A5046656516- Genetic Associations and Epidemiology
- Functional Brain Connectivity Studies
- Dementia and Cognitive Impairment Research
- Alzheimer's disease research and treatments
- Bioinformatics and Genomic Networks
- Advanced Neuroimaging Techniques and Applications
- Epigenetics and DNA Methylation
- Genetics and Neurodevelopmental Disorders
- Health, Environment, Cognitive Aging
- Intergenerational Family Dynamics and Caregiving
- Neural and Behavioral Psychology Studies
- Telomeres, Telomerase, and Senescence
- Tryptophan and brain disorders
- Genetics, Aging, and Longevity in Model Organisms
- Memory and Neural Mechanisms
- Schizophrenia research and treatment
- Cognitive Abilities and Testing
- Nerve injury and regeneration
- Genomics and Rare Diseases
- Neuroscience and Neuropharmacology Research
- Birth, Development, and Health
- Photoreceptor and optogenetics research
- Blood Pressure and Hypertension Studies
- Neurogenesis and neuroplasticity mechanisms
- Advanced MRI Techniques and Applications
Umeå University
2014-2024
Karolinska Institutet
2020-2023
University of California, San Diego
2016-2019
Oslo University Hospital
2014-2016
University of Oslo
2014-2016
Imagerie et Cerveau
2013
Allen Institute for Brain Science
2011
Background Identifying individuals at risk for developing Alzheimer disease (AD) is of utmost importance. Although genetic studies have identified AD-associated SNPs in APOE and other genes, information has not been integrated into an epidemiological framework prediction. Methods findings Using genotype data from 17,008 AD cases 37,154 controls the International Genomics Alzheimer's Project (IGAP Stage 1), we (at p < 10−5). We then these a Cox proportional hazard model using subset 6,409...
Cross-sectional estimates of age-related changes in brain structure and function were compared with 6-y longitudinal estimates. The results indicated increased sensitivity the approach as well qualitative differences. Critically, cross-sectional analyses suggestive frontal overrecruitment, whereas revealed underrecruitment advancing age. observation overrecruitment reflected a select elderly sample. However, when followed over time, this sample showed reduced recruitment. These findings...
By integrating behavioral measures and imaging data, previous investigations have explored the relationship between biological markers of aging cognitive functions. Evidence from functional structural neuroimaging has revealed that hippocampal volume activation patterns in medial temporal lobe (MTL) may predict performance old age. Most past demonstrations age-related differences brain structure–function were based on cross-sectional comparisons. Here, 6-year intraindividual change magnetic...
Schizophrenia is associated with widespread cognitive impairments. Although deficits are one of the factors most strongly functional outcome in schizophrenia, current treatment strategies largely fail to ameliorate these To develop more efficient patients a better understanding pathogenesis needed. Accumulating evidence indicates that genetic risk schizophrenia may contribute dysfunction.To identify genomic regions jointly influencing and domains reaction time verbal-numerical reasoning, as...
Several studies have linked the KIBRA rs17070145 T polymorphism to superior episodic memory in healthy humans. One study investigated effect of on brain activation patterns (Papassotiropoulos et al., 2006) and observed increased hippocampal noncarriers allele during retrieval. Noncarriers were interpreted need more reach same performance level as carriers. Using large behavioral ( N = 2230) fMRI 83) samples, we replicated performance, but found carriers There was no evidence compensatory...
The dorsolateral pFC (DLPFC) is a key region for working memory. It has been proposed that the DLPFC dynamically recruited depending on task demands. By this view, high recruitment low-demanding tasks along with weak upregulation at higher demands reflects low efficiency. Here, fMRI BOLD signal during memory maintenance and manipulation was examined in relation to aging catechol-O-methyltransferase (COMT) Val(158)Met status large representative sample (n = 287). efficiency hypothesis...
Mounting evidence indicates that the polygenic basis of late-onset Alzheimer's disease can be harnessed to identify individuals at greatest risk for cognitive decline. We have previously developed and validated a hazard score comprising 31 single nucleotide polymorphisms predicting dementia age onset. In this study, we examined whether scores are associated with: (i) regional tracer uptake using amyloid PET; (ii) volume loss longitudinal MRI; (iii) post-mortem amyloid-β protein tau...
The complement cascade plays a role in synaptic pruning and plasticity, which seem to be involved cognitive functions psychiatric disorders. Genetic variants the closely related CSMD1 CSMD2 genes, are implicated regulation, associated with schizophrenia. Since patients schizophrenia often show impairments, we tested whether also per se. We took discovery-replication approach, using well-characterized Scandinavian cohorts. A total of 1637 SNPs 206 were for association NCNG sample (Norwegian...
Identifying asymptomatic older individuals at elevated risk for developing Alzheimer disease (AD) is of clinical importance. Among 1,081 adults, a recently validated polygenic hazard score (PHS) significantly predicted time to AD dementia and steeper longitudinal cognitive decline, even after controlling APOE ɛ4 carrier status. Older in the highest PHS percentiles showed incidence rates. decline among with moderate high Consortium Establish Registry Alzheimer's Disease (amyloid) Braak (tau)...
Schizophrenia is a highly heritable and polygenic disease, identified common genetic variants have shown weak individual effects. Many studies reported altered working memory (WM)-related brain activation in schizophrenia, preferentially the frontal lobe. Such differences activations could reflect inherited alterations possibly involved disease etiology, or rather secondary disease-related mechanisms. The use of risk scores (PGRS) based on large number polymorphisms with small effects...
Objectives Bipolar disorder (BD) is a highly heritable with polygenic inheritance. Among the most consistent findings from functional magnetic imaging (fMRI) studies are limbic hyperactivation and dorsal hypoactivation. However, relation between reported brain abnormalities underlying genetic risk remains elusive. This first cross-sectional study applying whole-brain explorative approach to investigate potential influence of BD case-control status on activation. Methods A score (PGRS) was...
Improved prediction of progression to Alzheimer's Disease (AD) among older individuals with mild cognitive impairment (MCI) is high clinical and societal importance. We recently developed a polygenic hazard score (PHS) that predicted age AD onset above beyond APOE. Here, we used data from the Neuroimaging Initiative (ADNI) further explore potential utility PHS for predicting development in adults MCI. examined predictive value alone combination baseline structural magnetic resonance imaging...
Childhood trauma increases risk of a range mental disorders including psychosis. Whereas the mechanisms are unclear, previous evidence has implicated atypical processing emotions among core cognitive models, in particular suggesting altered attentional allocation towards negative stimuli and increased negativity bias. Here, we tested association between childhood brain activation during emotional face patients diagnosed with psychosis continuum disorders. In particular, if was associated...
Abstract Most people’s cognitive abilities decline with age, significant and partly genetically driven, individual differences in rate of change. Although APOE ɛ4 genetic scores for late-onset Alzheimer’s disease (LOAD) have been related to during preclinical stages dementia, there is limited knowledge concerning factors implied normal aging. In the present study, we examined three potential predictors age-related as follows: (1) allele, (2) a polygenic score general ability (PGS-cog), (3)...
Abstract Background Leukocyte telomere length (LTL) has been shown to predict Alzheimer’s disease (AD), albeit inconsistently. Failing account for the competing risks between AD, other dementia types, and mortality, can be an explanation inconsistent findings in previous time-to-event analyses. Furthermore, studies indicate that association LTL AD is non-linear may differ depending on apolipoprotein E ( APOE ) ε4 allele carriage, strongest genetic predictor. Methods We analyzed whether...
Multiple marker analysis of the genome-wide association study (GWAS) data has gained ample attention in recent years. However, because ultra high-dimensionality GWAS data, such is challenging. Frequently used penalized regression methods often lead to large number false positives, whereas Bayesian are computationally very expensive. Motivated ameliorate these issues simultaneously, we consider novel approach using non-local priors an iterative variable selection framework.We develop a...
Abstract Leukocyte telomere length (LTL) is a proposed biomarker for aging-related disorders, including cognitive decline and dementia. Long-term longitudinal studies measuring intra-individual changes in both LTL outcomes are scarce, precluding strong conclusions about potential relationship between shortening decline. This study investigated associations baseline levels memory performance across an up to 20-year follow-up 880 dementia-free participants from population-based (mean age: 56.8...
Objective: Antipsychotic drugs were incidentally discovered in the 1950s, but their mechanisms of action are still not understood. Better understanding schizophrenia pathogenesis could shed light on actions current and reveal novel "druggable" pathways for unmet therapeutic needs. Recent genome-wide association studies offer unprecedented opportunities to characterize disease gene networks uncover drug-disease relationships. Polygenic overlap between risk genes antipsychotic drug targets has...
Polygenic risk for schizophrenia has been associated with lower cognitive ability and age-related change in healthy individuals. Despite well-established neuropsychological sex differences patients, genetic studies on relation to phenotypes are scarce. Here, we investigated whether the effect of a polygenic score (PRS) childhood, midlife, late-life function individuals is modified by sex, if PRS linked accelerated decline. Using longitudinal data set from aged 25-100 years (N = 1459)...