Biology subjects

Sorensen, O.

Publications and source records attributed to Sorensen, O..

4 recordsLinked to original sources

bioRxiv2019

Self-reported sleep relates to hippocampal atrophy across the adult lifespan - results from the Lifebrain consortium

BackgroundPoor sleep is associated with multiple age-related neurodegenerative and neuropsychiatric conditions. The hippocampus plays a special role in sleep and sleep-dependent cognition, and accelerated hippocampal atrophy is typically seen with higher age. Hence, it is critical to establish how the relationship between sleep and hippocampal volume loss unfolds across the adult lifespan.\n\nMethodsSelf-reported sleep measures and MRI-derived hippocampal volumes were obtained from 3105 cognitively normal participants (18-90 years) from major European brain studies in the Lifebrain consortium. Hippocampal volume change was estimated from 5116 MRIs from 1299 participants, covering up to 11 years. Cross-sectional analyses were repeated in a sample of 21390 participants from the UK Biobank.\n\nResultsThe relationship between self-reported sleep and age differed across sleep items. Sleep duration, efficiency, problems, and use of medication worsened monotonously with age, whereas subjective sleep quality, sleep latency, and daytime tiredness improved. Women reported worse sleep in general than men, but the relationship to age was similar. No cross-sectional sleep - hippocampal volume relationships was found. However, worse sleep quality, efficiency, problems, and daytime tiredness were related to greater hippocampal volume loss over time, with high scorers showing on average 0.22% greater annual loss than low scorers. Simulations showed that longitudinal effects were too small to be detected as age-interactions in cross-sectional analyses.\n\nConclusionsWorse self-reported sleep is associated with higher rates of hippocampal decline across the adult lifespan. This suggests that sleep is relevant to understand individual differences in hippocampal atrophy, but limited effect sizes call for cautious interpretation.

neuroscience↗

bioRxiv2019

Genetic risk for Alzheimer`s disease predicts hippocampal volume through the lifespan

INTRODUCTIONIt is unknown whether genetic risk for Alzheimers disease (AD) represents a stable influence on the brain from early in life, or whether effects are age-dependent. It is critical to characterize the effects of genetic risk factors on the primary neural substrate of AD, the hippocampus, throughout life.\n\nMETHODSRelations of polygenic risk score (PGS) for AD, including variants in Apolipoprotein E (APOE) with hippocampal volume and its change were assessed in a healthy longitudinal lifespan sample (n = 1181, 4-95 years), followed for up to 11 years with a total of 2690 MRI scans.\n\nRESULTSAD-PGS showed a significant negative effect on hippocampal volume. Offset effects of AD-PGS and APOE {varepsilon}4 were present in hippocampal development, and interactions between age and genetic risk on volume change were not consistently observed. DISCUSSION: Endophenotypic manifestation of polygenic risk for AD may be seen across the lifespan in healthy persons.\n\nHighlightsO_LIGenetic risk for AD affects the hippocampus throughout the lifespan\nC_LIO_LIAPOE {varepsilon}4 carriers have smaller hippocampi in development\nC_LIO_LIDifferent effects of genetic risk at different ages were not consistently observed\nC_LIO_LIGenetic factors increasing risk for AD impact healthy persons throughout life\nC_LIO_LIA broader population and age range are relevant targets for attempts to prevent AD\nC_LI

neuroscience↗

bioRxiv2019

Volumetric and microstructural regional changes of the hippocampus underlying development of extended delay long-term memory

Episodic memory function improves through childhood and adolescence, in part due to structural maturation of the medial temporal cortex. Although partly different processes support long-term memory over shorter vs. longer intervals, memory is usually assessed after less than an hour. The aim of the present study was to test whether there are unique developmental changes in extended memory, and whether these are related to structural maturation of sub-regions of the hippocampus. 650 children and adolescents from 4.1 to 24.8 years were assessed in total 962 times (mean interval {approx} 1.8 years). Memory was assessed by the California Verbal Learning Test (CVLT) and the Rey Complex Figure Test (CFT). In addition to 30 min recall, an extended delay recall condition was administered {approx} 10 days after encoding. We found unique developmental effects on extended delay memory independently of 30 min recall performance. For visuo-constructive memory, this could be accounted for by visuo-constructive ability levels. Performance was modestly related to anterior and posterior hippocampal volume and mean diffusion. The relationships did not show an anterior-posterior hippocampal axis difference. In conclusion, extended delay memory shows unique development, likely due to changes in encoding depth or efficacy, or improvements of long-term consolidation processes.\n\nHighlightsO_LIUnique developmental effects on episodic memories over days rather than minutes\nC_LIO_LIDevelopment of visuoconstructive recall explainable by visuoconstructive abilitity\nC_LIO_LIDevelopment of verbal recall cannot be explained by verbal ability\nC_LIO_LIModest relationships between memory and hippocampal structural features\nC_LI

neuroscience↗

bioRxiv2019

Cellular correlates of cortical thinning throughout the lifespan

Cortical thinning occurs throughout the entire life and extends to late-life neurodegeneration, yet the neurobiological substrates are poorly understood. Here, we used a virtual-histology technique and gene expression data from the Allen Human Brain Atlas to compare the regional profiles of longitudinal cortical thinning through life (4004 MRIs) with those of gene expression for several neuronal and non-neuronal cell types. The results were replicated in three independent longitudinal datasets. We found that inter-regional profiles of cortical thinning related to expression profiles for marker genes of CA1 pyramidal cells, astrocytes and microglia during development and in aging. During the two stages of life, the relationships went in opposite directions: greater gene expression related to less thinning in development and vice versa in aging. The association between cortical thinning and cell-specific gene expression was also present in mild cognitive impairment and Alzheimers Disease. These findings suggest a role of astrocytes and microglia in promoting and supporting neuronal growth and dendritic structures through life that affects cortical thickness during development, aging, and neurodegeneration. Overall, the findings contribute to our understanding of the neurobiology underlying variations in MRI-derived estimates of cortical thinning through life and late-life disease.

neuroscience↗