| 1. |
- Bousquet, Jean, et al.
(författare)
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Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018) : Change management in allergic rhinitis and asthma multimorbidity using mobile technology
- 2019
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 143:3, s. 864-879
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Tidskriftsartikel (refereegranskat)abstract
- Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional.
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| 2. |
- Menditto, Enrica, et al.
(författare)
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Adherence to treatment in allergic rhinitis using mobile technology : The MASK Study
- 2019
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Ingår i: Clinical and Experimental Allergy. - : WILEY. - 0954-7894 .- 1365-2222. ; 49:4, s. 442-460
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mobile technology may help to better understand the adherence to treatment. MASK-rhinitis (Mobile Airways Sentinel NetworK for allergic rhinitis) is a patient-centred ICT system. A mobile phone app (the Allergy Diary) central to MASK is available in 22 countries. Objectives: To assess the adherence to treatment in allergic rhinitis patients using the Allergy Diary App. Methods: An observational cross-sectional study was carried out on all users who filled in the Allergy Diary from 1 January 2016 to 1 August 2017. Secondary adherence was assessed by using the modified Medication Possession Ratio (MPR) and the Proportion of days covered (PDC) approach. Results: A total of 12143 users were registered. A total of 6949 users reported at least one VAS data recording. Among them, 1887 users reported >= 7 VAS data. About 1195 subjects were included in the analysis of adherence. One hundred and thirty-six (11.28%) users were adherent (MPR >= 70% and PDC <= 1.25), 51 (4.23%) were partly adherent (MPR >= 70% and PDC = 1.50) and 176 (14.60%) were switchers. On the other hand, 832 (69.05%) users were non-adherent to medications (MPR <70%). Of those, the largest group was non-adherent to medications and the time interval was increased in 442 (36.68%) users. Conclusion and clinical relevance: Adherence to treatment is low. The relative efficacy of continuous vs on-demand treatment for allergic rhinitis symptoms is still a matter of debate. This study shows an approach for measuring retrospective adherence based on a mobile app. This also represents a novel approach for analysing medication-taking behaviour in a real-world setting.
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| 6. |
- Hibar, Derrek P., et al.
(författare)
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Novel genetic loci associated with hippocampal volume
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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| 7. |
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| 8. |
- Satizabal, Claudia L., et al.
(författare)
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Genetic architecture of subcortical brain structures in 38,851 individuals
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
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Tidskriftsartikel (refereegranskat)abstract
- Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
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| 9. |
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| 10. |
- Bousquet, J., et al.
(författare)
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Daily allergic multimorbidity in rhinitis using mobile technology : A novel concept of the MASK study
- 2018
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 73:8, s. 1622-1631
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Forskningsöversikt (refereegranskat)abstract
- BackgroundMultimorbidity in allergic airway diseases is well known, but no data exist about the daily dynamics of symptoms and their impact on work. To better understand this, we aimed to assess the presence and control of daily allergic multimorbidity (asthma, conjunctivitis, rhinitis) and its impact on work productivity using a mobile technology, the Allergy Diary. MethodsWe undertook a 1-year prospective observational study in which 4 210 users and 32585days were monitored in 19 countries. Five visual analogue scales (VAS) assessed the daily burden of the disease (i.e., global evaluation, nose, eyes, asthma and work). Visual analogue scale levels <20/100 were categorized as "Low" burden and VAS levels 50/100 as "High" burden. ResultsVisual analogue scales global measured levels assessing the global control of the allergic disease were significantly associated with allergic multimorbidity. Eight hypothesis-driven patterns were defined based on "Low" and "High" VAS levels. There were <0.2% days of Rhinitis Low and Asthma High or Conjunctivitis High patterns. There were 5.9% days with a Rhinitis HighAsthma Low pattern. There were 1.7% days with a Rhinitis HighAsthma HighConjunctivitis Lowpattern. A novel Rhinitis HighAsthma HighConjunctivitis High pattern was identified in 2.9% days and had the greatest impact on uncontrolled VAS global measured and impaired work productivity. Work productivity was significantly correlated with VAS global measured levels. ConclusionsIn a novel approach examining daily symptoms with mobile technology, we found considerable intra-individual variability of allergic multimorbidity including a previously unrecognized extreme pattern of uncontrolled multimorbidity.
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| 16. |
- Eyjolfsdottir, H., et al.
(författare)
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Targeted delivery of nerve growth factor to the cholinergic basal forebrain of Alzheimer's disease patients: application of a second-generation encapsulated cell biodelivery device
- 2016
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Ingår i: Alzheimers Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Targeted delivery of nerve growth factor (NGF) has emerged as a potential therapy for Alzheimer's disease (AD) due to its regenerative effects on basal forebrain cholinergic neurons. This hypothesis has been tested in patients with AD using encapsulated cell biodelivery of NGF (NGF-ECB) in a first-in-human study. We report our results from a third-dose cohort of patients receiving second-generation NGF-ECB implants with improved NGF secretion. Methods: Four patients with mild to moderate AD were recruited to participate in an open-label, phase Ib dose escalation study with a 6-month duration. Each patient underwent stereotactic implant surgery with four NGF-ECB implants targeted at the cholinergic basal forebrain. The NGF secretion of the second-generation implants was improved by using the Sleeping Beauty transposon gene expression technology and an improved three-dimensional internal scaffolding, resulting in production of about 10 ng NGF/device/day. Results: All patients underwent successful implant procedures without complications, and all patients completed the study, including implant removal after 6 months. Upon removal, 13 of 16 implants released NGF, 8 implants released NGF at the same rate or higher than before the implant procedure, and 3 implants failed to release detectable amounts of NGF. Of 16 adverse events, none was NGF-, or implant-related. Changes from baseline values of cholinergic markers in cerebrospinal fluid (CSF) correlated with cortical nicotinic receptor expression and Mini Mental State Examination score. Levels of neurofilament light chain (NFL) protein increased in CSF after NGF-ECB implant, while glial fibrillary acidic protein (GFAP) remained stable. Conclusions: The data derived from this patient cohort demonstrate the safety and tolerability of sustained NGF release by a second-generation NGF-ECB implant to the basal forebrain, with uneventful surgical implant and removal of NGF-ECB implants in a new dosing cohort of four patients with AD.
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| 17. |
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| 18. |
- Göçeroǧlu, Arda, et al.
(författare)
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ANCA-associated glomerulonephritis : Risk factors for renal relapse
- 2016
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:12
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Tidskriftsartikel (refereegranskat)abstract
- Relapse in ANCA-associated vasculitis (AAV) has been studied previously, but there are few studies on renal relapse in particular. Identifying patients at high risk of renal relapse may aid in optimizing clinical management. We investigated which clinical and histological parameters are risk factors for renal relapse in ANCA-associated glomerulonephritis (AAGN). Patients (n = 174) were newly diagnosed and had mild±moderate or severe renal involvement. Data were derived from two trials of the European Vasculitis Society: MEPEX and CYCAZAREM. The Cox regression model was used to identify parameters increasing the instantaneous risk (= rate) of renal relapse (useful for instant clinical decisions). For identifying predictors of renal relapse during follow-up, we used Fine & Gray's regression model. Competing events were end-stage renal failure and death. The cumulative incidence of renal relapse at 5 years was 9.5% (95% CI: 4.8±14.3%). In the Cox model, sclerotic class AAGN increased the instantaneous risk of renal relapse. In Fine & Gray's model, the absence of interstitial infiltrates at diagnosis was predictive for renal relapse. In this study we used two different models to identify possible relationships between clinical and histopathological parameters at time of diagnosis of AAV with the risk of experiencing renal relapse. Sclerotic class AAGN increased the instantaneous risk of renal relapse. This association is most likely due to the high proportion of sclerosed glomeruli reducing the compensatory capacity. The absence of interstitial infiltrates increased the risk of renal relapse which is a warning sign that patients with a relatively benign onset of disease may also be prone to renal relapse. Renal relapses occurring in patients with sclerotic class AAGN and renal relapses occurring in patients without interstitial infiltrates were mutually exclusive, which may indicate that they are essentially different.
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| 19. |
- Ismail, MA, et al.
(författare)
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27-Hydroxycholesterol impairs neuronal glucose uptake through an IRAP/GLUT4 system dysregulation
- 2017
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 214:3, s. 699-717
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Tidskriftsartikel (refereegranskat)abstract
- Hypercholesterolemia is associated with cognitively deteriorated states. Here, we show that excess 27-hydroxycholesterol (27-OH), a cholesterol metabolite passing from the circulation into the brain, reduced in vivo brain glucose uptake, GLUT4 expression, and spatial memory. Furthermore, patients exhibiting higher 27-OH levels had reduced 18F-fluorodeoxyglucose uptake. This interplay between 27-OH and glucose uptake revealed the engagement of the insulin-regulated aminopeptidase (IRAP). 27-OH increased the levels and activity of IRAP, countered the IRAP antagonist angiotensin IV (AngIV)–mediated glucose uptake, and enhanced the levels of the AngIV-degrading enzyme aminopeptidase N (AP-N). These effects were mediated by liver X receptors. Our results reveal a molecular link between cholesterol, brain glucose, and the brain renin-angiotensin system, all of which are affected in some neurodegenerative diseases. Thus, reducing 27-OH levels or inhibiting AP-N maybe a useful strategy in the prevention of the altered glucose metabolism and memory decline in these disorders.
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| 23. |
- Mijalkov, M., et al.
(författare)
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BRAPH: A graph theory software for the analysis of brain connectivity
- 2017
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 12:8
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Tidskriftsartikel (refereegranskat)abstract
- The brain is a large-scale complex network whose workings rely on the interaction between its various regions. In the past few years, the organization of the human brain network has been studied extensively using concepts from graph theory, where the brain is represented as a set of nodes connected by edges. This representation of the brain as a connectome can be used to assess important measures that reflect its topological architecture. We have developed a freeware MatLab-based software (BRAPH-BRain Analysis using graPH theory) for connectivity analysis of brain networks derived from structural magnetic resonance imaging (MRI), functional MRI (fMRI), positron emission tomography (PET) and electroencephalogram (EEG) data. BRAPH allows building connectivity matrices, calculating global and local network measures, performing non-parametric permutations for group comparisons, assessing the modules in the network, and comparing the results to random networks. By contrast to other toolboxes, it allows performing longitudinal comparisons of the same patients across different points in time. Furthermore, even though a user-friendly interface is provided, the architecture of the program is modular (object-oriented) so that it can be easily expanded and customized. To demonstrate the abilities of BRAPH, we performed structural and functional graph theory analyses in two separate studies. In the first study, using MRI data, we assessed the differences in global and nodal network topology in healthy controls, patients with amnestic mild cognitive impairment, and patients with Alzheimer's disease. In the second study, using resting-state fMRI data, we compared healthy controls and Parkinson's patients with mild cognitive impairment.
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| 24. |
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| 26. |
- Schöll, Michael, 1980, et al.
(författare)
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Early astrocytosis in autosomal dominant Alzheimer's disease measured in vivo by multi-tracer positron emission tomography
- 2015
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Studying autosomal dominant Alzheimer's disease (ADAD), caused by gene mutations yielding nearly complete penetrance and a distinct age of symptom onset, allows investigation of presymptomatic pathological processes that can identify a therapeutic window for disease-modifying therapies. Astrocyte activation may occur in presymptomatic Alzheimer's disease (AD) because reactive astrocytes surround beta-amyloid (A beta) plaques in autopsy brain tissue. Positron emission tomography was performed to investigate fibrillar A beta, astrocytosis and cerebral glucose metabolism with the radiotracers C-11-Pittsburgh compound-B (PIB), C-11-deuterium-L-deprenyl (DED) and F-18-fluorodeoxyglucose (FDG) respectively in presymptomatic and symptomatic ADAD participants (n = 21), patients with mild cognitive impairment (n = 11) and sporadic AD (n = 7). Multivariate analysis using the combined data from all radiotracers clearly separated the different groups along the first and second principal components according to increased PIB retention/decreased FDG uptake (component 1) and increased DED binding (component 2). Presymptomatic ADAD mutation carriers showed significantly higher PIB retention than non-carriers in all brain regions except the hippocampus. DED binding was highest in presymptomatic ADAD mutation carriers. This suggests that non-fibrillar A beta or early stage plaque depostion might interact with inflammatory responses indicating astrocytosis as an early contributory driving force in AD pathology. The novelty of this finding will be investigated in longitudinal follow-up studies.
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| 27. |
- Schön, Thomas, et al.
(författare)
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Effects of a food supplement rich in arginine in patients with smear positive pulmonary tuberculosis - A randomised trial
- 2011
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Ingår i: Tuberculosis. - : Elsevier. - 1472-9792 .- 1873-281X. ; 91:5, s. 370-377
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Tidskriftsartikel (refereegranskat)abstract
- In tuberculosis (TB), the production of nitric oxide (NO) is confirmed but its importance in host defense is debated. Our aim was to investigate whether a food supplement rich in arginine could enhance clinical improvement in TB patients by increased NO production. Smear positive TB patients from Gondar, Ethiopia (n = 180) were randomized to a food supplementation rich in arginine (peanuts, equivalent to 1 g of arginine/day) or with a low arginine content (wheat crackers, locally called daboqolo) during four weeks. The primary outcome was cure rate according to the WHO classification and secondary outcomes were sputum smear conversion, weight gain, sedimentation rate, reduction of cough and chest X-ray improvement as well as levels of NO in urine (uNO) or exhaled air (eNO) at two months. There was no effect of the intervention on the primary outcome (OR 1.44, 95% CI: 0.69-3.0, p = 0.39) or secondary outcomes. In the subgroup analysis according to HIV status, peanut supplemented HIV+/TB patients showed increased cure rate (83.8% (31/37) vs 53.1% (17/32), p andlt; 0.01). A low baseline eNO (andlt; 10 ppb) in HIV+/TB patients was associated with a decreased cure rate. We conclude that nutritional supplementation with a food supplement rich in arginine did not have any overall clinical effect. In the subgroup of HIV positive TB patients, it significantly increased the cure rate and as an additional finding in this subgroup, low initial levels of NO in exhaled air were associated with a poor clinical outcome but this needs to be confirmed in further studies.
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| 28. |
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| 29. |
- Voevodskaya, O., et al.
(författare)
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Brain myoinositol as a potential marker of amyloid-related pathology: A longitudinal study
- 2019
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 92:5
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo investigate the association between longitudinal changes in proton magnetic resonance spectroscopy (MRS) metabolites and amyloid pathology in individuals without dementia, and to explore the relationship between MRS and cognitive decline.MethodsIn this longitudinal multiple time point study (a subset of the Swedish BioFINDER), we included cognitively healthy participants, individuals with subjective cognitive decline, and individuals with mild cognitive impairment. MRS was acquired serially in 294 participants (670 individual spectra) from the posterior cingulate/precuneus. Using mixed-effects models, we assessed the association between MRS and baseline -amyloid (A), and between MRS and the longitudinal Mini-Mental State Examination, accounting for APOE, age, and sex.ResultsWhile baseline MRS metabolites were similar in A positive (A+) and negative (A-) individuals, in the A+ group, the estimated rate of change was +1.9%/y for myo-inositol (mI)/creatine (Cr) and -2.0%/y for N-acetylaspartate (NAA)/mI. In the A- group, mI/Cr and NAA/mI yearly change was -0.05% and +1.2%; however, this was not significant across time points. The mild cognitive impairment A+ group showed the steepest MRS changes, with an estimated rate of +2.93%/y (p = 0.07) for mI/Cr and -3.55%/y (p < 0.01) for NAA/mI. Furthermore, in the entire cohort, we found that A+ individuals with low baseline NAA/mI had a significantly higher rate of cognitive decline than A+ individuals with high baseline NAA/mI.ConclusionWe demonstrate that the longitudinal change in mI/Cr and NAA/mI is associated with underlying amyloid pathology. MRS may be a useful noninvasive marker of A-related processes over time. In addition, we show that in A+ individuals, baseline NAA/mI may predict the rate of future cognitive decline.
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| 30. |
- Wester Trejo, Maria A.C., et al.
(författare)
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Renal relapse in antineutrophil cytoplasmic autoantibody-associated vasculitis : unpredictable, but predictive of renal outcome
- 2019
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Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 58:1, s. 103-109
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To determine predictors of renal relapse and end-stage renal failure (ESRF) in patients with ANCA-associated vasculitis. Methods: Data from four European Vasculitis Society randomized controlled trials, conducted roughly simultaneously between 15 March 1995 and 30 September 2002, was pooled to determine predictors of long-term renal outcome. The respective trial inclusion criteria covered the entire spectrum of disease severity. Baseline predictors of time to first renal relapse and time to ESRF were assessed by competing events analysis and Cox proportional hazards regression. The effect of renal relapse on time to ESRF was assessed by adding renal relapses to the competing events analysis as a time-varying covariate. Results: The number of patients participating was 535; mean serum creatinine (±s.d.) at entry was 341 ± 321 µmol/l and 19.7% developed ESRF. One or more renal relapse(s) was experienced by 101 patients. Multivariable regression analysis demonstrated that, in addition to impaired baseline renal function, developing ⩾1 renal relapse was an independent risk factor for ESRF (subhazard ratio 9; 95% CI 4, 19; P < 0.001). No predictive factors for renal relapse were found. Conclusion: In addition to baseline renal function, the occurrence of renal relapses is an important determinant of ESRF in patients with ANCA-associated vasculitis. We did not find any clinical predictors for renal relapse itself, including disease activity elsewhere. In light of the silent nature of renal relapse in ANCA-associated vasculitis, we stress the need for long-term vigilant monitoring for early signs of renal relapse and propose performing 3-monthly urinalysis. This will enable timely treatment and help further improve renal outcome.
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| 33. |
- Aguilar, C., et al.
(författare)
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Automated CT-based segmentation and quantification of total intracranial volume
- 2015
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Ingår i: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 25:11, s. 3151-3160
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To develop an algorithm to segment and obtain an estimate of total intracranial volume (tICV) from computed tomography (CT) images. Materials and methods Thirty-six CT examinations from 18 patients were included. Ten patients were examined twice the same day and eight patients twice six months apart (these patients also underwent MRI). The algorithm combines morphological operations, intensity thresholding and mixture modelling. The method was validated against manual delineation and its robustness assessed from repeated imaging examinations. Using automated MRI software, the comparability with MRI was investigated. Volumes were compared based on average relative volume differences and their magnitudes; agreement was shown by a Bland-Altman analysis graph. Results We observed good agreement between our algorithm and manual delineation of a trained radiologist: the Pearson's correlation coefficient was r = 0.94, tICVml[manual] = 1.05 x tICVml[automated] - 33.78 (R-2 = 0.88). Bland-Altman analysis showed a bias of 31 mL and a standard deviation of 30 mL over a range of 1265 to 1526 mL. Conclusions tICV measurements derived from CT using our proposed algorithm have shown to be reliable and consistent compared to manual delineation. However, it appears difficult to directly compare tICV measures between CT and MRI.
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| 45. |
- Duits, F. H., et al.
(författare)
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Synaptic proteins in CSF as potential novel biomarkers for prognosis in prodromal Alzheimer's disease
- 2018
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Ingår i: Alzheimers Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: We investigated whether a panel of 12 potential novel biomarkers consisting of proteins involved in synapse functioning and immunity would be able to distinguish patients with Alzheimer's disease (AD) and patients with mild cognitive impairment (MCI) from control subjects. Methods: We included 40 control subjects, 40 subjects with MCI, and 40 subjects with AD from the Amsterdam Dementia Cohort who were matched for age and sex (age 65 +/- 5 years, 19 [48%] women). The mean follow-up of patients with MCI was 3 years. Two or three tryptic peptides per protein were analyzed in cerebrospinal fluid using parallel reaction monitoring mass spectrometry. Corresponding stable isotope-labeled peptides were added and used as reference peptides. Multilevel generalized estimating equations (GEEs) with peptides clustered per subject and per protein (as within-subject variables) were used to assess differences between diagnostic groups. To assess differential effects of individual proteins, we included the diagnosis x protein interaction in the model. Separate GEE analyses were performed to assess differences between stable patients and patients with progressive MCI (MCI-AD). Results: There was a main effect for diagnosis (p < 0.01) and an interaction between diagnosis and protein (p < 0.01). Analysis stratified according to protein showed higher levels in patients with MCI for most proteins, especially in patients with MCI-AD. Chromogranin A, secretogranin II, neurexin 3, and neuropentraxin 1 showed the largest effect sizes; beta values ranged from 0.53 to 0.78 for patients with MCI versus control subjects or patients with AD, and from 0.67 to 0.98 for patients with MCI-AD versus patients with stable MCI. In contrast, neurosecretory protein VGF was lower in patients with AD than in patients with MCI (beta = -0.93 [SE 0.22]) and control subjects (beta = 0.46 [SE 0.19]). Conclusions: Our results suggest that several proteins involved in vesicular transport and synaptic stability are elevated in patients with MCI, especially in patients with MCI progressing to AD dementia. This may reflect early events in the AD pathophysiological cascade. These proteins may be valuable as disease stage or prognostic markers in an early symptomatic stage of the disease.
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| 46. |
- Ekman, U, et al.
(författare)
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The A/T/N biomarker scheme and patterns of brain atrophy assessed in mild cognitive impairment
- 2018
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 8431-
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to evaluate the A/T/N biomarker scheme in relation with brain atrophy patterns in individuals with mild cognitive impairment (MCI). Of the 154 participants with MCI, 74 progressed to AD within 36-months, and 80 remained stable. In addition, 101 cognitively healthy participants and 102 participants with AD were included. The A/T/N classification was assessed with cerebrospinal fluid markers. Each individual was rated as either positive (abnormal) or negative (normal) on each biomarker. Brain atrophy was assessed with visual ratings from magnetic resonance imaging. None of the individuals with MCI progressed to AD if they had a negative “A” biomarker in conjunction with minimal atrophy. In contrary, several individuals with MCI progressed to AD if they had a positive “A” biomarker in conjunction with minimal atrophy. Numerous individuals with MCI showed inconsistency in the neurodegeneration domain (“N”) regarding t-tau and atrophy. The assessment of the A/T/N classification scheme in addition with brain atrophy patterns in MCI, increases the knowledge of the clinical trajectories and the variability within the neurodegeneration domain. This emphasises that individuals with MCI display heterogeneous longitudinal patterns closely connected to their biomarker profiles, which could have important clinical implications.
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| 47. |
- Enache, D, et al.
(författare)
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Medial temporal lobe atrophy and depressive symptoms in elderly patients with and without Alzheimer disease
- 2015
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Ingår i: Journal of geriatric psychiatry and neurology. - : SAGE Publications. - 0891-9887 .- 1552-5708. ; 28:1, s. 40-48
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Tidskriftsartikel (refereegranskat)abstract
- To determine whether depressive symptoms are associated with medial temporal lobe atrophy in older people with and without Alzheimer disease (AD).Method:A total of 368 memory clinic patients with AD, mild cognitive impairment, and subjective cognitive impairment (SCI) were included. Depressive symptoms were defined as a score of 8 or higher on Cornell Scale for Depression in Dementia or use of antidepressant medications. Magnetic resonance imaging and computer tomography scans were rated for medial temporal lobe atrophy (MTA), using the Scheltens scale. For a subsample (n = 57 patients), hippocampal volume was manually traced.Results:Based on visual assessment, AD patients with depressive symptoms had less atrophy of the right medial temporal lobe (odds ratio [OR] for having MTA: 0.39; 95% confidence interval [CI] 0.16-0.99) and decreased scores on Scheltens scale for the left medial temporal lobe (OR: 0.43, 95% CI 0.19-0.96) in comparison to AD patients without depressive symptoms. In the subgroup where manual tracing was used to measure hippocampal volume, people with SCI experiencing depressive symptoms had smaller right (mean difference: 0.28 cm3; P = .005) and left (mean difference 0.32 cm3; P = .002) hippocampal volumes compared to people with SCI who did not have depressive symptoms.Conclusion:Hippocampal atrophy was more pronounced among patients having SCI with depressive symptoms, while the medial temporal lobe was less atrophic in patients having AD with depressive symptoms than those without depressive symptoms. These findings suggest that different mechanisms underlie depression in older people with and without AD and may explain some of the inconsistent observations in previous studies.
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