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- W1583630595 abstract "textabstractThe brain is by far the most complicated structure of the human being, and its malfunction ischaracterized by various degrees and types of morbidity. Several brain functions deteriorate withincreasing age during life. Cognitive decline and age-related brain pathology are common in theelderly, but these changes may also become manifest early in life and preceding the onset of clinicalsymptoms of disease. The detection of early changes may be relevant for therapeutic interventions toprevent disease, and are therefore also increasingly targeted in genetic research as endophenotypes.Endophenotypes are defined as heritable phenotypes that are related to the disease of interest, andare typically approached as quantitative outcomes, i.e., instead of hypertension, the endophenotypeof interest is systolic or diastolic blood pressure. In contrast to classical risk factors in epidemiology,an endophenotype is by definition not uniquely associated to a single disease. Blood pressure forexample, is consistently associated to various clinically relevant outcomes such as stroke, myocardialinfarction and heart failure. There is an increasing interest in the genetic research of endophenotypes,and genome-wide association studies of endophenotypes have been very successful. In thisthesis I focus on cognitive function and age-related brain changes early in life as endophenotypes forlate-life brain disease and as targets for early prevention.Cognitive deterioration can be seen in pre-clinical stages of neurodegenerative andneuropsychiatric disorders like dementia, schizophrenia, bipolar disorder and attention deficithyperactivity disorder (ADHD). Cognitive function is a broad concept referring to multiplecognitive domains, among which memory, language, executive function and visuospatial ability.Although the domains are highly correlated, it is known that specific domains are related tospecific diseases. Cognitive function is in part determined by our genetic make-up. Theheritability is estimated to around 40% and there have been various studies that have tried toidentify genes explaining the heritability of cognitive functions. These included candidate genestudies, linkage studies and genome-wide association studies. The genesand chromosomal regions that have been found so far are partly explained by genes relatedto neuropsychiatric disease, and partly by genes related to dementia and Alzheimer’s disease(AD) with the Apolipoprotein E gene as genetic factor with one of the strongest effects. In thestudies presented here, we will focus on a cognitive test battery targeting AD. Dementia isone of the most common causes of morbidity and mortality in the Western society (prevalenceof 25 million cases worldwide), in which Alzheimer disease accounts for over 70% of cases. Regarding the high prevalence and major impact of these diseases, early diagnosis andtreatment strategies have a high priority in neuroscience. Identifying risk factors for cognitivedecline would benefit our increasingly elderly population." @default.
- W1583630595 created "2016-06-24" @default.
- W1583630595 creator A5030952632 @default.
- W1583630595 date "2010-05-12" @default.
- W1583630595 modified "2023-09-24" @default.
- W1583630595 title "Genetic Determinants of Cognitive Function and Age-Related Brain Changes" @default.
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