| 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. |
- Nägga, Katarina, 1962-, et al.
(författare)
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Evaluation of factors of importance for clinical dementia diagnosis
- 2005
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 19:5-6, s. 289-298
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Tidskriftsartikel (refereegranskat)abstract
- Diagnosing clinical dementia is based on an assessment of different variables, such as the patient’s medical history, known risk factors, and biochemical features. Partial least squares discriminant analysis was used to evaluate variables of importance for diagnosing dementia in a clinical dementia population. Polymorphism for genotypes of glutathione S-transferase (GST) and sulfotransferase 1A1, hypothetically of importance in dementia disorders, was also included in the analysis. The study population consisted of 73 patients with Alzheimer’s disease (AD), 14 with mixed dementia, 75 patients with vascular dementia, and 28 control cases. We found that several of the variables, such as the presence of ApoE4 allele, high cerebrospinal fluid levels of total tau protein, low levels of β-amyloid<sub>(1–42)</sub>, and a low score on the Mini-Mental State Examination, facilitated a discrimination between the diagnoses compared with the controls. The different diagnoses overlapped. There were indications that genotypes of GSTs contributed to a subgrouping within AD.
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| 3. |
- 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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| 4. |
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| 5. |
- 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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| 6. |
- Olaison, Anna, 1974-, et al.
(författare)
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‘Do you have a future when you are 93?’ Frail older person’s perceptions about the future and end of life – a qualitative interview study in primary care
- 2022
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Ingår i: Scandinavian Journal of Primary Health Care. - : Taylor & Francis Group. - 0281-3432 .- 1502-7724. ; 40:4, s. 417-425
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To explore frail older persons’ perceptions of the future and the end of life.Design: Qualitative content analysis of individual semi-structured interviews.Setting: Nine primary health care centres in both small and middle-sized municipalities in Sweden that participated in the intervention project Proactive healthcare for frail elderly persons.Subjects/Patients: The study includes 20 older persons (eight women and 12 men, aged 76–93 years).Main outcome measures: Frail older persons’ perceptions of the future and end of life.Results: The analysis uncovered two main categories: Dealing with the future and Approaching the end of life. Dealing with the future includes two subcategories: Plans and reflections and Distrust and delay. Approaching the end of life includes three subcategories: Practical issues, Worries and realism, and Keeping it away.Conclusion: This study highlights the diverse ways older people perceive future and the end of life. The results make it possible to further understand the complex phenomenon of frail older persons’ perceptions on the future and the end of life.
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| 7. |
- Olaison, Anna, 1974-, et al.
(författare)
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Maneuvering the care puzzle: Experiences of participation in care by frail older persons with significant care needs living at home
- 2021
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Ingår i: International Journal of Qualitative Studies on Health and Well-being. - : Informa UK Limited. - 1748-2623 .- 1748-2631. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Despite evidence that older persons want to be involved in care, little is known about how frail older people with significant care needs living at home experience participation in care provided by different stakeholders. This study investigates the experiences of participation in care by older people following their involvement in an intervention of a health care model called Focused Primary care (FPC). Methods: Individual semi-structured interviews were conducted with 20 older persons in five municipalities in Sweden. Results: The results show that older persons highlighted opportunities and limitations fo rparticipation on a personal level i.e., conditions for being involved in direct care and in relation to independence. Experiences of participation on organizational levels were reported to a lesser degree. This included being able to understand the organizational system underpinning care. The relational dimensions of caregiving were emphasized by the older persons as the most central aspects of caregiving in relation to participation. Conclusions: Primary care should involve older persons more directly in planning and execution of care on all levels. An ongoing connection with one specialized elderly teamand a coordinating person in Primary care who safeguards relationships is important for providing participation in care for frail older persons with significant care needs living at home
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| 8. |
- 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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| 9. |
- 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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| 10. |
- 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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| 11. |
- 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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| 12. |
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| 13. |
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| 14. |
- 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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| 15. |
- 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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| 16. |
- 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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| 17. |
- 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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| 18. |
- 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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| 19. |
- 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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| 20. |
- 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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| 21. |
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| 22. |
- Johansson, Maria M., 1967-, et al.
(författare)
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Maintaining health-related quality of life from 85 to 93 years of age despite decreased functional ability
- 2019
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Ingår i: British Journal of Occupational Therapy. - : Sage Publications. - 0308-0226 .- 1477-6006. ; 82:6, s. 348-356
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionThe ‘oldest-old’ is the most rapidly growing age group in Sweden and in the western world. This group is known to be at great risk of increased functional dependency and the need for help in their daily lives. The aim of this research was to examine how the oldest-old change over time regarding health-related quality of life, cognition, depression and ability to perform activities of daily living and investigate what factors explain health-related quality of life at age 85 and 93 years.MethodsIn this study, 60 individuals from the Swedish Elderly in Linköping Screening Assessment study were followed from age 85 to 93 years. Measurements used were EQ-5D, Geriatric Depression Scale, Mini Mental State Examination and ability to perform activities of daily living. Nonparametric statistics and regression analyses were used.ResultsAlthough the individuals had increased mobility problems, decreased ability to manage activities of daily living, and thus had increased need of assistance, they scored their health-related quality of life at age 93 years at almost the same level as at age 85 years. No depression and low dependence in activities of daily living speaks in favour of higher health-related quality of life.ConclusionsHealth-related quality of life can be maintained during ageing despite decreased functional ability and increased need of assistance in daily life.
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| 23. |
- Landgren, Sara, 1980, et al.
(författare)
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A novel ARC gene polymorphism is associated with reduced risk of Alzheimer's disease
- 2012
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Ingår i: Journal of Neural Transmission. - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 119:7, s. 833-842
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) is the most common neurodegenerative disease, and is clinically characterized by cognitive disturbances and the accumulation of the amyloid beta (A beta) peptides in plaques in the brain. Recent studies have shown the links between AD and the immediate-early gene Arc (activity-regulated cytoskeleton-associated protein), involved in synaptic plasticity and memory consolidation. For example, AD mouse models show a decreased expression of Arc mRNA in the brain. In additional, acute A beta application to brain slices leads to a widespread ARC protein diffusion, unlike the normal defined localization to synapses. In this study, we investigated genetic variation in human ARC and the risk of developing AD. To this end, we genotyped 713 subjects diagnosed with AD and 841 controls without dementia. ARC was sequenced in a group of healthy individuals, and seven previously known SNPs and three novel SNPs were identified. Two of the newly found SNPs were intronic and one, +2852(G/A), was located in the 3'UTR. Three tag SNPs were selected, including the novel SNP +2852(G/A), to relate to risk of AD, Mini Mental State Examination (MMSE) scores and cerebrospinal fluid (CSF) biomarker levels of total tau (T-tau), hyperphosphorylated tau181 (P-tau(181)) and A beta(1-42). The AA genotype of the newly found 3'-UTR SNP +2852(A/G), was associated with a decreased risk of AD (p (c) = 0.005; OR = 0.74; 95 % CI: 0.61-0.89). No associations of single SNPs or haplotypes with MMSE score or CSF biomarkers were found. Here we report a novel ARC SNP associated with a reduced risk of developing AD. To our knowledge, this is the first study associating a gene variant of ARC with any disease. The location of the SNP within the 3'UTR indicates that dendritic targeting of ARC mRNA could be involved in the molecular mechanisms underlying this protective function. However, further investigation of the importance of this SNP for ARC function, ARC processing and the pathology of AD is needed.
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| 24. |
- Ludvigsson, Mikael, 1976-
(författare)
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Subsyndromal depression hos äldre äldre personer
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Bakgrund: Subsyndromal depression (SSD) eller subklinisk depression är ett vanligt affektivt tillstånd som kan beskrivas som depressivitet under gränsen för vad som kallas syndromal eller egentlig depressiv episod. Förekomsten av SSD har rapporterats vara ungefär 10 % i populationen, eller ungefär 2-3 gånger högre än förekomsten av syndromal depression. SSD jämfört med icke-depression (ND) är associerat med en lägre aktivitetsförmåga (ADL, Activities of Daily Living), lägre kognitiv funktion, lägre subjektiv hälsa, sämre psykiska utfall och en högre dödlighet. Emellertid har flertalet studier om SSD hos äldre gjorts i åldersgruppen yngre äldre (60-80 års ålder), medan få studier har undersökt SSD hos äldre äldre personer (80+ års ålder). Eftersom många aspekter (t ex multisjukdom, skörhet, funktionsförmågor och socialt beroende) generellt förändras mellan yngre äldre och äldre äldre åldrar, så finns det ett behov av ökad kunskap om SSD hos äldre äldre. Syftet med denna avhandling var att beskriva SSD, eller det komplexa området mellan syndromal depression och normalt åldrande, hos äldre äldre personer.Metod: studie 1 baserades på kvalitativa intervjuer (n=27), medan studier 2-4 till stor del baserades på data från en prospektiv observationsstudie av en kohort, ”Elderly in Linköping Screening Assessment” (ELSA85). ELSA85 hade en populationsbaserad design där man följde personer från 85 års ålder i tre uppföljande mätvågor. Depressivitet mättes med 15- frågeversionen av Geriatric Depression Scale (GDS-15), som också användes för att definiera SSD i studierna.Resultat: Analysen av de kvalitativa intervjuerna (studie 1) resulterade i fyra teman (livet går ned och kroppen sviktar, att klara sig själv, att hänga med, och att ta en dag i taget), vilka tillsammans gav en helhetsbild av SSD i de högsta åldrarna. I en jämförelse mellan SSD, ND och syndromal depression, så skiljde sig SSD kvalitativt från syndromal depression, men däremot inte tydligt från ND. En tvärsnittsanalys av data från baslinjen av studien (studie 2) identifierade associerade faktorer till SSD bland äldre äldre personer, och enligt analysen med multipel logistisk respektive linjär regression så var det fyra domäner (sociodemografiska faktorer, sviktande fysisk funktion, neuropsykiatriska faktorer och existentiella faktorer) som var signifikant associerade med SSD.I en fem års longitudinell uppföljning (studie 3) visades att direkta hälso- och sjukvårdskostnader per överlevnadsmånad och person var förhöjd hos personer med SSD jämfört med ND med ett storleksförhållande 1.45 (€634 vs €436), vilket var en signifikant skillnad även när man kontrollerade för somatisk multisjukdom. I en åtta års longitudinell uppföljning visades att dödligheten var förhöjd (dödsintensitet eller Hazard ratio (HR))=1.33) för personer med SSD jämfört med ND, liksom sjuklighet avseende personlig ADL (P-ADL), instrumentell ADL (IADL), ensamhet, subjektiv hälsa, och depressivitet. Däremot var inte kognitiv snabbhet, exekutiva funktioner eller global kognitiv funktion signifikant försämrade när man hade kontrollerat för relevanta variabler.Slutsatser: SSD hos äldre äldre personer ser olika ut hos olika personer, och personal i hälso- och sjukvården bör vara uppmärksamma på även andra depressiva tecken förutom de klassiska symtomen i diagnosregistren. SSD hos äldre äldre är associerat med förhöjda sjukvårdskostnader, förhöjd sjuklighet och dödlighet. Med tanke på den höga förekomsten av SSD och den demografiska utvecklingen med ökande antal äldre äldre personer i samhället, så indikerar fynden behovet av att utveckla kliniska och samhälleliga strategier för att förebygga SSD och associerade negativa utfall.
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| 25. |
- Ludvigsson, Mikael, 1976-
(författare)
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Subsyndromal Depression in Very Old Persons
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Subsyndromal depression (SSD) or subthreshold depression is a common affective condition that can be described as depressiveness below the threshold of what is called a syndromal or a major depressive episode. The point prevalence for SSD has been reported to be about 10% in the community, or about two or three times higher than the prevalence for syndromal depression. In elderly persons, SSD compared to non-depression (ND) is associated with impaired activities of daily living, lower cognitive function, lower self-perceived health, worse psychiatric outcomes and higher mortality. However, most studies on SSD in elderly persons have been done in the young old age group (age 60-80 years), while few studies have investigated SSD in very old persons (age 80+). As many aspects (e.g. multimorbidity, frailty, functional decline and social dependence) change between the young old and the very old ages, there is a need for more knowledge about SSD in the very old. The overall aim of this doctoral thesis was to describe SSD, or the complex area between syndromal depression and normal aging, in very old persons.Method: Paper 1 was based on qualitative interviews (n=27), while papers 2-4 were based largely on data from a prospective observational cohort study “Elderly in Linköping Screening Assessment” (ELSA85), with a population-based design following the participants from the age of 85 in three waves of follow-up. The 15-item Geriatric Depression Scale (GDS-15) was used for measuring depressiveness and to define SSD in the studies.Results: The analysis of the qualitative interviews (paper 1) resulted in four themes (life curve and the body go down, to manage on one’s own, to keep up with life, and taking one day at a time), giving a comprehensive picture of SSD in very old age. In a comparison among SSD, ND and syndromal depression, SSD differed qualitatively from syndromal depression, but not clearly from ND. A cross-sectional analysis of data from baseline (paper 2) identified factors associated with SSD in very old persons, and according to analyses with multiple logistic and linear regressions, four domains (sociodemographic factors, declining physical functioning, neuropsychiatric factors, and existential factors) were significantly associated with SSD.A five-year longitudinal follow-up (paper 3) showed that direct healthcare costs per month of survival for persons with SSD exceeded those of persons with ND by a ratio of 1.45 (€634 vs €436), a difference that was significant even after controlling for somatic multimorbidity.An eight-year longitudinal follow-up (paper 4) showed that mortality was elevated (hazard ratio=1.33) for persons with SSD compared to ND, as were morbidity regarding basic ADL, IADL, loneliness, self-perceived health and depressiveness, whereas cognitive speed, executive functions and global cognitive function were not significantly impaired when adjusting for covariates.Conclusion: SSD in very old persons has a different presentation in different persons, and healthcare personnel should be attentive to other depressive signs beside the classical ones in the diagnostic classification registries. SSD in the very old is associated with elevated direct healthcare costs, morbidity and mortality. Considering the high prevalence of SSD and the demographic development of increasing numbers of very old people, the findings highlight the need to develop clinical and societal strategies to prevent SSD and associated negative outcomes.
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| 26. |
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| 27. |
- Marcusson, Jan, 1958-, et al.
(författare)
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Galantamine demonstrates efficacy and safety in elderly patients with Alzheimer disease
- 2003
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Ingår i: Alzheimer Disease and Associated Disorders. - : Ovid Technologies (Wolters Kluwer Health). - 0893-0341 .- 1546-4156. ; 17:SUPPL. 3
-
Tidskriftsartikel (refereegranskat)abstract
- Alzheimer disease (AD) treatment guidelines state that cholinergic agents are not cost-effective in patients with more severe disease. Because many physicians may deem an older patient unlikely to respond to treatment, older AD patients may remain untreated. Galantamine (Reminyl), a novel cholinergic agent, is effective in mild to moderate AD. This post hoc analysis of pooled phase III galantamine clinical trials was designed to assess whether older (=80 years) and younger (=79 years) AD patients experience similar benefits with galantamine based on changes in the ADAS-cog and CIBIC-plus. Mean ADAS-cog scores for older patients treated with galantamine 24 mg/day significantly improved versus baseline and versus placebo at month 3. Cognitive improvement was maintained versus placebo at month 6, the ADAS-cog score for placebo patients dropped below baseline at month 6. Change in CIBIC-plus for galantamine was significantly different from placebo at months 5 to 6. Mean ADAS-cog score in older patients taking galantamine for 12 months remained above baseline. The score for patients taking placebo for 6 months before switching to galantamine did not differ significantly from baseline at 12 months but was lower than in patients receiving galantamine for 12 months. Incidence of adverse events in patients > 80 years was similar to that in the overall study population. Galantamine maintained cognitive and global function in patients > 80 years with mild to moderate AD for at least 5 to 6 months and cognitive efficacy for 12 months. Prescribing approved therapies such as galantamine for older patients with AD is recommended.
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| 28. |
- Marcusson, Jan, et al.
(författare)
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Proactive healthcare for frail elderly persons : study protocol for a prospective controlled primary care intervention in Sweden
- 2019
-
Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 9:5
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction The provision of healthcare services is not dedicated to promoting maintenance of function and does not target frail older persons at high risk of the main causes of morbidity and mortality. The aim of this study is to evaluate the effects of a proactive medical and social intervention in comparison with conventional care on a group of persons aged 75 and older selected by statistical prediction.Methods and analysis In a pragmatic multicentre primary care setting (n=1600), a prediction model to find elderly (75+) persons at high risk of complex medical care or hospitalisation is used, followed by proactive medical and social care, in comparison with usual care. The study started in April 2017 with a run-in period until December 2017, followed by a 2-year continued intervention phase that will continue until the end of December 2019. The intervention includes several tools (multiprofessional team for rehabilitation, social support, medical care home visits and telephone support). Primary outcome measures are healthcare cost, number of hospital care episodes, hospital care days and mortality. Secondary outcome measures are number of outpatient visits, cost of social care and informal care, number of prescribed drugs, health-related quality of life, cost-effectiveness, sense of security, functional status and ability. We also study the care of elderly persons in a broader sense, by covering the perspectives of the patients, the professional staff and the management, and on a political level, by using semistructured interviews, qualitative methods and a questionnaire.Ethics and dissemination Approved by the regional ethical review board in Linköping (Dnr 2016/347-31). The results will be presented in scientific journals and scientific meetings during 2019–2022 and are planned to be used for the development of future care models.
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| 29. |
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| 30. |
- Mattsson, Niklas, 1979, et al.
(författare)
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CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment.
- 2009
-
Ingår i: JAMA : the journal of the American Medical Association. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 302:4, s. 385-93
-
Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Small single-center studies have shown that cerebrospinal fluid (CSF) biomarkers may be useful to identify incipient Alzheimer disease (AD) in patients with mild cognitive impairment (MCI), but large-scale multicenter studies have not been conducted. OBJECTIVE: To determine the diagnostic accuracy of CSF beta-amyloid(1-42) (Abeta42), total tau protein (T-tau), and tau phosphorylated at position threonine 181 (P-tau) for predicting incipient AD in patients with MCI. DESIGN, SETTING, AND PARTICIPANTS: The study had 2 parts: a cross-sectional study involving patients with AD and controls to identify cut points, followed by a prospective cohort study involving patients with MCI, conducted 1990-2007. A total of 750 individuals with MCI, 529 with AD, and 304 controls were recruited by 12 centers in Europe and the United States. Individuals with MCI were followed up for at least 2 years or until symptoms had progressed to clinical dementia. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive and negative likelihood ratios (LRs) of CSF Abeta42, T-tau, and P-tau for identifying incipient AD. RESULTS: During follow-up, 271 participants with MCI were diagnosed with AD and 59 with other dementias. The Abeta42 assay in particular had considerable intersite variability. Patients who developed AD had lower median Abeta42 (356; range, 96-1075 ng/L) and higher P-tau (81; range, 15-183 ng/L) and T-tau (582; range, 83-2174 ng/L) levels than MCI patients who did not develop AD during follow-up (579; range, 121-1420 ng/L for Abeta42; 53; range, 15-163 ng/L for P-tau; and 294; range, 31-2483 ng/L for T-tau, P < .001). The area under the receiver operating characteristic curve was 0.78 (95% confidence interval [CI], 0.75-0.82) for Abeta42, 0.76 (95% CI, 0.72-0.80) for P-tau, and 0.79 (95% CI, 0.76-0.83) for T-tau. Cut-offs with sensitivity set to 85% were defined in the AD and control groups and tested in the MCI group, where the combination of Abeta42/P-tau ratio and T-tau identified incipient AD with a sensitivity of 83% (95% CI, 78%-88%), specificity 72% (95% CI, 68%-76%), positive LR, 3.0 (95% CI, 2.5-3.4), and negative LR, 0.24 (95% CI, 0.21-0.28). The positive predictive value was 62% and the negative predictive value was 88%. CONCLUSIONS: This multicenter study found that CSF Abeta42, T-tau, and P-tau identify incipient AD with good accuracy, but less accurately than reported from single-center studies. Intersite assay variability highlights a need for standardization of analytical techniques and clinical procedures.
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| 31. |
- Neselius, Sanna, et al.
(författare)
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CSF-Biomarkers in Olympic Boxing: Diagnosis and Effects of Repetitive Head Trauma
- 2012
-
Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 7:4
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Sports-related head trauma is common but still there is no established laboratory test used in the diagnostics of minimal or mild traumatic brain injuries. Further the effects of recurrent head trauma on brain injury markers are unknown. The purpose of this study was to investigate the relationship between Olympic (amateur) boxing and cerebrospinal fluid (CSF) brain injury biomarkers. Methods: The study was designed as a prospective cohort study. Thirty Olympic boxers with a minimum of 45 bouts and 25 non-boxing matched controls were included in the study. CSF samples were collected by lumbar puncture 1-6 days after a bout and after a rest period for at least 14 days. The controls were tested once. Biomarkers for acute and chronic brain injury were analysed. Results: NFL (mean +/- SD, 5326 +/- 553 vs 135 +/- 51 ng/L p = 0.001), GFAP (496 +/- 238 vs 247 +/- 147 ng/L pless than0.001), T-tau (58 +/- 26 vs 49 +/- 21 ng/L pless than0.025) and S-100B (0.76 +/- 0.29 vs 0.60 +/- 0.23 ng/L p = 0.03) concentrations were significantly increased after boxing compared to controls. NFL (402 +/- 434 ng/L p = 0.004) and GFAP (369 +/- 113 ng/L p = 0.001) concentrations remained elevated after the rest period. Conclusion: Increased CSF levels of T-tau, NFL, GFAP, and S-100B in greater than80% of the boxers demonstrate that both the acute and the cumulative effect of head trauma in Olympic boxing may induce CSF biomarker changes that suggest minor central nervous injuries. The lack of normalization of NFL and GFAP after the rest period in a subgroup of boxers may indicate ongoing degeneration. The recurrent head trauma in boxing may be associated with increased risk of chronic traumatic brain injury.
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| 32. |
- Neselius, Sanna, et al.
(författare)
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Increased CSF Levels of Phosphorylated Neurofilament Heavy Protein following Bout in Amateur Boxers.
- 2013
-
Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 8:11
-
Tidskriftsartikel (refereegranskat)abstract
- Diagnosis of mild TBI is hampered by the lack of imaging or biochemical measurements for identifying or quantifying mild TBI in a clinical setting. We have previously shown increased biomarker levels of protein reflecting axonal (neurofilament light protein and tau) and glial (GFAP and S-100B) damage in cerebrospinal fluid (CSF) after a boxing bout. The aims of this study were to find other biomarkers of mild TBI, which may help clinicians diagnose and monitor mild TBI, and to calculate the role of APOE ε4 allele genotype which has been associated with poor outcome after TBI.
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| 33. |
- Neselius, Sanna, et al.
(författare)
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Neurological assessment and its relationship to CSF biomarkers in amateur boxers.
- 2014
-
Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6
-
Tidskriftsartikel (refereegranskat)abstract
- Mild traumatic brain injury (TBI) or concussion is common in many sports. Today, neuropsychological evaluation is recommended in the monitoring of a concussion and in return-to-play considerations. To investigate the sensitivity of neuropsychological assessment, we tested amateur boxers post bout and compared with controls. Further the relationship between neuropsychological test results and brain injury biomarkers in the cerebrospinal fluid (CSF) were investigated.
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| 34. |
- Neselius, Sanna, et al.
(författare)
-
Olympic boxing is associated with elevated levels of the neuronal protein tau in plasma
- 2013
-
Ingår i: Brain Injury. - : Informa Healthcare. - 0269-9052 .- 1362-301X. ; 27:4, s. 425-433
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim of this study was to investigate if olympic (amateur) boxing is associated with elevation of brain injury biomarkers in peripheral blood compared to controls. less thanbrgreater than less thanbrgreater thanMaterials and methods: Thirty olympic boxers competing in at least 47 bouts were compared to 25 controls. Blood was collected from the controls at one occasion and from the boxers within 1-6 days after a bout and after a rest period of at least 14 days. Tau concentration in plasma was determined using a novel single molecule ELISA assay and S-100B, glial fibrillary acidic protein, brain-derived neurotrophic factor and amyloid beta 1-42 were determined using standard immunoassays. less thanbrgreater than less thanbrgreater thanResults: None of the boxers had been knocked-out during the bout. Plasma-tau was significantly increased in the boxers after a bout compared to controls (mean +/- SD, 2.46 +/- 5.10 vs. 0.79 +/- 0.961 ngL(-1), p = 0.038). The other brain injury markers did not differ between the groups. Plasma-tau decreased significantly in the boxers after a resting period compared to after a bout (p = 0.030). less thanbrgreater than less thanbrgreater thanConclusions: Olympic boxing is associated with elevation of tau in plasma. The repetitive minimal head injury in boxing may lead to axonal injuries that can be diagnosed with a blood test.
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| 35. |
- Nord, Magnus, 1967-, et al.
(författare)
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Cost-Effectiveness of Comprehensive Geriatric Assessment Adapted to Primary Care
- 2022
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Ingår i: Journal of the American Medical Directors Association. - : Elsevier. - 1525-8610 .- 1538-9375. ; 23:12, s. 2003-2009
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives To estimate the cost-effectiveness of a pragmatic trial of comprehensive geriatric assessment adapted to primary care, compared with care as usual. Design Within-trial cost-effectiveness study of a prospective controlled multicenter trial. Setting and Participants Nineteen primary care practices in Sweden. The original trial included 1304 individuals aged ≥75 years at high risk of hospitalization selected using a prediction model. From the original trial, 369 individuals participated in the cost-effectiveness analysis, 185 in the intervention group and 184 in the control group. Mean age was 83.9 years and 57% of the participants were men. Methods We obtained health care costs from administrative registries. Community costs and health-related quality of life data were obtained from a questionnaire sent to participants. Health-related quality of life was measured using EQ-5D-3L and quality-adjusted life years were calculated. We analyzed all outcomes according to intention to treat, and adjusted them to age, gender, and risk score (risk of hospitalization in the next 12 months). The primary outcome was the incremental cost-effectiveness ratio associated with the intervention at follow-up after 24 months. Results The difference in total cost (incremental cost) between intervention and control groups was USD −11,275 (95% CI −407 to −22,142). The incremental effect in quality-adjusted life years was −0.05 (95% CI −0.17 to 0.08). In the cost-effectiveness plane that illustrates the uncertainty of the analysis, 77.9 of the observations were within the south-east quadrant, implying lower cost and greater effect in the intervention group. Conclusions and Implications The results suggests that a primary care comprehensive geriatric assessment intervention delivered to older adults at high risk of hospitalization is cost-effective at follow-up after 24 months. The use of a prediction model to select participants and an intervention with a low cost is promising but requires further study.
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| 36. |
- Nord, Magnus, 1967-
(författare)
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Proactive Primary Care for Older Adults at High Risk of Hospital Admission
- 2022
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Demographic change is leading to a higher proportion of older adults in most parts of the world. A minority of older adults have poor health, but this group has high care needs due to frailty and/or multimorbidity. Guidelines for the management of frailty emphasise early detection of frailty and recommend comprehensive care approaches in primary care, but the evidence for these interventions is low. To provide effective and individualised care, the health system needs to identify these patients and develop proactive interventions to improve quality of life and avoid treatments that are of no benefit to the individual. The aim of this thesis was to study the effects of a proactive primary care working model in which vulnerable older adults were identified and received individually tailored care, using an adaptation of comprehensive geriatric assessment (CGA). Methods: A pragmatic controlled trial was conducted in 19 primary care practices in Sweden from 2017 to 2020. A predictive model, using electronic medical records to assess the risk of hospital admission, selected participants at high risk. Participants in the intervention practices were offered a comprehensive geriatric assessment in their primary care practice and subsequent follow-up by a team consisting of a nurse and the patient's doctor. A new CGA tool - PASTEL (Primary care ASsessment Tool for Elders) was used for assessment and care planning. The primary outcome for the intervention was hospital care days and secondary outcomes were hospital care episodes, mortality, outpatient visits, healthcare costs and cost-effectiveness. The outcomes were adjusted for age, sex and risk score and ana-lysed according to intention-to-treat. The predictive model was validated, and performance was assessed using the C-statistic. Focus group interviews were conducted to explore primary care nurses' and doctors' experiences with the new tool PASTEL. Results: 1304 older adults were included in the trial. The mean age was 82.2 years, 51% were female. During the follow-up period of 24 months, the relative risk reduction of hospital care days in the intervention group was - 22% (CI 95% = -35% to - 4%, p = 0.02) compared with usual care. There was no significant difference in mortality and outpatient visits. The reduction in healthcare costs was - € 4324 (- € 7962 to - € 686, p = 0.02). The intervention was cost-effective compared with usual care, mainly due to lower costs.The predictive model had an AUC of 0.69 (CI 0.68- 0.70). Primary care staff considered PASTEL valuable and feasible in the primary care context.In conclusion, the results of this thesis indicate that vulnerable older adults at risk of hospitalisation can be identified by a predictive model. Proactive intervention with a comprehensive geriatric assessment adapted to pri-mary care can reduce the need for hospital care. Future studies in similar contexts are needed to determine whether these results are generalisable.
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| 37. |
- Nägga, Katarina, 1962-, et al.
(författare)
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Associated physical disease in a demented population
- 1998
-
Ingår i: Aging (Milan, Italy). - : Springer Science and Business Media LLC. - 0394-9532. ; 10:6, s. 440-4
-
Tidskriftsartikel (refereegranskat)abstract
- Clinical experience indicates that physical diseases are probably underdiagnosed in patients suffering from dementia. We investigated the prevalence of physical diseases in patients with different types of dementia by means of a retrospective patient record survey including 236 inpatients and outpatients referred for dementia evaluation to the Dementia Investigation Unit, University Hospital in Linköping during 1994. Forty-four patients had dementia of the Alzheimer type, 78 had vascular dementia, 28 had dementia due to multiple etiologies, 42 were not demented, and 44 patients could not be classified by the DSM IV criteria. The physical diseases were registered as separate diagnoses comprising all newly-diagnosed physical diseases and previously known diseases that had exacerbated and contributed to the medical contact. Sixty-four percent of the patients had previously unknown physical diseases and/or exacerbation of previously known diseases. The most common physical conditions were cobalamin deficiency and infectious diseases, which occurred in 27% and 24% of the patients, respectively. There was no difference in the number or kinds of diagnoses between the diagnostic groups. Associated physical diseases were underdiagnosed in patients referred for dementia evaluation. We suggest that thorough medical investigation and adequate treatment are of importance in the management of dementia.
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| 38. |
- Nägga, Katarina, 1962-, et al.
(författare)
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Cobalamin, folate, methylmalonic acid, homocysteine, and gastritis markers in dementia
- 2003
-
Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 16:4, s. 269-275
-
Tidskriftsartikel (refereegranskat)abstract
- The prevalence of dementia disorders, cobalamin and/or folate deficiency as well as gastritis increases with age. To investigate whether there is an association between these conditions, plasma homocysteine (Hcy), serum methylmalonic acid, serum cobalamin and blood folate concentrations were measured. Gastritis was indirectly diagnosed by measuring serum antibodies against H,K-ATPase, Helicobacter pylori and intrinsic factor, using enzyme-linked immunosorbent assays. The studied groups consisted of 47 patients with Alzheimer’s disease (AD), 9 with AD pathology in combination with additive vascular lesions, 59 with vascular dementia, 8 who were cognitively impaired, and 101 control cases. Plasma Hcy concentrations were significantly elevated in the dementia groups, with the highest levels in patients with vascular pathology. We conclude that hyperhomocysteinemia is a common finding in patients with dementia disorders of different etiologies. The markers for gastritis did not contribute to an elucidation of a possible connection between this condition, dementia disorders, or cobalamin/folate deficiency.
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| 39. |
- Nägga, Katarina, 1962-, et al.
(författare)
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CT brain findings in clinical dementia investigation : underestimation of mixed dementia
- 2004
-
Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 18:1, s. 59-66
-
Tidskriftsartikel (refereegranskat)abstract
- Dementia has been found to display a more heterogeneous clinical picture than previously recognized. We investigated brain changes on computed tomography (CT) in a clinical dementia population consisting of 67 cases with Alzheimer's disease (AD), 13 with mixed dementia (AD and vascular dementia, VaD), 71 with VaD, and 12 cases that were not demented. Temporal cortical atrophy and atrophy around the temporal horns were more common in patients with mixed dementia compared to patients with VaD and the non-demented, respectively. Frontal white matter changes were present in 64% of AD, in 85% of mixed dementia and in 79% of VaD cases, but there were no differences between the dementia groups. Lacunes were present in almost 40% of AD cases and in 80 and 85% of VaD and mixed dementia cases, respectively. Only 14% of the VaD cases had large infarcts on the CT. We conclude that large infarcts were rare, even in VaD cases. The increased incidence of white matter changes and lacunes in AD patients strongly indicates an underestimation of the mixed dementia diagnosis. More distinct criteria for this diagnostic category are warranted.
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| 40. |
- Nägga, Katarina, 1962-, et al.
(författare)
-
Gaba transporters (GAT-1) in Alzheimer´s disease.
- 1999
-
Ingår i: Journal of neural transmission. - 0300-9564 .- 1435-1463. ; 106:11-12, s. 1141-1149
-
Tidskriftsartikel (refereegranskat)abstract
- The presynaptically located gamma-aminobutyric acid (GABA) transporter (GAT-1) was studied in a group of patients with Alzheimer's disease (AD) and in a control group using the GAT-1 selective radioligand [H-3]tiagabine. Post mortem brain tissue from frontal cortex, temporal cortex, and caudate nucleus from 18 AD patients and 23 age-matched controls were studied. The binding was saturable (Kd 26 nM) and region specific. There were no significant differences between the groups with respect to the binding capacity (Bmax) and binding affinity (Kd). The unaltered [H-3]tiagabine binding to GAT-1 protein indicates that intrinsic GABA neurons are spared in Alzheimer's disease.
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| 41. |
- Ólafsdóttir, María, et al.
(författare)
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Dementia in Primary Care : Why the Low Detection Rate?
- 2001
-
Ingår i: Scandinavian Journal of Primary Health Care. - : Informa UK Limited. - 0281-3432 .- 1502-7724. ; 19:3, s. 194-198
-
Tidskriftsartikel (refereegranskat)abstract
- Objective - The aim of the present study was to find reasons for the low detection rate of dementia in primary care. Another aim was to investigate the attitudes and knowledge on dementia among Swedish general practitioners (GPs).Design - Two-hundred-and-twenty-eight postal questionnaires were distributed to GPs in the county of Östergötland. Setting - Primary care in Sweden.Main outcome measures - The opinions of GPs on dementia management in primary care.Results - The response rate was 67%. GPs showed a good knowledge of dementia diseases but underestimated the occurrence of dementia. They presented a positive attitude towards managing patients with dementia and considered that existing drug therapy justified an active search for patients with dementia in primary care, but they believed the efficacy of the drugs to be limited. Assessing the social environment of patients and organising social support were regarded as the most difficult tasks in the management of demented patients.Conclusion - The study indicates that the main obstacles are a lack of resources and a sceptical attitude to the benefits of drug treatment. Co-operation between the community services, specialist clinics and the primary care team should be improved.
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| 42. |
- Ólafsdóttir, María, et al.
(författare)
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Detection of Dementia in Primary Care : The Linköping Study
- 2000
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 11:4, s. 223-229
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Tidskriftsartikel (refereegranskat)abstract
- We examined to what extent dementia and cognitive impairment are detected in a primary health care centre. A systematic sample of patients aged 70 years and above, who attended a primary health care centre for a doctor’s consultation (n = 350) were examined with a neuropsychiatric examination and an interview with a close informant. Dementia was diagnosed according to DSM-III-R. Medical records from the health centre were examined for entries on cognitive decline or dementia, other diagnoses and prescribed drugs. The prevalence of dementia was 16.3% and a further 3.1% had questionable dementia. Cognitive disturbances or dementia were noted in case records in 15 out of 57 (26%) demented cases, and in 1 out of 11 (9%) questionable dementias. Compared to non-demented patients, the demented had more diagnoses and a higher number of prescribed drugs. Severity and duration of dementia were associated with an increased detection.
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| 43. |
- Ólafsdóttir, María, et al.
(författare)
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Mental Disorders Among Elderly People in Primary Care : The Linköping Study
- 2001
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Ingår i: Acta Psychiatrica Scandinavica. - : Wiley. - 0001-690X .- 1600-0447. ; 104:1, s. 12-18
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aims of this study were to describe the prevalence of mental disorders among elderly patients in primary care and to compare diagnoses from psychiatric interview with diagnoses in medical records.Method: Patients aged 70 years and above attending a primary care centre (N=350) were studied using a psychiatric and medical record examination.Results: The prevalence of mental disorder according to the psychiatric interview was 33% (16% dementia, 17% other mental disorders). Only 49% of these had any psychiatric diagnosis in case records and 17–38% received specific treatments. The frequency of psychiatric symptoms among those with no mental disorder was between 1% and 66%. Patients with mental disorders were more often females, had more visits to a doctor, more diagnoses in medical records, and were prescribed more drugs.Conclusion: Mental disorders and symptoms are common among the elderly in primary care. More effort should be made to increase the recognition rate.
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| 44. |
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| 45. |
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| 46. |
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| 47. |
- Rosén, Christoffer, 1986, et al.
(författare)
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Cerebrospinal fluid profiles of amyloid β-related biomarkers in Alzheimer's disease.
- 2012
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Ingår i: Neuromolecular medicine. - : Springer Science and Business Media LLC. - 1559-1174 .- 1535-1084. ; 14:1, s. 65-73
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Tidskriftsartikel (refereegranskat)abstract
- The amyloid cascade hypothesis on the pathogenesis of Alzheimer's disease (AD) states that amyloid β (Aβ) accumulation in the brain is a key factor that initiates the neurodegenerative process. Aβ is generated from amyloid precursor protein (APP) through sequential cleavages by BACE1 (the major β-secretase in the brain) and γ-secretase. The purpose of this study was to characterize APP metabolism in vivo in AD patients versus cognitively healthy subjects by examining alterations in cerebrospinal fluid (CSF) biomarkers. We measured BACE1 activity and concentrations of α- and β-cleaved soluble APP (sAPPα and sAPPβ, respectively) and Aβ40 in CSF, biomarkers that all reflect the metabolism of APP, in 75 AD patients and 65 cognitively healthy controls. These analytes were also applied in a multivariate model to determine whether they provided any added diagnostic value to the core CSF AD biomarkers Aβ42, T-tau, and P-tau. We found no significant differences in BACE1 activity or sAPPα, sAPPβ, and Aβ40 concentrations between AD patients and controls. A multivariate model created with all analytes did not improve the separation of AD patients from controls compared with using the core AD biomarkers alone, highlighting the strong diagnostic performance of Aβ42, T-tau, and P-tau for AD. However, AD patients in advanced clinical stage, as determined by low MMSE score (≤20), had lower BACE1 activity and sAPPα, sAPPβ, and Aβ40 concentrations than patients with higher MMSE score, suggesting that these markers may be related to the severity of the disease.
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| 48. |
- Segernäs Kvitting, Anna, 1977-, et al.
(författare)
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Accuracy of the Cognitive Assessment Battery in a Primary Care Population
- 2019
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Ingår i: Dementia and Geriatric Cognitive Disorders Extra. - : S. Karger. - 1664-5464. ; 9:2, s. 294-301
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Tidskriftsartikel (refereegranskat)abstract
- Background: There are several cognitive assessment tools used in primary care, e.g., the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment. The Cognitive Assessment Battery (CAB) was introduced as a sensitive tool to detect cognitive decline in primary care. However, primary care validation is lacking. Therefore, we investigated the accuracy of the CAB in a primary care population. Objective: To investigate the accuracy of the CAB in a primary care population. Methods: Data from 46 individuals with cognitive impairment and 33 individuals who visited the primary care with somatic noncognitive symptoms were analyzed. They were investigated with the MMSE, the CAB, and a battery of neuropsychological tests; they also underwent consultation with a geriatric specialist. The accuracy of the CAB was assessed using c-statistics and the area under the receiver operating characteristic curve (AUC) was used to quantify the binary outcomes (“no cognitive impairment” or “cognitive impairment”).Results: The “cognitive impairment” group was significantly different from the unimpaired group for all the subtests of the CAB. When accuracy was based on binary significant reduction or not in one or several domains of the CAB, the AUC varied between 0.685 and 0.772. However, when a summation or logistic regression of several subcategories was performed, using the numerical values for each subcategory, the AUC was >0.9. For comparison, the AUC for the MMSE was 0.849.Conclusions: The accuracy of the CAB in a primary care population is poor to good when using binary cutoffs. Accuracy can be improved to high when using a summation or logistic regression of the numerical data of the subcategories. Considering CAB time, lack of adequate age norms, and a good accuracy for the MMSE, implementation of the CAB in primary care is not recommended at present based on the results of this study.
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| 49. |
- Segernäs Kvitting, Anna, 1977-, et al.
(författare)
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Age-Normative MMSE Data for Older Persons Aged 85 to 93 in a Longitudinal Swedish Cohort
- 2019
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Ingår i: Journal of The American Geriatrics Society. - : Wiley-Blackwell Publishing Inc.. - 0002-8614 .- 1532-5415. ; 67:3, s. 534-538
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/OBJECTIVES: Normative Mini-mental state examination (MMSE) reference values in elderly are scarce. Therefore, the aim is to present normative MMSE values for 85-93 year olds.DESIGN: A longitudinal age cohort study.SETTING: A population study of the residents in the municipality of Linköping, Sweden.PARTICIPANTS: Residents (n = 650) born in 1922 during the course of 2007. In total, 374 individuals participated and were tested with MMSE at age 85, 280 of these were willing and able to also participate at age 86, 107 at age 90 and 51 at age 93.MEASUREMENTS: MMSE, from 0-30, with lower scores denoting more impaired cognition.RESULTS: Median MMSE values for the total population over the ages 85, 86, 90 and 93 years was 28 for all ages investigated. The 25th percentile values were 26, 26, 26 and 27, respectively. For a "brain healthy" sub-group median values were 28, 29, 28, and 28. The 25th percentile values were 27, 28, 26 and 27, respectively. Comparisons for age-effects showed no differences when all individuals for each age group were compared. When only the individuals reaching 93 years of age (n = 50) were analyzed, there was a significant lowering of MMSE in that age group.CONCLUSION: The literature is variable and in clinical practice a low (24) MMSE cut off is often used for possible cognitive impairment in old age. The present data indicate that MMSE 26 is a reasonable cut off for possible cognitive decline in older persons up to the age of 93. J Am Geriatr Soc 67:534-538, 2019.
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| 50. |
- Segernäs Kvitting, Anna, 1977-
(författare)
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Dementia diagnostics in primary care : with a focus on cognitive testing
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundAge is the greatest risk factor for developing dementia and the total number of people aged 60 years and above is expected to more than double globally from 2013 to 2050 (1). Primary health care (PHC) is important for basic diagnostic evaluations. Objective test measurements have been shown to be more reliable than a patient's subjective memory complaints in dementia assessments (2). However, several studies indicate the low use of objective cognitive screening tools in dementia diagnostics in PHC (3). Some general practitioners (GPs) do not perceive today’s cognitive instruments as helpful in the diagnostic process and administration problems have been reported in PHC (4, 5).The overall aim of this thesis was to investigate the accuracy of several cognitive tests used in dementia assessments in PHC, especially among older patients: A Quick Test of Cognitive Speed (AQT), Cognistat and Cognitive Assessment Battery (CAB). The normative values of the Mini Mental Status Examination (MMSE) in the oldest old was also studied.MethodsThe studies included in this thesis are from two different study populations.Studies I, II and IV. Patients with and without cognitive symptoms were recruited from four primary health care centres in Sweden between 2007 and 2009.Study III. The Elderly in Linköping Screening Assessment (ELSA 85) cohort-population examined people born in 1922 in the municipality of Linköping, Sweden.ResultsStudy I. Results showed that AQT is a usable test for dementia diagnosis in PHC. Sensitivity for AQT is superior to the Clock Drawing Test (CDT), equivalent to MMSE and the combination MMSE and CDT. The AUC for AQT was 0.773, valued good enough.Study II. Overall, the results for Cognistat in this study are superior to MMSE and CDT, also in combination. Cognistat is promising for improved dementia diagnosis in PHC with a quick and easily administered multi-domain test for dementia assessments.Study III. This study presents valuable information about normative MMSE data for the oldest patients. Results, suggest using the 25th percentile in MMSE of 25 to 26 points, and indicate that MMSE 26 is as a reasonable cut-off for cognitive decline and further medical evaluation in older persons aged from 85 to 93 years.Study IV. In summary, the additive value of the CAB test in dementia investigations in PHC is not obvious. In addition to questionable accuracy, the test is quite time consuming and normative values are scarce. By introducing the numerical sum (CABsum) the accuracy was increased.ConclusionIn conclusion, objective cognitive tests are an important part of dementia diagnosis in PHC and there is a need for improved instruments and norm-values. From our results, several cognitive quick tests are usable in PHC - MMSE, AQT and Cognistat - but they have some disadvantages. MMSE 26 is a reasonable cut-off for cognitive decline in the oldest patients 85 to 93 years from a well-educated population with quite good socioeconomic. There is a great interest in finding short and better multi-domain instruments but the additive value of CAB in dementia investigations in PHC is questionable.
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