Search

Background/objectives: The associations of reproductive history and motor function are controversial., Design: Prospective cohort study with 10 years of follow-up., Setting: Three French cities between 1999 and 2011., Participants: A total of 3043 community-dwelling women from the Three-City Dijon study population., Measurements: We examined the cross-sectional and longitudinal association of age at menopause, artificial menopause, and parity with walking speed (WS) using linear regression and linear mixed models, respectively. Cox proportional models were used to examine the association of characteristics of reproductive life with disability., Results: Mean baseline WS was 143.8 cm/s. Artificial menopause was associated with slower WS at baseline (β = -3.29; 95% confidence interval [CI] = -5.83 to -0.74; P = .01). Reproductive life characteristics had no effect on change in WS. Increasing age at menopause was associated with reduced disability risk (hazard ratio [HR] for 5-year increase = 0.92; 95% CI = 0.87-0.99; P = .02), while parity increased disability risk (HR for ≥3 vs 0 children = 1.53; 95% CI = 1.22-1.93; P < .01)., Conclusion: These findings show that early age at menopause and higher parity have a deleterious effect on motor function that persists in older people. J Am Geriatr Soc 68:585-594, 2020., (© 2019 The American Geriatrics Society.)

Differences in health status by socioeconomic position (SEP) tend to be more evident at older ages, suggesting the involvement of a biological mechanism responsive to the accumulation of deleterious exposures across the lifespan. DNA methylation (DNAm) has been proposed as a biomarker of biological aging that conserves memory of endogenous and exogenous stress during life.We examined the association of education level, as an indicator of SEP, and lifestyle-related variables with four biomarkers of age-dependent DNAm dysregulation: the total number of stochastic epigenetic mutations (SEMs) and three epigenetic clocks (Horvath, Hannum and Levine), in 18 cohorts spanning 12 countries.The four biological aging biomarkers were associated with education and different sets of risk factors independently, and the magnitude of the effects differed depending on the biomarker and the predictor. On average, the effect of low education on epigenetic aging was comparable with those of other lifestyle-related risk factors (obesity, alcohol intake), with the exception of smoking, which had a significantly stronger effect.Our study shows that low education is an independent predictor of accelerated biological (epigenetic) aging and that epigenetic clocks appear to be good candidates for disentangling the biological pathways underlying social inequalities in healthy aging and longevity.

Physical activity is key for successful ageing, but questions remain regarding the optimal physical activity pattern. We examined the cross-sectional association between physical activity and successful ageing using data on 3,749 participants (age range = 60-83years) of the Whitehall II study. The participants underwent a clinical assessment, completed a 20-item physical activity questionnaire, and wore a wrist-mounted accelerometer for 9 days. Successful ageing was defined as good cognitive, motor, and respiratory functioning, along with absence of disability, mental health problems, and major chronic diseases. Time spent in moderate-to-vigorous physical activity (MVPA) episodes assessed by accelerometer was classified as "short" (1-9.59 minutes) and "long" (≥10 minutes) bouts. Linear multivariate regression showed that successful agers (N = 789) reported 3.79 (95% confidence interval (CI): 1.39-6.19) minutes more daily MVPA than other participants. Accelerometer data showed this difference to be 3.40 (95% CI:2.44-4.35) minutes for MVPA undertaken in short bouts, 4.16 (95% CI:3.11-5.20) minutes for long bouts, and 7.55 (95% CI:5.86-9.24) minutes for all MVPA bouts lasting 1 minute or more. Multivariate logistic regressions showed that participants undertaking ≥150 minutes of MVPA per week were more likely to be successful agers with both self-reported (Odd Ratio (OR) = 1.29,95% (CI):1.09-1.53) and accelerometer data (length bout ≥1 minute:OR = 1.92, 95%CI:1.60-2.30). Successful agers practice more MVPA, having both more short and long bouts, than non-successful agers.

Obesity, whose prevalence is increasing, is associated with poor functional status at older ages. However, much of this evidence is cross-sectional with little known about longitudinal associations. We examined associations of body mass index (BMI), and change in BMI, with change in objective [walking speed (WS)] and self-reported (disability) measures of motor decline. Analyses included participants (65-85 years) from the Dijon center of the Three-City study (France) with up to five WS (N = 4007) and six disability assessments (N = 4478) over 11 years. Data were analyzed using regression models for repeated measures. Mean baseline WS was 153 cm/s. Compared to normal weight persons, obese participants at baseline walked slower and reported more disability; they also experienced 45% faster WS decline (-18.63 vs. -12.85 cm/s/10 years, P = 0.002). Participants who lost or gained weight had 47% (-18.85 cm/s/10 years, P < 0.001) and 33% (-17.08 cm/s/10 years, P = 0.002) respectively greater WS decline than participants in the normal BMI change category. 24% of participants reported disability at least once during the follow-up, those who lost or gained weight had a 1.63 and 1.34 respectively higher odds of disability than participants in the normal BMI change category (P = 0.001). Associations remained after adjustment for covariates. In conclusion, obesity is associated with worse motor performances, a higher risk of disability, and faster motor decline. Our results underline the interest of repeated BMI and motor assessments to identify those at higher risk of disability.

We examined the effect of salivary cortisol on cognitive performance and decline in 3229 adults (79% men), mean age 61 years. Six saliva samples over the day along with a cognition test battery were administered twice in 5 years. In fully-adjusted cross-sectional analyses from 2002 to 2004, higher waking cortisol was associated with higher reasoning score (β = 0.08, 95% confidence interval: 0.01, 0.15) but this finding was not replicated using data from 2007 to 2009. Over the mean 5 years follow-up there was decline in all cognitive tests but this decline did not vary as a function of cortisol levels; the exception was among APOE e4 carriers where a flatter diurnal slope and higher bedtime cortisol were associated with faster decline in verbal fluency. Changes in cortisol measures between 2002/2004 and 2007/2009 or chronically elevated levels were not associated with cognitive performance in 2007/2009. These results, based on a large sample of community-dwelling adults suggest that variability in hypothalamic-pituitary-adrenal function is not a strong contributor to cognitive aging., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The prediction of successful aging by midlife body mass index (BMI) and waist circumference (WC) was examined., Methods: BMI/WC were assessed in 4869 persons (mean age 51.2, range 42-63 in 1991/1993) and survival and successful aging (alive, no chronic disease at age >60 years, not in the worst age- and sex-standardized quintile of cognitive, physical, respiratory,cardiovascular, and mental health) ascertained over a 16-year follow-up, analyzed using logistic regression adjusted for sociodemographic factors and health behaviors., Results: 507 participants died, 1008 met the criteria for successful aging. Those with BMI ≥ 30 kg/m(2) had lower odds of successful aging (odds ratio or OR) = 0.37; 95% confidence interval or CI: 0.27, 0.50) and survival (OR = 0.55; 95% CI: 0.41, 0.74) compared to BMI between 18.5 and 25 kg/m(2) . Those with a large WC (≥102/88 cm in men/women) had lower odds of successful aging (OR = 0.41; 95% CI: 0.31, 0.54) and survival (OR = 0.57; 95% CI: 0.44, 0.73) compared with those with a small waist (<94/80 cm in men/women). Analysis with finer categories showed lower odds of successful aging starting at BMI ≥ 23.5 kg/m(2) and WC 82/68 cm in men/women., Conclusions: Optimal midlife BMI and WC for successful aging might be substantially below the current thresholds used to define obesity., (Copyright © 2013 The Obesity Society.)

Background: Vascular risk factors are associated with increased risk of cognitive impairment and dementia, but their association with motor function, another key feature of aging, has received little research attention. We examined the association between trajectories of the Framingham general cardiovascular disease risk score (FRS) over midlife and motor function later in life., Methods: A total of 5376 participants of the Whitehall II cohort study (29% women) who had up to four repeat measures of FRS between 1991-1993 (mean age=48.6 years) and 2007-2009 (mean age=65.4 years) and without history of stroke or coronary heart disease in 2007-2009 were included. Motor function was assessed in 2007-2009 through objective tests (walking speed, chair rises, balance, finger tapping, grip strength). We used age- and sex-adjusted linear mixed models., Results: Participants with poorer performances for walking speed, chair rises, and balance in 2007-2009 had higher FRS concurrently and also in 1991-1993, on average 16 years earlier. These associations were robust to adjustment for cognition, socio-economic status, height, and BMI, and not explained by incident mobility limitation prior to motor assessment. No association was found with finger tapping and grip strength., Conclusions: Cardiovascular risk early in midlife is associated with poor motor performances later in life. Vascular risk factors play an important and under-recognized role in motor function, independently of their impact on cognition, and suggest that better control of vascular risk factors in midlife may prevent physical impairment and disability in the elderly., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objective: To examine the association between alcohol consumption in midlife and subsequent cognitive decline., Methods: Data are from 5,054 men and 2,099 women from the Whitehall II cohort study with a mean age of 56 years (range 44-69 years) at first cognitive assessment. Alcohol consumption was assessed 3 times in the 10 years preceding the first cognitive assessment (1997-1999). Cognitive tests were repeated in 2002-2004 and 2007-2009. The cognitive test battery included 4 tests assessing memory and executive function; a global cognitive score summarized performances across these tests. Linear mixed models were used to assess the association between alcohol consumption and cognitive decline, expressed as z scores (mean = 0, SD = 1)., Results: In men, there were no differences in cognitive decline among alcohol abstainers, quitters, and light or moderate alcohol drinkers (<20 g/d). However, alcohol consumption ≥36 g/d was associated with faster decline in all cognitive domains compared with consumption between 0.1 and 19.9 g/d: mean difference (95% confidence interval) in 10-year decline in the global cognitive score = -0.10 (-0.16, -0.04), executive function = -0.06 (-0.12, 0.00), and memory = -0.16 (-0.26, -0.05). In women, compared with those drinking 0.1 to 9.9 g/d of alcohol, 10-year abstainers showed faster decline in the global cognitive score (-0.21 [-0.37, -0.04]) and executive function (-0.17 [-0.32, -0.01])., Conclusions: Excessive alcohol consumption in men (≥36 g/d) was associated with faster cognitive decline compared with light to moderate alcohol consumption.

Objective: The reserve hypothesis accounts for the lack of direct relationship between brain pathology and its clinical manifestations. Research has mostly focused on cognition; our objective is to examine whether the reserve hypothesis applies to motor function. We investigated whether education, a marker of reserve, modifies the association between white matter lesions (WMLs), a marker of vascular brain damage, and maximum walking speed (WS), an objective measure of motor function. We also examined the cross-sectional and longitudinal association between education and WS., Methods: Data are from 4,010 participants aged 65-85 years in the longitudinal Three-City-Dijon Study with up to 4 WS measures over 10 years. We examined the interaction between education and WMLs for baseline WS. We studied the association between education and repeated WS measures using linear mixed models, and the role of covariates in explaining the education-WS association., Results: Education was strongly associated with baseline WS; the difference in mean WS between the high and low education groups (0.145 m/s, 95% confidence interval = 0.125-0.165) was equivalent to 7.4 years of age. WMLs were associated with slow WS only in the low education group (p interaction = 0.026). WS declined significantly over time (-0.194 m/s/10 years, 95% confidence interval = -0.206, -0.182), but education did not influence rate of decline. Anthropometric characteristics, parental education, general health, and cognition had the strongest role in explaining the baseline education-WS association., Conclusions: Participants with more education were less susceptible to WMLs' effect on motor function. Higher education was associated with better motor performances but not with motor decline. These results are consistent with the passive reserve hypothesis.

Objective: To examine the association of body mass index (BMI) and metabolic status with cognitive function and decline., Methods: A total of 6,401 adults (71.2% men), aged 39-63 years in 1991-1993, provided data on BMI (normal weight 18.5-24.9 kg/m(2), overweight 25-29.9 kg/m(2); and obese ≥30 kg/m(2)) and metabolic status (abnormality defined as 2 or more of 1) triglycerides ≥1.69 mmol/L or lipid-lowering drugs, 2) systolic blood pressure ≥130 mm Hg, diastolic blood pressure ≥85 mm Hg, or antihypertensive drugs, 3) glucose ≥5.6 mmol/L or medications for diabetes, and 4) high-density lipoprotein cholesterol <1.04 mmol/L for men and <1.29 mmol/L for women). Four cognitive tests (memory, reasoning, semantic, and phonemic fluency) were administered in 1997-1999, 2002-2004, and 2007-2009, standardized to z scores, and averaged to yield a global score., Results: Of the participants, 31.0% had metabolic abnormalities, 52.7% were normal weight, 38.2% were overweight, and 9.1% were obese. Among the obese, the global cognitive score at baseline (p = 0.82) and decline (p = 0.19) over 10 years was similar in the metabolically normal and abnormal groups. In the metabolically normal group, the 10-year decline in the global cognitive score was similar (p for trend = 0.36) in the normal weight (-0.40; 95% confidence interval [CI] -0.42 to -0.38), overweight (-0.42; 95% CI -0.45 to -0.39), and obese (-0.42; 95% CI -0.50 to -0.34) groups. However, in the metabolically abnormal group, the decline on the global score was faster among obese (-0.49; 95% CI -0.55 to -0.42) than among normal weight individuals (-0.42; 95% CI -0.50 to -0.34), (p = 0.03)., Conclusions: In these analyses the fastest cognitive decline was observed in those with both obesity and metabolic abnormality.

Objectives: To estimate 10 year decline in cognitive function from longitudinal data in a middle aged cohort and to examine whether age cohorts can be compared with cross sectional data to infer the effect of age on cognitive decline., Design: Prospective cohort study. At study inception in 1985-8, there were 10,308 participants, representing a recruitment rate of 73%., Setting: Civil service departments in London, United Kingdom., Participants: 5198 men and 2192 women, aged 45-70 at the beginning of cognitive testing in 1997-9., Main Outcome Measure: Tests of memory, reasoning, vocabulary, and phonemic and semantic fluency, assessed three times over 10 years., Results: All cognitive scores, except vocabulary, declined in all five age categories (age 45-49, 50-54, 55-59, 60-64, and 65-70 at baseline), with evidence of faster decline in older people. In men, the 10 year decline, shown as change/range of test × 100, in reasoning was -3.6% (95% confidence interval -4.1% to -3.0%) in those aged 45-49 at baseline and -9.6% (-10.6% to -8.6%) in those aged 65-70. In women, the corresponding decline was -3.6% (-4.6% to -2.7%) and -7.4% (-9.1% to -5.7%). Comparisons of longitudinal and cross sectional effects of age suggest that the latter overestimate decline in women because of cohort differences in education. For example, in women aged 45-49 the longitudinal analysis showed reasoning to have declined by -3.6% (-4.5% to -2.8%) but the cross sectional effects suggested a decline of -11.4% (-14.0% to -8.9%)., Conclusions: Cognitive decline is already evident in middle age (age 45-49).

Lung function predicts mortality; whether it is associated with functional status in the general population remains unclear. This study examined the association of lung function with multiple measures of functioning in early old age. Data are drawn from the Whitehall II study; data on lung function (forced expiratory volume in 1 s, height FEV(1)), walking speed (2.44 m), cognitive function (memory and reasoning) and self-reported physical and mental functioning (SF-36) were available on 4,443 individuals, aged 50-74 years. In models adjusted for age, 1 standard deviation (SD) higher height-adjusted FEV(1) was associated with greater walking speed (beta=0.16, 95% CI: 0.13, 0.19), memory (beta=0.09, 95% CI: 0.06, 0.12), reasoning (beta=0.16, 95% CI: 0.13, 0.19) and self-reported physical functioning (beta=0.13, 95% CI: 0.10, 0.16). Socio-demographic measures, health behaviours (smoking, alcohol, physical activity, fruit/vegetable consumption), body mass index (BMI) and chronic conditions explained two-thirds of the association with walking speed and self-assessed physical functioning and over 80% of the association with cognitive function. Our results suggest that lung function is a good 'summary' measure of overall functioning in early old age.

Background: Previous reports have shown links between cognitive function and physical performance in the elderly people, but it is unclear whether some specific cognitive domains are more strongly associated with measures of physical function such as walking speed. We investigated cross-sectional and longitudinal relationships between performance in five cognitive tests and walking speed among community-dwelling elderly people in the Dijon center (France) of the Three-City Study., Methods: At baseline, 3,769 participants aged 65-85 years had measurements of 6-m walking speed, global cognition (Mini-Mental State Examination), verbal fluency (Isaacs Set Test [IST]), psychomotor speed (Trail Making Test part A [TMT-A]), executive function (TMT part B), and memory (Benton Visual Retention Test). After a mean follow-up of 7 years, walking speed was again measured in 1,732 of these participants., Results: In cross-sectional analyses, slower maximum walking speed (MWS) at baseline was significantly associated with poorer performance in each cognitive test. The association was stronger with TMT-A (beta [SE] = -.127 [0.014], p < .0001) and IST (beta [SE] = .120 [0.014], p < .0001) than with the other tests. Only TMT-A (beta [SE] = -.053 [0.021], p = .01) and IST (beta [SE] = .063 [0.022], p = .004) were associated with the degree of MWS decline over time., Conclusions: This study shows both cross-sectional and longitudinal associations between cognition and walking speed among community-dwelling elderly people. Poorer verbal fluency and slower psychomotor speed were more specifically associated with slower baseline MWS and with a stronger decline in MWS over time.

BackgroundNeurological disorders are increasingly recognised as major causes of death and disability worldwide. The aim of this analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 is to provide the most comprehensive and up-to-date estimates of the global, regional, and national burden from neurological disorders.MethodsWe estimated prevalence, incidence, deaths, and disability-adjusted life-years (DALYs; the sum of years of life lost [YLLs] and years lived with disability [YLDs]) by age and sex for 15 neurological disorder categories (tetanus, meningitis, encephalitis, stroke, brain and other CNS cancers, traumatic brain injury, spinal cord injury, Alzheimer's disease and other dementias, Parkinson's disease, multiple sclerosis, motor neuron diseases, idiopathic epilepsy, migraine, tension-type headache, and a residual category for other less common neurological disorders) in 195 countries from 1990 to 2016. DisMod-MR 2.1, a Bayesian meta-regression tool, was the main method of estimation of prevalence and incidence, and the Cause of Death Ensemble model (CODEm) was used for mortality estimation. We quantified the contribution of 84 risks and combinations of risk to the disease estimates for the 15 neurological disorder categories using the GBD comparative risk assessment approach.FindingsGlobally, in 2016, neurological disorders were the leading cause of DALYs (276 million [95% UI 247-308]) and second leading cause of deaths (9·0 million [8·8-9·4]). The absolute number of deaths and DALYs from all neurological disorders combined increased (deaths by 39% [34-44] and DALYs by 15% [9-21]) whereas their age-standardised rates decreased (deaths by 28% [26-30] and DALYs by 27% [24-31]) between 1990 and 2016. The only neurological disorders that had a decrease in rates and absolute numbers of deaths and DALYs were tetanus, meningitis, and encephalitis. The four largest contributors of neurological DALYs were stroke (42·2% [38·6-46·1]), migraine (16·3% [11·7-20·8]), Alzheimer's and other dementias (10·4% [9·0-12·1]), and meningitis (7·9% [6·6-10·4]). For the combined neurological disorders, age-standardised DALY rates were significantly higher in males than in females (male-to-female ratio 1·12 [1·05-1·20]), but migraine, multiple sclerosis, and tension-type headache were more common and caused more burden in females, with male-to-female ratios of less than 0·7. The 84 risks quantified in GBD explain less than 10% of neurological disorder DALY burdens, except stroke, for which 88·8% (86·5-90·9) of DALYs are attributable to risk factors, and to a lesser extent Alzheimer's disease and other dementias (22·3% [11·8-35·1] of DALYs are risk attributable) and idiopathic epilepsy (14·1% [10·8-17·5] of DALYs are risk attributable).InterpretationGlobally, the burden of neurological disorders, as measured by the absolute number of DALYs, continues to increase. As populations are growing and ageing, and the prevalence of major disabling neurological disorders steeply increases with age, governments will face increasing demand for treatment, rehabilitation, and support services for neurological disorders. The scarcity of established modifiable risks for most of the neurological burden demonstrates that new knowledge is required to develop effective prevention and treatment strategies.FundingBill & Melinda Gates Foundation.

Pathologic features of Parkinson's disease (PD) include death of dopaminergic neurons in the substantia nigra, presence of α-synuclein containing Lewy bodies, and iron accumulation in PD-related brain regions. The observed iron accumulation may be contributing to PD etiology but it also may be a byproduct of cell death or cellular dysfunction. To elucidate the possible role of iron accumulation in PD, we investigated genetic variation in 16 genes related to iron homeostasis in three case-control studies from the United States, Australia, and France. After screening 90 haplotype tagging single nucleotide polymorphisms (SNPs) within the genes of interest in the US study population, we investigated the five most promising gene regions in two additional independent case-control studies. For the pooled data set (1289 cases, 1391 controls) we observed a protective association (OR=0.83, 95% CI: 0.71-0.96) between PD and a haplotype composed of the A allele at rs1880669 and the T allele at rs1049296 in transferrin (TF; GeneID: 7018). Additionally, we observed a suggestive protective association (OR=0.87, 95% CI: 0.74-1.02) between PD and a haplotype composed of the G allele at rs10247962 and the A allele at rs4434553 in transferrin receptor 2 (TFR2; GeneID: 7036). We observed no associations in our pooled sample for haplotypes in SLC40A1, CYB561, or HFE. Taken together with previous findings in model systems, our results suggest that TF or a TF-TFR2 complex may have a role in the etiology of PD, possibly through iron misregulation or mitochondrial dysfunction within dopaminergic neurons.

Background: Most of the evidence on the association between unhealthy behaviors and disability comes from studies in the elderly, where reverse causation and selection bias may distort associations; thus, studies based on midlife trajectories of health behaviors are needed. We examined the association of trajectories of four health behaviors (physical activity, fruit and vegetable consumption, smoking, alcohol), starting in midlife and over 20 years, with subsequent disability risk in early old age (range = 54-84 years) in the Whitehall II cohort study.Methods: Disability was assessed three times over 3 years. A hierarchical disability indicator was constructed; participants were considered disabled if they reported difficulties with mobility and instrumental activities of daily living or with mobility and instrumental and basic activities of daily living. Behavior trajectories were defined using group-based trajectory models. Multivariable generalized estimating equations logistic models were used to examine their independent associations with disability.Results: Of 6,825 participants, 19.2% reported being disabled at least once. In mutually adjusted models, participants with persistent inactivity or declining physical activity, recent ex- or current smokers, and persistent/recent abstainers or persistent heavy drinkers had a higher disability risk, whereas fruit and vegetable consumption was not associated with disability. Disability risk increased progressively with the number of unhealthy behavior trajectories: the odds ratio of disability for 2-3 unhealthy trajectories was 2.69 (95% confidence interval = 2.26-3.19); these associations remained after adjustment for a wide range of covariates.Conclusions: Unhealthy behavior trajectories in midlife are associated with greater disability risk later in life. [ABSTRACT FROM AUTHOR]

Abstract: Parkinson''s disease (PD) is the most common cause of the parkinsonian syndromes and the most frequent neurodegenerative disease after Alzheimer''s disease. Because of the ageing of Western populations, an increasing number of persons will be affected with PD in the future and neither curative treatments nor preventive measures have been identified. PD is considered as a multifactorial disease, resulting from the effect of environmental factors and genetic susceptibility. Increasing age and male sex appear to be associated with an increased risk of PD. In addition, recent epidemiological studies have identified environmental exposures that influence the risk of PD. This review provides an overview of the epidemiologic evidence for environmental etiologies in PD; we will focus on two environmental exposures that have been quite consistently associated with PD – cigarette smoking and pesticide exposure – and will summarize briefly the findings for other exposures. Understanding the mechanisms underlying these epidemiological associations is an essential step for the understanding of the etiology of this neurodegenerative condition and, ideally, to develop neuroprotective drugs. [Copyright &y& Elsevier]

Walking speed (WS) represents an objective measure of motor function and health. We aimed to develop usual (UWS) and fast WS (FWS) norms for the general population using a regression-based approach, while considering age, sex, height, and education. Cross-sectional analysis of a population-based study. French Constances study (45-69 years). UWS/FWS were measured over 3 m (dynamic start) using photoelectric cells. We addressed selection effects (related to survey sampling and nonresponse) and missing data using a combination of inverse probability weighting (IPW) and multiple imputation (MI). Norms by sex, age, height, and education (

The article presents the results from Whitehall II cohort study concerning the onset of cognitive decline before the age of 60 participated by civil servants in London, England. The research reveals the significant cognitive decline over 10 years estimated from linear mixed models with three waves of data and expressed as percentage change which is known not to decline with age. The study was funded in part by the National Institutes of Health and the British Medical Research Council.

Abstract: We investigated the relationship of anthropometric markers of obesity with quantitative magnetic resonance imaging markers of brain aging, including measures of total brain volume (TBV), gray matter volume (GMV), hippocampal volume, white matter hyperintensity volume (WMHV), and brain infarcts, and examined causality using Mendelian randomization (MR). Analyses were performed in 1779 individuals (60.4% women, 72.8 ± 4.1 years of age) from the 3C-Dijon population-based cohort study (N = 1555 for the MR). Larger waist-to-hip-ratio (WHR) and waist circumference (WC) were associated with lower TBV (p = 0.0001 and p = 0.005), and lower GMV (p = 0.0008 and p = 0.003), independently of age, gender, body mass index (BMI), and vascular risk factors. Higher BMI, WC, and WHR were associated with larger WMHV and WC with brain infarcts, before adjusting for vascular risk factors only. We used MR to investigate the inverse relationship between WHR and GMV. One valid instrumental variable was available in women only (rs6905288), which was associated with GMV (p = 0.015). Age and BMI-adjusted effect estimates from the MR analysis confirmed the inverse association between GMV and WHR and are in favor of a causal association. [Copyright &y& Elsevier]

Abstract: Cerebral white matter lesions are associated with poorer motor performances in the elderly, but the role of gray matter atrophy remains largely unknown. We investigated the cross-sectional relation between brain regional gray matter volumes and walking speed over 6m in the 3C-Dijon study, a large population-based study of community-dwelling persons aged 65years and over (N=1623). Regional gray matter volumes were obtained using an automated anatomical labeling parcellation method. Multivariable analyses were performed using a semi-Bayes approach. After adjustment for potential confounders, persons who walked slower had a smaller volume of basal ganglia (regression coefficient [β]=0.054, standard error [SE]=0.028, p=0.05). In more detailed analyses, the volume of the caudate nucleus had a preponderant role on this association (β=0.049, SE=0.019, p=0.009), and walking speed decreased progressively with the volume of the caudate nucleus (p for linear trend<0.001). These results underline the role of gray matter subcortical structures, in particular of the caudate nucleus, in the age-related decline of motor performances among community-dwelling elderly subjects. [Copyright &y& Elsevier]