Arterial stiffness and white matter integrity in the elderly: A diffusion tensor and magnetization transfer imaging study.

BACKGROUND AND PURPOSE: The stiffness of large arteries and increased pulsatility can have an impact on the brain white matter (WM) microstructure, however those mechanisms are still poorly understood. The aim of this study was to investigate the association between central artery stiffness, axonal and myelin integrity in 54 cognitively unimpaired elderly subjects (65-75 years old). METHODS: The neuronal fiber integrity of brain WM was assessed using diffusion tensor metrics and magnetization transfer imaging as measures of axonal organization (Fractional anisotropy, Radial diffusivity) and state of myelination (Myelin volume fraction). Central artery stiffness was measured by carotid-femoral pulse wave velocity (cfPWV). Statistical analyses included 4 regions (the corpus callosum, the internal capsule, the corona radiata and the superior longitudinal fasciculus) which have been previously denoted as vulnerable to increased central artery stiffness. RESULTS: cfPWV was significantly associated with fractional anisotropy and radial diffusivity (p < 0.05, corrected for multiple comparisons) but not with myelin volume fraction. Findings from this study also show that improved executive function performance correlates with Fractional anisotropy positively (p < 0.05 corrected) as well as with myelin volume fraction and radial diffusivity negatively (p < 0.05 corrected). CONCLUSIONS: These findings suggest that arterial stiffness is associated with axon degeneration rather than demyelination. Controlling arterial stiffness may play a role in maintaining the health of WM axons in the aging brain.

Arterial stiffness, cognitive impairment and dementia: confounding factor or real risk?

Large artery stiffness is a frequent condition that arises with ageing, and is accelerated by the presence of co-morbidities like hypertension, obesity and diabetes. Although epidemiological studies have indicated an association between arterial stiffness, cognitive impairment and dementia, the precise effects of stiff arteries on the brain remains obscure. This is because, in humans, arterial stiffness is often accompanied by other factors such as age, high blood pressure, atherosclerosis and inflammation, which could themselves damage the brain independently of stiffness. Therefore, the question remains: is arterial stiffness a true risk for cognitive decline? Or, is it a confounding factor? In this review, we provide an overview of arterial stiffness and its impact on brain function based on human and animal studies. We summarize the evidence linking arterial stiffness to cognitive dysfunction and dementia, and discuss the role of new animal models to better understand the mechanisms by which arterial stiffness affects the brain. We close with an overview of treatments to correct stiffness and discuss the challenges to translate them to real patient care. This article is part of the Special Issue "Vascular Dementia".

Midlife physical activity engagement is associated with later-life brain health.

The relationship between midlife physical activity (PA), and cognition and brain health in later life is poorly understood with conflicting results from previous research. Investigating the contribution of midlife PA to later-life cognition and brain health in high-risk populations will propel the development of health guidance for those most in need. The current study examined the association between midlife PA engagement and later-life cognition, grey matter characteristics and resting-state functional connectivity in older individuals at high-risk for Alzheimer's disease. The association between midlife PA and later-life cognitive function was not significant but was moderated by later-life PA. Meanwhile, greater midlife moderate-to-vigorous PA was associated with greater grey matter surface area in the left middle frontal gyrus. Moreover, greater midlife total PA was associated with diminished functional connectivity between bilateral middle frontal gyri and middle cingulum, supplementary motor areas, and greater functional connectivity between bilateral hippocampi and right cerebellum, Crus II. These results indicate the potentially independent contribution of midlife PA to later-life brain health.

Arterial stiffness and age moderate the association between physical activity and global cognition in older adults.

BACKGROUND: Evidence supports that time spent on physical activity has beneficial effects on cognition in older adults. Nevertheless, whether these beneficial effects are still present at the intersection of different levels of arterial stiffness and age is uncertain. METHODS: One hundred and ten healthy older adults aged 60-75 years were examined for arterial stiffness [carotid-femoral pulse wave velocity (cf-PWV)], global cognition (composite score of Montreal Cognitive Assessment, and Mini-Mental State Examination), and self-reported physical activity (PACED diary). Using PROCESS macro for SPSS, we evaluated if cf-PWV (moderator 1), and age (moderator 2) moderate the relationship between physical activity (X) and global cognition (Y). The threshold for high stiffness was set at 8.5 m/s based on previous studies that reported this cut-off as more appropriate for classifying cerebrovascular risk groups. RESULTS: Physical activity had a positive effect on cognition in young-elderly adults (<68.5 years) with a cf-PWV of at least 8.5 m/s (ß = 0.48, SE = 0.193, P = 0.014, 95% CI = 0.100--0.868) and in elderly adults (≥68.5 years) with a cf-PWV of less than 8.5 m/s (ß = 0.56, SE = 0.230, P = 0.017, 95% CI = 0.104-1.018). This was not the case in elderly adults with a cf-PWV of at least 8.5 m/s (ß = 0.00, SE = 0.193, P = 0.998, 95% CI = -0.362 to 361), or in young-elderly adults with a cf-PWV of less than 8.5 m/s (ß = 0.16, SE = 0.247, P = 0.501, 95% CI = -0.326 to 656). CONCLUSION: The interaction between arterial stiffness and age moderated the effect of physical activity on global cognition. Time spent on physical activity alone might not be sufficient to achieve cognitive benefit over a specific threshold of arterial stiffness and age.

Associations Between Relative Morning Blood Pressure, Cerebral Blood Flow, and Memory in Older Adults Treated and Controlled for Hypertension.

[Figure: see text].

Sex-moderated association between body composition and cognition in older adults.

BACKGROUND: Some studies have reported an association between body composition and cognition in older adults, but underlying mechanisms and physiological factors remain poorly understood. Moreover, sex-related differences in metabolic health and age-related cognitive decline have gained major interest lately. The present study investigated the potential moderating effect of sex on the relationship between body composition and cognition in older adults. METHODS: Global cognition, assessed by the Montreal Cognitive Assessment (MoCA), and body composition, measured using dual-energy x-ray absorptiometry (DXA), were analyzed in 155 women and 65 men aged 60 years old or more. Moderation analyses were computed to determine if sex moderates the effect of the different body composition parameters on the MoCA while controlling for the body mass index and the level of education of the participants. RESULTS: Sex moderated the association between total lean mass, trunk lean mass, arms lean mass, and the MoCA score. These body composition parameters were positively associated with cognition only in men. Fat mass was not associated with cognition in any sex. CONCLUSION: Overall, higher lean mass and in particular trunk and arms lean mass was associated with higher cognitive abilities in older men. Longitudinal studies or intervention studies are needed to further identify physiological mechanisms that sustain the relationship between lean mass and cognition.

Arterial stiffness cut-off value and white matter integrity in the elderly.

OBJECTIVE: Central artery stiffness is a confirmed predictor of cardiovascular health status that has been consistently associated with cognitive dysfunction and dementia. The European Society of Hypertension has established a threshold of arterial stiffness above which a cardiovascular event is likely to occur. However, the threshold at which arterial stiffness alters brain integrity has never been established. METHODS: The aim of this study is to determine the arterial stiffness cut-off value at which there is an impact on the white matter microstructure. This study has been conducted with 53 cognitively elderly without dementia. The integrity of the white matter was assessed using diffusion tensor metrics. Central artery stiffness was evaluated by measuring the carotid-femoral pulse wave velocity (cfPWV). The statistical analyses included 4 regions previously denoted vulnerable to increased central arterial stiffness (the corpus callosum, the internal capsule, the corona radiata and the superior longitudinal fasciculus). RESULTS: The results of this study call into question the threshold value of 10 m/s cfPWV established by the European Society of Hypertension to classify patients in neuro-cardiovascular risk groups. Our results suggest that the cfPWV threshold value would be approximately 8.5 m/s when the microstructure of the white matter is taken as a basis for comparison. CONCLUSIONS: Adjustment of the cfPWV value may be necessary for a more accurate distinction between lower and higher risk group of patients for white matter microstructural injury related to arterial stiffness. Targeting the highest risk group for prevention methods may, in turn, help preserve brain health and cognitive functions.

Diurnal blood pressure loads are associated with lower cognitive performances in controlled-hypertensive elderly individuals.

INTRODUCTION: Hypertension in midlife adults is associated with cognitive decline later in life. In individuals treated for hypertension, blood pressure (BP) loads have been associated with end organ damages. This study examines whether BP load inversely correlates with performance in cognitive tasks in normotensive or controlled hypertensive (CHT) individuals. METHODS: Participants between 60 and 75 years old were divided into normotensive participants who did not receive antihypertensive treatment (n = 49) and CHT patients (n = 28). They were evaluated for BP using ambulatory blood pressure monitoring and cognitive functions with tests assessing cognitive flexibility, working and episodic memory, and processing speed. RESULTS: Analysis of covariance between normotensive and CHT participants revealed lower cognitive performances on immediate and delayed recall and total number of words of the Rey Auditory Verbal Learning Test (P < 0.001). Spearman's correlations between BP loads and cognitive performances revealed inversed associations between diurnal systolic (SBP) loads and performances on the Trail Making Test Part B (TMTB) (P = 0.009), the TMTB-TMT Part A (P = 0.013), the Switching Cost of the color-word interference test (P = 0.020) and the Digit-Symbol Substitution Score tests (P = 0.018) in CHT. Diurnal diastolic (DBP) loads were inversely correlated to the TMTB (P = 0.014) and TMTB-TMT Part A (P = 0.006). In normotensive subjects, diurnal SBP loads were associated with the delayed recall of the Rey Auditory Verbal Learning Test (P = 0.031) and to the three components of the digit span (P < 0.05). CONCLUSION: Diurnal BP loads are associated with lower cognitive performances in CHT individuals. These results suggest a lowering of target levels of diurnal BPs and/or its variability.