| 1. |
- Allentoft, Morten E., et al.
(författare)
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Population genomics of post-glacial western Eurasia
- 2024
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
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Tidskriftsartikel (refereegranskat)abstract
- Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.
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| 2. |
- Allentoft, Morten E., et al.
(författare)
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100 ancient genomes show repeated population turnovers in Neolithic Denmark
- 2024
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625, s. 329-337
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Tidskriftsartikel (refereegranskat)abstract
- Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales1–4. However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution5–7. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (13C and 15N content), mobility (87Sr/86Sr ratio) and vegetation cover (pollen). We observe that Danish Mesolithic individuals of the Maglemose, Kongemose and Ertebølle cultures form a distinct genetic cluster related to other Western European hunter-gatherers. Despite shifts in material culture they displayed genetic homogeneity from around 10,500 to 5,900 calibrated years before present, when Neolithic farmers with Anatolian-derived ancestry arrived. Although the Neolithic transition was delayed by more than a millennium relative to Central Europe, it was very abrupt and resulted in a population turnover with limited genetic contribution from local hunter-gatherers. The succeeding Neolithic population, associated with the Funnel Beaker culture, persisted for only about 1,000 years before immigrants with eastern Steppe-derived ancestry arrived. This second and equally rapid population replacement gave rise to the Single Grave culture with an ancestry profile more similar to present-day Danes. In our multiproxy dataset, these major demographic events are manifested as parallel shifts in genotype, phenotype, diet and land use.
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| 3. |
- Holmgren, Madelene, et al.
(författare)
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Diagnostic separation of conventional ⩾50% carotid stenosis and near-occlusion with phase-contrast MRI
- 2024
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Ingår i: European Stroke Journal. - : Sage Publications. - 2396-9873 .- 2396-9881. ; 9:1, s. 135-143
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The aim of this study was to assess sensitivity, specificity and interrater reliability of phase-contrast MRI (PC-MRI) for diagnosing carotid near-occlusion. Patients and methods: Prospective cross-sectional study conducted between 2018 and 2021. We included participants with suspected 50%–100% carotid stenosis on at least one side, all were examined with CT angiography (CTA) and PC-MRI and both ICAs were analyzed. Degree of stenosis on CTA was the reference test. PC-MRI-based blood flow rates in extracranial ICA and intracranial cerebral arteries were assessed. ICA-cerebral blood flow (CBF) ratio was defined as ICA divided by sum of both ICAs and Basilar artery. Results: We included 136 participants. The ICAs were 102 < 50% stenosis, 88 conventional ⩾50% stenosis (31 with ⩾70%), 49 near-occlusion, 12 occlusions, 20 unclear cause of small distal ICA on CTA and one excluded. For separation of near-occlusion and conventional stenoses, ICA flow rate and ICA-CBF ratio had the highest area under the curve (AUC; 0.98–0.99) for near-occlusion. ICA-CBF ratio ⩽0.225 was 90% (45/49) sensitive and 99% (188/190) specific for near-occlusion. Inter-rater reliability for this threshold was excellent (kappa 0.98). Specificity was 94% (29/31) for cases with ⩾70% stenosis. PC-MRI had modest performance for separating <50% and conventional ⩾50% stenosis (highest AUC 0.74), and eight (16%) of near-occlusions were not distinguishable from occlusion (no visible flow). Conclusion: ICA-CBF ratio ⩽0.225 on PC-MRI is an accurate and reliable method to separate conventional ⩾50% stenosis and near-occlusion that is feasible for routine use. PC-MRI should be considered further as a potential standard method for near-occlusion detection, to be used side-by-side with established modalities as PC-MRI cannot separate other degrees of stenosis.
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| 4. |
- Holmgren, Madelene, et al.
(författare)
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Phase-contrast magnetic resonance imaging of intracranial and extracranial blood flow in carotid near-occlusion
- 2024
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Ingår i: NEURORADIOLOGY. - : Springer Nature. - 0028-3940 .- 1432-1920.
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Compare extracranial internal carotid artery flow rates and intracranial collateral use between conventional >= 50% carotid stenosis and carotid near-occlusion, and between symptomatic and asymptomatic carotid near-occlusion. Methods We included patients with >= 50% carotid stenosis. Degree of stenosis was diagnosed on CTA. Mean blood flow rates were assessed with four-dimensional phase-contrast MRI. Results We included 110 patients of which 83% were symptomatic, and 38% had near-occlusion. Near-occlusions had lower mean internal carotid artery flow (70 ml/min) than conventional >= 50% stenoses (203 ml/min, P < .001). Definite use of >= 1 collateral was found in 83% (35/42) of near-occlusions and 10% (7/68) of conventional stenoses (P < .001). However, there were no differences in total cerebral blood flow (514 ml/min vs. 519 ml/min, P = .78) or ipsilateral hemispheric blood flow (234 vs. 227 ml/min, P = .52), between near-occlusions and conventional >= 50% stenoses, based on phase-contrast MRI flow rates. There were no differences in total cerebral or hemispheric blood flow, or collateral use, between symptomatic and asymptomatic near-occlusions. Conclusion Near-occlusions have lower internal carotid artery flow rates and more collateral use, but similar total cerebral blood flow and hemispheric blood flow, compared to conventional >= 50% carotid stenosis.
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| 5. |
- Press, R, et al.
(författare)
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Autologous haematopoietic stem cell transplantation: a viable treatment option for CIDP
- 2014
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 85:6, s. 618-624
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Only 70-80% of patients with chronic inflammatory demyelinating polyneuropathy (CIDP) respond satisfactorily to the established first-line immunomodulatory treatments. Autologous haematopoietic stem cell transplantation (AHSCT) has been performed as a last treatment resort in a few therapy-refractory cases with CIDP. We describe the results of AHSCT in 11 consecutive Swedish patients with therapy-refractory CIDP with a median follow-up time of 28 months. METHOD: Case data were gathered retrospectively for AHSCT treatments in 11 patients with CIDP refractory to the first-line immunomodulatory treatments, intravenous high-dose immunoglobulin, corticosteroids and plasma exchange and to one or more second-line treatments used in 10 of the 11 patients. RESULTS: The median Inflammatory Neuropathy Cause and Treatment (INCAT) score within 1 month prior to AHSCT was 6 and the Rankin score 4. Total INCAT and Rankin scores improved significantly within 2-6 months after AHSCT and continued to do so at last follow-up. The motor action potential amplitudes (CMAP) improved already within 4 months (median) after AHSCT. Three of the 11 patients relapsed during the follow-up period, requiring retransplantation with AHSCT in one. Eight of the 11 patients maintained drug-free remission upon last follow-up. AHSCT was safe but on the short term associated with a risk of cytomegalovirus (CMV) and Epstein-Barr virus reactivation, CMV disease, haemorrhagic cystitis and pancreatitis. CONCLUSIONS: Our results though hampered by the limited number of patients and the lack of a control group suggest AHSCT to be efficacious in therapy-refractory CIDP, with a manageable complication profile. Confirmation of these results is necessary through randomised controlled trials.
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| 6. |
- Fischer, Anders, 1951, et al.
(författare)
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Vittrup Man-The life-history of a genetic foreigner in Neolithic Denmark.
- 2024
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Ingår i: PloS one. - 1932-6203. ; 19:2
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Tidskriftsartikel (refereegranskat)abstract
- The lethally maltreated body of Vittrup Man was deposited in a Danish bog, probably as part of a ritualised sacrifice. It happened between c. 3300 and 3100 cal years BC, i.e., during the period of the local farming-based Funnel Beaker Culture. In terms of skull morphological features, he differs from the majority of the contemporaneous farmers found in Denmark, and associates with hunter-gatherers, who inhabited Scandinavia during the previous millennia. His skeletal remains were selected for transdisciplinary analysis to reveal his life-history in terms of a population historical perspective. We report the combined results of an integrated set of genetic, isotopic, physical anthropological and archaeological analytical approaches. Strontium signature suggests a foreign birthplace that could be in Norway or Sweden. In addition, enamel oxygen isotope values indicate that as a child he lived in a colder climate, i.e., to the north of the regions inhabited by farmers. Genomic data in fact demonstrates that he is closely related to Mesolithic humans known from Norway and Sweden. Moreover, dietary stable isotope analyses on enamel and bone collagen demonstrate a fisher-hunter way of life in his childhood and a diet typical of farmers later on. Such a variable life-history is also reflected by proteomic analysis of hardened organic deposits on his teeth, indicating the consumption of forager food (seal, whale and marine fish) as well as farmer food (sheep/goat). From a dietary isotopic transect of one of his teeth it is shown that his transfer between societies of foragers and farmers took place near to the end of his teenage years.
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| 7. |
- Karalija, Nina, 1984-, et al.
(författare)
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Longitudinal Dopamine D2 Receptor Changes and Cerebrovascular Health in Aging
- 2022
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Ingår i: Neurology. - 1526-632X .- 0028-3878. ; 99, s. e1278-e1289
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: Cross-sectional studies suggest marked dopamine (DA) decline in aging, but longitudinal evidence is lacking. The aim of this study was to estimate within-person decline rates for DA D2-like receptors (DRD2) in aging and examine factors that may contribute to individual differences in DRD2 decline rates. METHODS: We investigated 5-year within-person changes in DRD2 availability in a sample of older adults. At both occasions, PET with 11C-raclopride and MRI were used to measure DRD2 availability in conjunction with structural and vascular brain integrity. RESULTS: Longitudinal analyses of the sample (baseline: n = 181, ages: 64-68 years, 100 men and 81 women; 5-year follow-up: n = 129, 69 men and 60 women) revealed aging-related striatal and extrastriatal DRD2 decline, along with marked individual differences in rates of change. Notably, the magnitude of striatal DRD2 decline was ∼50% of past cross-sectional estimates, suggesting that the DRD2 decline rate has been overestimated in past cross-sectional studies. Significant DRD2 reductions were also observed in select extrastriatal regions, including hippocampus, orbitofrontal cortex (OFC), and anterior cingulate cortex (ACC). Distinct profiles of correlated DRD2 changes were found across several associative regions (ACC, dorsal striatum, and hippocampus) and in the reward circuit (nucleus accumbens and OFC). DRD2 losses in associative regions were associated with white matter lesion progression, whereas DRD2 losses in limbic regions were related to reduced cortical perfusion. DISCUSSION: These findings provide the first longitudinal evidence for individual and region-specific differences of DRD2 decline in older age and support the hypothesis that cerebrovascular factors are linked to age-related dopaminergic decline.
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| 8. |
- Karalija, Nina, 1984-, et al.
(författare)
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Longitudinal support for the correlative triad among aging, dopamine D2-like receptor loss, and memory decline
- 2024
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Ingår i: NEUROBIOLOGY OF AGING. - 0197-4580 .- 1558-1497. ; 136, s. 125-132
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Tidskriftsartikel (refereegranskat)abstract
- Dopamine decline is suggested to underlie aging -related cognitive decline, but longitudinal examinations of this link are currently missing. We analyzed 5 -year longitudinal data for a sample of healthy, older adults (baseline: n = 181, age: 64-68 years; 5 -year follow-up: n = 129) who underwent positron emission tomography with 11C- raclopride to assess dopamine D2 -like receptor (DRD2) availability, magnetic resonance imaging to evaluate structural brain measures, and cognitive tests. Health, lifestyle, and genetic data were also collected. A datadriven approach (k -means cluster analysis) identified groups that differed maximally in DRD2 decline rates in age -sensitive brain regions. One group (n = 47) had DRD2 decline exclusively in the caudate and no cognitive decline. A second group (n = 72) had more wide -ranged DRD2 decline in putamen and nucleus accumbens and also in extrastriatal regions. The latter group showed significant 5 -year working memory decline that correlated with putamen DRD2 decline, along with higher dementia and cardiovascular risk and a faster biological pace of aging. Taken together, for individuals with more extensive DRD2 decline, dopamine decline is associated with memory decline in aging.
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| 9. |
- Nyberg, Lars, 1966-, et al.
(författare)
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Longitudinal stability in working memory and frontal activity in relation to general brain maintenance
- 2022
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Cognitive functions are well-preserved for some older individuals, but the underlying brain mechanisms remain disputed. Here, 5-year longitudinal 3-back in-scanner and offline data classified individuals in a healthy older sample (baseline age = 64–68 years) into having stable or declining working-memory (WM). Consistent with a vital role of the prefrontal cortex (PFC), WM stability or decline was related to maintained or reduced longitudinal PFC functional responses. Subsequent analyses of imaging markers of general brain maintenance revealed higher levels in the stable WM group on measures of neurotransmission and vascular health. Also, categorical and continuous analyses showed that rate of WM decline was related to global (ventricles) and local (hippocampus) measures of neuronal integrity. Thus, our findings support a role of the PFC as well as general brain maintenance in explaining heterogeneity in longitudinal WM trajectories in aging.
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| 10. |
- Olivo, G., et al.
(författare)
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Immediate effects of a single session of physical exercise on cognition and cerebral blood flow: A randomized controlled study of older adults
- 2021
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Ingår i: Neuroimage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 225
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Tidskriftsartikel (refereegranskat)abstract
- Background: Regular physical activity is beneficial for cognitive performance in older age. A single bout of aerobic physical exercise can transiently improve cognitive performance. Researchers have advanced improvements in cerebral circulation as a mediator of long-term effects of aerobic physical exercise on cognition, but the immediate effects of exercise on cognition and cerebral perfusion are not well characterized and the effects in older adults are largely unknown. Methods: Forty-nine older adults were randomized to a 30-min aerobic exercise at moderate intensity or relaxation. Groups were matched on age and cardiovascular fitness (VO2 max). Average Grey Matter Blood Flow (GMBF), measured by a pulsed arterial-spin labeling (pASL) magnetic resonance imaging (MRI) acquisition, and working memory performance, measured by figurative n-back tasks with increasing loads were assessed before and 7 min after exercising/resting. Results: Accuracy on the n-back task increased from before to after exercising/resting regardless of the type of activity. GMBF decreased after exercise, relative to the control (resting) group. In the exercise group, higher n-back performance after exercise was associated with lower GMBF in the right hippocampus, left medial frontal cortex and right orbitofrontal cortex, and higher cardiovascular fitness was associated with lower GMBF. Conclusion: The decrease of GMBF reported in younger adults shortly after exercise also occurs in older adults and relates to cardiovascular fitness, potentially supporting the link between cardiovascular fitness and cerebrovascular reactivity in older age.
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