We examined the development of international adoptees from infancy to young adulthood, and factors influencing developmental outcomes in middle childhood, adolescence and young adulthood. The... Show moreWe examined the development of international adoptees from infancy to young adulthood, and factors influencing developmental outcomes in middle childhood, adolescence and young adulthood. The results for cognitive development (Chapter 2) showed that early malnutrition influenced cognitive and health-related outcomes, but its consequences did not extend to socioeconomic success later in life. The human brain seems capable of adapting to changing environmental influences, but earlier placement in a positive family environment should be preferred (see also Chapter 1). The adoptees in the Leiden Longitudinal Adoption Study were exposed to few adversities due to their early adoptive placement, and the combination with the nurturing environment of a permanent adoptive family resulted in positive cognitive and socio-emotional outcomes (Chapters 2 and 3). Our results for longitudinal (sensitivity) and concurrent relations (reactivity to infant crying) with attachment representations in young adulthood (Chapters 3 and 4) clearly point to this role of the family environment in predicting social-emotional outcomes. High parenting quality is important, also in families where children do not share a common genetic basis with their parents. In sum, adoption can be seen as a positive intervention and the (adoptive) family environment matters for children growing up from infants to young adults. Show less
The general objective of this thesis was to investigate whether early clinical alterations and structural and functional brain markers could be detected in carriers of the Huntington__s disease... Show moreThe general objective of this thesis was to investigate whether early clinical alterations and structural and functional brain markers could be detected in carriers of the Huntington__s disease gene (referred to as carriers) who are still without manifest motor signs. We aimed to detect brain deficits using MRI and found smaller basal ganglia volumes in carriers compared to non carriers. Also, we demonstrated an increased amount of hypointensities in basal ganglia of carriers and suggested this may reflect excessive iron deposition. Furthermore, we showed strong associations between MRI characteristics and clinical variables suggesting that a combination of these measures may shed more light on the contribution of different kinds of pathological processes to the changing phenotype. When using memory activation during EEG registration early funcional brain changes, reflected in reduced alpha power, could be demonstrated in carriers. Furthermore, remarkably strong associations were found between the P3 Event-Related Potential and basal ganglia volumes. Subtle clinical abnormalities in motor function, executive function and memory could be demonstrated in carriers, especially over time. This study showed that several biomarkers provide new and important information on premanifest HD. The mulitfactorial approach offers new insights into the relation between clinical phenomena and abnormalities in the neural substrate Show less
The main objective of this thesis was to clarify the observed reversal of effect of classical risk factors for dementia and mortality with increasing age and to gain better insight in the... Show moreThe main objective of this thesis was to clarify the observed reversal of effect of classical risk factors for dementia and mortality with increasing age and to gain better insight in the biological mechanism behind the relation between both phenotypic and genetic variation in apolipoprotein E (apoE) and cognitive function. Although high cholesterol levels in midlife associate with worse cognitive function and dementia in late-life, this association attenuates and even reverses with increasing age. In memory outpatient clinic patients high blood pressure associated with better cognitive function, only in patients with structural brain damage. In the Leiden 85-Plus Study, a decline in global cognitive function preceded declines in total cholesterol levels, HDL cholesterol levels, and blood pressure, and not vice versa. Moreover, mortality was associated with larger declines in body mass index, total cholesterol levels, HDL cholesterol levels, and blood pressure. High plasma apoE levels associated with worse cognitive function, whereas offspring from Alzheimer__s disease patients had lower plasma apoE levels when measured in midlife compared to offspring from cognitively intact controls. Finally, high serum calcium levels were strongly associated with worse cognitive function in APOE _3_4 carriers, to a lesser extent in _3_3 carriers, but not in _2_3 carriers. 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
