| 1. |
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| 2. |
- Jansen, Willemijn J, et al.
(författare)
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Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum.
- 2022
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 79:3, s. 228-243
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Tidskriftsartikel (refereegranskat)abstract
- One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.Alzheimer disease biomarkers detected on PET or in CSF.Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.Among the 19097 participants (mean [SD] age, 69.1 [9.8] years; 10148 women [53.1%]) included, 10139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P=.04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P=.004), subjective cognitive decline (9%; 95% CI, 3%-15%; P=.005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P=.004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P=.18).This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.
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| 3. |
- Mattsson, Niklas, et al.
(författare)
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Prevalence of the apolipoprotein E epsilon 4 allele in amyloid beta positive subjects across the spectrum of Alzheimers disease
- 2018
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Ingår i: Alzheimer's & Dementia. - : ELSEVIER SCIENCE INC. - 1552-5260 .- 1552-5279. ; 14:7, s. 913-924
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Apolipoprotein E (APOE) epsilon 4 is the major genetic risk factor for Alzheimers disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid beta(A beta) pathology. Methods: We included 3451 A beta+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE epsilon 4 prevalence in relation to age, sex, education, and geographical location. Results: The APOE epsilon 4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in A beta+ cognitively normal and A beta+ mild cognitive impairment (P amp;lt;.05) but not in A beta+ AD dementia (P =.66). The prevalence was highest in Northern Europe but did not vary by sex or education. Discussion: The APOE E4 prevalence in AD was higher than that in previous studies, which did not require presence of A beta pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location. (C) 2018 the Alzheimers Association. Published by Elsevier Inc. All rights reserved.
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| 4. |
- Mattsson, Niklas, et al.
(författare)
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Prevalence of the apolipoprotein E ε4 allele in amyloid β positive subjects across the spectrum of Alzheimer's disease
- 2018
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Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 14:7, s. 913-924
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Apolipoprotein E (APOE) ε4 is the major genetic risk factor for Alzheimer's disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid β (Aβ) pathology. Methods: We included 3451 Aβ+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE ε4 prevalence in relation to age, sex, education, and geographical location. Results: The APOE ε4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in Aβ+ cognitively normal and Aβ+ mild cognitive impairment (P <.05) but not in Aβ+ AD dementia (P =.66). The prevalence was highest in Northern Europe but did not vary by sex or education. Discussion: The APOE ε4 prevalence in AD was higher than that in previous studies, which did not require presence of Aβ pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location.
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| 5. |
- Jansen, Willemijn J, et al.
(författare)
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Association of Cerebral Amyloid-β Aggregation With Cognitive Functioning in Persons Without Dementia.
- 2018
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 75:1, s. 84-95
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral amyloid-β aggregation is an early event in Alzheimer disease (AD). Understanding the association between amyloid aggregation and cognitive manifestation in persons without dementia is important for a better understanding of the course of AD and for the design of prevention trials.To investigate whether amyloid-β aggregation is associated with cognitive functioning in persons without dementia.This cross-sectional study included 2908 participants with normal cognition and 4133 with mild cognitive impairment (MCI) from 53 studies in the multicenter Amyloid Biomarker Study. Normal cognition was defined as having no cognitive concerns for which medical help was sought and scores within the normal range on cognitive tests. Mild cognitive impairment was diagnosed according to published criteria. Study inclusion began in 2013 and is ongoing. Data analysis was performed in January 2017.Global cognitive performance as assessed by the Mini-Mental State Examination (MMSE) and episodic memory performance as assessed by a verbal word learning test. Amyloid aggregation was measured with positron emission tomography or cerebrospinal fluid biomarkers and dichotomized as negative (normal) or positive (abnormal) according to study-specific cutoffs. Generalized estimating equations were used to examine the association between amyloid aggregation and low cognitive scores (MMSE score ≤27 or memory z score≤-1.28) and to assess whether this association was moderated by age, sex, educational level, or apolipoprotein E genotype.Among 2908 persons with normal cognition (mean [SD] age, 67.4 [12.8] years), amyloid positivity was associated with low memory scores after age 70 years (mean difference in amyloid positive vs negative, 4% [95% CI, 0%-7%] at 72 years and 21% [95% CI, 10%-33%] at 90 years) but was not associated with low MMSE scores (mean difference, 3% [95% CI, -1% to 6%], P=.16). Among 4133 patients with MCI (mean [SD] age, 70.2 [8.5] years), amyloid positivity was associated with low memory (mean difference, 16% [95% CI, 12%-20%], P<.001) and low MMSE (mean difference, 14% [95% CI, 12%-17%], P<.001) scores, and this association decreased with age. Low cognitive scores had limited utility for screening of amyloid positivity in persons with normal cognition and those with MCI. In persons with normal cognition, the age-related increase in low memory score paralleled the age-related increase in amyloid positivity with an intervening period of 10 to 15 years.Although low memory scores are an early marker of amyloid positivity, their value as a screening measure for early AD among persons without dementia is limited.
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| 6. |
- Jansen, Willemijn J, et al.
(författare)
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Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis.
- 2015
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Ingår i: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 313:19, s. 1924-38
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral amyloid-β aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies.
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| 7. |
- Semb, G, et al.
(författare)
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Erratum
- 2017
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Ingår i: Journal of plastic surgery and hand surgery. - 2000-6764. ; 51:2, s. 158-158
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Tidskriftsartikel (refereegranskat)
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| 8. |
- Mattsson, Niklas, 1979, et al.
(författare)
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Age and diagnostic performance of Alzheimer disease CSF biomarkers.
- 2012
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Ingår i: Neurology. - : American Academy of Neurology (AAN). - 1526-632X .- 0028-3878. ; 78:7, s. 468-76
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Tidskriftsartikel (refereegranskat)abstract
- Core CSF changes in Alzheimer disease (AD) are decreased amyloid β(1-42), increased total tau, and increased phospho-tau, probably indicating amyloid plaque accumulation, axonal degeneration, and tangle pathology, respectively. These biomarkers identify AD already at the predementia stage, but their diagnostic performance might be affected by age-dependent increase of AD-type brain pathology in cognitively unaffected elderly.
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| 9. |
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| 10. |
- Smyth, Joshua M., et al.
(författare)
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Computing Components of Everyday Stress Responses : Exploring Conceptual Challenges and New Opportunities
- 2023
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Ingår i: Perspectives on Psychological Science. - : Sage Publications. - 1745-6916 .- 1745-6924. ; 18:1, s. 110-124
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Tidskriftsartikel (refereegranskat)abstract
- Repeated assessments in everyday life enables collecting ecologically valid data on dynamic, within-persons processes. These methods have widespread utility and application and have been extensively used for the study of stressors and stress responses. Enhanced conceptual sophistication of characterizing intraindividual stress responses in everyday life would help advance the field. This article provides a pragmatic overview of approaches, opportunities, and challenges when intensive ambulatory methods are applied to study everyday stress responses in "real time." We distinguish between three stress-response components (i.e., reactivity, recovery, and pileup) and focus on several fundamental questions: (a) What is the appropriate stress-free resting state (or "baseline") for an individual in everyday life? (b) How does one index the magnitude of the initial response to a stressor (reactivity)? (c) Following a stressor, how can recovery be identified (e.g., when the stress response has completed)? and (d) Because stressors may not occur in isolation, how can one capture the temporal clustering of stressors and/or stress responses (pileup)? We also present initial ideas on applying this approach to intervention research. Although we focus on stress responses, these issues may inform many other dynamic intraindividual constructs and behaviors (e.g., physical activity, physiological processes, other subjective states) captured in ambulatory assessment.
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| 11. |
- Allard, Per, et al.
(författare)
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Dopamine uptake sites in Parkinson's disease and in dementia of the Alzheimer type.
- 1994
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Ingår i: Brain Research. - 0006-8993 .- 1872-6240. ; 637:1-2, s. 262-6
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Tidskriftsartikel (refereegranskat)abstract
- The binding of [3H]GBR-12935 to dopamine (DA) uptake sites was studied in post-mortem putamen from a control group and from patients with Parkinson's disease (PD) or dementia of the Alzheimer type (DAT). The specific binding (Bmax) was almost completely abolished in the PD group and reduced by 65% in the DAT group. There were no significant differences in apparent binding affinity (Kd) between the DAT group and controls. The decreases in [3H]GBR-12935 binding to DA uptake sites in this study indicate a marked degeneration of DA neurites in the putamen in PD and also in DAT.
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| 12. |
- Almeida, David M., et al.
(författare)
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Everyday stress components and physical activity : examining reactivity, recovery and pileup
- 2020
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Ingår i: Journal of behavioral medicine. - : Springer. - 0160-7715 .- 1573-3521. ; 43:1, s. 108-120
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Tidskriftsartikel (refereegranskat)abstract
- The experience of naturally-occurring stress in daily life has been linked with lower physical activity levels. However, most of this evidence comes from general and static reports of stress. Less is known how different temporal components of everyday stress interfere with physical activity. In a coordinated secondary analysis of data from two studies of adults, we used intensive, micro-longitudinal assessments (ecological momentary assessments, EMA) to investigate how distinct components of everyday stress, that is, reactivity to stressor events, recovery from stressor events, and pileup of stressor events and responses predict physical activity. Results showed that components of everyday stress predicted subsequent physical activity especially for indicators of stress pileup. In both studies, the accumulation of stress responses over the previous 12 h was more predictive of subsequent physical activity than current stress reactivity or recovery responses. Results are compared to the effects of general measures of perceived stress that showed an opposite pattern of results. The novel everyday stress approach used here may be fruitful for generating new insights into physical activity specifically and health behaviors in general.
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| 13. |
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| 14. |
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| 15. |
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| 16. |
- Blennow, Kaj, 1958, et al.
(författare)
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No association between the alpha2-macroglobulin (A2M) deletion and Alzheimer's disease, and no change in A2M mRNA, protein, or protein expression.
- 2000
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Ingår i: Journal of neural transmission (Vienna, Austria : 1996). - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 107:8-9, s. 1065-79
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Tidskriftsartikel (refereegranskat)abstract
- A polymorphism consisting of a deletion near the 5' splice site of exon 18 on the alpha2-macroglobulin (A2M) gene (A2M-2) has been suggested to be associated with Alzheimer's disease (AD) in family-based studies. We studied the A2M-2 allele together with the ApoE alleles in a large series on patients with AD (n = 449) and age-matched controls (n = 349). Neuropathologically confirmed diagnoses were available in 199 cases (94 AD and 107 control cases). We found no increase in A2M-2 genotype or allele frequencies in AD (27.5% and 14.6%) versus controls (26.4% and 14.9%). In contrast, a marked increase (p < 0.0001) in ApoE epsilon4 genotype or allele frequencies was found in AD (66.6% and 41.2%) as compared with controls (29.8% and 16.5%), suggesting sufficient statistical power in our sample. No relation was found between the A2M-2 and the ApoE epsilon4 allele. No change in A2M exon 17-18 mRNA size or sequence or A2M protein size was found in cases carrying the A2M-2 deletion, suggesting that there is no biological consequences of the A2M intronic deletion. No change in A2M protein level in cerebrospinal fluid was found in AD, suggesting that the A2M-2 allele does not effect the A2M protein expression in the brain. The lack of an association between the A2M-2 allele and AD in the present study, and the lack of abnormalities in the A2M mRNA or protein suggest that the A2M-2 allele is not associated with AD.
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| 17. |
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| 18. |
- Hardy, J, et al.
(författare)
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Transmitter deficits in Alzheimer's disease.
- 1985
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Ingår i: Neurochemistry International. - 0197-0186 .- 1872-9754. ; 7:4, s. 545-63
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Tidskriftsartikel (refereegranskat)abstract
- The pattern of neurotransmitter pathway losses in Alzheimer's disease are reviewed. Deficits of the cholinergic pathway from the nucleus basalis, the noradrenergic pathway from the locus coeruleus and the serotoninergic pathway from the raphe nuclei are established. Cortical somatostatin interneurons are affected and dopaminergic neurons may be affected although these may be late or secondary phenomena in the disease process. Other neuronal systems, particularly in the hippocampus and temporal cortex, are also damaged. However, the disease is not one of generalised neuronal atrophy since some neurons are selectively spared. The established pathway-specific losses are discussed in relation to the clinical symptomatology and the pathology of the disorder. The biochemical and histological findings are compared with similar measurements made on tissues from other dementing disorders in an attempt to trace features common to dementias. Finally, as an addendum, a hypothesis is briefly outlined which attempts to explain the common features of the affected neurons and the pathogenesis of the disorder.
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| 19. |
- Lindblom, P, et al.
(författare)
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Tesaglitazar, a dual PPAR-α/γ agonist, hamster carcinogenicity, investigative animal and clinical studies
- 2012
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Ingår i: Toxicologic pathology. - : SAGE Publications. - 1533-1601 .- 0192-6233. ; 40:1, s. 18-32
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Tidskriftsartikel (refereegranskat)abstract
- Tesaglitazar was developed as a dual peroxisome proliferator–activated receptor (PPARα/γ). To support the clinical program, a hamster carcinogenicity study was performed. The only neoplastic findings possibly related to treatment with tesaglitazar were low incidences of hemangioma and hemangiosarcoma in the liver of male animals. A high-power, two-year investigative study with interim necropsies was performed to further elucidate these findings. Treatment with tesaglitazar resulted in changes typical for exaggerated PPARα pharmacology in rodents, such as hepatocellular hypertrophy and hepatocellular carcinoma, but not an increased frequency of hemangiosarcomas. At the highest dose level, there was an increased incidence of sinusoidal dilatation and hemangiomas. No increased endothelial cell (EC) proliferation was detected in vivo, which was confirmed by in vitro administration to ECs. Immunohistochemistry and gene expression analyses indicated increased cellular stress and vascular endothelial growth factor (VEGF) expression in the liver, which may have contributed to the sinusoidal dilatation. A two-fold increase in the level of circulating VEGF was detected in the hamster at all dose levels, whereas no effect on VEGF was observed in patients treated with tesaglitazar. In conclusion, investigations have demonstrated that tesaglitazar does not produce hemangiosarcomas in hamster despite a slight effect on vascular morphology in the liver.
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| 20. |
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| 21. |
- Smyth, Joshua M., et al.
(författare)
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Everyday stress response targets in the science of behavior change
- 2018
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Ingår i: Behaviour Research and Therapy. - : Elsevier. - 0005-7967 .- 1873-622X. ; 101, s. 20-29
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Tidskriftsartikel (refereegranskat)abstract
- Stress is an established risk factor for negative health outcomes, and responses to everyday stress can interfere with health behaviors such as exercise and sleep. In accordance with the Science of Behavior Change (SOBC) program, we apply an experimental medicine approach to identifying stress response targets, developing stress response assays, intervening upon these targets, and testing intervention effectiveness. We evaluate an ecologically valid, within-person approach to measuring the deleterious effects of everyday stress on physical activity and sleep patterns, examining multiple stress response components (i.e., stress reactivity, stress recovery, and stress pile-up) as indexed by two key response indicators (negative affect and perseverative cognition). Our everyday stress response assay thus measures multiple malleable stress response targets that putatively shape daily health behaviors (physical activity and sleep). We hypothesize that larger reactivity, incomplete recovery, and more frequent stress responses (pile-up) will negatively impact health behavior enactment in daily life. We will identify stress-related reactivity, recovery, and response in the indicators using coordinated analyses across multiple naturalistic studies. These results are the basis for developing a new stress assay and replicating the initial findings in a new sample. This approach will advance our understanding of how specific aspects of everyday stress responses influence health behaviors, and can be used to develop and test an innovative ambulatory intervention for stress reduction in daily life to enhance health behaviors. (C) 2017 Elsevier Ltd. All rights reserved.
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| 22. |
- Stawski, Robert S., et al.
(författare)
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Age Differences in Everyday Stressor-Related Negative Affect : A Coordinated Analysis
- 2019
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Ingår i: Psychology and Aging. - : Amercican Psychological Association. - 0882-7974 .- 1939-1498. ; 34:1, s. 91-105
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Tidskriftsartikel (refereegranskat)abstract
- Advancing age is often characterized by preserved or even enhanced emotion regulation, which is thought to manifest in terms of age-related reductions in the within-person association between stressors and negative affect. Existing research from ecological momentary assessment and end-of-day daily diary studies examining such age-related benefits have yielded mixed results, potentially due to differences in samples, design, and measurement of everyday stressors and negative affect. We conducted a coordinated analysis of 5 ecological momentary assessments and 2 end-of-day daily diary studies to examine adult age differences in the within-person association between everyday stressors and negative affect. Reported stressor occurrences are robustly associated with higher negative affect, regardless of study design and sample characteristics. Across studies, interactions between age and everyday stressors predicting negative affect revealed a pattern of age-related decreases in the stressor-negative affect association, but this interaction was only significant for 2 studies. Further, examination of statistical power of the included studies suggests that, despite differences in the number of repeated assessments, power to detect within-person stressor-negative affect associations is quite good. In contrast, despite possessing wider age ranges, observed age differences were relatively small in magnitude, and studies are potentially underpowered to detect age differences in these within-person associations. We discuss the importance of study design, interval of repeated assessments and number of participants for examining age differences in everyday stressors and negative affect, as well as the virtue of coordinated analyses for detecting consistent direction of associations, but inconsistent patterns of statistical significance.
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| 23. |
- Zawadzki, Matthew J., et al.
(författare)
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Understanding stress reports in daily life : a coordinated analysis of factors associated with the frequency of reporting stress
- 2019
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Ingår i: Journal of behavioral medicine. - : Springer. - 0160-7715 .- 1573-3521. ; 42:3, s. 545-560
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Tidskriftsartikel (refereegranskat)abstract
- Although stress is a common experience in everyday life, a clear understanding of how often an individual experiences and reports stress is lacking. Notably, there is little information regarding factors that may influence how frequently stress is reported, including which stress dimension is measured (i.e., stressorsdid an event happen, subjective stresshow stressed do you feel, conditional stresshow stressful a stressor was) and the temporal features of that assessment (i.e., time of day, day of study, weekday vs. weekend day). The purpose of the present study was to conduct a coordinated analysis of five independent ecological momentary assessment studies utilizing varied stress reporting dimensions and temporal features. Results indicated that, within days, stress was reported at different frequencies depending on the stress dimension. Stressors were reported on 15-32% of momentary reports made within a day; across days, the frequency ranged from 42 to 76% of days. Depending on the cutoff, subjective stress was reported more frequently ranging about 8-56% of all moments within days, and 40-90% of days. Likewise, conditional stress ranged from just 3% of moments to 22%, and 11-69% of days. For the temporal features, stress was reported more frequently on weekdays (compared to weekend days) and on days earlier in the study (relative to days later in the study); time of day was inconsistently related to stress reports. In sum, stress report frequency depends in part on how stress is assessed. As such, researchers may wish to measure stress in multiple ways and, in the case of subjective and conditional stress with multiple operational definitions, to thoroughly characterize the frequency of stress reporting.
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| 24. |
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| 25. |
- Allard, Per, et al.
(författare)
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[3H]GBR-12935 binding to cytochrome P450 in the human brain.
- 1994
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Ingår i: Journal of Neurochemistry. - 0022-3042 .- 1471-4159. ; 62:1, s. 342-8
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Tidskriftsartikel (refereegranskat)abstract
- The presence of multiple [3H]GBR-12935 binding sites in the human brain has been revealed in several recent studies. One site represents the dopamine uptake site. In rat brain it was demonstrated that [3H]GBR-12935 also binds to nondopaminergic "piperazine acceptor sites." One of these sites has been identified as cytochrome P450IID1 in canine brain. [3H]GBR-12935 binding to the piperazine acceptor sites in the human brain was investigated in the present study. A pharmacological definition of the piperazine acceptor sites is presented: the [3H]GBR-12935 binding fraction that could be discriminated by 10 microM GBR-12909 in the presence of 0.3 microM mazindol. This binding fraction was saturable, with binding affinity in the range of 3-8 nM. It was also demonstrated that the piperazine acceptor or cytochrome P450-sensitive drugs cis-flupentixol and proadifen (SKF 525 A) compete for the same binding sites, suggesting the cytochrome P450 nature of the binding. The findings presented support the proposal that at least part of this fraction represents cytochrome P450IID6, the human form of P450IID1. The distribution of [3H]GBR-12935 binding to the suggested P450IID6-site in 12 brain regions was examined, without significant differences in binding densities between the regions. The significance of the present findings on the cytochrome P450 system in brain is discussed.
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| 26. |
- Allard, Per, et al.
(författare)
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[3H]GBR-12935 binding to dopamine uptake sites in rat striatum.
- 1990
-
Ingår i: Neuropsychobiology. - 0302-282X .- 1423-0224. ; 23:4, s. 177-81
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Tidskriftsartikel (refereegranskat)abstract
- The binding of the selective dopamine uptake inhibitor [3H]GBR-12935 to rat striatum was studied. Competition by mazindol and dopamine against [3H]GBR-12935 binding revealed monophasic binding curves. The addition of 100 microM dopamine to the mazindol competition inhibited only 80% of the binding, indicating more than one [3H]GBR-12935 binding site in rat striatum. When a binding fraction that could be discriminated by 1 microM mazindol or 1 mM dopamine was defined as specific binding, a single site binding model was obtained. The [3H]GBR-12935 binding was of protein nature, since it was abolished after protease treatment. Drug inhibition studies with the addition of low concentrations of mazindol and dopamine resulted in alterations in apparent Kd values only, suggesting competitive inhibition by these compounds against [3H]GBR-12935 binding. It is concluded that the [3H]GBR-12935 binding to rat striatum discriminated by 1 microM mazindol reflects binding to the substrate recognition site for the dopamine uptake.
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| 27. |
- Allard, Per, et al.
(författare)
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[3H]GBR-12935 binding to human cerebral cortex is not to dopamine uptake sites.
- 1994
-
Ingår i: Journal of Neurochemistry. - 0022-3042 .- 1471-4159. ; 62:1, s. 338-41
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Tidskriftsartikel (refereegranskat)abstract
- The binding of the dopamine uptake inhibitor [3H]GBR-12935 to 16 regions of the human brain was investigated in competition experiments with increasing concentrations of GBR-12909, mazindol, and dopamine. The methodology used included a relatively high tissue concentration (8 mg/ml) and addition of 5 mM KCl in the assay buffer. GBR-12909 inhibited 80-90% of the binding in most regions, whereas dopamine only inhibited the binding in the striatum. Mazindol inhibited only part of the cortical binding at concentrations of > 1 microM, whereas the inhibition in the caudate and the putamen also contained a high-affinity component representing the dopamine uptake site. It is concluded that the [3H]GBR-12935 binding sensitive to GBR-12909 cannot be regarded as specific binding to the dopamine uptake site because the displaceable binding most likely is not related to the dopamine uptake site.
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| 28. |
- Allard, Per, et al.
(författare)
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[3H]WIN 35,428 binding in the human brain.
- 1996
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Ingår i: Brain Research. - 0006-8993 .- 1872-6240. ; 706:2, s. 347-50
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Tidskriftsartikel (refereegranskat)abstract
- The binding of [3H]WIN 35,428 was studied in post-mortem human brain, including extrastriatal regions. In the putamen, dopamine almost completely inhibited the [3H]WIN 35,428 binding. Paroxetine inhibited the binding with similar affinity as cocaine, in the range 200-300 nM. In the frontal cortex, [3H]WIN 35,428 labelled cocaine- and alaproclate sensitive binding sites, of which a major fraction was of protein nature. The elucidation of the cocaine sensitive sites in the frontal cortex should be the subject of further research.
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| 29. |
- Allard, Per, et al.
(författare)
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Age-correlated loss of dopamine uptake sites labeled with [3H]GBR-12935 in human putamen.
- 1989
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Ingår i: Neurobiology of Aging. - 0197-4580 .- 1558-1497. ; 10:6, s. 661-4
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Tidskriftsartikel (refereegranskat)abstract
- The effects of age (19-100 years) upon dopamine uptake sites labeled with [3H]GBR-12935 in human postmortem putamen from 20 individuals were studied. There was a 70% decrease in binding density (Bmax) over the adult age range. No significant changes in binding affinity (Kd) were detected, the mean Kd being 1.0 +/- 0.2 nM (mean +/- S.E.M.). Nor were there any changes in binding related to the postmortem delay. Based on the findings that [3H]GBR-12935 labels the uptake site for dopamine, it is suggested that the age-related loss of [3H]GBR-12935 binding in human putamen reflects a degeneration of dopamine neurites.
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| 30. |
- Allard, Per, et al.
(författare)
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Loss of dopamine uptake sites labeled with [3H]GBR-12935 in Alzheimer's disease.
- 1990
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Ingår i: European Neurology. - 0014-3022 .- 1421-9913. ; 30:4, s. 181-5
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Tidskriftsartikel (refereegranskat)abstract
- The binding of the dopamine uptake inhibitor [3H]GBR-12935 to postmortem putamen from a control group and patients with Alzheimer's disease/senile dementia of Alzheimer type (AD/SDAT) or vascular dementia (VD) was studied. The binding density (Bmax) in AD/SDAT was significantly reduced to 50% of control. A reduction of Bmax in VD was also noted, but it did not reach statistical significance. No differences in apparent binding affinity (Kd) between controls and dementia groups were obtained. The concentrations of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT) and homovanillic acid were also determined. The concentrations of DA and DOPAC were reduced by 30-40% in AD/SDAT and VD, but the reductions did not reach statistical significance. The concentration of 3-MT was reduced by 40% in AD/SDAT and by 30% in VD. The [3H]GBR-12935-binding densities correlated significantly with corresponding concentrations of DA in control brains. It is suggested that the loss of [3H]GBR-12935-binding sites in human putamen in AD/SDAT reflects a degeneration of dopamine neurites.
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| 31. |
- Allard, Per, et al.
(författare)
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Reduced number of caudate nucleus dopamine uptake sites in vascular dementia.
- 1999
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Ingår i: Dementia and Geriatric Cognitive Disorders. - 1420-8008 .- 1421-9824. ; 10:2, s. 77-80
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Tidskriftsartikel (refereegranskat)abstract
- The dopamine (DA) uptake sites in the caudate nucleus were studied in patients with vascular dementia (VAD) and in a control group using the presynaptic DA uptake site marker [3H][2beta-carbomethoxy-3beta-(4-fluorophenyl) tropane] as radioligand. There was a significant decrease in the number of DA uptake sites in the VAD group, while the binding affinity was unchanged. The present results indicate that in the patients investigated, the cerebrovascular disease process involves dopaminergic neuron terminals in the caudate nucleus. Our findings are discussed in relation to the reductions in number of DA uptake sites that have previously been revealed in Alzheimer's and Parkinson's diseases.
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| 32. |
- Allard, Per, et al.
(författare)
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Unaltered [3H]GBR-12935 binding after chronic treatment with dopamine active drugs.
- 1990
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Ingår i: Psychopharmacology. - 0033-3158 .- 1432-2072. ; 102:3, s. 291-4
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Tidskriftsartikel (refereegranskat)abstract
- Rats were injected intraperitoneally with haloperidol 0.5 mg/kg, raclopride 1 mg/kg, bromocriptine 2.5 mg/kg, d-amphetamine 2.5 mg/kg, or cocaine 10 mg/kg twice daily for 21 days. The animals were sacrificed 72 h after last injection. Control rats were injected with saline, following the same schedule. The radioligand [3H]GBR-12935 was used as a presynaptic marker for dopamine neurites. There were no significant differences in [3H]GBR-12935 binding to striatum between drug-treated rats and controls.
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| 33. |
- Andersson, A, et al.
(författare)
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Platelet [3H]paroxetine binding to 5-HT uptake sites in Alzheimer's disease.
- 1991
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Ingår i: Neurobiology of Aging. - 0197-4580 .- 1558-1497. ; 12:5, s. 531-4
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Tidskriftsartikel (refereegranskat)abstract
- Platelet serotonin (5-hydroxytryptamine, 5-HT) uptake sites were studied in a control group (n = 30) and an Alzheimer group (n = 40) using [3H]paroxetine as radioligand. The maximum number of binding sites (Bmax) for control (1250 +/- 60 fmol/mg protein) was not different from the Alzheimer group (1280 +/- 40 fmol/mg protein). There were no differences in apparent binding affinity (Kd): 0.046 (0.024-0.062) nM for control and 0.040 (0.027-0.061) nM for Alzheimer. Thus even though several previous studies have demonstrated marked atrophy of 5-HT containing neurites and 5-HT uptake sites in Alzheimer's disease, these findings are not found in the periphery on platelets. The platelet 5-HT uptake site cannot be used as a peripheral marker of Alzheimer's disease.
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| 34. |
- Bagheri, Maryam
(författare)
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Neuroprotective Effect of Genistein : Studies in Rat Models of Parkinson’s and Alzheimer’s Disease
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Parkinson’s disease (PD) and Alzheimer’s disease (AD) are neurodegenerative disorders that mainly affect the elderly population. It is believed that oxidative stress is involved in development of both these diseases and that estrogen deficiency is a risk factor for development of AD. Genistein is a plant-derived compound that is similar in structure to estrogen and has anti-oxidative properties. The general objective of the present research was to evaluate the effects of genistein on neurodegeneration in rat models of PD and AD.Using a rat model of PD, we found that a single intraperitoneal dose of genistein 1 h before intrastriatal injection of 6-hydroxydopamine (6-OHDA) attenuated apomorphine-induced rotational behavior and protected the neurons of substantia nigra pars compacta against 6-OHDA toxicity.To produce an animal model of AD, we injected Aβ1–40 into the hippocampus of rats. Using groups of these Aβ1–40-lesioned animals, the involvement of estrogen receptors (ERs) was evaluated by intracerebroventricular injection of the estrogen receptor antagonist fulvestrant, and the role of oxidative stress was studied by measuring levels of malondialdehyde (MDA), nitrite, and superoxide dismutase (SOD) activity. The results showed that intrahippocampal injection of Aβ1–40 caused the following: lower spontaneous alternation score in Y-maze tasks, impaired retention and recall capability in the passive avoidance test, and fewer correct choices and more errors in a radial arm maze (RAM task), elevated levels of MDA and nitrite, and a signiHcant reduction in SOD activity in the brain tissue. Furthermore, hippocampus in theses rats exhibited Aβ1–40 immunoreactive aggregates close to the lateral blade of the dentate gyrus (DGlb), extensive neuronal degeneration in the DGlb, high intracellular iNOS+ and nNOS+ immunoreactivity, and extensive astrogliosis.Genistein pretreatment ameliorated the Aβ-induced impairment of short-term spatial memory, and this effect occurred via an estrogenic pathway and through attenuation of oxidative stress. Genistein also ameliorated the degeneration of neurons, inhibited the formation of Aβ1–40-positive aggregates, and alleviated Aβ1–40-induced astrogliosis in the hippocampus.
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| 35. |
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| 36. |
- Bergendal, B., et al.
(författare)
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Living with facial disfigurement- Strategies for individuals and care management
- 2011
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Ingår i: Special Care in Dentistry. - : Wiley-Blackwell. - 0275-1879. ; 31:6, s. 216-9
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Tidskriftsartikel (refereegranskat)abstract
- Individuals and families affected by craniofacial disorders have expressed dissatisfaction with their experiences in the healthcare system, with day care, and in school situations. To capture their views, focus group encounters were done in a group of young individuals with these disorders and in a group of parents whose children were affected. The aim was to synthesize their attitudes and experiences into improved strategies for parents, teenagers, and professionals in the healthcare system. Their views were compiled into a document that emphasizes the responsibilities of persons with craniofacial disorders and their parents to actively seek information on diagnosis and treatment options and to participate in decisions on therapy. The conclusion was that it is not lack of specific knowledge but rather a lack of implementation of existing recommendations that makes living with facial disfigurement difficult for many individuals and their families. © 2011 Special Care Dentistry Association and Wiley Periodicals, Inc.
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| 37. |
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| 38. |
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| 39. |
- Duits, Flora H., et al.
(författare)
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The cerebrospinal fluid "Alzheimer profile": Easily said, but what does it mean?
- 2014
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Ingår i: Alzheimer's & Dementia. - : Elsevier. - 1552-5260 .- 1552-5279. ; 10:6, s. 713-723
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to identify the most useful definition of the "cerebrospinal fluid Alzheimer profile," based on amyloid-beta(1-42) (A beta(42)), total tau, and phosphorylated tau (p-tau), for diagnosis and prognosis of Alzheimers disease (AD). Methods: We constructed eight Alzheimer profiles with previously published combinations, including regression formulas and simple ratios. We compared their diagnostic accuracy and ability to predict dementia due to AD in 1385 patients from the Amsterdam Dementia Cohort. Results were validated in an independent cohort (n = 1442). Results: Combinations outperformed individual biomarkers. Based on the sensitivity of the best performing regression formulas, cutoffs were chosen at 0.52 for the tau/A beta(42) ratio and 0.08 for the p-tau/A beta(42) ratio. Ratios performed similar to formulas (sensitivity, 91%-93%; specificity, 81%-84%). The same combinations best predicted cognitive decline in mild cognitive impairment patients. Validation confirmed these results, especially regarding the tau/A beta(42) ratio. Conclusions: A tau/A beta(42) ratio of greater than0.52 constitutes a robust cerebrospinal fluid Alzheimer profile. We recommend using this ratio to combine biomarkers.
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| 40. |
- Garcia, J., et al.
(författare)
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Association of insulin-like growth factor-1 receptor polymorphism in dementia
- 2006
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 22:5-6, s. 439-444
-
Tidskriftsartikel (refereegranskat)abstract
- There is an increasing interest in how oxidative stress can cause cells to go into apoptosis in both normal ageing and in neurodegenerative disorders. Previous research has implicated insulin-like growth factor-1 (IGF-1) as being involved in the pathogenesis in Alzheimer's disease (AD) by protecting the neurons through reducing neuronal susceptibility to oxidative stress. IGF-1 receptor (IGF-1R) polymorphisms alter cerebral and systemic levels of IGF-1 and may alter the function of the receptor. We genotyped the IGF-1R gene by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) to assess whether this gene polymorphism can be linked to dementia. We used leukocyte DNA from 72 patients with AD, 75 patients with vascular dementia (VaD), 14 patients with mixed dementia (AD+VaD), and a control group consisting of 209 individuals without a history of progressive neurological disorders. Analysis of gene frequency for gender revealed a significant difference between female VaD patients and female controls carrying at least one A allele (OR = 1.8, CI 95% 1.1-2.9, p = 0.02), but not for male patients. In addition, we found a strong tendency to a difference between all cases of female dementia patients and controls carrying the A allele (OR = 1.5, CI 95% 0.99-2.2, p = 0.054). Our results suggest that the A allele of IGF-1R may be involved in the pathogenesis of VaD in females. Copyright © 2006 S. Karger AG.
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| 41. |
- Geisner, B, et al.
(författare)
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Psoriasis and somatostatin in serum
- 2007
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Ingår i: Acta dermato-venereologica. - : Medical Journals Sweden AB. - 0001-5555. ; 87:6, s. 538-539
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 42. |
- Hansson, G, et al.
(författare)
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Intact brain serotonin system in vascular dementia
- 1996
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Ingår i: Dementia (Basel, Switzerland). - : S. Karger AG. - 1013-7424. ; 7:4, s. 196-200
-
Tidskriftsartikel (refereegranskat)abstract
- Pre- and postsynaptic elements of the 5-hydroxytryptamine (5-HT, serotonin) system were studied in a control group and in patients with vascular dementia (VAD). The 5-HT uptake site was used as a presynaptic marker for 5-HT terminals and 5-HT1A and 5HT2 receptors were used as postsynaptic markers. The binding sites were quantified with radioligand binding techniques, where the radioligands used were [<sup>3</sup>H]paroxetine, [<sup>3</sup>H]8-OH-DPAT and [<sup>3</sup>H]ketanserin, respectively. The presynaptic uptake site was studied in frontal and temporal cortices and caudate nucleus. 5-HT1A and 5-HT2 receptors were studied only in frontal and temporal cortices. There were no differences between control and VAD groups in any of the regions investigated with respect to the number of binding sites (B<sub>max</sub>) and binding affinity (K<sub>d</sub>). This indicates that both pre- and postsynaptic parts of the 5-HT system are intact in these brain areas in VAD.
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| 43. |
- Marcusson-Clavertz, David, et al.
(författare)
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Relationships between daily stress responses in everyday life and nightly sleep
- 2022
-
Ingår i: Journal of behavioral medicine. - : Springer. - 0160-7715 .- 1573-3521. ; 55, s. 518-532
-
Tidskriftsartikel (refereegranskat)abstract
- Stress and sleep are related, but the nature and time course of this relation is not well understood. We explored the within-person associations of three components of emotional responses to everyday stressors, indexed by negative affect, reactivity (initial response to a stressor), recovery (persistence of the post-stressor response), and pile-up (accumulation of stress episodes), with sleep indicators. We conducted coordinated analyses of data in several studies employing ecological momentary assessments, which captured naturally occurring, self-reported stress and sleep. We defined proximal reactivity as the emotional response to the stressor moment in question compared to an immediate pre-stressor state, and distal reactivity as the emotional response to the stressor moment in question compared to a typical stressor-free state for that person. Results in two of three studies showed that people reported significantly lower sleep quality following days on which they experienced higher levels of distal reactivity to stressors. Days with greater distal reactivity also predicted significantly more difficulty falling asleep in one of two studies. There was no clear association between proximal reactivity and subsequent sleep. Associations of recovery or pile-up with subsequent sleep emerged only in single studies. Poorer sleep quality was significantly related to higher next day levels of negative affect in all three studies, but there were no consistent relations between sleep and next day stress reactivity, recovery, or pile-up. These exploratory analyses suggest that distal reactivity is associated with a heightened risk of experiencing poor sleep quality the following night, and as such the former may serve as a candidate for potential targets for the remediation of the negative effects of stress on sleep.
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| 44. |
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| 45. |
- Marcusson, J, et al.
(författare)
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Alzheimers sjukdom och andra kognitiva sjukdomar. 3e uppl.
- 2011
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Denna tredje upplaga ger en övergripande bild av kunskapsläget samtidigt som boken i dag har det största djupet och bredden inom demensområdet på den svenska marknaden. Samtliga kapitel har omarbetats och texterna har utökats samtidigt som en ny layout och färgbilder ger boken ett helt nytt läsarvänligt format. Boken vänder sig till samtliga grundutbildningar som berör demenssjukdomarna men också till alla de yrkeskategorier som på olika sätt möter personer med kognitiva sjukdomar. Även drabbade patienter och deras närstående har visat sig ha stort intresse av en lärobok där aktuell kunskap om sjukdomarna och deras konsekvenser belyses.
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| 46. |
- Nagga, K, et al.
(författare)
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GABA transporters (GAT-1) in Alzheimer's disease
- 1999
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Ingår i: Journal of neural transmission (Vienna, Austria : 1996). - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 106:11-12, s. 1141-1149
-
Tidskriftsartikel (refereegranskat)
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| 47. |
- Nägga, Katarina, et al.
(författare)
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Cerebrospinal fluid phospho-tau, total tau and β-amyloid1-42 in the differentiation between Alzheimer's disease and vascular dementia
- 2002
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 14:3-4, s. 183-190
-
Tidskriftsartikel (refereegranskat)abstract
- The two most frequently examined biomarkers in the diagnosis of dementia are cerebrospinal fluid (CSF) tau and β-amyloid1-42 (Aβ1-42). An assay for tau phosphorylated at threonine 181 (phospho-tau) has recently been developed. We studied these three markers in patients with possible Alzheimer's disease (AD; n = 23), probable AD (n = 50), AD with relevant cerebrovascular disease (AD with CVD; n = 14), possible vascular dementia (VaD; n = 39), probable VaD (n = 36), cognitively impaired (n = 13) and 27 neurologically healthy controls. Compared with the controls, tau levels were significantly increased in possible AD, probable AD, AD with CVD and probable VaD. Aβ1-42 was decreased in all dementia groups compared with the controls. In contrast, phospho-tau levels were increased only in probable AD compared with the controls. From the results of the present study, it is concluded that neither measurement of phospho-tau, tau nor Aβ1-42 in CSF can discriminate entirely between dementia and cognitively non-disturbed controls or between dementia of different aetiologies in the clinical diagnostic procedure.
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| 48. |
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| 49. |
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| 50. |
- Rizell, Sara, 1963, et al.
(författare)
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Scandcleft randomized trials of primary surgery for unilateral cleft lip and palate: dental anomalies in 8-year olds
- 2020
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Ingår i: European Journal of Orthodontics. - : Oxford University Press (OUP). - 0141-5387 .- 1460-2210. ; 42:1, s. 8-14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Children born with unilateral cleft lip and palate (UCLP) are reported to display several dental anomalies including agenesis, supernumeraries, as well as variations in dental size, shape, and path of eruption. The extensive sample of individuals with UCLP included in the Scandcleft randomized control trials offers the opportunity to study more rare conditions, which is seldom possible with limited samples. Objectives: The aim was to study dental anomalies at 8 years of age in children born with UCLP included in the Scandcleft randomized control trials. Methods: Panoramic and intraoral radiographs from 425 individuals (279 males and 146 females) with a mean age of 8.1 years were assessed by four orthodontists regarding dental anomalies. Results: Agenesis was found in 52.5 per cent and supernumerary teeth in 16.9 per cent of the participants. The cleft lateral was missing in 43.8 per cent and was found peg shaped in 44.7 per cent.The distribution of ectopic eruption was 14.6 per cent, mainly affecting maxillary first molars, while transposition was found in 3.4 per cent of the individuals. In addition, infraocclusion of one or several primary molars was registered in 7.2 per cent of the participants. Conclusion: We conclude that 8-year-old children born with UCLP display multiple dental anomalies. The Scandcleft sample allowed rarely studied conditions such as infraocclusion of primary molars and transposition to be studied in children born with UCLP.
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