The general aim of this thesis was to study the frequency, causes and consequences of pathologic brain aging specifically focusing on sub-clinical and clinical MRI manifestations of vascular (small... Show moreThe general aim of this thesis was to study the frequency, causes and consequences of pathologic brain aging specifically focusing on sub-clinical and clinical MRI manifestations of vascular (small vessel disease) and neurodegenerative (brain atrophy) disease. A second aim was to improve the accuracy of the tools to quantify brain tissue so to better reflect the imaging characteristics of older people. All data presented in this thesis are from the AGES-Reykjavik Study including 5764 elderly men and women. The data is based on cross-sectional and longitudinal assessments of the brain with MRI measures. Show less
The primary aim of this thesis was to investigate the complex relationship between pain, neuropsychiatric symptoms, and ADL functioning in persons with dementia. Furthermore, we studied the... Show moreThe primary aim of this thesis was to investigate the complex relationship between pain, neuropsychiatric symptoms, and ADL functioning in persons with dementia. Furthermore, we studied the psychometric properties of a new and universal observational pain assessment instrument Pain Assessment In Impaired Cognition: PAIC.The results of this thesis show that pain in nursing home residents with dementia is related to a decline in ADL functions, independent of dementia severity. Specifically, a decline in the ADL activities transferring and bathing.Additionally, the psychometric evaluation of the PAIC presented in this thesis not only results in a promising measurement instrument, but also provides useful information for the development and improvement of educational programmes that contribute to the utilization of the PAIC15. Show less
Vitamin D is a hormone produced in the skin via a non-enzymatic process involving ultraviolet light.It is well known that the physiology of aging makes older people particularly susceptible to... Show moreVitamin D is a hormone produced in the skin via a non-enzymatic process involving ultraviolet light.It is well known that the physiology of aging makes older people particularly susceptible to vitamin D deficiency and that, if untreated, it can have serious health consequences. This thesis deliberates on the topics of vitamin D supplementation in older people in light of the current guidelines and on the possible additional effects of ultraviolet light beyond vitamin D synthesis on nursing home residents. We present a cross-sectional study in nursing home residents aged 70 years and over designed to evaluate the efficacy of vitamin D supplementation in achieving vitamin D sufficiency. We also discuss the different supplementation strategies for nursing home residents and community dwelling persons aged 70 years and over based on a survey administered to general practitioners and elderly care physicians in the Netherlands.In the second part we concentrate on additional effects of ultraviolet light beyond vitamin D synthesis. We describe our systematic review of literature on the effect of ultraviolet light, when applied to the skin or eyes, on mood, depression and well-being. We present also our randomized controlled trial on the effect of ultraviolet radiation compared with oral vitamin D supplementation on the well-being of nursing home residents with dementia. Further we use the data of the RCT to carry out a post-hoc analysis to compare the effect of vitamin D alone compared with ultraviolet radiation on the blood pressure of old people with dementia. Show less
As the number of patients suffering from dementia is still growing, most of the patients display behavioral symptoms at some time during the disease and these behavioral symptoms lower the quality... Show moreAs the number of patients suffering from dementia is still growing, most of the patients display behavioral symptoms at some time during the disease and these behavioral symptoms lower the quality of life and increase the burden of caregivers, adequate management of these symptoms is warranted. However, the etiology and management of behavioral symptoms is complex, resulting in (mis)use of pharmacological interventions: a cure which is often worse than the disease. In healthy adults, caffeine is known to influence behavior. Four different studies were conducted to see if caffeine is an easy to adjust cause or a pragmatic intervention for behavioral symptoms in patients with dementia. Based on these studies, we conclude caffeine can influence behavior in persons with dementia, but most likely not in all persons, not in all situations and not all of the time; but it can have an influence. In clinical practice it is advisable to consider caffeine as a possible moderator in the clinical assessment of behavioral symptoms in persons with dementia. Show less
In this thesis, longitudinal analyses have been performed on the PROPARK-Cohort, a hospital-based cohort of 421 patients followed for a period of five years. The main focus of this thesis was... Show moreIn this thesis, longitudinal analyses have been performed on the PROPARK-Cohort, a hospital-based cohort of 421 patients followed for a period of five years. The main focus of this thesis was to determine which predictors and associated factors contributed to the development of certain non-motor symptoms in Parkinson’s disease (PD). Strengths of our cohort study include the length of the follow-up period, broad clinical characterization, limited loss-to-follow-up and the large cohort size. The following non-motor symptoms have been addressed in this thesis: psychosis (hallucinations), dementia, excessive daytime sleepiness (EDS), insomnia, depression and anxiety. We found that while certain non-motor symptoms are inherent components of PD that increase in severity as the disease progresses, others symptoms such as excessive daytime sleepiness are inarguably caused by antiparkinsonian medication. For the future, we hope to see more longitudinal data on the disease progression in PD from large cohorts. Knowledge from longitudinal studies does not only contribute to more insight in the underlying pathobiology of PD, but it could also help the caregiver to monitor patients with particular risk factors more closely and adjust treatment if necessary. Show less
This thesis describes several state-of-the-art challenge methods to study the cholinergic system in humans by measuring the effects of compounds that selectively act upon muscarinic or... Show moreThis thesis describes several state-of-the-art challenge methods to study the cholinergic system in humans by measuring the effects of compounds that selectively act upon muscarinic or nicotinic acetylcholine receptors. The thesis reveals part of the complexity of the cholinergic system, its changes related to aging, its relationship with cognitive function and performance, and its role in inflammation. Additionally, the methodology described in the thesis provides controlled circumstances using repeated measurement of drug concentrations and effects during a pharmacologic cholinergic challenge that can be used in drug development of new compounds with cholinergic activity. Show less
