported but have not yet been fully characterized. Here, we describe the in vivo imaging signatures of both NAWM and WMH in a large group of community-dwelling older people of similar age using biomarkers derived from magnetic resonance imaging that collectively reflect white matter integrity, myelination, and brain water content. Fractional anisotropy (FA) and magnetization transfer ratio (MTR) were significantly lower, whereas mean diffusivity (MD) and longitudinal relaxation time (T1) were significantly higher, in WMH than NAWM (p < 0.0001), with MD providing the largest difference between NAWM and WMH. Receiver operating characteristic analysis on each biomarker showed that MD differentiated best between NAWM and WMH, identifying 94.6% of the lesions using a threshold of 0.747 × 10(-9) m(2)s(-1) (area under curve, 0.982; 95% CI, 0.975-0.989). Furthermore, the level of deterioration of NAWM was strongly associated with the severity of WMH, with MD and T1 increasing and FA and MTR decreasing in NAWM with increasing WMH score, a relationship that was sustained regardless of distance from the WMH. These multimodal imaging data indicate that WMH have reduced structural integrity compared with surrounding NAWM, and MD provides the best discriminator between the 2 tissue classes even within the mild range of WMH severity, whereas FA, MTR, and T1 only start reflecting significant changes in tissue microstructure as WMH become more severe., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To examine associations between complexity of main lifetime occupation and cognitive performance in later life., Methods: Occupational complexity ratings for data, people, and things were collected from the Dictionary of Occupational Titles for 1,066 individuals (men = 534, women = 532) in the Lothian Birth Cohort 1936. IQ data were available from mean age 11 years. Cognitive ability data across the domains of general ability, processing speed, and memory were available at mean age 70 years., Results: General linear model analyses indicated that complexity of work with people and data were associated with better cognitive performance at age 70, after including age 11 IQ, years of education, and social deprivation., Conclusions: The current findings are supportive of the differential preservation hypotheses that more stimulating environments preserve cognitive ability in later life, although the continued effects into old age are still debated. Studies that have early-life cognitive ability measures are rare, and the current study offers interesting prospects for future research that may further the understanding of successful aging., (© 2014 American Academy of Neurology.)

Objective: To explore associations between the 5-factor model (FFM; neuroticism, extraversion, openness/intellect, agreeableness, and conscientiousness), personality traits, and measures of whole-brain integrity in a large sample of older people, and to test whether these associations are mediated by health-related behaviors., Method: Participants from the Lothian Birth Cohort 1936 completed the International Personality Item Pool measure, a 5-factor public-domain personality measure (http://ipip.ori.org), and underwent a structural magnetic resonance brain scan at the mean age of 73 years, yielding 3 measures of whole brain integrity: average white matter fractional anisotropy (FA), brain-tissue loss, and white matter hyperintensities (N = 529 to 565). Correlational and mediation analyses were used to test the potential mediating effects of health-related behaviors on the associations between personality and integrity., Results: Lower conscientiousness was consistently associated with brain-tissue loss (β = -0.11, p < 0.01), lower FA (β = 0.16, p < 0.001) and white matter hyperintensities (β = -0.10, p < 0.05). Smoking, alcohol consumption, diet, physical activity, body mass index and a composite health-behavior variable displayed significant associations with measures of brain integrity (range of r = 0.10 to 0.25). The direct effects of conscientiousness on brain integrity were mediated to some degree by health behaviors, with the proportions of explained direct effects ranging from 0.1% to 13.7%., Conclusion: Conscientiousness was associated with all 3 measures of brain integrity, which we tentatively interpret as the effects of personality on brain aging. Small proportions of the direct effects were mediated by individual health behaviors. RESULTS provide initial indications that lifetime stable personality traits may influence brain health in later life through health-promoting behaviors.

Associations between brain cortical tissue volume and cognitive function in old age are frequently interpreted as suggesting that preservation of cortical tissue is the foundation of successful cognitive aging. However, this association could also, in part, reflect a lifelong association between cognitive ability and cortical tissue. We analyzed data on 588 subjects from the Lothian Birth Cohort 1936 who had intelligence quotient (IQ) scores from the same cognitive test available at both 11 and 70 years of age as well as high-resolution brain magnetic resonance imaging data obtained at approximately 73 years of age. Cortical thickness was estimated at 81 924 sampling points across the cortex for each subject using an automated pipeline. Multiple regression was used to assess associations between cortical thickness and the IQ measures at 11 and 70 years. Childhood IQ accounted for more than two-third of the association between IQ at 70 years and cortical thickness measured at age 73 years. This warns against ascribing a causal interpretation to the association between cognitive ability and cortical tissue in old age based on assumptions about, and exclusive reference to, the aging process and any associated disease. Without early-life measures of cognitive ability, it would have been tempting to conclude that preservation of cortical thickness in old age is a foundation for successful cognitive aging when, instead, it is a lifelong association. This being said, results should not be construed as meaning that all studies on aging require direct measures of childhood IQ, but as suggesting that proxy measures of prior cognitive function can be useful to take into consideration.

Objectives: The effect of occupational characteristics on cognitive change over 20 years was examined., Method: Occupational characteristics--intellectual challenge, physical hazards, and psychological demands--were assessed in the Glostrup 1914 Cohort when aged 60 years, and cognitive ability was assessed by 4 cognitive ability tests at ages 60, 70, and 80., Results: Individuals in more intellectually challenging occupations had higher cognitive ability (r = .27-.38, p < .01), whereas those in more physically hazardous occupations performed more poorly (r = -.12 and -.13 at ages 50 and 60, p < .05). In growth curve models, intellectual challenge continued to be associated with cognitive ability, controlling for sex, education, and social class. However, the association was reversed after accounting for cognitive ability at age 50; of 2 individuals with the same baseline level of cognitive ability, the one in the more intellectually challenging occupation had lower subsequent cognitive ability. The association of physical hazards with lower cognitive ability level did not remain after adjustment for the basic demographics, and none of the occupational characteristics were associated with cognitive change between age 60 and 80., Discussion: Notwithstanding the reversal of the effect of occupational intellectual challenge on cognitive ability level after accounting for pre-exiting cognitive differences, there was no evidence for long-term effects of occupational characteristics on cognitive change in old age.

Cognitive decline is a feared aspect of growing old. It is a major contributor to lower quality of life and loss of independence in old age. We investigated the genetic contribution to individual differences in nonpathological cognitive ageing in five cohorts of older adults. We undertook a genome-wide association analysis using 549 692 single-nucleotide polymorphisms (SNPs) in 3511 unrelated adults in the Cognitive Ageing Genetics in England and Scotland (CAGES) project. These individuals have detailed longitudinal cognitive data from which phenotypes measuring each individual's cognitive changes were constructed. One SNP--rs2075650, located in TOMM40 (translocase of the outer mitochondrial membrane 40 homolog)--had a genome-wide significant association with cognitive ageing (P=2.5 × 10(-8)). This result was replicated in a meta-analysis of three independent Swedish cohorts (P=2.41 × 10(-6)). An Apolipoprotein E (APOE) haplotype (adjacent to TOMM40), previously associated with cognitive ageing, had a significant effect on cognitive ageing in the CAGES sample (P=2.18 × 10(-8); females, P=1.66 × 10(-11); males, P=0.01). Fine SNP mapping of the TOMM40/APOE region identified both APOE (rs429358; P=3.66 × 10(-11)) and TOMM40 (rs11556505; P=2.45 × 10(-8)) as loci that were associated with cognitive ageing. Imputation and conditional analyses in the discovery and replication cohorts strongly suggest that this effect is due to APOE (rs429358). Functional genomic analysis indicated that SNPs in the TOMM40/APOE region have a functional, regulatory non-protein-coding effect. The APOE region is significantly associated with nonpathological cognitive ageing. The identity and mechanism of one or multiple causal variants remain unclear.

Cerebral white matter hyperintensities (WMH) reflect accumulating white matter damage with aging and impair cognition. The role of childhood intelligence is rarely considered in associations between cognitive impairment and WMH. We studied community-dwelling older people all born in 1936, in whom IQ had been assessed at age 11 years. We assessed medical histories, current cognitive ability and quantified WMH on MR imaging. Among 634 participants, mean age 72.7 (SD 0.7), age 11 IQ was the strongest predictor of late life cognitive ability. After accounting for age 11 IQ, greater WMH load was significantly associated with lower late life general cognitive ability (β = -0.14, p < 0.01) and processing speed (β = -0.19, p < 0.001). WMH were also associated independently with lower age 11 IQ (β = -0.08, p < 0.05) and hypertension. In conclusion, having more WMH is significantly associated with lower cognitive ability, after accounting for prior ability, age 11IQ. Early-life IQ also influenced WMH in later life. Determining how lower IQ in youth leads to increasing brain damage with aging is important for future successful cognitive aging., (Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.)

Brain tissue deterioration is a significant contributor to lower cognitive ability in later life; however, few studies have appropriate data to establish how much influence prior brain volume and prior cognitive performance have on this association. We investigated the associations between structural brain imaging biomarkers, including an estimate of maximal brain volume, and detailed measures of cognitive ability at age 73 years in a large (N = 620), generally healthy, community-dwelling population. Cognitive ability data were available from age 11 years. We found positive associations (r) between general cognitive ability and estimated brain volume in youth (male, 0.28; females, 0.12), and in measured brain volume in later life (males, 0.27; females, 0.26). Our findings show that cognitive ability in youth is a strong predictor of estimated prior and measured current brain volume in old age but that these effects were the same for both white and gray matter. As 1 of the largest studies of associations between brain volume and cognitive ability with normal aging, this work contributes to the wider understanding of how some early-life factors influence cognitive aging., (Copyright © 2013 Elsevier Inc. All rights reserved.)

In these studies we determined whether progressive pulmonary inflammation associated with aging in surfactant protein D (Sftpd)-/- mice leads to an exacerbated response to ozone. In Sftpd-/- mice, but not wild-type (WT) mice, age-related increases in numbers of enlarged vacuolated macrophages were observed in the lung, along with alveolar wall rupture, type 2 cell hyperplasia, and increased bronchoalveolar lavage protein and cell content. Numbers of heme oxygenase+ macrophages also increased with age in Sftpd-/- mice, together with classically (iNOS+) and alternatively (mannose receptor+, YM-1+, or galectin-3+) activated macrophages. In both WT and Sftpd-/- mice, increasing age from 8 to 27 wk was associated with reduced lung stiffness, as reflected by decreases in resistance and elastance spectra; however, this response was reversed in 80-wk-old Sftpd-/- mice. Ozone exposure (0.8 ppm, 3 h) caused increases in lung pathology, alveolar epithelial barrier dysfunction, and numbers of iNOS+ macrophages in 8- and 27-wk-old Sftpd-/-, but not WT mice at 72 h postexposure. Conversely, increases in alternatively activated macrophages were observed in 8-wk-old WT mice following ozone exposure, but not in Sftpd-/- mice. Ozone also caused alterations in both airway and tissue mechanics in Sftpd-/- mice at 8 and 27 wk, but not at 80 wk. These data demonstrate that mild to moderate pulmonary inflammation results in increased sensitivity to ozone; however, in senescent mice, these responses are overwhelmed by the larger effects of age-related increases in baseline inflammation and lung injury.

Objective: The present study investigates associations between brain white matter tract integrity and cognitive abilities in community-dwelling older people (N = 655). We explored two potential confounds of white matter tract-cognition associations in later life: (a) whether the associations between tracts and specific cognitive abilities are accounted for by general cognitive ability (g); and (b) how the presence of atrophy and white matter lesions affect these associations., Method: Tract integrity was determined using quantitative diffusion magnetic resonance imaging tractography (tract-averaged fractional anisotropy [FA]). Using confirmatory factor analysis, we compared first-order and bifactor models to investigate whether specific tract-ability associations were accounted for by g., Results: Significant associations were found between g and FA in bilateral anterior thalamic radiations (r range: .16-.18, p < .01), uncinate (r range: .19-.26, p < .001), arcuate fasciculi (r range: .11-.12, p < .05), and the splenium of corpus callosum (r = .14, p < .01). After controlling for g within the bifactor model, some significant specific cognitive domain associations remained. Results also suggest that the primary effects of controlling for whole brain integrity were on g associations, not specific abilities., Conclusion: Results suggest that g accounts for most of, but not all, the tract-cognition associations in the current data. When controlling for age-related overall brain structural changes, only minor attenuations of the tract-cognition associations were found, and these were primarily with g. In totality, the results highlight the importance of controlling for g when investigating associations between specific cognitive abilities and neuropsychology variables.

Cytomegalovirus infection has been implicated in cognitive impairment in studies using brief clinical assessments though findings are inconsistent. The association between cytomegalovirus infection, measured as serostatus or a semiquantitative assessment of antibody level, and cognitive abilities in a sample of older adults was examined. Cytomegalovirus status was assessed at a mean age of 70 years in 1061 participants of the Lothian Birth Cohort 1936. Cognitive ability scores were available for general cognitive ability, processing speed, memory, and vocabulary. Background demographic and environmental factors included father's social class, years of education, childhood cognitive ability, overcrowding in childhood, and access to indoor toilet facilities. Cytomegalovirus seropositive individuals had lower cognitive ability at age 70: mean IQ was 99.1 (SD, 15.1) versus 102.4 (SD, 13.1) in seronegative individuals (t = 3.65; p < 0.001). The likelihood of contracting cytomegalovirus infection by age 70 was predicted by a number of demographic and environmental factors and, after accounting for these, cytomegalovirus infection (considered as serostatus) was not cognitively detrimental. Within cytomegalovirus seropositive individuals, however, higher cytomegalovirus antibody levels were associated with lower general cognitive ability., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Social networks and support have been proposed as cognitively protective in old age. As studies often consider these social factors in isolation the question of which characteristics of the social environment are beneficial remains., Objective: The current study examined associations between measures of social networks (including contact with friends/family, marital status and living arrangement), feelings of loneliness and social support, and a range of cognitive outcomes., Methods: Social network, loneliness and support data were available in the Lothian Birth Cohort 1936 (LBC1936, n = 1,091) at age 70. Participants completed a battery of cognitive tests, and factor scores were available for general cognitive ability, and the cognitive domains of processing speed and memory. Childhood cognitive ability data from age 11 were also available., Results: When examined in separate ANCOVAs, lower loneliness and more social support were significantly associated with better cognitive abilities at age 70, though not memory (independently of age, sex, childhood cognitive ability and social class), accounting for about 0.5-1.5% of the variance. When the social factors were considered simultaneously, higher loneliness remained associated with lower general cognitive ability (ηp(2) = 0.005, p = 0.046), and those living alone (ηp(2) = 0.007, p = 0.014) or with less social support (ηp(2) = 0.007, p = 0.016) had slower processing speed. When these final models were repeated including a depression symptoms score as a covariate, the associations between loneliness and general cognitive ability, and social support and processing speed, were no longer significant. However, the association between living alone and processing speed remained (ηp(2) = 0.006, p = 0.031)., Conclusions: Of the social factors considered, loneliness, social support and living arrangement were most consistently associated with aspects of cognitive ability in older people, and these associations appeared to be partly, though not wholly, accounted for by symptoms of depression. Although longitudinal follow-up is required to examine the causal direction of the effects more definitively, it may be beneficial to promote the development of interventions to reduce loneliness and social isolation, and to increase social support., (Copyright © 2013 S. Karger AG, Basel.)

This cohort profile describes the origins, tracing, recruitment, testing and follow-up of the University of Edinburgh-based Lothian Birth Cohorts of 1921 (LBC1921; N = 550) and 1936 (LBC1936; N = 1091). The participants undertook a general intelligence test at age 11 years and were recruited for these cohorts at mean ages of 79 (LBC1921) and 70 (LBC1936). The LBC1921 have been examined at mean ages of 79, 83, 87 and 90 years. The LBC1936 have been examined at mean ages of 70 and 73 years, and are being seen at 76 years. Both samples have an emphasis on the ageing of cognitive functions as outcomes. As they have childhood intelligence test scores, the cohorts' data have been used to search for determinants of lifetime cognitive changes, and also cognitive change within old age. The cohorts' outcomes also include a range of physical and psycho-social aspects of well-being in old age. Both cohorts have a wide range of variables: genome-wide genotyping, demographics, psycho-social and lifestyle factors, cognitive functions, medical history and examination, and biomarkers (from blood and urine). The LBC1936 participants also have a detailed structural magnetic resonance imaging (MRI) brain scan. A range of scientific findings is described, to illustrate the possible uses of the cohorts.

Objectives: Increased participation in leisure and physical activities may be cognitively protective. Whether activity might protect the integrity of the brain's white matter, or reduce atrophy and white matter lesion (WML) load, was examined in the Lothian Birth Cohort 1936 (n = 691), a longitudinal study of aging., Methods: Associations are presented between self-reported leisure and physical activity at age 70 years and structural brain biomarkers at 73 years. For white matter integrity, principal components analysis of 12 major tracts produced general factors for fractional anisotropy (FA) and mean diffusivity. Atrophy, gray and normal-appearing white matter (NAWM) volumes, and WML load were assessed using computational image processing methods; atrophy and WML were also assessed visually., Results: A higher level of physical activity was associated with higher FA, larger gray and NAWM volumes, less atrophy, and lower WML load. The physical activity associations with atrophy, gray matter, and WML remained significant after adjustment for covariates, including age, social class, and health status. For example, physical activity (standardized β = -0.09, nonstandardized β = -0.09, p = 0.029) and stroke (standardized β = 0.18, nonstandardized β = 0.69, p = 0.003) each had an independent effect on rated WML load. Leisure activity was associated with NAWM volume, but was nonsignificant after including covariates., Conclusions: In this large, narrow-age sample of adults in their 70s, physical activity was associated with less atrophy and WML. Its role as a potential neuroprotective factor is supported; however, the direction of causation is unclear from this observational study.

Objectives: To examine the cognitively protective effect of leisure and physical activities while accounting for prior cognitive ability, a rarely considered confounder of the previously reported associations between activity and cognitive aging., Design: Longitudinal cohort study., Setting: Glostrup, Denmark., Participants: Community-dwelling sample of adults recruited into the Glostrup 1914 Cohort (baseline N = 802). All were born in 1914 and were assessed at ages 50, 60, 70, and 80. New participants were recruited during the study to counter attrition., Measurements: On each occasion, cognitive ability was assessed using four tests, which defined a general cognitive ability score. Self-reported participation in leisure and physical activities was also collected. In general, physical activity was summarized on a 3- or 4-point scale, and leisure activity as none versus some (ages 50 and 60) or according to participation in a list of common activities (age 70). The effect of activity-leisure and physical-on the level of cognitive ability and cognitive change over time from age 60 to 80 was examined in growth curve models., Results: Greater activity (leisure or physical) was consistently associated with a higher level of cognitive ability. Adjusting for baseline cognitive ability (age 50) attenuated these associations, suggesting that associations between activity and cognition reported in old age are largely a consequence of preserved differentiation. A small but significant association remained between greater physical activity at age 60 or 70 and less cognitive decline., Conclusion: The association between more-frequent leisure activity and less cognitive decline mainly reflects the positive cross-sectional association between activity and cognition, although the link that remains between greater physical activity and a more-successful cognitive aging trajectory is of particular relevance to those who are developing interventions., (© 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.)

Objective: To investigate whether and to what extent mortality is predictable from facial photographs of older people., Methods: High-quality facial photographs of 292 members of the Lothian Birth Cohort 1921, taken at the age of about 83 years, were rated in terms of apparent age, health, attractiveness, facial symmetry, intelligence, and well-being by 12 young-adult raters. Cox proportional hazards regression was used to study associations between these ratings and mortality during a 7-year follow-up period., Results: All ratings had adequate reliability. Concurrent validity was found for facial symmetry and intelligence (as determined by correlations with actual measures of fluctuating asymmetry in the faces and Raven Standard Progressive Matrices score, respectively), but not for the other traits. Age as rated from facial photographs, adjusted for sex and chronological age, was a significant predictor of mortality (hazard ratio = 1.36, 95% confidence interval = 1.12-1.65) and remained significant even after controlling for concurrent, objectively measured health and cognitive ability, and the other ratings. Health as rated from facial photographs, adjusted for sex and chronological age, significantly predicted mortality (hazard ratio = 0.81, 95% confidence interval = 0.67-0.99) but not after adjusting for rated age or objectively measured health and cognition. Rated attractiveness, symmetry, intelligence, and well-being were not significantly associated with mortality risk., Conclusions: Rated age of the face is a significant predictor of mortality risk among older people, with predictive value over and above that of objective or rated health status and cognitive ability.

Active lifestyles might protect cognitive abilities; however, studies rarely consider the reverse causal direction. Activity-cognition associations might reflect stable intelligence differences rather than a protective effect of activity. The Lothian Birth Cohort 1936 (n = 1091) completed cognitive tests aged 70, having taken an intelligence test aged 11. Activity (assessed by participation in 15 activities that produced a socio-intellectual activity factor, and by physical activity) was positively associated with cognition (r = .08 to .32, p ≤ .05). When age-11 IQ and adult social class were controlled, only physical activity remained significantly associated with general cognitive ability and processing speed.

A novel analysis of magnetic resonance imaging (MRI) scans based on multispectral image fusion was used to quantify iron deposits in basal ganglia and microbleeds in 143 nondemented subjects of the generally healthy Lothian Birth Cohort, who were tested for general cognitive ability (intelligence) at mean ages of 11, 70, and 72 years. Possessing more iron deposits at age 72 was significantly associated with lower general cognitive ability at age 11, 70, and 72, explaining 4% to 9% of the variance. The relationships with old age general cognitive ability remained significant after controlling for childhood cognition, suggesting that iron deposits are related to lifetime cognitive decline. Most iron deposits were in the basal ganglia, with few microbleeds. While iron deposits in the general population have so far been dismissed in the literature, our results show substantial associations with cognitive functioning. The pattern of results suggests that iron deposits are not only a biomarker of general cognitive ability in old age and age-related cognitive decline, but that they are also related to the lifelong-stable trait of intelligence., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Understanding the determinants of healthy mental ageing is a priority for society today. So far, we know that intelligence differences show high stability from childhood to old age and there are estimates of the genetic contribution to intelligence at different ages. However, attempts to discover whether genetic causes contribute to differences in cognitive ageing have been relatively uninformative. Here we provide an estimate of the genetic and environmental contributions to stability and change in intelligence across most of the human lifetime. We used genome-wide single nucleotide polymorphism (SNP) data from 1,940 unrelated individuals whose intelligence was measured in childhood (age 11 years) and again in old age (age 65, 70 or 79 years). We use a statistical method that allows genetic (co)variance to be estimated from SNP data on unrelated individuals. We estimate that causal genetic variants in linkage disequilibrium with common SNPs account for 0.24 of the variation in cognitive ability change from childhood to old age. Using bivariate analysis, we estimate a genetic correlation between intelligence at age 11 years and in old age of 0.62. These estimates, derived from rarely available data on lifetime cognitive measures, warrant the search for genetic causes of cognitive stability and change.

Unlabelled: BACKGROUND/STUDY CONTEXT: Minor physical anomalies are thought to be markers of development and increased frequency of such anomalies has been linked to lower levels of intelligence. Here the authors examine a finger curvature anomaly, and evaluate its potential as a marker of the causes of cognitive aging., Methods: Participants were members of the Lothian Birth Cohort 1921 (LBC 1921). Intelligence was assessed at ages 11, 79, and 87. In wave 3, at age 87, 192 participants had both hands scanned with a high-resolution flatbed scanner and the curvature of the fifth digit was measured with image editing software. Multiple regression analyses were conducted to examine the proportion of unique variance in cognitive decline that could be explained by the finger curvature anomaly., Results: Finger curvature was significantly associated with cognitive decline across the life span (β= -.19, p= .02). Curvature was not associated with intelligence at age 11 or with decline during the period age 79 to age 87., Conclusion: Continuously varying minor physical anomalies may accumulate to provide a marker of factors impacting life span cognitive change. Curvature anomalies may reflect the common causes underlying cognitive and physical decline.

Unlabelled: BACKGROUND/STUDY CONTEXT: Visual working memory (VWM) has been shown to be particularly age sensitive. Determining which measures share variance with this cognitive ability in older adults may help to elucidate the key factors underlying the effects of aging., Methods: Predictors of VWM (measured by a modified Visual Patterns Test) were investigated in a subsample (N = 44, mean age = 73) of older adults from the Lothian Birth Cohort 1936 (LBC1936; Deary et al., 2007 , BMC Geriatrics, 7, 28). Childhood intelligence (Moray House Test) and contemporaneous measures of processing speed (four-choice reaction time), executive function (verbal fluency; block design), and spatial working memory (backward spatial span), were assessed as potential predictors., Results: All contemporaneous measures except verbal fluency were significantly associated with VWM, and processing speed had the largest effect size (r = -.53, p < .001). In linear regression analysis, even after adjusting for childhood intelligence, processing speed and the executive measure associated with visuospatial organization accounted for 35% of the variance in VWM., Conclusion: Processing speed may affect VWM performance in older adults via speed of encoding and/or rate of rehearsal, while executive resources specifically associated with visuospatial material are also important.

Differences in genomic structure between individuals are ubiquitous features of human genetic variation. Specific copy number variants (CNVs) have been associated with susceptibility to numerous complex psychiatric disorders, including attention-deficit-hyperactivity disorder, autism-spectrum disorders and schizophrenia. These disorders often display co-morbidity with low intelligence. Rare chromosomal deletions and duplications are associated with these disorders, so it has been suggested that these deletions or duplications may be associated with differences in intelligence. Here we investigate associations between large (≥500kb), rare (<1% population frequency) CNVs and both fluid and crystallized intelligence in community-dwelling older people. We observe no significant associations between intelligence and total CNV load. Examining individual CNV regions previously implicated in neuropsychological disorders, we find suggestive evidence that CNV regions around SHANK3 are associated with fluid intelligence as derived from a battery of cognitive tests. This is the first study to examine the effects of rare CNVs as called by multiple algorithms on cognition in a large non-clinical sample, and finds no effects of such variants on general cognitive ability.

Low blood levels of B vitamins have been implicated in age-associated cognitive impairment. The present study investigated the association between genetic variation in folate metabolism and age-related cognitive decline in the ninth decade of life. Both the 677C>T (rs1801133) polymorphism and the scarcely studied 1298A>C (rs1801131) polymorphism of the MTHFR gene were assessed in relation to cognitive change over 8 years in older community-dwelling individuals. MTHFR genotype was determined in 476 participants of the Lothian Birth Cohort 1921, whose intelligence was measured in childhood in the Scottish Mental Survey of 1932. Cognitive performance on the domains of verbal memory, reasoning and verbal fluency was assessed at mean age of 79 (n = 476) and again at mean ages of 83 (n = 275) and 87 (n = 180). Using linear mixed models, the MTHFR 677C>T and 1298A>C variants were not associated with the rate of cognitive change between 79 and 87 years, neither in the total sample, nor in a subsample of individuals with erythrocyte folate levels below the median. APOE E4 allele carrier status did not interact with MTHFR genotype in affecting change in cognitive performance over 8 years. No significant combined effect of the two polymorphisms was found. In conclusion, MTHFR 677C>T and 1298A>C polymorphisms were not associated with individual change in cognitive functioning in the ninth decade of life. Although polymorphisms in the MTHFR gene may cause disturbances in folate metabolism, they do not appear to be accompanied by changes in cognitive functioning in old age., (© 2011 The Authors. Genes, Brain and Behavior © 2011 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.)

Investigating the predictors of age-related cognitive change is a research priority. However, it is first necessary to discover the long-term stability of measures of cognitive ability because prior cognitive ability level might contribute to the amount of cognitive change experienced within old age. These two issues were examined in the Lothian Birth Cohorts of 1921 and 1936. Cognitive ability data were available from age 11 years when the participants completed the Moray House Test No. 12 (MHT). The Lothian Birth Cohort 1936 (LBC1936) completed the MHT a second time at age 70. The Lothian Birth Cohort 1921 (LBC1921) completed the MHT at ages 79 and 87. We examined cognitive stability and change from childhood to old age in both cohorts, and within old age in the LBC1921. Raw stability coefficients for the MHT from 11-70, 11-79, and 11-87 years were .67, .66, and .51, respectively; and larger when corrected for range restriction in the samples. Therefore, minimum estimates of the variance in later-life MHT accounted for by childhood performance on the same test ranged from 26-44%. This study also examined, in the LBC1921, whether MHT score at age 11 influenced the amount of change in MHT between ages 79 and 87. It did not. Higher intelligence from early life was apparently protective of intelligence in old age due to the stability of cognitive function across the lifespan, rather than because it slowed the decline experienced in later life., ((c) 2011 APA, all rights reserved.)

Understanding human cognitive ageing is important to improve the health of an increasing elderly population. Serum uric acid levels have been linked to many ageing illnesses and are also linked to cognitive functioning, though the direction of the association is equivocal. SLC2A9, a urate transporter, influences uric acid levels. This study first tested four SLC2A9 SNPs, previously associated with uric acid levels, in approximately 1000 Scots: the Lothian Birth Cohort 1936 (LBC1936). These participants were tested on general cognitive ability at ages 11 and 70. At age 70, they took a battery of diverse cognitive tests. Two replication cohorts were investigated. First, the LBC1921, who were tested on general cognitive ability at age 11. At ages 79 (n = 520), 83 (n = 281) and age 87 (n = 177), they completed cognitive ability test batteries. Second, the Edinburgh Type 2 Diabetes Study (ET2DS) were tested for cognitive abilities aged between 60 and 75 years (n = 1066). All analyses were adjusted for age, gender, body mass index and either childhood cognitive ability test score (LBC) or vocabulary-a measure of prior cognitive ability in ET2DS. Significant associations were detected with SLC2A9 and a general memory factor in LBC1936 and other individual cognitive ability tests (lowest P = 0.0002). The association with logical memory replicated in LBC1921 at all ages (all P < 0.05). These associations were not replicated in ET2DS (all P > 0.1). If the positive associations withstand, then this study could suggest that higher uric acid levels may be associated with increased performance on memory-related tasks.

It is unknown whether the relationship between raised inflammatory biomarker levels and late-life cognitive ability is causal. We explored this issue by testing the association between genetic regulators of plasma C-reactive protein (CRP) and cognition. Data were analysed from four cohorts based in central Scotland (Total N = 4,782). Associations were tested between variants in the CRP gene and both plasma CRP levels and a battery of neuropsychological tests, including a vocabulary-based estimate of peak prior cognitive ability and a general (summary) cognitive factor score, or 'g'. CRP levels were associated with a number of variants in the CRP gene (SNPs), including rs1205, rs1130864, rs1800947, and rs1417938 (P range 4.2e-06 to 0.041). Higher CRP levels were also associated with vocabulary-adjusted cognitive ability, used here to estimate lifetime cognitive change (P range 1.7e-04 to 0.038). After correction for multiple testing and adjustment for age and sex, no statistically significant associations were found between the SNPs and cognition. CRP is unlikely to be a causal determinant of late-life cognitive ability.

Pulmonary morbidity and mortality resulting from exposure to fine particulate matter (PM) increases with age. The present studies analyzed potential mechanisms underlying increased susceptibility of the elderly to PM using diesel exhaust (DE) as a model. Mice (2 m and 18 m) were exposed to DE (0, 300, and 1000 microg/m(3)) for 3 h once (single) or 3 h/day for 3 days (repeated). Bronchoalveolar lavage fluid (BAL), serum and lung tissue were collected 0 and 24 h later. Exposure to DE resulted in structural alterations in the lungs of older but not younger mice, including patchy thickening of the alveolar septa and inflammatory cell localization in alveolar spaces. These effects were most pronounced 24 h after a single exposure to the higher dose of DE. Significant increases in BAL nitrogen oxides were also noted in older mice, as well as expression of lipocalin 24p3, an oxidative stress marker in the lung with no effects in younger mice. Following DE inhalation, expression of Tumor Necrosis Factor alpha (TNFalpha) was upregulated in lungs of both younger and older mice; however, this was attenuated in older animals. Whereas exposure to DE resulted in increases in lung Interleukin-6 (IL-6) expression in both older and younger mice, IL-8 increased only in older animals. In younger mice, constitutive expression of manganese superoxide dismutase (MnSOD) decreased after DE exposure, while in older mice, constitutive MnSOD was not detectable and DE had no effect on expression of this antioxidant. Taken together, these results suggest that altered generation of inflammatory mediators and MnSOD may contribute to increased susceptibility of older mice to inhaled DE.

Objective: To test the hypothesis that increased levels of inflammatory and hemostatic markers are associated with poorer cognitive performance and to assess the influence of childhood intelligence quotient (IQ) and current cardiovascular disease (CVD) risk factors on this relationship. Blood inflammatory markers have been shown to predict late-life cognition, although the mechanism through which this occurs is unknown., Methods: Levels of the biomarkers C-reactive protein and fibrinogen were measured in 1053 Scottish participants (50.2% female) from the Lothian Birth Cohort 1936 ranging in age from 67 to 71 years. Biomarker levels were tested for their association with diverse cognitive abilities., Results: Significant cross-sectional associations were found between the biomarkers and various cognitive abilities: their effect size was around 1% of the variance and was in the direction of higher marker levels conferring poorer cognitive performance. With the exception of the reaction time measures (and fibrinogen), these associations could be explained by childhood IQ, CVD risk factors, or both. Importantly, both the inflammatory markers at age 70 years were associated (p < .001) with childhood IQ., Conclusions: Whereas inflammatory marker levels predict contemporaneous general cognitive ability, the results support a model of reverse causation because childhood IQ predicts late-life inflammation. This might be through its association with later life CVD risk factors or because it is a measure of system integrity. Unlike general cognitive ability, the association between inflammatory markers (particularly fibrinogen) and processing speed was maintained in the presence of childhood IQ and/or CVD risk factor adjustments. This might also reflect variation in physiological integrity.

The e4 allele of the apolipoprotein E (APOE) gene confers risk of Alzheimer's disease and, in some studies, relates to cognitive ability and decline in older people without Alzheimer's disease. Its relationship with processing speed, a contributor to cognitive decline with age, is largely unknown. This study tests the association of APOE with cognition and speed, with and without covarying childhood mental ability. The 1,013 participants were tested on cognitive ability at age 11 as part of the Scottish Mental Survey of 1947 and, at age 70, were tested on reasoning, working memory, information processing speed, and executive function. The results showed that APOE was associated with the general cognitive factor, 2 nonverbal tests, and choice reaction time (RT) variability; as expected, the e4 allele was the risk allele. RT measures and a general speed factor were nonlinearly related to APOE when factoring childhood ability (p < .05): The correlation between childhood ability and speed was lower in e4 allele carriers. APOE has an influence on nonverbal cognition in old age and interacts with childhood IQ to influence processing speed.

APOE e4-related memory deficits were reported in a normal population aged between 50 and 60 when controlling for general cognitive ability in early adulthood. This extended findings of APOE e4 effects on cognitive ability in 60-80-year-olds to a younger group and confirmed that this effect relates to changes in memory ability with age. The present study tests the association of APOE e4 variation with verbal and spatial memory in a sample of 70-year-olds both adjusted and non-adjusted for childhood and adult general cognitive ability. The 1,013 participants comprise surviving members of the 1947 Scottish Mental Survey resident in the Lothian area of Scotland. They were tested on general cognitive ability at age 11 years and followed up at about age 70 with tests of verbal (immediate and delayed) and spatial memory. General linear models were used to test the association between variation in the APOE polymorphism (e4 presence vs. absence) and memory measures. Of the eight measures tested, Spatial span forward was significantly associated with APOE e4 variation (P = 0.04) when adjusting for IQ, whereas Logical memory immediate was associated with APOE e4 variation (P = 0.04) in the analysis not controlling for IQ. Neither of these tests was significant when a correction for multiple testing was applied. APOE e4 does not influence memory abilities in a normal population of 70-year-olds.

Introduction: Age-associated cognitive decline-or normal (non-pathological, normative, usual) cognitive ageing-is an important human experience which differs in extent between individuals. The determinants of the differences in age-related cognitive decline are not fully understood. Progress in the field is taking place across many areas of biomedical and psychosocial sciences., Areas of Agreement and Controversy: The phenotype of normal cognitive ageing is well described. Some mental capabilities are well maintained into old age. From early adulthood, there are declines in mental domains such as processing speed, reasoning, memory and executive functions, some of which is underpinned by a decline in a general cognitive factor. There are contributions to understanding individual differences in normal cognitive ageing from genetics, general health and medical disorders such as atherosclerotic disease, biological processes such as inflammation, neurobiological changes, diet and lifestyle. Many of these effect sizes are small; some are poorly replicated; and in some cases, there is the possibility of reverse causation, with prior cognitive ability causing the supposed 'cause' of cognitive ability in old age., Emerging Areas for Developing Research: Genome-wide scans are a likely source to establish genetic contributions. The role of vascular factors in cognitive ageing is increasingly studied and understood. The same applies to diet, biomarkers such as inflammation and lifestyle factors such as exercise. There are marked advances in brain imaging, affording better in vivo studies of brain correlates of cognitive changes. There is growing appreciation that factors affecting general bodily ageing also influence cognitive functions in old age.

Background: Identifying the determinants of cognitive aging is a research priority; however, few studies are able to examine the influence of pre-morbid cognitive ability on later changes in cognitive function., Objective: To examine the association between childhood cognitive ability and cognitive change from age 79 to 83 in the presence of other demographic and lifestyle indicators., Methods: The participants took a test of mental ability when aged 11 as part of the Scottish Mental Survey 1932. Cognitive ability based on Raven's Matrices, Verbal Fluency, and Logical Memory was assessed at ages 79 and 83. We used both linear regression and latent variable growth curve modeling to compare methods and results., Results: Using linear regression, childhood mental ability was a significant predictor of cognitive change from 79 to 83, accounting for about 1.4% of the variance. Sex, education, social class, smoking status and alcohol intake were non-significant. In contrast, using latent variable growth curve modeling, there was no association between childhood mental ability and cognitive change. Sex (male), years of education, drinking status (positive), and childhood IQ were associated with better cognitive ability at age 79. The difference in results was due to the inability of linear regression to account completely for test-specific variance., Conclusion: Within a group of non-demented older people, greater childhood mental ability was associated with level of cognitive ability at age 79, but not with change in cognitive ability to age 83. To obtain accurate results regarding covariates of change, it is important to use methodology that can appropriately allocate all measured sources of variance., ((c) 2008 S. Karger AG, Basel.)

Background: Cognitive ageing is a major burden for society and a major influence in lowering people's independence and quality of life. It is the most feared aspect of ageing. There are large individual differences in age-related cognitive changes. Seeking the determinants of cognitive ageing is a research priority. A limitation of many studies is the lack of a sufficiently long period between cognitive assessments to examine determinants. Here, the aim is to examine influences on cognitive ageing between childhood and old age., Methods/design: The study is designed as a follow-up cohort study. The participants comprise surviving members of the Scottish Mental Survey of 1947 (SMS1947; N = 70,805) who reside in the Edinburgh area (Lothian) of Scotland. The SMS1947 applied a valid test of general intelligence to all children born in 1936 and attending Scottish schools in June 1947. A total of 1091 participants make up the Lothian Birth Cohort 1936. They undertook: a medical interview and examination; physical fitness testing; extensive cognitive testing (reasoning, memory, speed of information processing, and executive function); personality, quality of life and other psycho-social questionnaires; and a food frequency questionnaire. They have taken the same mental ability test (the Moray House Test No. 12) at age 11 and age 70. They provided blood samples for DNA extraction and testing and other biomarker analyses. Here we describe the background and aims of the study, the recruitment procedures and details of numbers tested, and the details of all examinations., Discussion: The principal strength of this cohort is the rarely captured phenotype of lifetime cognitive change. There is additional rich information to examine the determinants of individual differences in this lifetime cognitive change. This protocol report is important in alerting other researchers to the data available in the cohort.