| 1. |
- Edvardsson, Maria, et al.
(författare)
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Classification of ≥80-year-old individuals into healthy, moderately healthy, and frail based on different frailty scores affects the interpretation of laboratory results
- 2022
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Ingår i: Asian Journal of Medical Sciences. - : Nepal Journals Online (NepJOL). - 2467-9100 .- 2091-0576. ; 13:9, s. 63-71
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Tidskriftsartikel (refereegranskat)abstract
- Background: Interpretation laboratory analyses are crucial when assessing the patient’s condition. Reference intervals from apparently healthy and disease-free individuals may cause problems when outcomes from elderly patients with chronic diseases and on medications are being interpreted. Elderly individuals are a heterogeneous group ranging from individuals managing their daily life independently to individuals with diseases and impairment, in need of nursing care around the clock, that is, frail; a term widely used although there is no consensus on the definition.Aims and Objectives: The aim of the study was to study the effect of classification of elderly into healthy, moderately healthy, and frail, based on activities of daily living (ADL) and Mini-Mental State Examination (MMSE) or frailty index (FI), on the interpretation of outcomes regarding: Albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, and gamma-glutamyltransferase (γ-GT) levels.Materials and Methods: Individuals ≥80 years (n=568) were classified either on ADL and MMSE or number of deficits, (FI).Results: Individuals classified as frail based on FI had lower mean levels for ALT, creatinine and γ-GT than individuals classified based on ADL and MMSE (P<0.05).Conclusion: The model to define health status to some extent affected laboratory analyte levels in ≥80 years old, classified as healthy, moderately healthy, and frail based on ADL and MMSE versus FI.
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| 2. |
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| 3. |
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| 4. |
- 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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| 5. |
- Agholme, Lotta, et al.
(författare)
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Amyloid-β Secretion, Generation, and Lysosomal Sequestration in Response to Proteasome Inhibition : Involvement of Autophagy
- 2012
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Ingår i: Journal of Alzheimer's Disease. - : I O S Press. - 1387-2877 .- 1875-8908. ; 31:2, s. 343-358
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Tidskriftsartikel (refereegranskat)abstract
- The proteasome is important for degradation of worn out and misfolded proteins. Decreased proteasome activity has been implicated in Alzheimer's disease (AD). Proteasome inhibition induces autophagy, but it is still unknown whether autophagy is beneficial or deleterious to AD neurons, as the autophagosome has been suggested as a site of amyloid-β (Aβ) generation. In this study, we investigated the effect of proteasome inhibition on Aβ accumulation and secretion, as well as the processing of amyloid-β protein precursor (AβPP) in AβPPSwe transfected SH-SY5Y neuroblastoma cells. We show that proteasome inhibition resulted in autophagy-dependent accumulation of Aβ in lysosomes, and increased levels of intracellular and secreted Aβ. The enhanced levels of Aβ could not be explained by increased amounts of AβPP. Instead, reduced degradation of the C-terminal fragment of AβPP (C99) by the proteasome makes C99 available for γ-secretase cleavage, leading to Aβ generation. Inhibition of autophagy after proteasome inhibition led to reduced levels of intracellular, but not secreted Aβ, and tended to further increase the C99 to AβPP ratio, supporting involvement of the autophagosome in Aβ generation. Furthermore, proteasome inhibition caused a reduction in cellular viability, which was reverted by inhibition of autophagy. Dysfunction of the proteasome could cause lysosomal accumulation of Aβ, as well as increased generation and secretion of Aβ, which is partly facilitated by autophagy. As a decrease in cellular viability was also detected, it is possible that upregulation of autophagy is an unsuccessful rescue mechanism, which instead of being protective, contributes to AD pathogenesis.
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| 6. |
- Agholme, Lotta, et al.
(författare)
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An In Vitro Model for Neuroscience: Differentiation of SH-SY5Y Cells into Cells with Morphological and Biochemical Characteristics of Mature Neurons
- 2010
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Ingår i: Journal of Alzheimer's Disease. - : Ios Press. - 1387-2877 .- 1875-8908. ; 20:4, s. 1069-1082
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Tidskriftsartikel (refereegranskat)abstract
- Neuroscience, including research on Alzheimers disease, is hampered by the lack of suitable in vitro models to study the human nervous system. To counteract this, many attempts to differentiate cell lines into more neuron-like cells have been performed, resulting in partial expression of neuronal features. Furthermore, it has been reported that neuroblastoma cell lines lack mature isoforms of tau. Our aim was to develop an improved in vitro model, generating sustainable cells with morphology and biochemistry of human, mature neurons. To obtain cells with neuronal differentiation and function, we investigated the effect of combining three-dimensional culturing of SH-SY5Y cells in extracellular matrix (ECM) gel with several factors reported to have neuro-differentiating effects. This resulted in cells with apparent neuronal morphology with long, extensively branched neurites. Further investigation revealed expression of several neurospecific markers including synapse protein Sv2 and nuclear marker NeuN, as well as the presence of synapses and axonal vesicle transport. In addition, these cells expressed mature tau isoforms, and tau protein expression was significantly increased compared to undifferentiated cells, reaching levels found in adult human brain. In conclusion, we found that pre-treatment with retinoic acid followed by ECM gel culturing in combination with brain derived neurotrophic factor, neuregulin beta(1), nerve growth factor, and vitamin D-3 treatment generated sustainable cells with unambiguous resemblance to adult neurons. These cells also expresses adult splicing forms of tau with neuronal localization, making this cellular in vitro model useful in many areas of neuroscience research, particularly the Alzheimers disease field.
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| 7. |
- Agholme, Lotta, et al.
(författare)
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Proteasome Inhibition Induces Stress Kinase Dependent Transport Deficits – Implications for Alzheimer’s Disease
- 2014
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Ingår i: Molecular and Cellular Neuroscience. - : Elsevier. - 1044-7431 .- 1095-9327. ; 58, s. 29-39
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease (AD) is characterized by accumulation of two misfolded and aggregated proteins, β-amyloid and hyperphosphorylated tau. Both cellular systems responsible for clearance of misfolded and aggregated proteins, the lysosomal and the proteasomal, have been shown to be malfunctioning in the aged brain and more so in AD patients. This malfunction could be the cause of β-amyloid and tau accumulation, eventually aggregating in plaques and tangles. We have investigated how decreased proteasome activity affects AD related pathophysiological changes of microtubule transport and stability, as well as tau phosphorylation. To do this, we used our recently developed neuronal model where human SH-SY5Y cells obtain neuronal morphology and function through differentiation. We found that exposure to low doses of the proteasome inhibitor MG-115 caused disturbed neuritic transport, together with microtubule destabilization and tau phosphorylation. Furthermore, reduced proteasome activity activated several kinases implicated in AD pathology, including JNK, c-Jun and ERK 1/2. Restoration of the microtubule transport was achieved by inhibiting ERK 1/2 activation, and simultaneous inhibition of both ERK 1/2 and c-Jun reversed the proteasome inhibition-induced tau phosphorylation. Taken together, this study suggests that a decrease in proteasome activity can, through activation of c-Jun and ERK 1/2, result in several events contributing to AD pathology. Restoring proteasome function or inhibiting ERK 1/2 and c-Jun could therefore be used as novel treatments against AD.
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| 8. |
- Agholme, Lotta
(författare)
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The involvement of degradation pathways and neuron-to-neuron transmission in Alzheimer’s disease
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Although the vast majority of Alzheimer’s disease (AD) cases are of the sporadic type, mutations causing the familial form have been the focus of AD research for decades. The disease is pathologically characterised by β-amyloid (Aβ) and tau protein aggregates in neuritic plaques and neurofibrillary tangles. Furthermore, it is known that AD pathology spreads throughout the brain, most often along the same anatomical pattern. However, so far no cause for the sporadic form of the disease has been found. Accumulation of protein aggregates as well as decreased activity of the protein degradation systems, lysosomes and proteasomes, is found in diseased brains. This indicates that defective degradation contributes to sporadic AD.The aim of this thesis was to develop an improved neuronal model, and study the effects of decreased proteasome function on tau phosphorylation and axonal transport. In addition, the effects on Aβ accumulation and generation upon proteasome inhibition were investigated. Finally, the possibility that intracellularly accumulated Aβ oligomers could be transferred from one neuron to another was tested.Differentiation of human SH-SY5Y neuroblastoma cells in an extracellular matrix gel, using a set of neurotrophic factors, resulted in cells with neuronal phenotype, expressing neuron specific markers and all six adult isoforms of tau. Within this neuronal model, we found that reduced proteasome activity inhibited neuritic transport, and caused tau phosphorylation in a c-Jun and ERK 1/2 dependent manner. Using proteasome inhibition in APP overexpressing cells, we found an autophagy dependent intralysosomal Aβ accumulation, together with elevation of intra- and extracellular concentrations of Aβ. Autophagy inhibition protected the cells from the toxicity induced by decreased proteasome activity. Finally, we could, as the first group, show that Aβ can be directly transferred from one neuron to another through connected neurites. Furthermore, accumulation of Aβ in the endo-lysosomal compartment of receiving cells caused toxicity and neurodegeneration.We believe that cells not able to degrade accumulated Aβ, due to increased generation or reduced degradative capacity, instead tries to clear its content through transfer to connected neurons. If not properly degraded in the receiving cell, this can accelerate AD pathology and cause neuritic and neuronal degeneration spreading throughout the brain. Increasing the activity of the degradative systems, or inhibiting transmission of Aβ between neurons could therefore be novel treatments for AD.
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| 9. |
- Allard, Per, et al.
(författare)
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Caudate nucleus dopamine D-2 receptors in vascular dementia
- 2002
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 14:1, s. 22-25
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Tidskriftsartikel (refereegranskat)abstract
- Caudate nucleus dopamine (DA) D-2 receptors were studied in patients with vascular dementia (VaD) and in a control group using [H-3]raclopride as a radioligand. There was no significant difference in the number of DA D-2 receptors in the VaD group as compared with controls. The binding affinity was significantly lower in the VaD group. When the VaD group was subdivided into subjects with or without neuroleptic treatment, there were no differences in the numbers of receptors as compared with controls, and the significant differences in binding affinity remained for both VaD subgroups. The present results are. discussed with reference to the previous finding of a reduced density of caudate nucleus DA uptake sites in the same VaD group and to results from studies on DA D-2 receptors in Alzheimer's disease and Parkinson's disease. Copyright (C) 2002 S. Karger AG, Basel.
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| 10. |
- Andersson, Lena B., et al.
(författare)
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Health-related quality of life and activities of daily living in 85-year-olds in sweden
- 2014
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Ingår i: Health and Social Care in the Community. - : John Wiley & Sons. - 0966-0410 .- 1365-2524. ; 22:4, s. 368-374
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Tidskriftsartikel (refereegranskat)abstract
- Few studies have examined health-related quality of life (HRQoL) with respect to daily living and health factors for relatively healthy elderly individuals. To this end, this study examines 85-year-olds’ reported HRQoL in relation to social support, perceived health, chronic diseases, health care use and instrumental activities of daily living. Data were collected from 360 participants (55% response rate) between March 2007 and March 2008 using a postal questionnaire and a home visit interview. HRQoL was assessed using the EQ-5D-3L. For the items in the EQ-5D-3L, more problems were related to lower HRQoL. Restricted mobility and occurrence of pain/discomfort was common. Lower HRQoL was associated with increased risk for depression, increased use of medication, increased number of chronic diseases, and more problems with instrumental activities of daily living (IADL). Health care use and health care costs was correlated to lower HRQoL. HRQoL is of importance to health care providers and must be considered together with IADL in the elderly population when planning interventions. These should take into account the specific needs and resources of the older individuals.
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| 11. |
- Andin, Josefine, et al.
(författare)
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Environmental enrichment induces changes in the mRNA expression of rat EAAC1 and NMDA but not in AMPA
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Interaction with the environment has a key role in refining the neuronal circuitry required for normal brain function throughout life. Profound effects of enriched environment has been shown on neuronal strucrure and chemistry in experimental animals. Epidemiological studies imply that this is true also in man, thus cognitive stimulation has a protective effect on neurodegeneration, e.g. Alzheimer's disease. Glutamatergic corticocortical pathways are imperative for cognitive functions, such as memory and learning, and long term porenriation relies on the AMPA and NMDAglutamate rcceptors. The glutamate signalling is also dependent on a fine-runed transport system, in the hippocampus primarily by theglutamate transporter EAACl. In this study we show how environmental enrichment modulates these parts of the glutamarergic system using in siru hybridization. This work demonstrates for the first time that environmental enrichment modulates the mRNA expression of EAAC1 which is significantly decreased in hippocampal and cortical areas. We also provide further evidence about the upregulation of NMDA mRNA after environmental enrichement, and show it to have a regionally and hemisphere specific regulation. The current work also confirms that AMPA mRNA is nor per se changed by environmental enrichment in adult animals. Taken together, our results extend the knowledge of the glutamatergic system and its modulation by environmental enrichment and could contribute to the development of strategies aimed at limiting pathological changes associated with glutamatergic dysfunctions.
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| 12. |
- Andin, Josefine, 1979-, et al.
(författare)
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Influence of environmental enrichment on steady-state mRNA levels for EAAC1, AMPA1 and NMDA2A receptor subunits in rat hippocampus
- 2007
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993 .- 1872-6240. ; 1174:1, s. 18-27
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Tidskriftsartikel (refereegranskat)abstract
- Interaction with the environment has a key role in refining the neuronal circuitry required for normal brain function throughout life. Profound effects of enriched environment have been shown on neuronal structure and chemistry in experimental animals. Epidemiological studies imply that this is true also in man, thus cognitive stimulation has a protective effect on neurodegeneration, e.g., in Alzheimer's disease. Glutamatergic pathways are imperative for cognitive functions, such as memory, learning and long-term potentiation, and relies on the AMPA and NMDA glutamate receptors and the hippocampus, with its specific subregions, is an important anatomical substrate in this. The glutamate signalling is also dependent on a fine-tuned transport system, in the hippocampus primarily achieved by the glutamate transporter EAAC1. In this study we show how environmental enrichment modulates these parts of the glutamatergic system using quantitative in situ hybridisation. This work demonstrates for the first time that environmental enrichment modulates the mRNA expression of EAAC1 which is significantly and region specifically decreased in the hippocampus. We also provide evidence for regional and hemisphere-specific upregulation of NMDA mRNA in the hippocampus after environmental enrichment. The current work also shows that AMPA mRNA of the hippocampus is not per se changed by environmental enrichment in adult animals. Taken together, our results extend the knowledge of the glutamatergic system of specific regions of the hippocampus and its modulation by environmental enrichment and could contribute to the development of strategies aimed at limiting pathological changes associated with glutamatergic dysfunctions. © 2007.
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| 13. |
- Andin, Josefine, 1979-, et al.
(författare)
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Modulation of neuronal glutamate transporter rEAAC1 mRNA expression in rat brain by amitriptyline
- 2004
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Ingår i: Brain Research. Molecular Brain Research. - : Elsevier BV. - 0169-328X .- 1872-6941. ; 126:1, s. 74-77
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Tidskriftsartikel (refereegranskat)abstract
- Glutamate transporters regulate the glutamate concentration in the synaptic cleft within the CNS, a regulation required for normal brain function. In several neurological conditions, the amount of glutamate is altered. One reason for the changes in glutamate concentration might be impaired glutamate transporter function. In this study, an in situ hybridisation technique has been used to elucidate changes in mRNA expression of the glutamate transporter, excitatory amino acid carrier 1 (EAAC1), after treatment with the tricyclic antidepressant (TCA) amitriptyline. The results lead to the suggestion that treatment with tricyclic antidepressants leads to changes in the EAAC1 mRNA expression in rat brain suggesting involvement of the glutamate system in the tricyclic treatment of depression.
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| 14. |
- Andin, Josefine, 1979-, et al.
(författare)
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Rivastigmine as a Modulator of the Neuronal Glutamate Transporter rEAAC1 mRNA Expression
- 2005
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 19:1, s. 18-23
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease is a neurodegenerative disorder that affects the cholinergic, glutamatergic and monoaminergic systems in the neocortex and hippocampus. Today, the major pharmacological treatment involves the use of acetylcholinesterase inhibitors (AChEIs). In this study, an in situ hybridisation technique (using digoxigenin-labelled cRNA probes) was used to elucidate changes in mRNA expression of the neuronal glutamate transporter, rat excitatory amino carrier 1 (rEAAC1), after treatment with the AChEI rivastigmine. Compared with saline-treated rats, the rats subchronically (3 days) and chronically (21 days), but not acutely, treated with rivastigmine showed a significant increase in rEAAC1 mRNA expression in the hippocampal areas cornu anterior 1 (CA1), CA2, CA3 and dentate gyrus (p < 0.01), but not in the cortical areas. These results provide the first evidence that the glutamatergic system is modulated following acetylcholinesterase inhibition by rivastigmine, a finding, which is likely to be of importance for the clinical effects.
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| 15. |
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| 16. |
- 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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| 17. |
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| 18. |
- Bielsten, Therese, et al.
(författare)
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Controlling the Uncontrollable : Patient Safety and Medication Management From the Perspective of Registered Nurses in Municipal Home Health Care
- 2022
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Ingår i: Global Qualitative Nursing Research. - : Sage Publications. - 2333-3936. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Most adverse events in health care are related to medication management and they are almost always preventable. Increased knowledge of patient safety related to medication management in home health care is an urgent issue to provide safe care for all patients regardless of where the health care takes place. This study explored patient safety within medication management in municipal home health care. Vignettes were used as stimulus during qualitative interviews with registered nurses. Three main themes with related subthemes were identified as challenges to patient safety within medication management in home health care: (1) challenges to information transfer, (2) challenges related to delegation, and (3) challenges of advanced medical treatments in the home. The issue of transfer of information permeated our findings. Coordinating medications, delegating tasks, along with more advanced care require clear communication between care providers to be compatible with patient safety within medication management in home health care.
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| 19. |
- Bjartmar, Lisa, 1966-, et al.
(författare)
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Long-term treatment with antidepressants, but not environmental stimulation, induces expression of NP2 mRNA in hippocampus and medial habenula
- 2010
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Ingår i: Brain Research. - : Elsevier. - 0006-8993 .- 1872-6240. ; 1328, s. 24-33
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Tidskriftsartikel (refereegranskat)abstract
- Neuronal Pentraxin 2 (NP2, Narp), known to mediate clustering of glutamatergic AMPA receptors at synapses, is involved in activity-dependent synaptogenesis and synaptic plasticity. In experimental settings, antidepressant treatment as well as a stimulating environment has a positive influence on cognition and hippocampal plasticity. This study demonstrates that NP2 mRNA is robustly expressed in the hippocampus and the medial habenula (MHb), both regions implicated in cognitive functions. Furthermore, NP2 mRNA expression is enhanced in the hippocampal subregions as well as in the MHb after long-term treatment with antidepressant drugs of various monoaminergic profiles, indicating a common mode of action of different antidepressant drugs. This effect occurs at the time frame where clinical response is normally achieved. In contrast, neither environmental enrichment nor deprivation has any influence on long-term NP2 mRNA expression. These findings support an involvement of NP2 in the pathway of antidepressant induced plasticity, but not EE induced plasticity; that NP2 might constitute a common link for the action of different types of antidepressant drugs and that the MHb could be a putative region for further studies of NP2.
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| 20. |
- Bjartmar, Lisa, 1966-
(författare)
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Pharmacological and Developmental Aspects on Neuronal Plasticity
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Neuronal plasticity means the ability of the brain, its cells and networks to adapt and adjust to new challenges, a process which is ongoing throughout life. The goal of this thesis was to gain better understanding of the molecular events that follow different types of stimulations of brain structures such as the hippocampus, a key region for cognitive functions with overriding control on the corticosteroid system. A better knowledge of the mechanisms involved in neuronal plasticity is fundamental in the development of strategies for improving health in patients suffering from major depression or cognitive disorders such as Alzheimer’s disease.Antidepressant drugs induce the expression of several genes involved in neuronal plasticity, a mechanism which may explain the several weeks time lag between treatment initiation and clinical effect commonly observed in patients. Besides, there are indications that disturbances in the corticosteroid system are involved in the pathogenesis of major depression. Therefore, the mRNA expression of the glucocorticoid receptors (GR) and mineralocorticoid receptors (MR) as well as of the immediate-early genes NGFI-A and NGFI-B was analyzed using in situ hybridization in the hippocampus and cortex after 21 days treatment with various antidepressant drugs having different monoaminergic profiles. The mRNA expression of the transcription factors was selectively increased depending on region and also on the monoaminergic profile of the drug given. Generally, drugs with less specificity for monoamines had an overall more anatomically wide-spread inducible effect.In a follow-up study the message expression of the synaptic protein NP2 was investigated in a similar setting where long-term (21 days) was compared with short-term (3 days) antidepressant treatment. In addition to the hippocampus, the medial habenula, a relay station within the limbic system was analyzed. Overall there was an upregulation of NP2 mRNA expression following long-term treatment irrespective of the monoaminergic profile of the drug. Simultaneously, NP2 mRNA was analyzed in rats exposed to enriched, normal or deprived environments respectively, an experimental setting known to affect neuronal plasticity. However, in contrast to the pharmacological treatment, this environmental stimulation did not lead to alterations in NP2 mRNA expression in any of the regions studied.Finally, the function of NP2 as well as the closely related proteins NP1 and NPR was investigated. The “knock-out mouse” technique was used to eliminate these neuronal pentraxins (NPs), both individually and in various combinations. Since previous data had suggested that the NPs are involved in synaptic development, axonal refinement in the visual system during development was analyzed in these animals. In the NP1/NP2 knock-out mice, synaptic formation, axonal development and refinement occurred at a significantly slower rate than in wild-type mice, indicating that the NPs may be necessary for activity-dependent synaptogenesis.In conclusion, the results of the studies constituting this thesis demonstrate that long-term treatment with antidepressant drugs, possessing different monoaminergic profiles, has selective effects on the expression of NGFI-A, NGFI-B, GR and MR in the mammalian brain. In general, the least selective drugs exhibit the most profound effect suggesting that induction of neuronal plasticity is more effective with multiple neuronal inputs. The results also show that NP2 expression is induced by antidepressant drugs, in contrast to environmental stimulation, supporting the presence of different pathways for inducing neuronal plasticity depending on type of stimuli. Finally, this thesis indicates that the neuronal pentraxins play an important part in synaptic development.
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| 21. |
- Bjartmar, Lisa, 1966-, et al.
(författare)
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Selective effects on NGFI-A, MR, GR and NGFI-B hippocampal mRNA expression after chronic treatment with different subclasses of antidepressants in the rat
- 2000
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Ingår i: Psychopharmacology. - : Springer Science and Business Media LLC. - 0033-3158 .- 1432-2072. ; 151:1, s. 7-12
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Tidskriftsartikel (refereegranskat)abstract
- There is a latency period of several weeks before the onset of clinical effect of antidepressant drugs. The detailed mechanisms underlying drug-induced adaptive neuronal changes are not known. To elucidate the involvement of changes in gene expression of candidate transcription factors, we treated rats for 21 days with buspirone, fluoxetine, 8-OH-DPAT and moclobemide. In situ hybridization was used to study mRNAs encoding NGFI-A, NGFI-B and the glucocorticoid receptors, MR and GR. NGFI-A mRNA expression increased profoundly in the hippocampal formation and the cerebral cortex after all drug treatments, especially after moclobemide treatment (77-122% increase), with the exception of buspirone. MR mRNA expression was induced in hippocampal CA1/CA2 subregions (27-37%) by all antidepressants, while moclobemide and 8-OH-DPAT significantly increased GR gene expression mainly in the CA1 region (31-44%). NGFI-B mRNA was significantly decreased in the hippocampal CA3 subfield (23%) and restrosplenial granular cortex (38%) by moclobemide treatment. There are selective effects of antidepressant drugs on specific transcription factors. These may be important for adaptive neuronal and neuroendocrine changes after antidepressant treatment including HPA axis negative feedback regulation.
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| 22. |
- 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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| 23. |
- Cederbrant, Karin, et al.
(författare)
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In vitro Lymphocyte Proliferation as Compared to Patch Test Using Gold, Palladium and Nickel
- 1997
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Ingår i: International Archives of Allergy and Immunology. - : S. Karger AG. - 1018-2438 .- 1423-0097. ; 112:3, s. 212-217
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Tidskriftsartikel (refereegranskat)abstract
- Background: A conventional lymphocyte transformation test (LTT) was compared to the commercially available MELISA® (memory lymphocyte immuno-stimulation assay), a lymphoproliferative assay that has been suggested to be a valuable instrument for the diagnosis of metal allergy. Sensitivity and specificity of the two assays were calculated using a patch test as a reference method.Methods: 34 patients were patch-tested for gold sodium thiosulfate, palladium chloride and nickel sulfate, and the lymphocyte proliferation to these metals was tested in vitro using mononuclear cells from peripheral blood.Results: No significant differences regarding sensitivity and specificity were found between MELISA and conventional LTT. The sensitivity varied between 55 and 95% and the specificity between 17 and 79%.Conclusions: The low specificity of the two in vitro assays suggests that they are not useful for diagnosis of contact allergy to the metals gold, palladium and nickel, since a large number of false-positive results will be obtained.
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| 24. |
- Classon, Elisabet, et al.
(författare)
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Relations between Concurrent Longitudinal Changes in Cognition, Depressive Symptoms, Self-Rated Health and Everyday Function in Normally Aging Octogenarians
- 2016
-
Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 11:8, s. e0160742-
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Tidskriftsartikel (refereegranskat)abstract
- Ability to predict and prevent incipient functional decline in older adults may help prolong independence. Cognition is related to everyday function and easily administered, sensitive cognitive tests may help identify at-risk individuals. Factors like depressive symptoms and self-rated health are also associated with functional ability and may be as important as cognition. The purpose of this study was to investigate the relationship between concurrent longitudinal changes in cognition, depression, self-rated health and everyday function in a well-defined cohort of healthy 85 year olds that were followed-up at the age of 90 in the Elderly in Linkoping Screening Assessment 85 study. Regression analyses were used to determine if cognitive decline as assessed by global (the Mini-Mental State Examination) and domain specific (the Cognitive Assessment Battery, CAB) cognitive tests predicted functional decline in the context of changes in depressive symptoms and self-rated health. Results showed deterioration in most variables and as many as 83% of these community-dwelling elders experienced functional difficulties at the age of 90. Slowing-down of processing speed as assessed by the Symbol Digits Modality Test (included in the CAB) accounted for 14% of the variance in functional decline. Worsening self-rated health accounted for an additional 6%, but no other variables reached significance. These results are discussed with an eye to possible preventive interventions that may prolong independence for the steadily growing number of normally aging old-old citizens.
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| 25. |
- Degerman Gunnarsson, Malin, 1969-
(författare)
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Biomarkers as Monitors of Drug Effect, Diagnostic Tools and Predictors of Deterioration Rate in Alzheimer’s Disease
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Decreased amyloid-ß42 (Aß42), increased total tau (t-tau) and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) reflect histopathological core changes in the most common dementia disorder, Alzheimer’s disease (AD). They discriminate AD from healthy controls and predict conversion to AD with a relatively high accuracy. Memantine, an uncompetitive NMDA-receptor antagonist, is indicated for symptomatic treatment of AD. The first aim of this thesis was to investigate effects of memantine on CSF concentrations of Aβ42, tau and p-tau. Secondly, the aim was to explore the relation between these CSF biomarkers and retention of the amyloid biomarker Pittsburgh compound B using positron emission tomography (PIB PET), regional glucose metabolism measured with 18Fluoro-2-deoxy-d-glucose (FDG) PET and neuropsychological test performance. The third aim was to investigate their possible utility as predictors of future rate of AD dementia deterioration. All patients in the studies were recruited from the Memory Clinic, Uppsala University Hospital. In study I CSF p-tau concentrations in 11 AD patients were reduced after twelve months treatment with memantine, indicating that this compound may affect a key pathological process in AD. Results from study II showed that the concentrations of CSF Aß42 are lower in PIB+ patients than in PIB- patients, and that the PIB retention was stable during 12 months. In study III 10 patients with the diagnoses AD (6 PIB+/4 PIB-) and 8 subjects (1 PIB+/7 PIB-) with frontotemporal dementia were included. PIB+ patients had lower psychomotor speed measured by performance on the Trail Making Test A and impaired visual episodic memory compared to the PIB- patients. The initial clinical diagnoses were changed in 33% of the patients (6/18) during follow-up. Study IV is the first-ever report of an association between high CSF tau and dying in severe dementia. These 196 AD patients were followed up to nine years after baseline lumbar puncture. Moreover, CSF t-tau concentrations above median was associated with an increased risk of rapid cognitive decline (OR 3.31 (95% CI 1.53-7.16), independently of baseline functional stage. Thus, a clear association between high levels of CSF t-tau and p-tau and a more aggressive course of the disease was shown.
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| 26. |
- Domert, Jakob, 1986-
(författare)
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Neuron-to-neuron propagation of neurodegenerative proteins; relation to degradative systems
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Alzheimer’s disease (AD) and Parkinson’s disease (PD) are defined by neurodegeneration and accumulations of misfolded proteins that spread through the brain in a well characterized manner. In AD these accumulations consist mainly of β-amyloid (Aβ) and tau, while in PD, α-synuclein (α-syn) make up the characteristic lewy pathology. The general aim of this thesis was to investigate mechanisms associated with neurotoxic peptide activity by Aβ, tau and α-syn in relation to cellular degradation and transfer with a cell-to-cell transfer model system. We found that intercellular transfer of oligomeric Aβ occurs independently of isoform. However, the amount of transfer correlates with each isoforms ability to resist degradation or cellular clearance. The Aβ1-42 isoform showed particular resistance to clearance, which resulted in higher levels of cell-to-cell transfer of the isoform and lysosomal stress caused by accumulation. As Aβ accumulations can inhibit the proteasomal degradation we investigated how reduced proteasomal degradation affected neuron-like cells. We found increased levels of phosphorylated tau protein, disturbed microtubule stability and impaired neuritic transport after reduced proteasomal activity. These changes was partly linked to c-Jun and ERK 1/2 kinase activity. We could also show that α-syn transferred from cell-to-cell in our model system, with a higher degree of transfer for the larger oligomer and fibrillar species. Similar to Aβ, α-syn mainly colocalized with lysosomes, before and after transfer. Lastly, we have developed our cell-to-cell transfer system into a model suitable for high throughput screening (HTS). The type of cells have been upgraded from SH-SY5Y cells to induced pluripotent stem cells (iPSCs), with a differentiation profile more similar to mature neurons. The next step will be screening a small molecular library for substances with inhibitory effect on cell-to-cell transfer of Aβ peptides. The importance of the degradative systems in maintaining protein homeostasis and prevent toxic accumulations in general is well known. Our findings shows the importance of these systems for neurodegenerative diseases and also highlight the link between degradation and cell-to-cell transfer. To restore or enhance the degradative systems would be an interesting avenue to treat neurodegenerative diseases. Another way would be to inhibit the transfer of misfolded protein aggregates. By using the HTS model we developed, a candidate substance with good inhibitory effect on transfer can hopefully be found.
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| 27. |
- Domert, Jakob, et al.
(författare)
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Spreading of Amyloid-β Peptides via Neuritic Cell-to-cell Transfer Is Dependent on Insufficient Cellular Clearance
- 2014
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Ingår i: Neurobiology of Disease. - : Elsevier. - 0969-9961 .- 1095-953X. ; 65, s. 82-92
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Tidskriftsartikel (refereegranskat)abstract
- The spreading of pathology through neuronal pathways is likely to be the cause of the progressive cognitive loss observed in Alzheimer's disease (AD) and other neurodegenerative diseases. We have recently shown the propagation of AD pathology via cell-to-cell transfer of oligomeric amyloid beta (Aβ) residues 1-42 (oAβ1-42) using our donor-acceptor 3-D co-culture model. We now show that different Aβ-isoforms (fluorescently labeled 1-42, 3(pE)-40, 1-40 and 11-42 oligomers) can transfer from one cell to another. Thus, transfer is not restricted to a specific Aβ-isoform. Although different Aβ isoforms can transfer, differences in the capacity to clear and/or degrade these aggregated isoforms result in vast differences in the net amounts ending up in the receiving cells and the net remaining Aβ can cause seeding and pathology in the receiving cells. This insufficient clearance and/or degradation by cells creates sizable intracellular accumulations of the aggregation-prone Aβ1-42 isoform, which further promotes cell-to-cell transfer; thus, oAβ1-42 is a potentially toxic isoform. Furthermore, cell-to-cell transfer is shown to be an early event that is seemingly independent of later appearances of cellular toxicity. This phenomenon could explain how seeds for the AD pathology could pass on to new brain areas and gradually induce AD pathology, even before the first cell starts to deteriorate, and how cell-to-cell transfer can act together with the factors that influence cellular clearance and/or degradation in the development of AD.
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| 28. |
- Dong, Huan-Ji, et al.
(författare)
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Health Consequences Associated with Being Overweight or Obese: A Swedish Population-Based Study of 85-Year-Olds
- 2012
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Ingår i: Journal of The American Geriatrics Society. - : Wiley-Blackwell. - 0002-8614 .- 1532-5415. ; 60:2, s. 243-250
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To determine whether being overweight or obese is associated with significant health outcomes in an 85-year-old population. less thanbrgreater than less thanbrgreater thanDESIGN: A cross-sectional population-based study. less thanbrgreater than less thanbrgreater thanSETTING: Linkoping, Sweden. less thanbrgreater than less thanbrgreater thanPARTICIPANTS: Three hundred thirty-eight people born in 1922 were identified using the local authoritys register. less thanbrgreater than less thanbrgreater thanMEASUREMENTS: Data related to sociodemographic characteristics, health-related quality of life (HRQoL), assistance use, and the presence of diseases were collected using a postal questionnaire. Anthropometry and functional status were assessed during home and geriatric clinic visits. Diseases were double-checked in the electronic medical records, and information about health service consumption was obtained from the local healthcare register. less thanbrgreater than less thanbrgreater thanRESULTS: Overweight (body mass index (BMI) 25.0-29.9 kg/m(2)) and obese (BMI andgt;= 30.0 kg/m(2)) participants perceived more difficulty performing instrumental activities of daily living (IADLs) and had more comorbidity than their normal-weight counterparts (BMI 18.5-24.9 kg/m(2)), but their overall HRQoL and health service costs did not differ from those of normal-weight participants. After controlling for sociodemographic factors, being overweight did not influence IADLs or any comorbidity, but obese participants were more likely to perceive greater difficulty in performing outdoor activities (odds ratio (OR) = 2.1, 95% confidence interval (CI) = 1.1-4) and cleaning (OR = 2.2, 95% CI = 1.2-4.2) than their normal-weight counterparts. Although obesity was also associated with multimorbidity (OR = 3, 95% CI = 1.2-8), the health service cost of each case of multimorbidity (n = 251) was highest in normalweight participants and nearly three times as much as in obese participants (ratio: 2.9, 95% CI = 1.1-8.1). less thanbrgreater than less thanbrgreater thanCONCLUSION: For 85-year-olds, being obese, as opposed to overweight, is associated with self-reported activity limitations and comorbidities. Overweight older adults living in their own homes in this population had well-being similar to that of those with normal weight.
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| 29. |
- Dong, Huan-Ji, 1981-
(författare)
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Health Maintenance in Very Old Age : Medical Conditions, Functional Outcome and Nutritional Status
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aim of this thesis was to provide better understanding of the underlying factors related to health maintenance in very old people, with a focus on medical conditions, functional outcome and nutritional status. Data were gathered from the ELSA 85 project (Elderly in Linköping Screening Assessment). The ELSA 85 project was started in 2007 with a population-based survey of 85-year-old individuals (n = 650) residing in Linköping municipality, Sweden. During the study period from 2007 to 2010, we conducted surveys by postal questionnaire, home visits, geriatric clinic visits, and reviews of electronic medical records as well as the database of health service consumption. A series of cross-sectional analyses were performed on multimorbidity, health service consumption, activities of daily living (ADLs), physical functioning and nutritional status.Of 650 eligible individuals, 496 (78% of those alive) completed the questionnaire (Paper I). Despite the prevalence of multimorbidity (68%) and frequent use of assistive technology for mobility (40%), the majority managed self-care (85%), usual activities (74%) and had high self-rated health (>60/100, visual analogue scale). Factors associated with in-patient care were an increased number of general practitioner visits, more use of assistive technology, community assistance, multimorbidity (≥2 chronic diseases) and/or heart failure and arrhythmia.Cluster analyses (n = 496, Paper II) revealed five clusters: vascular, cardiopulmonary, cardiac (only for men), somatic–mental (only for men), mental disease (only for women), and three other clusters related to ageing (one for men and two for women). Heart failure in men (odds ratio [OR], 2.4; 95% confidence interval [CI], 1–5.7) and women (OR, 3; 95% CI, 1.3–6.9) as a single morbidity explained more variance than morbidity clusters in models of emergency room visits. Men’s cardiac cluster (OR, 1.6; 95% CI, 1–2.7) and women’s cardiopulmonary cluster (OR, 1.7; 95% CI, 1.2–2.4) were significantly associated with hospitalization. The combination of the cardiopulmonary cluster with the men’s cardiac cluster (OR, 1.6; 95% CI, 1–2.4) and one of the women’s ageing clusters (OR, 0.5; 95% CI, 0.3–0.8) showed interaction effects on hospitalization.In Paper III, overweight (body mass index [BMI], 25–29.9 kg/m2) and obese (BMI, ≥30 kg/m2) individuals (n = 333) perceived more difficulty performing instrumental ADL (IADL) and had more comorbidities than their normal weight counterparts (BMI, 18.5–24.9 kg/m2). After controlling for socio-demographic factors, obese but not overweight individuals were more likely to perceive increased difficulty in performing outdoor activities (OR, 2.1; 95% CI, 1.1–4) and cleaning (OR, 2.2; 95% CI, 1.2–4.2) than their normal weight counterparts. Although obesity was also associated with multimorbidity (OR, 3; 95% CI, 1.2–8), the health service cost of each case of multimorbidity (n = 251) was highest in individuals of normal weight and nearly three times as much as in obese individuals (ratio, 2.9; 95% CI, 1.1–8.1).In Paper IV, 88-year-old obese women (n = 83) had greater absolute waist circumference, fat mass (FM) and fat-free mass (FFM), and lower handgrip strength (HS) corrected for FFM and HS-based ratios (HS/weight (Wt), HS/BMI, HS/FFM and HS/FM) than their normal weight and overweight counterparts. After adjusting for physical activity levels and the number of chronic diseases, the HS-based ratios explained more variance in physical functioning in Short Form-36 (R2, 0.52–0.54) than other single anthropometric or body composition parameters (R2, 0.45–0.51). Waist circumference, HS, and two HS-based ratios (HS/Wt and HS/FFM) were also associated with the number of IADL with no difficulty.In conclusion, the ELSA 85 population showed a fairly positive image of healthy perception, good functional ability as well as low use of health care among the majority of participants. Patterns of cardiac and pulmonary conditions were better associated than any single morbidity with hospitalization. Heart failure as a single morbidity was better associated than multimorbidity patterns with emergency room visits. For 85-year-olds, being obese, as opposed to overweight, was associated with self-reported activity limitations and comorbidities. Overweight elderly living in their own homes in this population had similar well-being to those of normal weight. In the cohort of 88-year-olds, obese women had high waist circumference, but their HS was relatively low in relation to their Wt and FFM. These parameters were better than BMI for predicting physical function and independent daily living.
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| 30. |
- Dong, Huan-Ji, et al.
(författare)
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Multimorbidity patterns of and use of health services by Swedish 85-year-olds: an exploratory study
- 2013
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Ingår i: BMC Geriatrics. - : BioMed Central. - 1471-2318. ; 13:120
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAs life expectancy continues to rise, more elderly are reaching advanced ages (≥80 years). The increasing prevalence of multimorbidity places additional demands on health-care resources for the elderly. Previous studies noted the impact of multimorbidity on the use of health services, but the effects of multimorbidity patterns on health-service use have not been well studied, especially for very old people. This study determines patterns of multimorbidity associated with emergency-room visits and hospitalization in an 85-year-old population.MethodsHealth and living conditions were reported via postal questionnaire by 496 Linköping residents aged 85 years (189 men and 307 women). Diagnoses of morbidity were reviewed in patients’ case reports, and the local health-care register provided information on the use of health services. Hierarchical cluster analysis was applied to evaluate patterns of multimorbidity with gender stratification. Factors associated with emergency-room visits and hospitalization were analyzed using logistic regression models.ResultsCluster analyses revealed five clusters: vascular, cardiopulmonary, cardiac (only for men), somatic–mental (only for men), mental disease (only for women), and three other clusters related to aging (one for men and two for women). Heart failure in men (OR = 2.4, 95% CI = 1–5.7) and women (OR = 3, 95% CI = 1.3–6.9) as a single morbidity explained more variance than morbidity clusters in models of emergency-room visits. Men's cardiac cluster (OR = 1.6; 95% CI = 1–2.7) and women's cardiopulmonary cluster (OR = 1.7, 95% CI = 1.2–2.4) were significantly associated with hospitalization. The combination of the cardiopulmonary cluster with the men’s cardiac cluster (OR = 1.6, 95% CI = 1–2.4) and one of the women’s aging clusters (OR = 0.5, 95% CI = 0.3–0.8) showed interaction effects on hospitalization.ConclusionIn this 85-year-old population, patterns of cardiac and pulmonary conditions were better than a single morbidity in explaining hospitalization. Heart failure was superior to multimorbidity patterns in explaining emergency-room visits. A holistic approach to examining the patterns of multimorbidity and their relationships with the use of health services will contribute to both local health care policy and geriatric practice.
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| 31. |
- Dong, Huan-Ji, et al.
(författare)
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Obese very old women have low relative handgrip strength, poor physical function, and difficulty in daily living
- 2015
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Ingår i: The Journal of Nutrition, Health & Aging. - : Springer. - 1279-7707 .- 1760-4788. ; 19:1, s. 20-25
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate how anthropometric and body composition variables, and handgrip strength (HS) affect physical function and independent daily living in 88-year-old Swedish women.Participants: A cross-sectional analysis of 83 community-dwelling women, who were 88 years old with normal weight (n=30), overweight (n=29), and obesity (n=24) in Linköping, Sweden, was performed.Measures: Assessments of body weight (Wt), height, waist circumference (WC), and arm circumference were performed by using an electronic scale and measuring tape. Tricep skinfold thickness was measured by a skinfold calliper. Fat mass (FM) and fat-free mass (FFM) were measured by bioelectrical impedance analysis, and HS was recorded with an electronic grip force instrument. Linear regression was used to determine the contributions of parameters as a single predictor or as a ratio with HS to physical function (Short Form-36, SF-36PF) and instrumental activities of daily living (IADL).Results: Obese women had greater absolute FM and FFM, and lower HS corrected for FFM and HS-based ratios (i.e., HS/Wt, HS/body mass index [BMI]) than their normal weight and overweight counterparts. After adjusting for physical activity levels and the number of chronic diseases, HS-based ratios explained more variance in SF-36PF scoring (R2: 0.52–0.54) than single anthropometric and body composition variables (R2: 0.45–0.51). WC, HS, and HS-based ratios (HS/Wt and HS/FFM) were also associated with the number of IADL with no difficulty.Conclusion: Obese very old women have a high WC, but their HS is relatively low in relation to their Wt and FFM. These parameters are better than BMI for predicting physical function and independent daily living.
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| 32. |
- Dong, Huan-Ji, et al.
(författare)
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Unaltered image of health maintenance : An observation of non-participants in a swedish cohort study of 85 to 86 years olds
- 2015
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Ingår i: Journal of Frailty & Aging. - Paris, France : Editions S E R D I. - 2260-1341 .- 2273-4309. ; 4:2, s. 93-99
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Tidskriftsartikel (refereegranskat)abstract
- Background: Selection bias is often inevitable in epidemiologic studies. It is not surprising that study conclusions based on participants’ health status are frequently questioned. Objective: This study aimed to assess whether the non-participants affected the characteristics of a general population of the very old people. Design, Setting and Participants: Prospective, cross-sectional (N=650, aged 85 years old) analysis and 1-year follow-up (n=273), in Linköping, Sweden. Measurements: We analysed data on health-related factors from a postal questionnaire, a home visit and a clinic visit at baseline and at the 1-year follow-up. We calculated the effect size to evaluate the degree of differences between the groups. Results: A greater proportion of non-participants resided in sheltered accommodation or nursing homes (participants vs non-response vs refusal, 11% vs 22% vs 40, P<0.001, φ=0.24). During the home visit or clinic visit, a higher proportion of dropouts reported mid-severe problems in EQ-5D domains (mobility and self-care) and limitations in personal activities of daily living, but the differences between participants and dropouts were very small (φ<0.2). No significant difference was found between the groups with regard to emergency room visits or hospital admissions, despite the fact that more participants than dropouts (φ=0.23) had multimorbidities (≥2 chronic diseases). Living in sheltered accommodation or a nursing home (odds ratio (OR), 2.8; 95% confidence interval (CI), 1.5-5), female gender (OR, 1.8; 95% CI, 1.1-3.1) and receiving more home visits in primary care (OR, 1.03; 95% CI, 1-1.06) contributed positively to drop out in the data collection stages over the study period. Conclusion: Non-participants were not considered to be a group with worse health. Mobility problems may influence very old people when considering further participation, which threatens attrition.
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| 33. |
- 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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| 34. |
- Edvardsson, Maria, et al.
(författare)
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Differences in levels of albumin, ALT, AST, gamma-GT and creatinine in frail, moderately healthy and healthy elderly individuals
- 2018
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : WALTER DE GRUYTER GMBH. - 1434-6621 .- 1437-4331. ; 56:3, s. 471-478
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Tidskriftsartikel (refereegranskat)abstract
- Background: Reference intervals are widely used as decision tools, providing the physician with information about whether the analyte values indicate ongoing disease process. Reference intervals are generally based on individuals without diagnosed diseases or use of medication, which often excludes elderly. The aim of the study was to assess levels of albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine and gamma-glutamyl transferase (gamma-GT) in frail, moderately healthy and healthy elderly indivuduals. Methods: Blood samples were collected from individuals amp;gt; 80 years old, nursing home residents, in the Elderly in Linkoping Screening Assessment and Nordic Reference Interval Project, a total of 569 individuals. They were divided into three cohorts: frail, moderately healthy and healthy, depending on cognitive and physical function. Albumin, ALT, AST, creatinine and gamma-GT were analyzed using routine methods. Results: Linear regression predicted factors for 34% of the variance in albumin were activities of daily living (ADL), gender, stroke and cancer. ADLs, gender and weight explained 15% of changes in ALT. For AST levels, ADLs, cancer and analgesics explained 5% of changes. Kidney disease, gender, Mini Mental State Examination (MMSE) and chronic obstructive pulmonary disease explained 25% of the variation in creatinine levels and MMSE explained three per cent of gamma-GT variation. Conclusions: Because a group of people are at the same age, they should not be assessed the same way. To interpret results of laboratory tests in elderly is a complex task, where reference intervals are one part, but far from the only one, to take into consideration.
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| 35. |
- Eriksson, IS, et al.
(författare)
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(3H)tiagabine binding to GABA uptake sites in human brain.
- 1999
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Ingår i: Brain Research. - 0006-8993 .- 1872-6240. ; 18:1-2, s. 183-188
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Tidskriftsartikel (refereegranskat)abstract
- The binding of [H-3]tiagabine ((RS-1-(4,4-(3-methyl-2-thienyl)-3-butenyl)-3 carboxylic acid) to homogenates of frozen post-mortem human brain has been characterized. Inhibition experiments with gamma-aminobutyric acid (GAB,4), GABA uptake inhibitors, ligands active at postsynaptic GABA receptors and receptors for other neurotransmitters, suggest that [H-3]tiagabine binds with high affinity to GABA uptake sites. Inhibition and kinetic experiments suggests that 70%-80% of the binding is to a high affinity site. Saturation experiments showed that the binding was saturable. B-max was 3.4 pmol/mg protein and K-d 16 nM in frontal cortex. The dissociation constants (K-d) measured in kinetic and equilibrium experiments were in the same range (16-56 nM). The regional distribution was studied in nine brain regions and the binding was heterogenous, with the highest binding in frontal cortex and parietal cortex and the lowest binding in nucleus caudatus and putamen. This is, to our knowledge, the first study on [H-3]tiagabine binding in human tissue. It is concluded that [H-3]tiagabine binding can be used as a specific marker for the GABA transporter GAT-1 in homogenates of human brain.
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| 36. |
- Franzon, Kristin
(författare)
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Independent Ageing in Very Old Swedish Men
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Predictors for survival have been investigated thoroughly, but less is known about how to reach high age with preserved physical and cognitive function. These functions are crucial to stay independent in daily life, which is highly valued by the oldest old.This thesis was based on data from the Uppsala Longitudinal Study in Adult Men. In 1970, all men born in 1920-24 and living in Uppsala were invited to the study, and 82% (n=2,322) participated in the first investigation. In this thesis, data are used from the investigations cycles at the ages of 50, 71, 87 and 92 years. Independent ageing was defined as follows: having independency in personal care and the ability to walk outdoors alone, being community-dwelling, having a Mini-Mental State Examination score of 25 points or greater, and having no diagnosed dementia.Thirty-seven percent of the original cohort survived to the age of 85. At a mean age of 87, 74% of the participants were independently aged, while at a mean age of 92 the prevalence of independent ageing was 64%. In Paper I, non-smoking and normal weight at a mean age of 50 were associated with independent ageing at a mean age of 87 years. In Paper II, never smoking, not being obese, and a high adherence to a Mediterranean-like diet at a mean age of 71 were associated with independent ageing at a mean age of 87. In both Papers I and II, high leisure time physical activity was associated with survival, but not with independent ageing. In Paper III, higher gait speed and hand grip strength and a faster chair stand test were cross-sectionally associated with independent ageing at a mean age of 87. Higher gait speed was also longitudinally associated with independent ageing five years. However, muscle mass and sarcopenia were not associated with the outcome. In Paper IV, a history of stroke, osteoarthritis, hip fracture and chronic obstructive pulmonary disease were associated with loss of independent ageing at a mean age of 92.Smoking, weight and diet are all modifiable risk factors associated with independent ageing. If decreased smoking and a normalised weight in the population could diminish stroke, hip fracture, chronic obstructive pulmonary disease and osteoarthritis, the prevalence of independent ageing could rise, even in nonagenarians. Additionally, a Mediterranean-like diet may contribute to both survival and independent ageing.
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| 37. |
- Fällman, Katarina, 1984-, et al.
(författare)
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Normative data for the oldest old: Trail Making Test A, Symbol Digit Modalities Test, Victoria Stroop Test and Parallel Serial Mental Operations
- 2020
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Ingår i: Aging, Neuropsychology and Cognition. - : ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD. - 1382-5585 .- 1744-4128. ; 27:4, s. 567-550
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Tidskriftsartikel (refereegranskat)abstract
- Normative data for evaluating cognitive function in the oldest old, aged 85 years and above, are currently sparse. The normative values used in clinical practice are often derived from younger old persons, from small sample sizes or from broad age spans (e.g. amp;gt;75 years) resulting in a risk of misjudgment in assessments of cognitive decline. This longitudinal study presents normative values for the Trail Making Test A (TMT-A), the Symbol Digit Modalities Test (SDMT), the Victoria Stroop Test (VST) and the Parallel Serial Mental Operations (PaSMO) from cognitively intact Swedes aged 85 years and above. 207 participants, born in 1922, were tested at 85, 90 (n = 68) and 93 (n = 35) years of age with a cognitive screening test battery. The participants were originally recruited for participation in the Elderly in Linkoping Screening Assessment. Normative values are presented as mean values and standard deviations, with and without adjustment for education. There were no clinically important differences between genders, but education had a significant effect on test results for the 85-year-olds. Age effects emerged in analyses of those participants who completed the entire study and were evident for TMT-A, SDMT, VST1 and PaSMO. When comparisons can be made, our results are in accordance with previous data for TMT-A, SDMT and VST, and we present new normative values for PaSMO.
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| 38. |
- Fällman, Katarina, et al.
(författare)
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Swedish normative data and longitudinal effects of aging for older adults : The Boston Naming Test 30-item and a short version of the Token Test
- 2022
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Ingår i: Applied neuropsychology. Adult. - : Routledge; Taylor & Francis. - 2327-9095 .- 2327-9109.
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Tidskriftsartikel (refereegranskat)abstract
- Naming ability and verbal comprehension are cognitive functions that may be affected both by normal aging and by disease. Neuropsychological testing is crucial to evaluate changes in language ability and reliable normative data for all ages are needed. We present clinically useful test norms, together with subsample analysis of longitudinal effects of aging, for two robust and well-known tests that evaluate naming ability and verbal comprehension where the present norms for older adults (aged 85 and older) are sparse or missing. Participants (n = 338) from a Swedish population-based study, the Elderly in Linkoping Screening Assessment, were cognitively evaluated with a cognitive screening battery at the age of 85 years and followed to the age of 93 years. Normative data at age 85 years were calculated from a sample (n = 207) that was determined as cognitively healthy after application of rigorous exclusion criteria. Effects of normal aging were investigated by analyzing follow-up performance at age 90 and 93 years for the subsample of cognitively healthy that completed the entire study. The evaluated tests in this study are Swedish versions of the Boston Naming Test 30-item Odd Version (BNT-30) and a short form of the Token Test, Part V (TokV). Analyzes of effects of aging showed that performance decreased with age for BNT-30, but not for TokV. Higher education was associated with better performance in both tests and men performed better than women on the BNT-30. Results also showed naming ability to be more sensitive to aging than verbal comprehension.
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| 39. |
- 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
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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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| 40. |
- Hallbeck, Martin, et al.
(författare)
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Neuron-to-Neuron Transmission of Neurodegenerative Pathology
- 2013
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Ingår i: The Neuroscientist. - : Sage Publications. - 1073-8584 .- 1089-4098. ; 19:6, s. 560-566
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Forskningsöversikt (refereegranskat)abstract
- One of the hallmarks of neurodegenerative dementia diseases is the progressive loss of mental functions and the ability to manage activities of daily life. This progression is caused by the spread of the disease to more and more brain areas via anatomical connections. The pathophysiological process responsible for this spread of disease has long been sought after. There has been an increased understanding that the driving force of these neurodegenerative diseases could be the small, soluble intraneuronal accumulations of neurodegenerative proteins rather than the large, extracellular accumulations. Recently we have shown that the mechanism of spread of Alzheimer's disease most likely depends on the neuron-to-neuron spread of such soluble intraneuronal accumulations of -amyloid through neuritic connections. Similar transmissions have been shown for several other neurodegenerative proteins but little is known about the cellular mechanisms and about any potential strategies that might stop this spread. Resolving these questions requires good cellular models. We have established a unique model of synaptic transmission between human neuronal-like cells, something that has previously been difficult to target. This opens the possibility of developing potential inhibitors of progression of these devastating diseases.
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| 41. |
- 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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| 42. |
- 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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| 43. |
- 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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| 44. |
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| 45. |
- Johansson, Inga-Maj, et al.
(författare)
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Chronic amitriptyline treatment induces hippocampal NGFI-A, glucocorticoid receptor and mineralocorticoid receptor mRNA expression in rats
- 1998
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Ingår i: Brain Research. Molecular Brain Research. - : Elsevier Science B.V.. - 0169-328X .- 1872-6941. ; 62:1, s. 92-95
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Tidskriftsartikel (refereegranskat)abstract
- Adult male rats were treated with the antidepressant drug amitriptyline for 21 days and the expression of specific transcription factors was examined. NGFI-A mRNA expression was increased in the hippocampus and in the cerebral cortex. MR mRNA was increased in the hippocampus while GR mRNA was increased in selective hippocampal regions. There was no change in the NGFI-B mRNA expression. Thus, NGFI-A may be a mediator of plasticity-related phenomena induced by antidepressant drugs.
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| 46. |
- Johansson, Maria, et al.
(författare)
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Clinical Utility of Cognistat in Multiprofessional Team Evalutations of Patients with Cognitive Impairment in Swedish Primary Care
- 2014
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Ingår i: International Journal of Family Medicine. - : Hindawi Publishing Corporation. - 2090-2042 .- 2090-2050. ; 2014, s. 649253-
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Tidskriftsartikel (refereegranskat)abstract
- Background. Diagnostic evaluations of dementia are often performed in primary health care (PHC). Cognitive evaluation requires validated instruments.Objective. To investigate the diagnostic accuracy and clinical utility of Cognistat in a primary care population.Methods. Participants were recruited from 4 PHC centres; 52 had cognitive symptoms and 29 were presumed cognitively healthy. Participants were tested using the Mini-Mental State Examination (MMSE), the Clock Drawing Test (CDT), and Cognistat. Clinical diagnoses, based on independent neuropsychological examination and a medical consensus discussion in secondary care, were used as criteria for diagnostic accuracy analyses.Results. The sensitivity, specificity, positive predictive value, and negative predictive value were 0.85, 0.79, 0.85, and 0.79, respectively, for Cognistat; 0.59, 0.91, 0.90, and 0.61 for MMSE; 0.26, 0.88, 0.75, and 0.46 for CDT; 0.70, 0.79, 0.82, and 0.65 for MMSE and CDT combined. The area under the receiver operating characteristic curve was 0.82 for Cognistat, 0.75 for MMSE, 0.57 for CDT, and 0.74 for MMSE and CDT combined.Conclusions. The diagnostic accuracy and clinical utility of Cognistat was better than the other tests alone or combined. Cognistat is well adapted for cognitive evaluations in PHC and can help the general practitioner to decide which patients should be referred to secondary care.
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| 47. |
- Johansson, Maria, et al.
(författare)
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Cognitive impairment and its consequences in everyday life : experiences of people with mild cognitive impairment or mild dementia and their relatives
- 2015
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Ingår i: International psychogeriatrics. - : Cambridge University Press. - 1041-6102 .- 1741-203X. ; 27:6, s. 949-958
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of this study was to explore experiences of cognitive impairment, its consequences in everyday life and need for support in people with mild cognitive impairment (MCI) or mild dementia and their relatives.Methods: A qualitative approach with an explorative design with interviews was chosen. The participants included five people with MCI and eight people with mild dementia and their relatives. All participants were recruited at a geriatric memory clinic in Sweden. The Grounded Theory method was used.Results: The following categories emerged: noticing cognitive changes; changed activity patterns; coping strategies; uncertainty about own ability and environmental reactions; support in everyday life; support from the healthcare system; consequences in everyday life for relatives; and support for relatives. The main findings were that people with MCI and dementia experienced cognitive changes that could be burdensome and changed activity patterns. Most of them, however, considered themselves capable of coping on their own. The relatives noticed cognitive changes and activity disruptions to a greater extent and tried to be supportive in everyday life. Degree of awareness varied and lack of awareness could lead to many problems in everyday life.Conclusions: Perceived cognitive impairment and its consequences in everyday life were individual and differed among people with MCI or dementia and their relatives. Thus, healthcare professionals must listen to both people with cognitive impairment and their relatives for optimal individual care planning. Support such as education groups and day care could be more tailored towards the early stages of dementia.
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| 48. |
- Johansson, Maria, 1967-
(författare)
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Cognitive impairment and its consequences in everyday life
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aim was to improve knowledge of the consequences of cognitive dysfunction in everyday life and of instruments to make these assessments. The thesis contains four studies each of different design using different populations.In study I, the relationship between cognitive function, ability to perform activities of daily living and perceived health-related quality of life were investigated in a population of 85-year-old individuals in the community of Linköping (n = 373). The study was part of the Elderly in Linköping Screening Assessment 85 (ELSA 85). Even mild cognitive dysfunction correlated with impaired ability to perform activities of daily living and lower health-related quality of life.In study II, the diagnostic accuracy and clinical utility of Cognistat, a cognitive screening instrument, were evaluated for identifying individuals with cognitive impairment in a primary care population. Cognistat has relatively good diagnostic accuracy with a sensitivity of 0.85, a specificity of 0.79 and a Clinical Utility Index (CUI) of 0.72. The corresponding values were 0.59, 0.91 and 0.53 for the Mini Mental State Examination (MMSE), and 0.26, 0.88 and 0.20 for the Clock Drawing Test (CDT).In study III, the aim was to develop an instrument measuring self-perceived or caregiver reported ability to perform everyday life activities in persons with suspected cognitive impairment or dementia and to perform psychometric testing of this instrument, named the Cognitive Impairment in Daily Life (CID). The CID was found to have good content validity.In study IV, experiences of cognitive impairment, its consequences in everyday life and the need for support in persons with mild cognitive impairment (MCI) or mild dementia and their relatives were explored. Interviews were performed with five people with MCI, eight people with mild dementia and their relatives (n = 13). The main finding was that persons with MCI and dementia experienced cognitive changes that could be burdensome and result in changed activity patterns.In conclusion, the findings support earlier research and show that cognitive dysfunction even at mild stages has an impact on everyday life and reduces perceived quality of life. To improve interventions for persons with cognitive impairment, it is important to assess not only cognitive function but also its consequences in everyday life activities.
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| 49. |
- Johansson, Maria, et al.
(författare)
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Development of an instrument for measuring activities of daily living in persons with suspected cognitive impairment
- 2016
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Ingår i: Scandinavian Journal of Occupational Therapy. - : Informa UK Limited. - 1103-8128 .- 1651-2014. ; 23:3, s. 230-239
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Tidskriftsartikel (refereegranskat)abstract
- Background: According to the Swedish National Board of Health and Welfare, structured assessment of function and activity has high priority when investigating for dementia.Aim/objectives: The aim was to develop and psychometrically test an instrument to measure self-reported and/or informant-reported ability to perform activities of daily living in persons with suspected cognitive impairment.Material and methods: The Cognitive Impairment in Daily Life (CID) instrument has been developed in several phases. Content validity was achieved through five expert panels using a Content Validity Index (CVI). The content was tested further in a pilot study of 51 patients and 49 relatives from primary care or a specialist memory clinic.Results: Content validity was good with a CVI index of 0.83. All patients considered that relevant activities were included. Most relatives considered that the activities included in the instrument were adequate and captured the patients’ difficulties in daily life. Some adjustments to the items and scale were suggested and these were done after each phase. In general, relatives indicated more difficulties than patients.Conclusion: The CID instrument seems promising in terms of content validity. Further testing of reliability and construct validity is ongoing.
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| 50. |
- Johansson, Maria M., et al.
(författare)
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Cognition, daily living, and health-related quality of life in 85-year-olds in Sweden
- 2012
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Ingår i: Aging, Neuropsychology and Cognition. - : Taylor & Francis. - 1382-5585 .- 1744-4128. ; 19:3, s. 421-432
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Tidskriftsartikel (refereegranskat)abstract
- This study investigates how cognition influences activities of daily living and health-related quality of life in 85-year-olds in Sweden (n = 373). Data collection included a postal questionnaire comprising demographics and health-related quality of life measured by the EQ-5D. The ability to perform personal activities of daily living (PADL) was assessed during a home visit that included administering the Mini Mental State Examination (MMSE). Cognitive impairment was shown in 108 individuals (29%). The majority were independent with respect to PADL. A larger number of participants with cognitive impairment reported that they needed assistance in instrumental activities of daily living (IADL) compared to the group without cognitive impairment. Impaired cognition was significantly related to problems with IADL. Significant but low correlations were found between cognition and health-related quality of life – higher ratings on perceived quality of life correlated with higher results on the MMSE.
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