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1.
Aging (Albany NY) ; 11(16): 5895-5923, 2019 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-31422385

RESUMO

Telomere length (TL) is associated with several aging-related diseases. Here, we present a DNA methylation estimator of TL (DNAmTL) based on 140 CpGs. Leukocyte DNAmTL is applicable across the entire age spectrum and is more strongly associated with age than measured leukocyte TL (LTL) (r ~-0.75 for DNAmTL versus r ~ -0.35 for LTL). Leukocyte DNAmTL outperforms LTL in predicting: i) time-to-death (p=2.5E-20), ii) time-to-coronary heart disease (p=6.6E-5), iii) time-to-congestive heart failure (p=3.5E-6), and iv) association with smoking history (p=1.21E-17). These associations are further validated in large scale methylation data (n=10k samples) from the Framingham Heart Study, Women's Health Initiative, Jackson Heart Study, InChianti, Lothian Birth Cohorts, Twins UK, and Bogalusa Heart Study. Leukocyte DNAmTL is also associated with measures of physical fitness/functioning (p=0.029), age-at-menopause (p=0.039), dietary variables (omega 3, fish, vegetable intake), educational attainment (p=3.3E-8) and income (p=3.1E-5). Experiments in cultured somatic cells show that DNAmTL dynamics reflect in part cell replication rather than TL per se. DNAmTL is not only an epigenetic biomarker of replicative history of cells, but a useful marker of age-related pathologies that are associated with it.

2.
Mol Psychiatry ; 2019 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-30760887

RESUMO

Polygenic scores can be used to distil the knowledge gained in genome-wide association studies for prediction of health, lifestyle, and psychological factors in independent samples. In this preregistered study, we used fourteen polygenic scores to predict variation in cognitive ability level at age 70, and cognitive change from age 70 to age 79, in the longitudinal Lothian Birth Cohort 1936 study. The polygenic scores were created for phenotypes that have been suggested as risk or protective factors for cognitive ageing. Cognitive abilities within older age were indexed using a latent general factor estimated from thirteen varied cognitive tests taken at four waves, each three years apart (initial n = 1091 age 70; final n = 550 age 79). The general factor indexed over two-thirds of the variance in longitudinal cognitive change. We ran additional analyses using an age-11 intelligence test to index cognitive change from age 11 to age 70. Several polygenic scores were associated with the level of cognitive ability at age-70 baseline (range of standardized ß-values = -0.178 to 0.302), and the polygenic score for education was associated with cognitive change from childhood to age 70 (standardized ß = 0.100). No polygenic scores were statistically significantly associated with variation in cognitive change between ages 70 and 79, and effect sizes were small. However, APOE e4 status made a significant prediction of the rate of cognitive decline from age 70 to 79 (standardized ß = -0.319 for carriers vs. non-carriers). The results suggest that the predictive validity for cognitive ageing of polygenic scores derived from genome-wide association study summary statistics is not yet on a par with APOE e4, a better-established predictor.

3.
Clin Epigenetics ; 10(1): 159, 2018 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-30572949

RESUMO

BACKGROUND: Epigenetic age acceleration (an older methylation age compared to chronological age) correlates strongly with various age-related morbidities and mortality. Chronic systemic inflammation is thought to be a hallmark of ageing, but the relationship between an increased epigenetic age and this likely key phenotype of ageing has not yet been extensively investigated. METHODS: We modelled the trajectories of the inflammatory biomarkers C-reactive protein (CRP; measured using both a high- and low-sensitivity assay) and interleukin-6 (IL-6) over the eighth decade in the Lothian Birth Cohort 1936. Using linear mixed models, we investigated the association between CRP and immune cell profiles imputed from the methylation data and examined the cross-sectional and longitudinal association between the inflammatory biomarkers and two measures of epigenetic age acceleration, derived from the Horvath and Hannum epigenetic clocks. RESULTS: We found that low-sensitivity CRP declined, high-sensitivity CRP did not change, and IL-6 increased over time within the cohort. CRP levels inversely associated with CD8+T cells and CD4+T cells and positively associated with senescent CD8+T cells, plasmablasts and granulocytes. Cross-sectionally, the Hannum, but not the Horvath, measure of age acceleration was positively associated with each of the inflammatory biomarkers, including a restricted measure of CRP (≤ 10 mg/L) likely reflecting levels relevant to chronic inflammation. CONCLUSIONS: We found a divergent relationship between inflammation and immune system parameters in older age. We additionally report the Hannum measure of epigenetic age acceleration associated with an elevated inflammatory profile cross-sectionally, but not longitudinally.


Assuntos
Envelhecimento/genética , Proteína C-Reativa/metabolismo , Metilação de DNA , Marcadores Genéticos , Inflamação/genética , Interleucina-6/metabolismo , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Estudos Transversais , Epigênese Genética , Feminino , Granulócitos/imunologia , Humanos , Modelos Lineares , Estudos Longitudinais , Contagem de Linfócitos , Masculino , Plasmócitos/imunologia
4.
Psychol Sci ; : 956797618804501, 2018 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-30359210

RESUMO

We examined reciprocal, time-ordered associations between age-related changes in fluid intelligence and depressive symptoms. Participants were 1,091 community-dwelling older adults from the Lothian Birth Cohort 1936 study who were assessed repeatedly at 3-year intervals between the ages of 70 and 79 years. On average, fluid intelligence and depressive symptoms worsened with age. There was also a dynamic-coupling effect, in which low fluid intelligence at a given age predicted increasing depressive symptoms across the following 3-year interval, whereas the converse did not hold. Model comparisons showed that this coupling parameter significantly improved overall fit and had a correspondingly moderately strong effect size, accounting on average for an accumulated 0.9 standard-deviation increase in depressive symptoms, following lower cognitive performance, across the observed age range. Adjustment for sociodemographic and health-related covariates did not significantly attenuate this association. This implies that monitoring for cognitive decrements in later life may expedite interventions to reduce related increases in depression risk.

5.
Ann Neurol ; 84(4): 576-587, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30179274

RESUMO

OBJECTIVE: To examine the relationship between carotid atherosclerosis and cerebral cortical thickness and investigate whether cortical thickness mediates the association between carotid atheroma and relative cognitive decline. METHODS: We assessed 554 community-dwelling subjects (male/female: 296/258) from the Lothian Birth Cohort 1936 who underwent brain magnetic resonance imaging and carotid Doppler ultrasound studies at age 73 years. The relationship between carotid atherosclerosis markers (internal carotid artery stenosis, intima-media thickness, velocity, pulsatility, and resistivity indexes) and vertex-wide cerebral cortical thickness was examined cross-sectionally, controlling for gender, extensive vascular risk factors (VRFs), and intelligence quotient at age 11 (IQ-11). We also determined the association between carotid stenosis and a composite measure of fluid intelligence at age 73 years. A mediation model was applied to examine whether cortical thickness mediated the relationship between carotid stenosis and cognitive function. RESULTS: A widespread negative association was identified between carotid stenosis (median = 15%) and cerebral cortical thickness at age 73 years, independent of the side of carotid stenosis, other carotid measures, VRFs, and IQ-11. This association increased in an almost dose-response relationship from mild to severe degrees of carotid stenosis, across the anterior and posterior circulation territories. A negative association was also noted between carotid stenosis and fluid intelligence (standardized beta coefficient = -0.151, p = 0.001), which appeared partly (approximately 22%) mediated by carotid stenosis-related thinning of the cerebral cortex. INTERPRETATION: The findings suggest that carotid stenosis represents a marker of processes that accelerate aging of the cerebral cortex and cognition that is in part independent of measurable VRFs. Cortical thinning within the anterior and posterior circulation territories partially mediated the relationship between carotid atheroma and fluid intelligence. Ann Neurol 2018;84:576-587.

6.
Int J Epidemiol ; 47(4): 1042-1042r, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29546429
7.
Transl Vis Sci Technol ; 7(2): 12, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29600120

RESUMO

Purpose: Semiautomated software applications derive quantitative retinal vascular parameters from fundus camera images. However, the extent of agreement between measurements from different applications is unclear. We evaluate the agreement between retinal measures from two software applications, the Singapore "I" Vessel Assessment (SIVA) and the Vessel Assessment and Measurement Platform for Images of the Retina (VAMPIRE), and examine respective associations between retinal and systemic outcomes. Method: Fundus camera images from 665 Lothian Birth Cohort 1936 participants were analyzed with SIVA and VAMPIRE. Intraclass correlation coefficients (ICC) and Bland-Altman plots assessed agreement between retinal parameters: measurements of vessel width, fractal dimension, and tortuosity. Retinal-systemic variable associations were assessed with Pearson's correlation, and intersoftware correlation magnitude differences were examined with Williams's test. Results: ICC values indicated poor to limited agreement for all retinal parameters (0.159-0.410). Bland-Altman plots revealed proportional bias in the majority, and systematic bias in all measurements. SIVA and VAMPIRE measurements were associated most consistently with systemic variables relating to blood pressure (SIVA r's from -0.122 to -0.183; VAMPIRE r's from -0.078 to -0.177). Williams's tests indicated significant differences in the magnitude of association between retinal and systemic variables for 7 of 77 comparisons (P < 0.05). Conclusions: Agreement between two common software applications was poor. Further studies are required to determine whether associations with systemic variables are software-dependent. Translational Relevance: Standardization of the measurement of retinal vascular parameters is warranted to ensure that they are reliable and application-independent. This would be an important step towards realizing the potential of the retina as a source of imaging-derived biomarkers that are clinically useful.

8.
PLoS One ; 13(2): e0192604, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29451880

RESUMO

OBJECTIVES: In this replication-and-extension study, we tested whether depressive symptoms, neuroticism, and allostatic load (multisystem physiological dysregulation) were related to lower baseline cognitive ability and greater subsequent cognitive decline in older adults, and whether these relationships were moderated by the E4 allele of the apolipoprotein E (APOE) gene. We also tested whether allostatic load mediated the relationships between neuroticism and cognitive outcomes. METHODS: We used data from the Lothian Birth Cohort 1936 (n at Waves 1-3: 1,028 [M age = 69.5 y]; 820 [M duration since Wave 1 = 2.98 y]; 659 [M duration since Wave 1 = 6.74 y]). We fitted latent growth curve models of general cognitive ability (modeled using five cognitive tests) with groups of APOE E4 non-carriers and carriers. In separate models, depressive symptoms, neuroticism, and allostatic load predicted baseline cognitive ability and subsequent cognitive decline. In addition, models tested whether allostatic load mediated relationships between neuroticism and cognitive outcomes. RESULTS: Baseline cognitive ability had small-to-moderate negative associations with depressive symptoms (ß range = -0.20 to -0.17), neuroticism (ß range = -0.27 to -0.23), and allostatic load (ß range = -0.11 to 0.09). Greater cognitive decline was linked to baseline allostatic load (ß range = -0.98 to -0.83) and depressive symptoms (ß range = -1.00 to -0.88). However, APOE E4 allele possession did not moderate the relationships of depressive symptoms, neuroticism and allostatic load with cognitive ability and cognitive decline. Additionally, the associations of neuroticism with cognitive ability and cognitive decline were not mediated through allostatic load. CONCLUSIONS: Our results suggest that APOE E4 status does not moderate the relationships of depressive symptoms, neuroticism, and allostatic load with cognitive ability and cognitive decline in healthy older adults. The most notable positive finding in the current research was the strong association between allostatic load and cognitive decline.


Assuntos
Apolipoproteínas E/genética , Envelhecimento Cognitivo , Depressão/psicologia , Neuroticismo , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino
9.
Soc Sci Med ; 196: 56-65, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29128786

RESUMO

International evidence suggests that green space has beneficial effects on general and mental health but little is known about how lifetime exposure to green space influences cognitive ageing. Employing a novel longitudinal life course approach, we examined the association between lifetime availability of public parks and cognitive ageing. Lifetime residential information was gathered from the participants of the Lothian Birth Cohort 1936 using a "life-grid" questionnaire at age 78 years. Parks information from 1949, 1969 and 2009 was used to determine a percentage of parks within a 1500 m buffer zone surrounding residence for childhood, adulthood, and later adulthood periods. Linear regressions were undertaken to test for association with age-standardised, residualised change in cognitive function (Moray House Test score) from age 11 to 70 years, and from age 70 to 76 (n = 281). The most appropriate model was selected using the results of a partial F-test, and then stratified by demographic, genetic and socioeconomic factors. The local provision of park space in childhood and adulthood were both important in explaining the change in cognitive function in later life. The association between childhood and adulthood park availability and change in the Moray House Test Score from age 70 to 76 was strongest for women, those without an APOE e4 allele (a genetic risk factor), and those in the lowest socioeconomic groups. Greater neighbourhood provision of public parks from childhood through to adulthood may help to slow down the rate of cognitive decline in later life, recognising that such environmental associations are always sensitive to individual characteristics.


Assuntos
Envelhecimento/psicologia , Cognição/fisiologia , Planejamento Ambiental/estatística & dados numéricos , Parques Recreativos/estatística & dados numéricos , Características de Residência/estatística & dados numéricos , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Reino Unido , Adulto Jovem
10.
Neurobiol Aging ; 62: 146-158, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29149632

RESUMO

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.


Assuntos
Envelhecimento/patologia , Envelhecimento/psicologia , Encéfalo/patologia , Cognição/fisiologia , Envelhecimento Cognitivo/fisiologia , Envelhecimento Cognitivo/psicologia , Inteligência/fisiologia , Fatores Socioeconômicos , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Estudos de Coortes , Estudos Transversais , Humanos , Neuroimagem , Tamanho do Órgão , Pontuação de Propensão , Substância Branca/diagnóstico por imagem , Substância Branca/patologia
11.
Aging (Albany NY) ; 9(12): 2489-2503, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29207374

RESUMO

Gene expression is influenced by both genetic variants and the environment. As individuals age, changes in gene expression may be associated with decline in physical and cognitive abilities. We measured transcriptome-wide expression levels in lymphoblastoid cell lines derived from members of the Lothian Birth Cohort 1936 at mean ages 70 and 76 years. Changes in gene expression levels were identified for 1,741 transcripts in 434 individuals. Gene Ontology enrichment analysis indicated an enrichment of biological processes involved in the immune system. Transcriptome-wide association analysis was performed for eleven cognitive, fitness, and biomedical aging-related traits at age 70 years (N=665 to 781) and with mortality. Transcripts for genes (F2RL3, EMILIN1 and CDC42BPA) previously identified as being differentially methylated or expressed in smoking or smoking-related cancers were overexpressed in smokers compared to non-smokers and the expression of transcripts for genes (HERPUD1, GAB2, FAM167A and GLS) previously associated with stress response, autoimmune disease and cancer were associated with telomere length. No associations between expression levels and other traits, or mortality were identified.

12.
Intelligence ; 62: 79-88, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28626274

RESUMO

Maintaining good cognitive function is important for successful aging, and it has been suggested recently that having and optimistic outlook may also be valuable. However few have studied the relationship between cognitive ability and dispositional optimism and pessimism in older age. It is unclear whether associations found previously between cognitive ability and pessimism in older age, are evident across the life course, and are consistent at different points in older age. In the present study we examined associations between dispositional optimism and pessimism measured in the eighth and ninth decade of life and childhood and older age cognitive ability, and lifetime change in cognitive ability. Participants were two independent narrow-age samples of older individuals with mean ages about 73 (n = 847) and 87 (n = 220) years from the Lothian Birth Cohorts of 1936 (LBC1936) and 1921 (LBC1921), respectively. Higher cognitive ability in childhood and older-age, and healthier cognitive change across the lifetime were associated with lower pessimism in older age: age-11 IQ (LBC1936: ß = - 0.17, p < 0.001; LBC1921: ß = - 0.29, p = 0.001), older-age IQ (LBC1936: ß = - 0.18, p < 0.001; LBC1921: ß = - 0.27, p < 0.001), cognitive change (LBC1936: ß = - 0.06, p < 0.04; LBC1921: ß = - 0.15, p = 0.05). Cognitive ability was not significantly associated with optimism in bivariate analyses, and after adjustment for covariates had only small associations with optimism and only in the LBC1936. The results are consistent with differential associations between cognitive functions and optimism and pessimism, and indicate that their associations with cognitive ability are similar in the eighth and ninth decades of life.

13.
BMJ ; 357: j2708, 2017 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-28659274

RESUMO

Objectives To examine the association between intelligence measured in childhood and leading causes of death in men and women over the life course.Design Prospective cohort study based on a whole population of participants born in Scotland in 1936 and linked to mortality data across 68 years of follow-up.Setting Scotland.Participants 33 536 men and 32 229 women who were participants in the Scottish Mental Survey of 1947 (SMS1947) and who could be linked to cause of death data up to December 2015.Main outcome measures Cause specific mortality, including from coronary heart disease, stroke, specific cancer types, respiratory disease, digestive disease, external causes, and dementia.Results Childhood intelligence was inversely associated with all major causes of death. The age and sex adjusted hazard ratios (and 95% confidence intervals) per 1 SD (about 15 points) advantage in intelligence test score were strongest for respiratory disease (0.72, 0.70 to 0.74), coronary heart disease (0.75, 0.73 to 0.77), and stroke (0.76, 0.73 to 0.79). Other notable associations (all P<0.001) were observed for deaths from injury (0.81, 0.75 to 0.86), smoking related cancers (0.82, 0.80 to 0.84), digestive disease (0.82, 0.79 to 0.86), and dementia (0.84, 0.78 to 0.90). Weak associations were apparent for suicide (0.87, 0.74 to 1.02) and deaths from cancer not related to smoking (0.96, 0.93 to 1.00), and their confidence intervals included unity. There was a suggestion that childhood intelligence was somewhat more strongly related to coronary heart disease, smoking related cancers, respiratory disease, and dementia in women than men (P value for interactions <0.001, 0.02, <0.001, and 0.02, respectively).Childhood intelligence was related to selected cancer presentations, including lung (0.75, 0.72 to 0.77), stomach (0.77, 0.69 to 0.85), bladder (0.81, 0.71 to 0.91), oesophageal (0.85, 0.78 to 0.94), liver (0.85, 0.74 to 0.97), colorectal (0.89, 0.83 to 0.95), and haematopoietic (0.91, 0.83 to 0.98). Sensitivity analyses on a representative subsample of the cohort observed only small attenuation of the estimated effect of intelligence (by 10-26%) after adjustment for potential confounders, including three indicators of childhood socioeconomic status. In a replication sample from Scotland, in a similar birth year cohort and follow-up period, smoking and adult socioeconomic status partially attenuated (by 16-58%) the association of intelligence with outcome rates.Conclusions In a whole national population year of birth cohort followed over the life course from age 11 to age 79, higher scores on a well validated childhood intelligence test were associated with lower risk of mortality ascribed to coronary heart disease and stroke, cancers related to smoking (particularly lung and stomach), respiratory diseases, digestive diseases, injury, and dementia.


Assuntos
Causas de Morte , Inteligência/fisiologia , Adolescente , Adulto , Idoso , Criança , Feminino , Seguimentos , Inquéritos Epidemiológicos , Humanos , Longevidade/fisiologia , Masculino , Pessoa de Meia-Idade , Carência Psicossocial , Medição de Risco , Escócia/epidemiologia , Fatores Socioeconômicos , Análise de Sobrevida
14.
Brain Struct Funct ; 222(8): 3477-3490, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28424895

RESUMO

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.


Assuntos
Envelhecimento , Encéfalo/anatomia & histologia , Idoso , Apolipoproteínas E/genética , Imagem de Difusão por Ressonância Magnética , Imagem de Tensor de Difusão , Feminino , Humanos , Individualidade , Masculino , Aptidão Física , Fatores de Risco , Fatores Socioeconômicos
15.
Br J Ophthalmol ; 101(7): 993-998, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28400371

RESUMO

AIM: To examine the relationship between retinal vascular morphology and cognitive abilities in a narrow-age cohort of community-dwelling older people. METHODS: Digital retinal images taken at age ∼73 years from 683 participants of the Lothian Birth Cohort 1936 (LBC1936) were analysed with Singapore I Vessel Assessment (SIVA) software. Multiple regression models were applied to determine cross-sectional associations between retinal vascular parameters and general cognitive ability (g), memory, processing speed, visuospatial ability, crystallised cognitive ability and change in IQ from childhood to older age. RESULTS: After adjustment for cognitive ability at age 11 years and cardiovascular risk factors, venular length-to-diameter ratio was nominally significantly associated with processing speed (ß=-0.116, p=0.01) and g (ß=-0.079, p=0.04). Arteriolar length-to-diameter ratio was associated with visuospatial ability (ß=0.092, p=0.04). Decreased arteriolar junctional exponent deviation and increased arteriolar branching coefficient values were associated with less relative decline in IQ between childhood and older age (arteriolar junctional exponent deviation: ß=-0.101, p=0.02; arteriolar branching coefficient: ß=0.089, p=0.04). Data are presented as standardised ß coefficients (ß) reflecting change in cognitive domain score associated with an increase of 1 SD unit in retinal parameter. None of these nominally significant associations remained significant after correction for multiple statistical testing. CONCLUSIONS: Retinal parameters contributed <1% of the variance in the majority of associations observed. Whereas retinal analysis may have potential for early detection of some types of age-related cognitive decline and dementia, our results present little evidence that retinal vascular features are associated with non-pathological cognitive ageing.


Assuntos
Envelhecimento , Cognição/fisiologia , Microvasos/diagnóstico por imagem , Vasos Retinianos/diagnóstico por imagem , Idoso , Arteríolas/diagnóstico por imagem , Estudos Transversais , Feminino , Humanos , Masculino , Estudos Retrospectivos , Singapura , Vênulas/diagnóstico por imagem
16.
J Cereb Blood Flow Metab ; 37(8): 3042-3052, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28155579

RESUMO

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


Assuntos
Estenose das Carótidas/psicologia , Transtornos Cognitivos/psicologia , Cognição/fisiologia , Envelhecimento Cognitivo/psicologia , Placa Aterosclerótica/psicologia , Idoso , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/enzimologia , Transtornos Cognitivos/epidemiologia , Envelhecimento Cognitivo/fisiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Modelos Neurológicos , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/epidemiologia , Ultrassonografia Doppler em Cores
17.
Intelligence ; 59: 115-126, 2016 Nov-Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27932854

RESUMO

It is critical to discover why some people's cognitive abilities age better than others'. We applied multivariate growth curve models to data from a narrow-age cohort measured on a multi-domain IQ measure at age 11 years and a comprehensive battery of thirteen measures of visuospatial, memory, crystallized, and processing speed abilities at ages 70, 73, and 76 years (n = 1091 at age 70). We found that 48% of the variance in change in performance on the thirteen cognitive measures was shared across all measures, an additional 26% was specific to the four ability domains, and 26% was test-specific. We tested the association of a wide variety of sociodemographic, fitness, health, and genetic variables with each of these cognitive change factors. Models that simultaneously included all covariates accounted for appreciable proportions of variance in the cognitive change factors (e.g. approximately one third of the variance in general cognitive change). However, beyond physical fitness and possession of the APOE e4 allele, very few predictors were incrementally associated with cognitive change at statistically significant levels. The results highlight a small number of factors that predict differences in cognitive ageing, and underscore that correlates of cognitive level are not necessarily predictors of decline. Even larger samples will likely be required to identify additional variables with more modest associations with normal-range heterogeneity in aging-related cognitive declines.

18.
J Neurosci ; 35(22): 8672-82, 2015 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-26041932

RESUMO

Understanding aging-related cognitive decline is of growing importance in aging societies, but relatively little is known about its neural substrates. Measures of white matter microstructure are known to correlate cross-sectionally with cognitive ability measures, but only a few small studies have tested for longitudinal relations among these variables. We tested whether there were coupled changes in brain white matter microstructure indexed by fractional anisotropy (FA) and three broad cognitive domains (fluid intelligence, processing speed, and memory) in a large cohort of human participants with longitudinal diffusion tensor MRI and detailed cognitive data taken at ages 73 years (n = 731) and 76 years (n = 488). Longitudinal changes in white matter microstructure were coupled with changes in fluid intelligence, but not with processing speed or memory. Individuals with higher baseline white matter FA showed less subsequent decline in processing speed. Our results provide evidence for a longitudinal link between changes in white matter microstructure and aging-related cognitive decline during the eighth decade of life. They are consistent with theoretical perspectives positing that a corticocortical "disconnection" partly explains cognitive aging.


Assuntos
Mapeamento Encefálico , Encéfalo/anatomia & histologia , Cognição/fisiologia , Inteligência , Substância Branca/anatomia & histologia , Idoso , Anisotropia , Estudos de Coortes , Imagem de Tensor de Difusão , Feminino , Humanos , Masculino , Estudos Retrospectivos , Estatística como Assunto
19.
PLoS One ; 10(3): e0121119, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25816017

RESUMO

PURPOSE: Cerebral microvascular disease is associated with dementia. Differences in the topography of the retinal vascular network may be a marker for cerebrovascular disease. The association between cerebral microvascular state and non-pathological cognitive ageing is less clear, particularly because studies are rarely able to adjust for pre-morbid cognitive ability level. We measured retinal vascular fractal dimension (Df) as a potential marker of cerebral microvascular disease. We examined the extent to which it contributes to differences in non-pathological cognitive ability in old age, after adjusting for childhood mental ability. METHODS: Participants from the Lothian Birth Cohort 1936 Study (LBC1936) had cognitive ability assessments and retinal photographs taken of both eyes aged around 73 years (n = 648). IQ scores were available from childhood. Retinal vascular Df was calculated with monofractal and multifractal analysis, performed on custom-written software. Multiple regression models were applied to determine associations between retinal vascular Df and general cognitive ability (g), processing speed, and memory. RESULTS: Only three out of 24 comparisons (two eyes × four Df parameters × three cognitive measures) were found to be significant. This is little more than would be expected by chance. No single association was verified by an equivalent association in the contralateral eye. CONCLUSIONS: The results show little evidence that fractal measures of retinal vascular differences are associated with non-pathological cognitive ageing.


Assuntos
Envelhecimento/fisiologia , Cognição/fisiologia , Memória/fisiologia , Vasos Retinianos/anatomia & histologia , Idoso , Doenças de Pequenos Vasos Cerebrais/diagnóstico , Doenças de Pequenos Vasos Cerebrais/epidemiologia , Feminino , Fractais , Humanos , Testes de Inteligência , Estudos Longitudinais , Masculino , Reino Unido/epidemiologia
20.
Int J Epidemiol ; 44(4): 1388-96, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25617346

RESUMO

BACKGROUND: The DNA methylation-based 'epigenetic clock' correlates strongly with chronological age, but it is currently unclear what drives individual differences. We examine cross-sectional and longitudinal associations between the epigenetic clock and four mortality-linked markers of physical and mental fitness: lung function, walking speed, grip strength and cognitive ability. METHODS: DNA methylation-based age acceleration (residuals of the epigenetic clock estimate regressed on chronological age) were estimated in the Lothian Birth Cohort 1936 at ages 70 (n = 920), 73 (n = 299) and 76 (n = 273) years. General cognitive ability, walking speed, lung function and grip strength were measured concurrently. Cross-sectional correlations between age acceleration and the fitness variables were calculated. Longitudinal change in the epigenetic clock estimates and the fitness variables were assessed via linear mixed models and latent growth curves. Epigenetic age acceleration at age 70 was used as a predictor of longitudinal change in fitness. Epigenome-wide association studies (EWASs) were conducted on the four fitness measures. RESULTS: Cross-sectional correlations were significant between greater age acceleration and poorer performance on the lung function, cognition and grip strength measures (r range: -0.07 to -0.05, P range: 9.7 x 10(-3) to 0.024). All of the fitness variables declined over time but age acceleration did not correlate with subsequent change over 6 years. There were no EWAS hits for the fitness traits. CONCLUSIONS: Markers of physical and mental fitness are associated with the epigenetic clock (lower abilities associated with age acceleration). However, age acceleration does not associate with decline in these measures, at least over a relatively short follow-up.


Assuntos
Envelhecimento/psicologia , Cognição , Metilação de DNA , Epigênese Genética , Aptidão Física , Idoso , Biomarcadores , Estudos Transversais , Epigenômica , Feminino , Força da Mão , Humanos , Modelos Lineares , Estudos Longitudinais , Masculino , Testes de Função Respiratória , Escócia , Caminhada
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