Changes in total cerebral blood flow and morphology in aging

In this thesis the reproducibility of new methods using MRI for measuring total cerebral blood flow and cerebrovascular reserve capacity was assessed. We used these methods to show that NO is an important factor in the hypoxia induced vasodilatation of vessels in the brain. It was shown that basal total cerebral blood flow in the elderly, in contrary to the young, is dependent on the NO pathway. White matter hyperintensities are seen in almost every elderly subject. We showed that besides the white matter hyperintensities there are also change because of aging in the normal appearing white matter. This was demonstrated with the use of magnetization transfer imaging. The appearance of the white matter hyperintensities seems to be independent of the changes in the normal appearing white matter which gives rise to the idea that both entities have different aetiologies. Using this technique we also showed that not all white matter hyperintensities are the same but that differences exists between white matter hyperintensities periventricular and in the deep white matter. Also, differences between frontal and occipital located periventricular white matter hyperintensities exists. Finally, we found that cognitive decline in the elderly is associated with a diminished total cerebral blood flow.Pathofysiologie, epidemiologie en therapie bij verouderin

Cerebral Perfusion and Aortic Stiffness Are Independent Predictors of White Matter Brain Atrophy in Type 1 Diabetic Patients Assessed With Magnetic Resonance Imaging

OBJECTIVE-To identify vascular mechanisms of brain atrophy in type 1 diabetes mellitus (DM) patients by investigating the relationship between brain volumes and cerebral perfusion and aortic stiffness using magnetic resonance imaging (MRI). RESEARCH DESIGN AND METHODS-Approval from the local institutional review board was obtained, and patients gave informed consent. Fifty-one type 1 DM patients (30 men; mean age 44 +/- 11 years; mean DM duration 23 +/- 12 years) and 34 age- and sex-matched healthy control subjects were prospectively enrolled. Exclusion criteria comprised hypertension, stroke, aortic disease, and standard MRI contraindications. White matter (WM) and gray matter (GM) brain volumes, total cerebral blood flow (tCBF), total brain perfusion, and aortic pulse wave velocity (PWV) were assessed using MRI. Multivariable linear regression analysis was used for statistics, with covariates age, sex, mean arterial pressure, BMI, smoking, heart rate, DM duration, and HbA(1c). RESULTS-Both WM and GM brain volumes were decreased in type 1 DM patients compared with control subjects (WM P = 0.04; respective GM P = 0.03). Total brain perfusion was increased in type 1 DM compared with control subjects (beta = -0.219, P < 0.05). Total CBF and aortic PWV predicted WM brain volume (beta = 0.352, P = 0.024 for tCBF; respective beta = 0.458, P = 0.016 for aortic PWV) in type 1 DM. Age was the independent predictor of GM brain volume (beta = -0.695, P < 0.001). CONCLUSIONS-Type 1 DM patients without hypertension showed WM and GM volume loss compared with control subjects concomitant with a relative increased brain perfusion. Total CBF and stiffness of the aorta independently predicted WM brain atrophy in type 1 DM. Only age predicted GM brain atrophy.Cardiovascular Aspects of Radiolog

Teacher Wellbeing: The Importance of Teacher–Student Relationships

Many studies have examined the importance of teacher-student relationships for the development of children. Much less is known, however, about how these relationships impact the professional and personal lives of teachers. This review considers the importance of teacher-student relationships for the wellbeing of teachers guided by the Transactional Model of Stress and Coping of Lazarus (1991). Based on theories on interpersonal relationships, it is postulated that teachers have a basic need for relatedness with the students in their class that originates from the close proximity between teacher and student. It is discussed that teachers internalize experiences with students in representational models of relationships that guide emotional responses in daily interactions with students, and changes teacher wellbeing in the long run. In addition, the notion of mental representations of relationships at different levels of generalization could offer a window to understand how individual teacher-student relationships may affect the professional and personal self-esteem of teachers. Lastly, it is argued that the influence of student misbehavior on teacher stress may be more fully understood from a relationship perspective. The review shows that few studies have directly tested these propositions and offers suggestions for future research

Morphological and Pathological Evolution of the Brain Microcirculation in Aging and Alzheimer’s Disease

Key pathological hallmarks of Alzheimer’s disease (AD), including amyloid plaques, cerebral amyloid angiopathy (CAA) and neurofibrillary tangles do not completely account for cognitive impairment, therefore other factors such as cardiovascular and cerebrovascular pathologies, may contribute to AD. In order to elucidate the microvascular changes that contribute to aging and disease, direct neuropathological staining and immunohistochemistry, were used to quantify the structural integrity of the microvasculature and its innervation in three oldest-old cohorts: 1) nonagenarians with AD and a high amyloid plaque load; 2) nonagenarians with no dementia and a high amyloid plaque load; 3) nonagenarians without dementia or amyloid plaques. In addition, a non-demented (ND) group (average age 71 years) with no amyloid plaques was included for comparison. While gray matter thickness and overall brain mass were reduced in AD compared to ND control groups, overall capillary density was not different. However, degenerated string capillaries were elevated in AD, potentially suggesting greater microvascular “dysfunction” compared to ND groups. Intriguingly, apolipoprotein ε4 carriers had significantly higher string vessel counts relative to non-ε4 carriers. Taken together, these data suggest a concomitant loss of functional capillaries and brain volume in AD subjects. We also demonstrated a trend of decreasing vesicular acetylcholine transporter staining, a marker of cortical cholinergic afferents that contribute to arteriolar vasoregulation, in AD compared to ND control groups, suggesting impaired control of vasodilation in AD subjects. In addition, tyrosine hydroxylase, a marker of noradrenergic vascular innervation, was reduced which may also contribute to a loss of control of vasoconstriction. The data highlight the importance of the brain microcirculation in the pathogenesis and evolution of AD

Heterogeneity in age-related white matter changes

White matter changes occur endemically in routine magnetic resonance imaging (MRI) scans of elderly persons. MRI appearance and histopathological correlates of white matter changes are heterogeneous. Smooth periventricular hyperintensities, including caps around the ventricular horns, periventricular lining and halos are likely to be of non-vascular origin. They relate to a disruption of the ependymal lining with subependymal widening of the extracellular space and have to be differentiated from subcortical and deep white matter abnormalities. For the latter a distinction needs to be made between punctate, early confluent and confluent types. Although punctate white matter lesions often represent widened perivascular spaces without substantial ischemic tissue damage, early confluent and confluent lesions correspond to incomplete ischemic destruction. Punctate abnormalities on MRI show a low tendency for progression, while early confluent and confluent changes progress rapidly. The causative and modifying pathways involved in the occurrence of sporadic age-related white matter changes are still incompletely understood, but recent microarray and genome-wide association approaches increased the notion of pathways that might be considered as targets for therapeutic intervention. The majority of differentially regulated transcripts in white matter lesions encode genes associated with immune function, cell cycle, proteolysis, and ion transport. Genome-wide association studies identified six SNPs mapping to a locus on chromosome 17q25 to be related to white matter lesion load in the general population. We also report first and preliminary data that demonstrate apolipoprotein E (ApoE) immunoreactivity in white matter lesions and support epidemiological findings indicating that ApoE is another factor possibly related to white matter lesion occurrence. Further insights come from modern MRI techniques, such as diffusion tensor and magnetization transfer imaging, as they provide tools for the characterization of normal-appearing brain tissue beyond what can be expected from standard MRI scans. There is a need for additional pre- and postmortem studies in humans, including these new imaging techniques