| 1. |
- Tucker, S., et al.
(författare)
-
Improving the mix of institutional and community care for older people with dementia : an application of the balance of care approach in eight European countries
- 2016
-
Ingår i: Aging and Mental Health. - Abingdon : Informa UK Limited. - 1360-7863 .- 1364-6915. ; 20:12, s. 1327-1338
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: To examine whether the mix of community and institutional long-term care (ILTC) for people with dementia (PwD) in Europe could be improved; assess the economic consequences of providing alternative services for particular groups of ILTC entrants and explore the transnational application of the ‘Balance of Care’ (BoC) approach. Method: A BoC study was undertaken in Estonia, Finland, France, Germany, the Netherlands, Spain, Sweden, and the UK as part of the RightTimePlaceCare project. Drawing on information about 2014 PwD on the margins of ILTC admission, this strategic planning framework identified people whose needs could be met in more than one setting, and compared the relative costs of the possible alternatives. Results: The findings suggest a noteworthy minority of ILTC entrants could be more appropriately supported in the community if enhanced services were available. This would not necessarily require innovative services, but more standard care (including personal and day care), assuming quality was ensured. Potential cost savings were identified in all countries, but community care was not always cheaper than ILTC and the ability to release resources varied between nations. Conclusions: This is believed to be the first transnational application of the BoC approach, and demonstrates its potential to provide a consistent approach to planning across different health and social care systems. Better comparative information is needed on the number of ILTC entrants with dementia, unit costs and outcomes. Nevertheless, the findings offer important evidence on the appropriateness of current provision, and the opportunity to learn from different countries' experience.
|
|
| 2. |
- Viitanen, Matti, 1950-
(författare)
-
Long-term effects of stroke
- 1987
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Stroke, which has an increasing incidence with age, causes an irreversible brain damage which may lead to impairment, disability and decreased life satisfaction or death.Risk factors for death, recurrent stroke and myocardial infarction, were analyzed in 409 stroke patients treated at the Stroke Unit, Department of Medicine, Umeå University Hospital, between Jan. 1, 1978 and Dec. 31, 1982. The causes of death were related with the time of survival. In fully co-operable (n=62) 4-6 year stroke survivors, the occurrence of motor and perceptual impairments, of self-care (ADL) disability and of self-reported decreased life satisfaction due to stroke was determined.The probability of survival was 77% three months after stroke, 69% after one year, and 37% after five years. Multivariate statistical analysis indicated that impairment of consciousness was the most important risk factor for death followed by age, previous cardiac failure, diabetes mellitus, intracerebral hemorrhage and male sex. During the first week, cerebrovascular disease (90%) was the most dominant primary cause of death, from the second to the fourth week pulmonary embolism (30%), bronchopneumonia during the second and third months and cardiac disease (37%) later than three months after stroke. The risk of recurrence was 14% during the first year after stroke and the accumulated risk of stroke recurrence after 5 years was 37% after stroke. The estimated probability of myocardial infarction was 7% at one year and 19% at 5 years. High age and a history of cardiac failure increased the risk of recurrent stroke. The risk of myocardial infarction was associated with high age, angina pectoris and diabetes mellitus. The highest risk of epilepsy was found between 6 and 12 months after stroke. Motor impairment prevailed in 36% of the long-term survivors, perceptual impairments in up to 57% and decreased ADL-capacity in 32%. As regards ecological perception, perceptual function variables were distinctly grouped into low and high level perception which together with motor function explained 71% of the variance of self-care ADL. While levels of global and of domain specific variables of life satisfaction appeared stable in clinically healthy reference populations aged 60 and 80 years, the stroke had produced a decrease in one or more aspects of life satisfaction for 61% of the long-term survivors. Although significantly associated with motor impairments and ADL disability, these changes could not only be attributed to physical problems.
|
|
| 3. |
- Almkvist, Ove, et al.
(författare)
-
Longitudinal cognitive decline in autosomal-dominant Alzheimer's disease varies with mutations in APP and PSEN1 genes
- 2019
-
Ingår i: Neurobiology of Aging. - : ELSEVIER SCIENCE INC. - 0197-4580 .- 1558-1497. ; 82, s. 40-47
-
Tidskriftsartikel (refereegranskat)abstract
- The purpose was to compare longitudinal cognitive changes in APP and PSEN1 gene mutation carriers and noncarriers from four autosomal-dominant Alzheimer's disease (ADAD) families across preclinical and early clinical stages of disease. Carriers (n = 34) with four different mutations (PSEN1(M146V), PSEN1(H163Y), APP(SWE), and APP(ARC)) and noncarriers (n = 41) were followed up longitudinally with repeated cognitive assessments starting many years before the expected clinical onset. The relationship between cognition and years to expected clinical onset, education, age, and type of mutation was analyzed using mixed-effects models. Results showed an education-dependent and time-related cognitive decline with linear and quadratic predictors in mutation carriers. Cognitive decline began close to the expected clinical onset and was relatively rapid afterward in PSEN1 mutation carriers, whereas decline was slower and started earlier than 10 years before expected clinical onset in APP mutation carriers. In noncarriers, the decline was minimal across time in accordance with normal aging. These results suggest that phenotypes for onset and rate of cognitive decline vary with PSEN1 and APP genes, suggesting a behavioral heterogeneity in ADAD. (C) 2019 Elsevier Inc. All rights reserved.
|
|
| 4. |
- Almkvist, Ove, et al.
(författare)
-
Predicting Cognitive Decline across Four Decades in Mutation Carriers and Non-carriers in Autosomal-Dominant Alzheimer's Disease
- 2017
-
Ingår i: Journal of the International Neuropsychological Society. - : CAMBRIDGE UNIV PRESS. - 1355-6177 .- 1469-7661. ; 23:3, s. 195-203
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim of this study was to investigate cognitive performance including preclinical and clinical disease course in carriers and non-carriers of autosomal-dominant Alzheimer's disease (adAD) in relation to multiple predictors, that is, linear and non-linear estimates of years to expected clinical onset of disease, years of education and age. Methods: Participants from five families with early-onset autosomal-dominant mutations (Swedish and Arctic APP, PSEN1 M146V, H163Y, and I143T) included 35 carriers (28 without dementia and 7 with) and 44 non-carriers. All participants underwent a comprehensive clinical evaluation, including neuropsychological assessment at the Memory Clinic, Karolinska University Hospital at Huddinge, Stockholm, Sweden. The time span of disease course covered four decades of the preclinical and clinical stages of dementia. Neuropsychological tests were used to assess premorbid and current global cognition, verbal and visuospatial functions, short-term and episodic memory, attention, and executive function. Results: In carriers, the time-related curvilinear trajectory of cognitive function across disease stages was best fitted to a formulae with three predictors: years to expected clinical onset (linear and curvilinear components), and years of education. In non-carriers, the change was minimal and best predicted by two predictors: education and age. The trajectories for carriers and non-carriers began to diverge approximately 10 years before the expected clinical onset in episodic memory, executive function, and visuospatial function. Conclusions: The curvilinear trajectory of cognitive functions across disease stages was mimicked by three predictors in carriers. In episodic memory, executive and visuospatial functions, the point of diverging trajectories occurred approximately 10 years ahead of the clinical onset compared to non-carriers.
|
|
| 5. |
- Ekblad, Laura L., et al.
(författare)
-
Midlife insulin resistance, APOE genotype, and late-life brain amyloid accumulation
- 2018
-
Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 0028-3878 .- 1526-632X. ; 90:13, s. e1150-e1157
-
Tidskriftsartikel (refereegranskat)abstract
- Objective To examine whether midlife insulin resistance is an independent risk factor for brain amyloid accumulation in vivo after 15 years, and whether this risk is modulated by APOE epsilon 4 genotype. Methods This observational study examined 60 elderly volunteers without dementia (mean age at baseline 55.4 and at follow-up 70.9 years, 55.5% women) from the Finnish population-based, nationwide Health2000 study with [C-11]Pittsburgh compound B-PET imaging in 2014-2016. The participants were recruited according to their homeostatic model assessment of insulin resistance (HOMA-IR) values in the year 2000, and their APOE epsilon 4 genotype. The exposure group (IR+, n = 30) consisted of individuals with HOMA-IR > 2.17 at baseline (highest tertile of the Health2000 study population), and the control group (IR-, n = 30) consisted of individuals with HOMA-IR < 1.25 at baseline (lowest tertile). The groups were enriched for APOE epsilon 4 carriers, resulting in 50% (n = 15) APOE epsilon 4 carriers in both groups. Analyses were performed with multivariate logistic and linear regression. Results An amyloid-positive PET scan was found in 33.3% of the IR-group and 60.0% of the IR+ group (odds ratio 3.0, 95% confidence interval 1.1-8.9, p = 0.04). The increased risk was seen in carriers and noncarriers of APOE epsilon 4 genotype. Higher midlife, but not late-life continuous HOMA-IR was associated with a greater brain amyloid burden at follow-up after multivariate adjustments for other cognitive and metabolic risk factors (ss = 0.11, 95% confidence interval 0.002-0.22, p = 0.04). Conclusions These results indicate that midlife insulin resistance is an independent risk factor for brain amyloid accumulation in elderly individuals without dementia.
|
|
| 6. |
- Toppala, Sini, et al.
(författare)
-
Association of Early β-Amyloid Accumulation and Neuroinflammation Measured With [11C]PBR28 in Elderly Individuals Without Dementia.
- 2021
-
Ingår i: Neurology. - : Wolters Kluwer. - 1526-632X .- 0028-3878. ; 96:12, s. e1608-e1619
-
Tidskriftsartikel (refereegranskat)abstract
- To examine whether early β-amyloid (Aβ) accumulation and metabolic risk factors are associated with neuroinflammation in elderly individuals without dementia.We examined 54 volunteers (mean age 70.0 years, 56% women, 51% APOE ɛ4 carriers) with the translocator protein (TSPO) tracer [11C]PBR28 to assess neuroinflammation and with [11C] Pittsburgh compound B (PiB) to assess cerebral Aβ accumulation. [11C]PBR28 and [11C]PiB standardized uptake value ratios (SUVRs) were quantified in 6 regions of interests by using the cerebellar cortex as a pseudo-reference and reference region, respectively. Fasting venous glucose, insulin, and high-sensitivity C-reactive protein (hs-CRP) values were determined. Homeostatic model assessment of insulin resistance (HOMA-IR) was calculated. A subset of individuals (n = 11) underwent CSF sampling, and Aβ40, Aβ42, total tau, phospho-tau, soluble TREM2, and YKL-40 levels were measured.Among the whole study group, no significant association was found between [11C]PiB and [11C]PBR28 SUVR composite scores (slope 0.02, p = 0.30). However, higher [11C]PiB binding was associated with higher [11C]PBR28 binding among amyloid-negative ([11C]PiB composite score ≤1.5) (TSPO genotype-, age- and sex-adjusted slope 0.26, p = 0.008) but not among amyloid-positive (slope -0.004, p = 0.88) participants. Higher CSF soluble TREM2 (rs = 0.72, p = 0.01) and YKL-40 (rs = 0.63, p = 0.04) concentrations were associated with a higher [11C]PBR28 composite score. Higher body mass index, HOMA-IR, and hs-CRP were associated with higher [11C]PBR28 binding in brain regions where Aβ accumulation is first detected in Alzheimer disease.While there was no association between amyloid and neuroinflammation in the overall study group, neuroinflammation was associated with amyloid among the subgroup at early stages of amyloid pathology.
|
|
| 7. |
- Toppala, Sini, et al.
(författare)
-
Midlife Insulin Resistance as a Predictor for Late-Life Cognitive Function and Cerebrovascular Lesions
- 2019
-
Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 72:1, s. 215-228
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Type 2 diabetes (T2DM) increases the risk for Alzheimer’s disease (AD) but not for AD neuropathology. The association between T2DM and AD is assumed to be mediated through vascular mechanisms. However, insulin resistance (IR), the hallmark of T2DM, has been shown to associate with AD neuropathology and cognitive decline.Objective: To evaluate if midlife IR predicts late-life cognitive performance and cerebrovascular lesions (white matter hyperintensities and total vascular burden), and whether cerebrovascular lesions and brain amyloid load are associated with cognitive functioning.Methods: This exposure-to-control follow-up study examined 60 volunteers without dementia (mean age 70.9 years) with neurocognitive testing, brain 3T-MRI and amyloid-PET imaging. The volunteers were recruited from the Finnish Health 2000 survey (n = 6062) to attend follow-up examinations in 2014–2016 according to their insulin sensitivity in 2000 and their APOE genotype. The exposure group (n = 30) had IR in 2000 and the 30 controls had normal insulin sensitivity. There were 15 APOE ɛ4 carriers per group. Statistical analyses were performed with multivariable linear models.Results: At follow-up the IR+group performed worse on executive functions (p = 0.02) and processing speed (p = 0.007) than the IR- group. The groups did not differ in cerebrovascular lesions. No associations were found between cerebrovascular lesions and neurocognitive test scores. Brain amyloid deposition associated with slower processing speed.Conclusion: Midlife IR predicted poorer executive functions and slower processing speed, but not cerebrovascular lesions. Brain amyloid deposition was associated with slower processing speed. The association between midlife IR and late-life cognition might not be mediated through cerebrovascular lesions measured here.
|
|
| 8. |
- Craggs, Lucinda, et al.
(författare)
-
Quantitative vascular pathology and phenotyping familial and sporadic cerebral small vessel diseases
- 2013
-
Ingår i: Brain Pathology. - : Wiley. - 1015-6305 .- 1750-3639. ; 23:5, s. 547-557
-
Tidskriftsartikel (refereegranskat)abstract
- We quantified vascular changes in the frontal lobe and basal ganglia of four inherited small vessel diseases (SVDs) including cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), pontine autosomal dominant microangiopathy and leukoencephalopathy (PADMAL), hereditary multi-infarct dementia of Swedish type (Swedish hMID), and hereditary endotheliopathy with retinopathy, nephropathy, and stroke (HERNS). Vascular pathology was most severe in CADASIL, and varied with marginally greater severity in the basal ganglia compared to the frontal lobe. The overall sclerotic index values in frontal lobe were in the order CADASIL ≥ HERNS > PADMAL > Swedish hMID > sporadic SVD, and in basal ganglia CADASIL > HERNS > Swedish hMID > PADMAL> sporadic SVD. The subcortical white matter was almost always more affected than any gray matter. We observed glucose transporter-1 (GLUT-1) protein immunoreactivities were most affected in the white matter indicating capillary degeneration whereas collagen IV (COL4) immunostaining was increased in PADMAL cases in all regions and tissue types. Overall, GLUT-1 : COL4 ratios were higher in the basal ganglia indicating modifications in capillary density compared to the frontal lobe. Our study shows that the extent of microvascular degeneration varies in these genetic disorders exhibiting common end-stage pathologies but is the most aggressive in CADASIL.
|
|
| 9. |
- Bernspång, Birgitta, et al.
(författare)
-
Perceptual function in the elderly and after stroke
- 1988
-
Ingår i: Scandinavian Journal of Caring Sciences. - : John Wiley & Sons. - 0283-9318 .- 1471-6712. ; 2:2, s. 75-79
-
Tidskriftsartikel (refereegranskat)abstract
- Perceptual function was assessed in 60 clinically healthy subjects aged about 60 (n=34) and 80 (n=26), and in stroke survivors who were assessed either early (n=109) or four to six years (n=75) after the stroke. Using two indices, one characterising low-order perception and the other higher-order perception, the clinically healthy subjects invariably had no impairment in the low-order index. Slight impairments occurred in 35% of 60-year-old and 77% of 80-year-old healthy subjects. Considerably more pronounced disturbances occurred in the stroke victims, among whom about 60% had impairment or higher-order perceptual function and about 10% had low-order perceptual deficits. Thus as higher-order perception is age dependent, it appears that in rehabilitation of stroke allowance should be made for predictable signs of advancing age.
|
|
| 10. |
- Heikela, H., et al.
(författare)
-
Hydroxysteroid (17 beta) dehydrogenase 12 is essential for metabolic homeostasis in adult mice
- 2020
-
Ingår i: American Journal of Physiology-Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 319:3, s. E494-E508
-
Tidskriftsartikel (refereegranskat)abstract
- Hydroxysteroid 17 beta dehydrogenase 12 (HSD17B12) is suggested to be involved in the elongation of very long chain fatty acids. Previously. we have shown a pivotal role for the enzyme during mouse development. In the present study we generated a conditional Hsd17b12 knockout (HSD17B12cKO) mouse model by breeding mice homozygous for a floxed Hsd17b12 allele with mice expressing the tamoxifen-inducible Cre recombinase at the ROSA26 locus. Gene inactivation was induced by administering tamoxifen to adult mice. The gene inactivation led to a 20% loss of body weight within 6 days, associated with drastic reduction in both white (83% males, 75% females) and brown (65% males. 60% females) fat, likely due to markedly reduced food and water intake. Furthermore, the knockout mice showed sickness behavior and signs of liver toxicity. specifically microvesicular hepatic steatosis and increased serum alanine aminotransferase (4.6-fold in males, 7.7-fold in females). The hepatic changes were more pronounced in females than males. Proinflammatory cytokines, such as interleukin-6 (IL-6), IL-17, and granulocyte colony-stimulating factor, were increased in the HSD17B12cKO mice indicating an inflammatory response. Serum lipidomics study showed an increase in the amount of dihydroceramides, despite the dramatic overall loss of lipids. In line with the proposed role for HSD17B12 in fatty acid elongation, we observed accumulation of ceramides, dihydroceramides, hexosylceramides, and lactosylceramides with shorter than 18-carbon fatty acid side chains in the serum. The results indicate that HSD17B12 is essential for proper lipid homeostasis and HSD17B12 deficiency rapidly results in fatal systemic inflammation and lipolysis in adult mice.
|
|
