| 1. |
- Ferreira, Daniel, et al.
(författare)
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The interactive effect of demographic and clinical factors on hippocampal volume : A multicohort study on 1958 cognitively normal individuals
- 2017
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Ingår i: Hippocampus. - : Wiley. - 1050-9631 .- 1098-1063. ; 27:6, s. 653-667
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease is characterized by hippocampal atrophy. Other factors also influence the hippocampal volume, but their interactive effect has not been investigated before in cognitively healthy individuals. The aim of this study is to evaluate the interactive effect of key demographic and clinical factors on hippocampal volume, in contrast to previous studies frequently investigating these factors in a separate manner. Also, to investigate how comparable the control groups from ADNI, AIBL, and AddNeuroMed are with five population-based cohorts. In this study, 1958 participants were included (100 AddNeuroMed, 226 ADNI, 155 AIBL, 59 BRC, 295 GENIC, 279 BioFiNDER, 398 PIVUS, and 446 SNAC-K). ANOVA and random forest were used for testing between-cohort differences in demographic-clinical variables. Multiple regression was used to study the influence of demographic-clinical variables on hippocampal volume. ANCOVA was used to analyze whether between-cohort differences in demographic-clinical variables explained between-cohort differences in hippocampal volume. Age and global brain atrophy were the most important variables in explaining variability in hippocampal volume. These variables were not only important themselves but also in interaction with gender, education, MMSE, and total intracranial volume. AddNeuroMed, ADNI, and AIBL differed from the population-based cohorts in several demographic-clinical variables that had a significant effect on hippocampal volume. Variability in hippocampal volume in individuals with normal cognition is high. Differences that previously tended to be related to disease mechanisms could also be partly explained by demographic and clinical factors independent from the disease. Furthermore, cognitively normal individuals especially from ADNI and AIBL are not representative of the general population. These findings may have important implications for future research and clinical trials, translating imaging biomarkers to the general population, and validating current diagnostic criteria for Alzheimer's disease and predementia stages.
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| 2. |
- Heiland, Emerald G, et al.
(författare)
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Cerebral small vessel disease, cardiovascular risk factors, and future walking speed in old age : a population-based cohort study.
- 2021
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Ingår i: BMC Neurology. - : BioMed Central. - 1471-2377. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The purpose of this study was to examine the associations between combined and individual cerebral small vessel disease (cSVD) markers on future walking speed over 9 years; and to explore whether these associations varied by the presence of cardiovascular risk factors (CRFs).METHODS: This population-based cohort study included 331 adults, aged ≥60 years, without limitation in walking speed (≥0.8 m/s). At baseline, cSVD markers, including white matter hyperintensities (WMH), lacunes, and perivascular spaces (PVS), were assessed on magnetic resonance imaging. The modifiable CRFs (physical inactivity, heavy alcohol consumption, smoking, hypertension, high total cholesterol, diabetes, and overweight/obese) were combined into a score. The association between baseline cSVD markers and the decline in walking speed was examined using linear mixed-effects models, whereas Cox proportional hazards models were used to estimate the association with walking speed limitation (defined as < 0.8 m/s) over the follow-up.RESULTS: Over the follow-up period, 76 (23.0%) persons developed walking speed limitation. Participants in the highest tertile of the combined cSVD marker score had a hazard ratio (HR) of 3.78 (95% confidence interval [CI] 1.70-8.45) for walking speed limitation compared with people in the lowest score tertile, even after adjusting for socio-demographics, CRFs, cognitive function, and chronic conditions. When investigating the cSVD markers individually, having the highest burden of WMH was associated with a significantly faster decline in walking speed (β coefficient - 0.020; 95% CI -0.035-0.004) and a greater HR of walking speed limitation (HR 2.78; 95% CI 1.31-5.89) compared with having the lowest WMH burden. Similar results were obtained for the highest tertile of PVS (HR 2.13; 95% CI 1.04-4.36). Lacunes were associated with walking speed limitation, but only in men. Having ≥4 CRFs and high WMH volume simultaneously, showed a greater risk of walking speed limitation compared with having ≥4 CRFs and low WMH burden. CRFs did not modify the associations between lacunes or PVS and walking speed.CONCLUSIONS: Combined cSVD markers strongly predict walking speed limitation in healthy older adults, independent of cognitive function, with WMH and PVS being the strongest contributors. Improving cardiovascular health may help to mitigate the negative effects of WMH on future walking speed.
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| 3. |
- Karshikoff, Bianka, et al.
(författare)
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Why sickness hurts : A central mechanism for pain induced by peripheral inflammation
- 2016
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Ingår i: Brain, behavior, and immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 57, s. 38-46
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Tidskriftsartikel (refereegranskat)abstract
- Low-grade systemic inflammation has been implicated in chronic pain, as well as in comorbid diseases like depression and fatigue. We have previously shown that women's pain perception and regulation is more affected by systemic inflammation than that of men. Here we investigated the neural substrates underlying these effects using an fMRI paradigm previously employed in a clinical population. Fifty-one participants (29 women) were injected with 0.6ng/kg lipopolysaccharide (LPS) or saline to induce a peripheral inflammatory response. The subjects were then tested with a pressure pain fMRI paradigm designed to capture descending pain inhibitory activity 2h after injection, and blood was sampled for cytokine analysis. The subjects injected with LPS became more pain sensitive compared to the placebo group, and the heightened pain sensitivity was paralleled by decreased activity in the ventrolateral prefrontal cortex and the rostral anterior cingulate cortex (rACC) compared to placebo; areas involved in descending pain regulation. The LPS group also had higher activity in the anterior insular cortex, an area underpinning affective and interoceptive pain processing. Women displayed overall less pain-evoked rACC activity compared to men, which may have rendered women less resilient to immune provocation, possibly explaining sex differences in LPS-induced pain sensitivity. Our findings elucidate the pain-related brain circuits affected by experimental peripheral inflammation, strengthening the theoretical link between systemic inflammation and weakened pain regulation in chronic pain disorders. The results further suggest a possible mechanism underlying the female predominance in many chronic pain disorders.
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