Patients with social anxiety disorder (SAD) are 'extremely shy': they are afraid of a negative evaluation by others and avoid social situations as much as possible, with negative influence on... Show morePatients with social anxiety disorder (SAD) are 'extremely shy': they are afraid of a negative evaluation by others and avoid social situations as much as possible, with negative influence on their lives. It is therefore important to gain insight in the factors that make children and adolescents vulnerable to develop SAD.SAD often runs in families: being ‘genetically close’ to a patient with SAD substantially increases the risk to develop the disorder. The studies summarized in this thesis aim to broaden our knowledge of this genetic vulnerability to SAD, by focusing on neurobiological endophenotypes as measured with structural and functional magnetic resonance imaging. We used data from the unique Leiden Family Lab study on Social Anxiety Disorder and demonstrated that several structural and functional brain alterations were genetically linked to the disorder. These results offer novel insights in the neurobiological pathways leading to SAD, and provide clues for prevention and intervention. Show less
With increasing age the prevalence of hypertension rises. High blood pressure at midlife is associated with cognitive impairment. Nevertheless, in older persons a lower rather than a higher... Show more With increasing age the prevalence of hypertension rises. High blood pressure at midlife is associated with cognitive impairment. Nevertheless, in older persons a lower rather than a higher blood pressure is associated with incident dementia. The main purpose of the work in this thesis was to explore the role of blood pressure in relation to cerebral structure, neurocognitive functioning and hemodynamics of the brain in old age. Therefore, we sought to determine whether discontinuation of antihypertensive therapy in persons aged 75 years and over with mild cognitive deficits and using antihypertensive medication (the Discontinuation of ANtihypertensive Treatment in Elderly people [DANTE] population) would improve their cognitive and psychological functioning. The assumption was that the increase in blood pressure after the discontinuation of antihypertensives would lead to a direct increase in cerebral blood flow and, as a consequence, to an improvement in cerebral functioning. An additional objective was to investigate possible underlying mechanisms in the relation between blood pressure and neurocognitive functioning. To enable this, brain MRI was used to determine whether (lower) blood pressure was associated with (micro)structural damage, cerebral small vessel disease and blood flow in the brain, and also whether the presence of cerebral (micro)structural damage was related to neurocognitive functioning. Show less
This thesis describes neuroimaging techniques to investigate brain networks in healthy aging and dementia. Functional and structural brain networks change with healthy and pathological... Show more This thesis describes neuroimaging techniques to investigate brain networks in healthy aging and dementia. Functional and structural brain networks change with healthy and pathological aging, with differences in network degeneration between different types of dementia. These disease-specific network differences suggest the potential of brain networks to improve diagnostic accuracy. However, at this moment, our findings are only applicable for groups of patients and not yet suitable as a diagnostic tool on an individual basis. Show less
Early dementias are difficult to distinguish from normal age-related memory decline. In the preclinical stages of Alzheimer’s disease and Huntington’s disease, brain functions are already changing... Show moreEarly dementias are difficult to distinguish from normal age-related memory decline. In the preclinical stages of Alzheimer’s disease and Huntington’s disease, brain functions are already changing, but this is not directly visible from the outside. Many research is aimed at discovering early disease markers. However, research using EEG registration during conventional eyes closed conditions revealed little additional information. The yield of EEG research can be improved by probing the weakest spot, which, in case of dementia, is memory. Karin van der Hiele introduced memory tests during EEG registration and found that early abnormalities in brain functioning can then be observed in Alzheimer’s disease and Huntington’s disease. An interesting finding came to light: the EEG in dementia displays a lot of muscle activity which is normally filtered out. However, the researchers decided not to throw this activity away but to measure it. Interestingly, they found that the amount of muscle activity was related to cognition and to the number of depressive complaints. It may pay to keep an open mind regarding the nature of the parameter to be measured. Show less
