Marc M. Budge

Body mass index in midlife and late‐life as a risk factor for dementia: a meta‐analysis of prospective studies

The relationship between body mass index (BMI) (in midlife and late‐life) and dementia was investigated in meta‐analyses of 16 articles reporting on 15 prospective studies. Follow‐ups ranged from 3.2 to 36.0 years. Meta‐analyses were conducted on samples including 25 624 participants evaluated for Alzheimers disease (AD), 15 435 participants evaluated for vascular dementia (VaD) and 30 470 followed for any type of dementia (Any Dementia). Low BMI in midlife was associated with 1.96 [95% confidence interval (CI): 1.32, 2.92] times the risk of developing AD. The pooled relative risks for AD, VaD and Any Dementia for overweight BMI in midlife compared with normal BMI were 1.35 (95% CI:1.19, 1.54), 1.33 (95% CI: 1.02, 1.75) and 1.26 (95% CI: 1.10, 1.44), respectively. The pooled relative risks of AD and Any Dementia for obese BMI in midlife compared to normal BMI were 2.04 (95% CI: 1.59, 2.62) and 1.64 (95% CI: 1.34, 2.00), respectively. Continuous BMI in late‐life was not associated with dementia. Small numbers of studies included in pooled analyses reduce generalizability of findings, and emphasize the need for publication of additional findings. We conclude that underweight, overweight and obesity in midlife increase dementia risk. Further research evaluating late‐life BMI and dementia is required.

Symmetric atlasing and model based segmentation: an application to the hippocampus in older adults

In model-based segmentation, automated region identification is achieved via registration of novel data to a pre-determined model. The desired structure is typically generated via manual tracing within this model. When model-based segmentation is applied to human cortical data, problems arise if left-right comparisons are desired. The asymmetry of the human cortex requires that both left and right models of a structure be composed in order to effectively segment the desired structures. Paradoxically, defining a model in both hemi-spheres carries a likelihood of introducing bias to one of the structures. This paper describes a novel technique for creating a symmetric average model in which both hemispheres are equally represented and thus left-right comparison is possible. This work is an extension of that proposed by Guimond et al. Hippocampal segmentation is used as a test-case in a cohort of 118 normal eld-erly subjects and results are compared with expert manual tracing.

Influence of Adiposity and Physical Activity on Arterial Stiffness in Healthy Children: The Lifestyle of Our Kids Study

Abstract—Childhood obesity is increasingly prevalent in the community and is related to adverse cardiovascular outcomes during adulthood. In this study of healthy children, we evaluated the influence of adiposity and physical activity on carotid-femoral pulse wave velocity (PWV), an index of arterial stiffness and a marker of cardiovascular risk in adults. In 573 community-based children (mean age: 10.1±0.3 years; 51% boys), we measured body mass index and waist circumference. Percentage body fat was quantitated by dual-energy x-ray absorptiometry. Cardiorespiratory fitness (CRF) and physical activity levels were assessed using a 20-m shuttle run and 7-day pedometer count, respectively. PWV was estimated by applanation tonometry. In univariate analysis, PWV was positively correlated with body mass index (r=0.34), waist circumference (r=0.32), and percentage body fat (r=0.32; P<0.001 for all) and negatively correlated with CRF (r=−0.23; P<0.001) and pedometer count (r=−0.08; P=0.046). In separate multivariable linear regression models, body mass index, waist circumference, and percentage of body fat were independently and positively associated with PWV (P<0.01 for all) after adjusting for age, sex, systolic blood pressure, mean arterial pressure, heart rate, and CRF (P<0.01 for all). The influence of CRF on PWV was attenuated after adjusting for adiposity. In conclusion, increased body mass and adiposity and decreased CRF are associated with arterial stiffening in healthy prepubescent children.

Blood Pressure-Related Cognitive Decline: Does Age Make a Difference?

Systolic and diastolic blood pressures have been inversely related to cognitive performance in prospective and cross-sectional studies. However, in large, community-based samples, these findings have been limited to older adults. In this 20-year longitudinal study, we examined the relationship between baseline blood pressure and cognitive decline for 529 participants using 2 age groups (18 to 46 years and 47 to 83 years). Cognitive performance was measured over multiple examinations with the Wechsler Adult Intelligence Scale from which 4 scores were derived by factor analysis. A 2-stage growth curve method of analysis was used to model cognitive change. Results indicated that higher levels of baseline systolic blood pressure, diastolic blood pressure, mean arterial pressure, and blood pressure categories as defined by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure were significantly associated with decline in Visualization/Fluid abilities in both younger and older age groups. Young adults are as susceptible to blood pressure-related longitudinal decline in cognitive performance as are older adults.

Vitamin B12 status and rate of brain volume loss in community-dwelling elderly.

Objectives: To investigate the relationship between markers of vitamin B12 status and brain volume loss per year over a 5-year period in an elderly population. Methods: A prospective study of 107 community-dwelling volunteers aged 61 to 87 years without cognitive impairment at enrollment. Volunteers were assessed yearly by clinical examination, MRI scans, and cognitive tests. Blood was collected at baseline for measurement of plasma vitamin B12, transcobalamin (TC), holotranscobalamin (holoTC), methylmalonic acid (MMA), total homocysteine (tHcy), and serum folate. Results: The decrease in brain volume was greater among those with lower vitamin B12 and holoTC levels and higher plasma tHcy and MMA levels at baseline. Linear regression analysis showed that associations with vitamin B12 and holoTC remained significant after adjustment for age, sex, creatinine, education, initial brain volume, cognitive test scores, systolic blood pressure, ApoE ε4 status, tHcy, and folate. Using the upper (for the vitamins) or lower tertile (for the metabolites) as reference in logistic regression analysis and adjusting for the above covariates, vitamin B12 in the bottom tertile (<308 pmol/L) was associated with increased rate of brain volume loss (odds ratio 6.17, 95% CI 1.25–30.47). The association was similar for low levels of holoTC (<54 pmol/L) (odds ratio 5.99, 95% CI 1.21–29.81) and for low TC saturation. High levels of MMA or tHcy or low levels of folate were not associated with brain volume loss. Conclusion: Low vitamin B12 status should be further investigated as a modifiable cause of brain atrophy and of likely subsequent cognitive impairment in the elderly.

Arterial Pulse Wave Velocity and Cognition With Advancing Age

We hypothesized that carotid-femoral pulse wave velocity (PWV), a marker of arterial stiffness, interacts with age such that the magnitude of associations between PWV and cognitive performance are greater with increasing age and that this interaction is observed despite adjustments for demographic variables, mean arterial pressure, and cardiovascular risk factors. PWV was estimated using applanation tonometry in 409 dementia- and stroke-free participants of the Maine-Syracuse Longitudinal Study (24 to 92 years of age; 62.3% women). Using linear regression analyses in a cross-sectional design, associations between PWV and age and the interaction of PWV and age were examined in relation to a global composite score, the Wechsler Adult Intelligence Scale Similarities test (abstract reasoning), and 4 cognitive domains indexed by multiple cognitive measures. Adjusting for age, gender, education, height, weight, heart rate, mean arterial pressure, and antihypertensive treatment, PWV-by-age interactions were obtained for the global, visual-spatial organization and memory, scanning and tracking, and verbal episodic memory composites, as well as similarities. The combination of higher PWV and age resulted in progressively lower cognitive performance. This finding was the same with an extended model, which also included adjustment for cardiovascular risk factors and other confounds. PWV interacts with age in a multiplicative way to exert a negative influence on cognitive performance level. Early interventions to prevent an increase in arterial stiffness could possibly play an important role in the preservation of cognitive ability.

Postprandial Hypotension Predicts All‐Cause Mortality in Older, Low‐Level Care Residents

Objectives: To evaluate which indices of blood pressure (BP) homeostasis are the strongest predictors of mortality in older low‐level‐care residents in long‐term health facilities.

Stability and predictability of the classification of mild cognitive impairment as assessed by episodic memory test performance over time

This study aimed to address the criteria and the stability of the classification of MCI. The Foresight Challenge cohort of 157 community-dwelling volunteers was assessed on 3 visits at 2-year intervals with episodic, semantic and working memory tests. Subjective memory complaints were assessed with the CAMDEX. Of the cohort, 2% had dementia and 31% were classified with MCI at visit 3, 43% with stable impairment from Time 1. Thirteen percent of those with objective memory impairment at Time 1 or 2 improved to control status by Time 3. Episodic memory tests were predictive for MCI at all timepoints, as were tests for praxis and Graded Naming, while at Time 3 spatial span lost predictive value, but processing speed became predictive. Decline in processing speed was seen in control and MCI groups, while memory performance and MMSE decline occurred only in the MCI group. The use of combined memory test scores gave better sensitivity to MCI than single tests. Subjective memory complaints were positive for 79% of the MCI group and 62.5% of controls. These findings would suggest consideration of modification of current MCI criteria. Our chief acknowledgement is to the individuals who volunteered to participate in the study. We acknowledge the support of Professor David Smith and Elizabeth King at OPTIMA and are grateful to the research nurses for administering the baseline screening tests. This work was supported by grants from the Medical Research Council, The Norman Collisson Foundation and The Clore Duffield Foundation.

Aortic stiffness for the detection of preclinical left ventricular diastolic dysfunction: pulse wave velocity versus pulse pressure.

Objective An age-dependent relationship between aortic and left ventricular (LV) stiffening has been observed in community-based adults. Our aim was to compare the performances of wave reflection-dependent (pulse pressure) and independent [carotid-femoral pulse wave velocity (PWV)] indexes of aortic stiffness to detect preclinical LV diastolic dysfunction. Methods In this case–control study, a stratified subsample of participants of a population-based echocardiographic survey with LV ejection fraction higher than 45% and without overt heart failure was randomly selected to undergo assessment of brachial blood pressure, LV diastolic function by Doppler echocardiography, and estimation of central aortic pressures and PWV by applanation tonometry. Results Of the 233 subjects (mean age 73 ± 6 years, 54% men), 84 had normal diastolic function, 99 had mild diastolic dysfunction, and 50 had moderate or severe diastolic dysfunction. Brachial pulse pressure, central pulse pressure, and PWV progressively increased according to the severity of diastolic dysfunction, independent of age and sex. The overall performance of PWV was superior to brachial pulse pressure [area under receiver operating characteristic curve (AUC): 0.70 versus 0.59, respectively; P = 0.005] and central pulse pressure (AUC: 0.70 versus 0.56, respectively; P = 0.001) for the detection of any diastolic dysfunction. Conclusion PWV appeared to be superior to central and brachial pulse pressure for the detection of diastolic dysfunction in older adults with ‘preserved’ LV ejection fraction.

Terminology for Describing the Elastic Behavior of Arteries

The ability to characterize and quantify the elastic behavior of arteries has become increasingly important, because its application has broadened from basic physiology to clinical domains and the prediction of cardiovascular risk. Consequently, it is imperative that terminology to communicate across these disciplines is consistent and meaningful. In 1960, Peterson et al1 suggested coining a new definition of elastic modulus, the ratio of stress to strain, in terms of the pulse pressure, ΔP, and the directly measurable parameters ΔD and D (diameter). This has subsequently become known as Peterson’s modulus (Ep), where ![Formula][1] In 1975, one of us (R.G.G.)2 suggested calling the inverse of Ep the arterial compliance , C, where ![Formula][2] However, since that date, various authors have used the term distensibility for this quantity (eg, most recently O’Rourke et al3), and the term compliance has also become strongly linked with adherence to medical advice. The authors would therefore suggest that this difference in terminology is best resolved by using the long-established, engineering term compressibility when referring to the inverse of the elastic modulus.4,5 Thus, use of the well-defined, longer-established terms, elastic modulus and compressibility , would replace the need to use the terms compliance and distensibility, about whose mathematical definition some confusion exists in the literature. The classic physics of elasticity is often said to have started in 1600 with the discovery by Hooke that the ratio of stress to strain in isotropic materials, within … [1]: /embed/graphic-1.gif [2]: /embed/graphic-2.gif