Year: 2010
Type: dissertation
Abstract: The brain is by far the most complicated structure of the human being, and its malfunction is \ncharacterized by various degrees and types of morbidity. Several brain functions deteriorate with \nincreasing age during life. Cognitive decline and age-related brain pathology are common in the \nelderly, but these changes may also become manifest early in life and preceding the onset of clinical \nsymptoms of disease. The detection of early changes may be relevant for therapeutic interventions to \nprevent disease, and are therefore also increasingly targeted in genetic research as endophenotypes. \nEndophenotypes are defined as heritable phenotypes that are related to the disease of interest, and \nare typically approached as quantitative outcomes, i.e., instead of hypertension, the endophenotype \nof interest is systolic or diastolic blood pressure. In contrast to classical risk factors in epidemiology, \nan endophenotype is by definition not uniquely associated to a single disease. Blood pressure for \nexample, is consistently associated to various clinically relevant outcomes such as stroke, myocardial \ninfarction and heart failure. There is an increasing interest in the genetic research of endophenotypes, \nand genome-wide association studies of endophenotypes have been very successful. In this \nthesis I focus on cognitive function and age-related brain changes early in life as endophenotypes for \nlate-life brain disease and as targets for early prevention. \nCognitive deterioration can be seen in pre-clinical stages of neurodegenerative and \nneuropsychiatric disorders like dementia, schizophrenia, bipolar disorder and attention deficit \nhyperactivity disorder (ADHD). Cognitive function is a broad concept referring to multiple \ncognitive domains, among which memory, language, executive function and visuospatial ability. \nAlthough the domains are highly correlated, it is known that specific domains are related to \nspecific diseases. Cognitive function is in part determined by our genetic make-up. The \nheritability is estimated to around 40% and there have been various studies that have tried to \nidentify genes explaining the heritability of cognitive functions. These included candidate gene \nstudies, linkage studies and genome-wide association studies. The genes \nand chromosomal regions that have been found so far are partly explained by genes related \nto neuropsychiatric disease, and partly by genes related to dementia and Alzheimer’s disease \n(AD) with the Apolipoprotein E gene as genetic factor with one of the strongest effects. In the \nstudies presented here, we will focus on a cognitive test battery targeting AD. Dementia is \none of the most common causes of morbidity and mortality in the Western society (prevalence \nof 25 million cases worldwide), in which Alzheimer disease accounts fo
Author: Maaike Schuur
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W1583630595