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1.
  • Simmons, Johanna, et al. (författare)
  • Validation of REAGERA-S : a new self-administered instrument to identify elder abuse and lifetime experiences of abuse in hospitalized older adults
  • 2020
  • Ingår i: Journal of Elder Abuse & Neglect. - : Taylor & Francis. - 0894-6566 .- 1540-4129. ; 32:2, s. 173-195
  • Tidskriftsartikel (refereegranskat)abstract
    • This study aimed to develop and validate REAGERA-S, a self-administered instrument to identify elder abuse as well as lifetime experiences of abuse in older adults. REAGERA-S consists of nine questions concerning physical, emotional, sexual, financial abuse and neglect. Participants were recruited among patients (≥ 65 years) admitted to acute in-hospital care (n = 179). Exclusion criteria were insufficient physical, cognitive, or language capacity to complete the instrument. A semi-structured interview conducted by a physician was used as a gold standard against which to assess the REAGERA-S. The final version was answered by 95 older adults, of whom 71 were interviewed. Sensitivity for lifetime experiences of abuse was 71.9% and specificity 92.3%. For elder abuse, sensitivity was 87.5% and specificity was 92.3%. REAGERA-S performed well in validation and can be recommended for use in hospitals to identify elder abuse as well as life-time experience of abuse among older adults.
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2.
  • af Geijerstam, Peder, Doktorand, 1983-, et al. (författare)
  • Orthostatic Hypotension and Cognitive Function in Individuals 85 Years of Age: A Longitudinal Cohort Study in Sweden
  • 2024
  • Ingår i: Aging and Disease. - Fort Wortht, TX, United States : Buck Institute for Age Research. - 2152-5250.
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Orthostatic hypotension (OH) is more common in the elderly, and associated with increased mortality. However, its implications in 85-year-olds are not known.Methods: In the prospective observational cohort study Elderly in Linköping Screening Assessment (ELSA 85), 496 individuals in Linköping, Sweden, were followed from age 85 years with cognitive assessments. Blood pressure (BP) was measured supine and after 1, 3, 5, and 10 minutes of standing. Participants with a BP fall of ≥20 mmHg systolic or ≥10 mmHg diastolic after 1 or 3 minutes were classified as classical continuous or classical transient OH depending on whether the BP fall was sustained or not, at subsequent measurements. Those with a BP fall of the same magnitude, but only after 5 or 10 minutes were classified as delayed OH.Results: Of participants, 329 took part in BP measurements and were included. Of these, 156 (47.4%) had classical OH (113 [34.3%] continuous classical, 38 [11.6%] transient classical), and 15 (4.6%) had delayed OH. Cognitive assessments were not markedly different between groups. After 8.6 years, 195 (59.3%) of the participants had died, and delayed vs no OH was associated with twice the risk of all-cause mortality, HR 2.15 (95% CI 1.12-4.12). Transient classical OH was associated with reduced mortality, HR 0.58 (95% CI 0.33-0.99), but not after multiple adjustments, and continuous classical OH was not associated with mortality.Conclusion: OH may have different implications for morbidity and mortality in 85-year-olds compared with younger populations.
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4.
  • Blennow, Kaj, 1958, et al. (författare)
  • No association between the alpha2-macroglobulin (A2M) deletion and Alzheimer's disease, and no change in A2M mRNA, protein, or protein expression.
  • 2000
  • 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
  • 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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5.
  • Borland, Emma, et al. (författare)
  • The Montreal Cognitive Assessment : Normative Data from a Large Swedish Population-Based Cohort
  • 2017
  • Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 59:3, s. 893-901
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The Montreal Cognitive Assessment (MoCA) has a high sensitivity for detecting cognitive dysfunction. Swedish normative data does not exist and international norms are often derived from populations where cognitive impairment has not been screened for and not been thoroughly assessed to exclude subjects with dementia or mild cognitive impairment. Objective: To establish norms for MoCA and develop a regression-based norm calculator based on a large, well-examined cohort. Methods: MoCA was administered on 860 randomly selected elderly people from a population-based cohort from the EPIC study. Cognitive dysfunction was screened for and further assessed at a memory clinic. After excluding cognitively impaired participants, normative data was derived from 758 people, aged 65-85. Results: MoCA cut-offs (-1 to -2 standard deviations) for cognitive impairment ranged from <25 to <21 for the lowest educated and <26 to <24 for the highest educated, depending on age group. Significant predictors for MoCA score were age, sex and level of education. Conclusion: We present detailed normative MoCA data and cut-offs according to the DSM-5 criteria for cognitive impairment based on a large population-based cohort of elderly individuals, screened and thoroughly investigated to rule out cognitive impairment. Level of education, sex, and age should be taken in account when evaluating MoCA score, which is facilitated by our online regression-based calculator that provide percentile and z-score for a subject's MoCA score.
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6.
  • Bränsvik, Vanja, et al. (författare)
  • Mortality in patients with behavioural and psychological symptoms of dementia : a registry-based study
  • 2021
  • Ingår i: Aging & Mental Health. - : Routledge. - 1360-7863 .- 1364-6915. ; 25:6, s. 1101-1109
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Behavioural and psychological symptoms of dementia (BPSD) are common in patients with dementia. In the elderly population, comorbidities frequently coexist with dementia and mortality in dementia is high. The aim of this study was to investigate the impact of BPSD on mortality in severe dementia.Methods: This study of 11,448 individuals was based on linked information from the Swedish BPSD registry, the National Patient Register and the Cause of Death register. BPSD was assessed with the Neuropsychiatric Inventory (NPI). Cox proportional hazards regressions were performed for survival analysis. To study different degrees of BPSD, data was categorized into groups: no (NPI, 0 points), mild (NPI, 1-3 points on >= 1 item), moderate (NPI, 4-8 points on >= 1 item) and severe (NPI, 9-12 points on >= 1 item) BPSD based on the highest score on any of the BPSD assessed (NPI items).Results: The presence of moderate or severe BPSD was associated with a stepwise increased risk of mortality (hazard ratio (HR), 1.31; 95% confidence interval (CI), 1.08-1.60 and HR 1.74; 95% CI 1.44-2.12, respectively) compared with individuals with no BPSD. In addition, there was an association between total NPI score and mortality (HR 1.01; 95% CI 1.007-1.010). The results remained significant after multivariable adjustment for age, sex, dementia diagnosis, medication, previous myocardial infarction, hip fracture and stroke.Conclusions: The results show a stepwise increase in mortality risk with increased BPSD, highlighting the importance of adequate management of BPSD to reduce mortality in dementia.
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7.
  • Byman, Elin, et al. (författare)
  • Alpha-amylase 1A copy number variants and the association with memory performance and Alzheimer's dementia
  • 2020
  • Ingår i: Alzheimers Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Previous studies have shown that copy number variation (CNV) in the alpha (alpha)-amylase gene (AMY1A) is associated with body mass index, insulin resistance, and blood glucose levels, factors also shown to increase the risk of Alzheimer's dementia (AD). We have previously demonstrated the presence of alpha-amylase in healthy neuronal dendritic spines and a reduction of the same in AD patients. In the current study, we investigate the relationship between AMY1A copy number and AD, memory performance, and brain alpha-amylase activity. Methods and materials The association between AMY1A copy number and development of AD was analyzed in 5422 individuals (mean age at baseline 57.5 +/- 5.9, females 58.2%) from the Malmo diet and cancer study genotyped for AMY1A copy number, whereof 247 where diagnosed with AD during a mean follow-up of 20 years. Associations between AMY1A copy number and cognitive performance where analyzed in 791 individuals (mean age at baseline 54.7 +/- 6.3, females 63%), who performed Montreal Cognitive Assessment (MoCA) test. Correlation analysis between alpha-amylase activity or alpha-amylase gene expression and AMY1A copy number in post-mortem hippocampal tissue from on demented controls (n = 8) and AD patients (n = 10) was also performed. Results Individuals with very high ( >= 10) AMY1A copy number had a significantly lower hazard ratio of AD (HR = 0.62, 95% CI 0.41-0.94) and performed significantly better on MoCA delayed word recall test, compared to the reference group with AMY1A copy number 6. A trend to lower hazard ratio of AD was also found among individuals with low AMY1A copy number (1-5) (HR = 0.74, 95% CI 0.53-1.02). A tendency towards a positive correlation between brain alpha-amylase activity and AMY1A copy number was found, and females showed higher brain alpha-amylase activity compared to males. Conclusion Our study suggests that the degree of alpha-amylase activity in the brain is affected by AMY1A copy number and gender, in addition to AD pathology. The study further suggests that very high AMY1A copy number is associated with a decreased hazard ratio of AD and we speculate that this effect is mediated via a beneficial impact of AMY1A copy number on episodic memory performance.
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8.
  • Dybjer, Elin, et al. (författare)
  • Polygenic risk of type 2 diabetes is associated with incident vascular dementia : a prospective cohort study
  • 2023
  • Ingår i: Brain Communications. - : Oxford University Press (OUP). - 2632-1297. ; 5:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Type 2 diabetes and dementia are associated, but it is unclear whether the two diseases have common genetic risk markers that could partly explain their association. It is also unclear whether the association between the two diseases is of a causal nature. Furthermore, few studies on diabetes and dementia have validated dementia end-points with high diagnostic precision. We tested associations between polygenic risk scores for type 2 diabetes, fasting glucose, fasting insulin and haemoglobin A1c as exposure variables and dementia as outcome variables in 29 139 adults (mean age 55) followed for 20–23 years. Dementia diagnoses were validated by physicians through data from medical records, neuroimaging and biomarkers in cerebrospinal fluid. The dementia end-points included all-cause dementia, mixed dementia, Alzheimer’s disease and vascular dementia. We also tested causal associations between type 2 diabetes and dementia through two-sample Mendelian randomization analyses. Seven different polygenic risk scores including single-nucleotide polymorphisms with different significance thresholds for type 2 diabetes were tested. A polygenic risk score including 4891 single-nucleotide polymorphisms with a P-value of <5e-04 showed the strongest association with different outcomes, including all-cause dementia (hazard ratio 1.11; Bonferroni corrected P = 3.6e-03), mixed dementia (hazard ratio 1.18; Bonferroni corrected P = 3.3e-04) and vascular dementia cases (hazard ratio 1.28; Bonferroni corrected P = 9.6e-05). The associations were stronger for non-carriers of the Alzheimer’s disease risk gene APOE ϵ4. There was, however, no significant association between polygenic risk scores for type 2 diabetes and Alzheimer’s disease. Furthermore, two-sample Mendelian randomization analyses could not confirm a causal link between genetic risk markers of type 2 diabetes and dementia outcomes. In conclusion, polygenic risk of type 2 diabetes is associated with an increased risk of dementia, in particular vascular dementia. The findings imply that certain people with type 2 diabetes may, due to their genetic background, be more prone to develop diabetes-associated dementia. This knowledge could in the future lead to targeted preventive strategies in clinical practice.
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9.
  • Dybjer, Elin, et al. (författare)
  • Pre-diabetes and diabetes are independently associated with adverse cognitive test results : A cross-sectional, population-based study
  • 2018
  • Ingår i: BMC Endocrine Disorders. - : Springer Science and Business Media LLC. - 1472-6823. ; 18:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Diabetes is a risk factor for cognitive impairment, but whether there is also a link between pre-diabetes and cognitive dysfunction is not yet fully established. The aim of this observational study was to investigate associations between pre-diabetes/diabetes and cognitive test results, and also between glucose levels measured during the Oral Glucose Tolerance Test (OGTT) and cognitive outcomes. Methods: During 2007-2012, in all 2994 people (mean age 72 years), residing in Malmö, Sweden, underwent a clinical examination including the OGTT, cardiovascular measurements including carotid-femoral pulse wave velocity (c-f PWV) and two cognitive tests, the Mini Mental State Examination (MMSE), measuring global cognitive function, and A Quick Test of Cognitive Speed (AQT), measuring processing speed and executive functioning. Regression analyses were performed to investigate associations between: (a) categories of normal or impaired glucose metabolism, and (b) OGTT measurements, respectively, as exposure variables and cognitive test results as outcomes. Adjustments were made for demographics, lifestyle factors and cardiovascular risk factors. Results: Participants with pre-diabetes and diabetes scored slightly worse cognitive test results compared to the control group. Results of participants with a long disease duration of diabetes since the baseline examination 13 years earlier were poorer (mean AQT test time 17.8 s slower than controls, p < 0.001). Linear associations were found between fasting and 2-h glucose and cognitive outcomes in the whole population, but also in a sub-analysis including only individuals without diabetes (for 2-h glucose and MMSE results: B = - 2.961, p = 0.005). Associations were stronger for older or less physically active individuals. When adjusting for cardiovascular risk factors, most correlations were non-significant. Conclusions: Pre-diabetes and diabetes are associated with minor deficits in global cognitive function, processing speed and executive functioning. Long-standing diabetes is associated with bigger deficits. There appears to be a continuous inverse correlation between glucose levels and cognitive test results, also for people without diabetes. Associations are stronger in older and less physically active individuals. Cardiovascular factors are important mediating factors in the pathway between diabetes and cognitive dysfunction.
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10.
  • Dybjer, Elin, et al. (författare)
  • Type 1 diabetes, cognitive ability and incidence of cardiovascular disease and death over 60 years of follow-up time in men
  • 2022
  • Ingår i: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 39:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims There are few cohorts of type 1 diabetes that follow individuals over more than half a century in terms of health outcomes. The aim of this study was to examine associations between type 1 diabetes, diagnosed before age 18, and long-term morbidity and mortality, and to investigate whether cognitive ability plays a role in long-term morbidity and mortality risk. Methods In a Swedish cohort, 120 men with type 1 diabetes and 469 without type 1 diabetes were followed between 18 and 77 years of age as regards morbidity and mortality outcomes, and impact of cognitive ability at military conscription for the outcomes. In Cox regression analyses and Kaplan-Meier analyses with log-rank tests, associations between diabetes and cognitive ability respectively, and outcomes (mortality, cardiovascular morbidity and diabetes complications) were investigated. Results Men with type 1 diabetes suffered from dramatically higher mortality (HR 4.62, 95% CI: 3.56-5.60), cardiovascular mortality (HR 5.60, 95% CI: 3.27-9.57), and cardiovascular events (HR 3.97, 95% CI: 2.79-5.64) compared to men without diabetes. Higher cognitive ability at military conscription was associated with lower mortality in men without diabetes, but was not associated with any outcome in men with diabetes. Conclusions In this historical cohort study with 60 years of follow-up time and a less effective treatment of diabetes than today, mortality rates and cardiovascular outcomes were high for men with type 1 diabetes. Morbidity or mortality did not differ between those that had low to normal or high cognitive ability among men with type 1 diabetes.
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11.
  • Ferreira, Daniel, et al. (författare)
  • The interactive effect of demographic and clinical factors on hippocampal volume : A multicohort study on 1958 cognitively normal individuals
  • 2017
  • Ingår i: Hippocampus. - : Wiley. - 1050-9631 .- 1098-1063. ; 27:6, s. 653-667
  • Tidskriftsartikel (refereegranskat)abstract
    • Alzheimer's disease is characterized by hippocampal atrophy. Other factors also influence the hippocampal volume, but their interactive effect has not been investigated before in cognitively healthy individuals. The aim of this study is to evaluate the interactive effect of key demographic and clinical factors on hippocampal volume, in contrast to previous studies frequently investigating these factors in a separate manner. Also, to investigate how comparable the control groups from ADNI, AIBL, and AddNeuroMed are with five population-based cohorts. In this study, 1958 participants were included (100 AddNeuroMed, 226 ADNI, 155 AIBL, 59 BRC, 295 GENIC, 279 BioFiNDER, 398 PIVUS, and 446 SNAC-K). ANOVA and random forest were used for testing between-cohort differences in demographic-clinical variables. Multiple regression was used to study the influence of demographic-clinical variables on hippocampal volume. ANCOVA was used to analyze whether between-cohort differences in demographic-clinical variables explained between-cohort differences in hippocampal volume. Age and global brain atrophy were the most important variables in explaining variability in hippocampal volume. These variables were not only important themselves but also in interaction with gender, education, MMSE, and total intracranial volume. AddNeuroMed, ADNI, and AIBL differed from the population-based cohorts in several demographic-clinical variables that had a significant effect on hippocampal volume. Variability in hippocampal volume in individuals with normal cognition is high. Differences that previously tended to be related to disease mechanisms could also be partly explained by demographic and clinical factors independent from the disease. Furthermore, cognitively normal individuals especially from ADNI and AIBL are not representative of the general population. These findings may have important implications for future research and clinical trials, translating imaging biomarkers to the general population, and validating current diagnostic criteria for Alzheimer's disease and predementia stages.
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12.
  • Glans, Isabelle, et al. (författare)
  • Association Between Dietary Habits in Midlife With Dementia Incidence Over a 20-Year Period
  • 2023
  • Ingår i: Neurology. - : LIPPINCOTT WILLIAMS & WILKINS. - 0028-3878 .- 1526-632X. ; 100:1, s. E28-E37
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and ObjectivesDementia cases are expected to triple during the next 30 years, highlighting the importance of finding modifiable risk factors for dementia. The aim of this study was to investigate whether adherence to conventional dietary recommendations or to a modified Mediterranean diet are associated with a subsequent lower risk of developing all-cause dementia, Alzheimer disease (AD), vascular dementia (VaD), or with future accumulation of AD-related beta-amyloid (A beta) pathology.MethodsBaseline examination in the prospective Swedish population-based Malmo Diet and Cancer Study took place in 1991-1996 with a follow-up for incident dementia until 2014. Nondemented individuals born 1923-1950 and living in Malmo were invited to participate. Thirty thousand four hundred forty-six were recruited (41% of all eligible). Twenty-eight thousand twenty-five had dietary data and were included in this study. Dietary habits were assessed with a 7-day food diary, detailed food frequency questionnaire, and 1-hour interview. Main outcomes were incident all-cause dementia, AD, or VaD determined by memory clinic physicians. Secondary outcome was A beta-accumulation measured using CSF A beta 42 (n = 738). Cox proportional hazard models were used to examine associations between diet and risk of developing dementia (adjusted for demographics, comorbidities, smoking, physical activity, and alcohol).ResultsSixty-one percent were women, and the mean (SD) age was 58.1 (7.6) years. One thousand nine hundred forty-three (6.9%) were diagnosed with dementia (median follow-up, 19.8 years). Individuals adhering to conventional dietary recommendations did not have lower risk of developing all-cause dementia (hazard ratio [HR] comparing worst with best adherence, 0.93, 95% CI 0.81-1.08), AD (HR 1.03, 0.85-1.23), or VaD (HR 0.93, 0.69-1.26). Neither did adherence to the modified Mediterranean diet lower the risk of developing all-cause dementia (HR 0.93 0.75-1.15), AD (HR 0.90, 0.68-1.19), or VaD (HR 1.00, 0.65-1.55). The results were similar when excluding participants developing dementia within 5 years or those with diabetes. No significant associations were found between diet and abnormal A beta accumulation, conventional recommendations (OR 1.28, 0.74-2.24) or modified Mediterranean diet (OR 0.85, 0.39-1.84).DiscussionIn this 20-year follow-up study, neither adherence to conventional dietary recommendations nor to modified Mediterranean diet were significantly associated with subsequent reduced risk for developing all-cause dementia, AD dementia, VaD, or AD pathology.
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13.
  • Glans, Isabelle, et al. (författare)
  • Associations of modifiable and non-modifiable risk factors with cognitive functions – a prospective, population-based, 17 years follow-up study of 3,229 individuals
  • 2024
  • Ingår i: Alzheimer's Research and Therapy. - 1758-9193. ; 16:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Although several cardiovascular, demographic, genetic and lifestyle factors have been associated with cognitive function, little is known about what type of cognitive impairment they are associated with. The aim was to examine the associations between different risk factors and future memory and attention/executive functions, and their interaction with APOE genotype. Methods: Participants from a large, prospective, population-based, Swedish study were included (n = 3,229). Linear regression models were used to examine baseline hypertension, body mass index (BMI), long-term glucose levels (HbA1c), different lipid levels, physical activity, alcohol consumption, smoking, education, APOE genotype, age and sex. All models were adjusted for follow-up time and basic demographics, and, in a second step, all significant predictors were included to examine independent effects. Follow-up outcomes were memory and attention/executive functions. Results: The mean age at baseline was 56.1 (SD 5.7) years and 59.7% were women. The mean follow-up time was 17.4 (range 14.3–20.8) years. When examining independent effects, APOE ε4 genotype(p < 0.01), and higher HbA1c(p < 0.001), were associated with future low memory function. Higher BMI (p < 0.05), and HbA1c(p < 0.05), lower high-density lipoprotein cholesterol (HDL-C)(p < 0.05)and stroke(p < 0.001) were associated with future low attention/executive function. The strongest factors associated with both better memory and attention/executive functions were higher education and alcohol consumption. Further, significant interaction effects between predictors and APOE genotype were found. For memory function, the protective effects of education were greater among ɛ4-carriers(p < 0.05). For attention/executive function, the protective effects of alcohol were greater among ɛ2 or ɛ4-carriers(p < 0.05). Also, attention/executive function was lower among ɛ4-carriers with higher BMI(p < 0.05) and ɛ2-carriers with higher HbA1c-levels(p < 0.05). Conclusions: Targeting cardiovascular risk factors in mid-life could have greater effect on future attention/executive functions rather than memory, whereas targeting diabetes could be beneficial for multiple cognitive domains. In addition, effects of different risk factors may vary depending on the APOE genotype. The varied cognitive profiles suggest that different mechanisms and brain regions are affected by the individual risk factors. Having detailed knowledge about the specific cognitive effects of different risk factors might be beneficial in preventive health counseling.
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14.
  • Gustavsson, Anna-Märta, et al. (författare)
  • Cerebral Microbleeds and White Matter Hyperintensities in Cognitively Healthy Elderly : A Cross-Sectional Cohort Study Evaluating the Effect of Arterial Stiffness
  • 2015
  • Ingår i: Central and Eastern European Migration Review. - : S. Karger. - 1664-5456 .- 2053-8871. ; 5:2, s. 41-51
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Arterial stiffness reflects the ageing processes in the vascular system, and studies have shown an association between reduced cognitive function and cerebral small vessel disease. Small vessel disease can be visualized as white matter hyperintensities (WMH) and lacunar infarcts but also as cerebral microbleeds on brain magnetic resonance imaging (MRI). We aimed to investigate if arterial stiffness influences the presence of microbleeds, WMH and cognitive function in a population of cognitively healthy elderly.METHODS: The study population is part of the Swedish BioFinder study and consisted of 208 individuals without any symptoms of cognitive impairment, who scored >27 points on the Mini-Mental State Examination. The participants (mean age, 72 years; 59% women) underwent MRI of the brain with visual rating of microbleeds and WMH. Arterial stiffness was measured with carotid-femoral pulse wave velocity (cfPWV). Eight cognitive tests covering different cognitive domains were performed.RESULTS: Microbleeds were detected in 12% and WMH in 31% of the participants. Mean (±standard deviation, SD) cfPWV was 10.0 (±2.0) m/s. There was no association between the presence of microbleeds and arterial stiffness. There was a positive association between arterial stiffness and WMH independent of age or sex (odds ratio, 1.58; 95% confidence interval, 1.04-2.40, p < 0.05), but the effect was attenuated when further adjustments for several cardiovascular risk factors were performed (p > 0.05). Cognitive performance was not associated with microbleeds, but individuals with WMH performed slightly worse than those without WMH on the Symbol Digit Modalities Test (mean ± SD, 35 ± 7.8 vs. 39 ± 8.1, p < 0.05). Linear regression revealed no direct associations between arterial stiffness and the results of the cognitive tests.CONCLUSIONS: Arterial stiffness was not associated with the presence of cerebral microbleeds or cognitive function in cognitively healthy elderly. However, arterial stiffness was related to the presence of WMH, but the association was attenuated when multiple adjustments were made. There was a weak negative association between WMH and performance in one specific test of attention. Longitudinal follow-up studies are needed to further assess the associations.
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15.
  • Gustavsson, Anna Märta, et al. (författare)
  • Midlife Atherosclerosis and Development of Alzheimer or Vascular Dementia
  • 2020
  • Ingår i: Annals of Neurology. - : John Wiley & Sons. - 0364-5134 .- 1531-8249. ; 87:1, s. 52-62
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To investigate whether midlife atherosclerosis is associated with different dementia subtypes and related underlying pathologies.METHODS: Participants comprised the cardiovascular cohort of the Swedish prospective population-based Malmö Diet and Cancer Study (N = 6,103). Carotid plaques and intima media thickness (IMT) were measured at baseline (1991-1994). Dementia incidence until 2014 was obtained from national registers. Diagnoses were reviewed and validated in medical records. In a cognitively unimpaired subcohort (n = 330), β-amyloid42 and tau were quantified in cerebrospinal fluid (CSF), and white matter hyperintensity volume, lacunar infarcts, and cerebral microbleeds were estimated on magnetic resonance imaging (2009-2015).RESULTS: During 20 years of follow-up, 462 individuals developed dementia (mean age at baseline = 57.5 ± 5.9 years, 58% women). Higher IMT in midlife was associated with an increased hazard ratio (HR) of all-cause dementia (adjusted HR = 1.14 [95% confidence interval (CI) = 1.03-1.26]) and vascular dementia (adjusted HR = 1.32 [95% CI = 1.10-1.57]) but not Alzheimer disease (AD) dementia (adjusted HR = 0.95 [95% CI = 0.77-1.17]). Carotid plaques were associated with vascular dementia when assessed as a 3-graded score (adjusted HR = 1.90 [95% CI = 1.07-3.38]). In the cognitively unimpaired subcohort (53.8 ± 4.6 years at baseline, 60% women), higher IMT in midlife was associated with development of small vessel disease (adjusted odds ratio [OR] = 1.47 [95% CI = 1.05-2.06]) but not significantly with abnormal CSF AD biomarkers (adjusted OR = 1.28 [95% CI = 0.87-1.90] for Aβ42 and 1.35 [95% CI = 0.86-2.13] for Aβ42 /p-tau). Carotid plaques revealed no significant association with any of the underlying brain pathologies.INTERPRETATION: Our findings support an association between midlife atherosclerosis and development of vascular dementia and cerebral small vessel disease but not between atherosclerosis and subsequent AD dementia or AD pathology. ANN NEUROL 2019.
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18.
  • Hansson, Oskar, et al. (författare)
  • Midlife physical activity is associated with lower incidence of vascular dementia but not Alzheimer's disease
  • 2019
  • Ingår i: Alzheimer's Research & Therapy. - : BMC. - 1758-9193. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Physical activity might reduce the risk of developing dementia. However, it is still unclear whether the protective effect differs depending on the subtype of dementia. We aimed to investigate if midlife physical activity affects the development of vascular dementia (VaD) and Alzheimer's disease (AD) differently in two large study populations with different designs.Methods: Using a prospective observational design, we studied whether long-distance skiers of the Swedish Vasaloppet (n = 197,685) exhibited reduced incidence of VaD or AD compared to matched individuals from the general population (n = 197,684) during 21 years of follow-up (median 10, interquartile range (IQR) 5-15 years). Next, we studied the association between self-reported physical activity, stated twice 5 years apart, and incident VaD and AD in 20,639 participants in the Swedish population-based Malmo Diet and Cancer Study during 18 years of follow-up (median 15, IQR 14-17 years). Finally, we used a mouse model of AD and studied brain levels of amyloid-beta, synaptic proteins, and cognitive function following 6 months of voluntary wheel running.Results Vasaloppet skiers (median age 36.0 years [IQR 29.0-46.0], 38% women) had lower incidence of all-cause dementia (adjusted hazard ratio (HR) 0.63, 95% CI 0.52-0.75) and VaD (adjusted HR 0.49, 95% CI 0.33-0.73), but not AD, compared to non-skiers. Further, faster skiers exhibited a reduced incidence of VaD (adjusted HR 0.38, 95% CI 0.16-0.95), but not AD or all-cause dementia compared to slower skiers. In the Malmo Diet and Cancer Study (median age 57.5 years [IQR 51.0-63.8], 60% women), higher physical activity was associated with reduced incidence of VaD (adjusted HR 0.65, 95% CI 0.49-0.87), but not AD nor all-cause dementia. These findings were also independent of APOE-epsilon 4 genotype. In AD mice, voluntary running did not improve memory, amyloid-beta, or synaptic proteins.Conclusions: Our results indicate that physical activity in midlife is associated with lower incidence of VaD. Using three different study designs, we found no significant association between physical activity and subsequent development of AD.
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19.
  • Hertze, Joakim, et al. (författare)
  • Changes in cerebrospinal fluid and blood plasma levels of IGF-II and its binding proteins in Alzheimer's disease : an observational study
  • 2014
  • Ingår i: BMC Neurology. - : BioMed Central. - 1471-2377. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The Insulin-like Growth Factor (IGF)-related system is implicated in neuroregeneration and cell repair, as well as regulating lifespan. IGF-II, one component of this system, has also been found to affect memory functions in a rat model. In this study we explored changes in the IGF-related system in patients with Alzheimer's disease (AD), including changes in IGF-II levels.METHODS: We measured blood plasma and cerebrospinal fluid (CSF) levels of IGF-I, IGF-II, IGFBP-2 and IGFBP-3 in 72 healthy controls and 92 patients with AD.RESULTS: We found significantly lower blood plasma levels of IGF-II and IGFBP-3 in patients with AD, compared with controls. The levels of IGF-II and IGFBP-2 were significantly elevated in the CSF from patients with AD. We also found correlations between established CSF biomarkers for AD (tau and P-tau) and components of the IGF system.CONCLUSIONS: CSF and blood plasma levels of IGF-II and some of its binding proteins are changed in patients with AD. Further investigation into this area may unravel important clues to the nature of this disease.
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20.
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21.
  • Holm, H, et al. (författare)
  • Beta-blocker therapy and risk of vascular dementia: A population-based prospective study
  • 2020
  • Ingår i: Vascular pharmacology. - : ELSEVIER SCIENCE INC. - 1537-1891 .- 1879-3649. ; 125
  • Tidskriftsartikel (refereegranskat)abstract
    • There are a few studies that report cognitive impairment as a complication of treatment with beta-blockers. We aimed to evaluate the longitudinal association between use of beta-blockers, as a class, and incident risk of all-cause dementia, vascular dementia, Alzheimers and mixed dementia in the prospective population-based Malmo Preventive Project. We included 18,063 individuals (mean age 68.2, males 63.4%) followed up for 84,506 person-years. Dementia cases were retrieved from the Swedish National Patient Register and validated by review of medical records and neuroimaging data. We performed propensity score matching analysis, resulting in 3720 matched pairs of beta-blocker users and non-users at baseline, and multivariable Cox proportional-hazards regression. Overall, 122 study participants (1.6%) were diagnosed with dementia during the follow-up. Beta-blocker therapy was independently associated with increased risk of developing vascular dementia, regardless of confounding factors (HR: 1.72, 95%CI 1.01-3.78; p = .048). Conversely, treatment with beta-blockers was not associated with increased risk of all-cause, Alzheimers and mixed dementia (HR:1.15; 95%CI 0.80-1.66; p = .44; HR:0.85; 95%CI 0.48-1.54; P = .59 and HR:1.35; 95%CI 0.56-3.27; p = .50, respectively). We observed that use of beta-blockers, as a class, is associated with increased longitudinal risk of vascular dementia in the general elderly population, regardless of cardiovascular risk factors, prevalent or incident history of atrial fibrillation, stroke, coronary events and heart failure. Further studies are needed to confirm our findings in the general population and to explore the mechanisms underlying the relationship between use of beta-blockers and increased risk of vascular dementia.
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22.
  • Holm, Hannes, et al. (författare)
  • Cognitive test results are associated with mortality and rehospitalization in heart failure: Swedish prospective cohort study
  • 2020
  • Ingår i: ESC Heart Failure. - : WILEY PERIODICALS, INC. - 2055-5822. ; 7:5, s. 2948-2955
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims We aimed to search for associations between cognitive test results with mortality and rehospitalization in a Swedish prospective heart failure (HF) patient cohort. Methods and results Two hundred and eighty-one patients hospitalized for HF (mean age, 74 years; 32% women) were assessed using cognitive tests: Montreal Cognitive Assessment (MoCA), A Quick Test of Cognitive speed, Trail Making Test A, and Symbol Digit Modalities Test. The mean follow-up time censored at rehospitalization or death was 13 months (interquartile range, 14) and 28 months (interquartile range, 29), respectively. Relations between cognitive test results, mortality, and rehospitalization risk were analysed using multivariable Cox regression model adjusted for age, sex, body mass index, systolic blood pressure, atrial fibrillation, diabetes, smoking, educational level, New York Heart Association class, and prior cardiovascular disease. A total of 80 patients (29%) had signs of cognitive impairment (MoCA score < 23 points). In the fully adjusted Cox regression model using standardized values per 1 SD change of each cognitive test, lower score on MoCA [hazard ratio (HR), 0.75; confidence interval (CI), 0.60-0.95;P = 0.016] and Symbol Digit Modalities Test (HR, 0.66; CI, 0.48-0.90;P = 0.008) yielded significant associations with increased mortality. Rehospitalization risk (n = 173; 62%) was significantly associated with lower MoCA score (HR, 0.84; CI, 0.71-0.99;P = 0.033). Conclusions Two included cognitive tests were associated with mortality in hospitalized HF patients, independently of traditional risk factors. In addition, worse cognitive test scores on MoCA heralded increased risk of rehospitalization.
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23.
  • Holm, Hannes, et al. (författare)
  • Longitudinal and postural changes of blood pressure predict dementia : the Malmö Preventive Project
  • 2017
  • Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 32:4, s. 327-336
  • Tidskriftsartikel (refereegranskat)abstract
    • The role of blood pressure (BP) changes in dementia is debatable. We aimed to analyse how resting and postural BP changes relate to incident dementia over a long-term follow-up. In the prospective population-based Malmö Preventive Project, 18,240 study participants (mean age: 45 ± 7 years, 63% male) were examined between 1974 and 1992 with resting and standing BP measurement, and re-examined between 2002 and 2006 at mean age of 68 ± 6 years with resting BP. A total of 428 participants (2.3%) were diagnosed with dementia through Dec 31, 2009. The association of resting and postural BP changes with risk of dementia was studied using multivariable-adjusted Cox regression models controlling for traditional risk factors. Diastolic BP (DBP) decrease on standing indicated higher risk of dementia [Hazard ratio (HR) per 10 mmHg: 1.22; 95% confidence interval (CI) 1.01–1.44, p = 0.036], which was mainly driven by increased risk in normotensive individuals. Higher systolic (SBP) and diastolic BP at re-examination was associated with lower risk of dementia (HR per 10 mmHg: 0.94; 95% CI 0.89–0.99, p = 0.011; and 0.87; 0.78–0.96, p = 0.006, respectively). Extreme decrease in SBP/DBP between baseline and re-examination (4th quartile; −7 ± 12/−15 ± 7 mmHg, respectively) indicated higher risk of dementia (HR 1.46; 95% CI 1.11–1.93, p = 0.008, and 1.54; 95% CI 1.14–2.08, p = 0.005; respectively) compared with reference group characterised by pronounced BP increase over the same period (1st quartile; +44 ± 13/+15 ± 7 mmHg). Diastolic BP decrease on standing in the middle age, decline in BP between middle-and advanced age, and lower BP in advanced age are independent risk factors of developing dementia.
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24.
  • Holm, Hannes, et al. (författare)
  • N-Terminal Prosomatostatin and Risk of Vascular Dementia
  • 2017
  • Ingår i: Cerebrovascular Diseases. - : S. Karger. - 1015-9770 .- 1421-9786. ; 44:5-6, s. 259-265
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Increased somatostatin plasma concentration has been found in patients with vascular dementia. However, it is unknown whether or not somatostatin levels may predict dementia development in the general population. To this end, we sought to assess the association of circulating N-terminal prosomatostatin (NT-proSST) with incident dementia among community-dwelling older adults.METHODS: In the prospective population-based Malmö Preventive Project, 5,347 study participants (mean age: 69 ± 6years; 70% men) provided plasma for the determination of NT-proSST concentration. Of these, 373 participants (7%) were diagnosed with dementia (120 Alzheimer's disease, 83 vascular, 102 mixed, and 68 other aetiology) during a follow-up period of 4.6 ± 1.3 years. The association of NT-proSST with the risk of dementia and its subtypes was studied using multivariable-adjusted Cox regression models controlling for age, gender, body mass index, systolic blood pressure, antihypertensive treatment, smoking, diabetes, lipid levels and prevalent stroke.RESULTS: Higher levels of NT-proSST were significantly associated with an increased risk of vascular dementia (hazard ratio [HR] per 1 SD: 1.29; 95% CI 1.05-1.59; p = 0.016), whereas no association was observed with Alzheimer's disease (HR per 1 SD: 0.99; 95% CI 0.81-1.20; p = 0.91), all-cause dementia (HR per 1 SD: 1.04; 95% CI 0.94-1.16; p = 0.44), and mixed dementia (HR per 1 SD: 0.98; 95% CI 0.79-1.21; p = 0.84). Levels of NT-proSST above 563 pmol/L (highest quartile) conferred distinctly increased risk of vascular dementia (HR 1.66; 95% CI 1.05-2.63; p = 0.029) compared with lower values.CONCLUSIONS: Higher levels of circulating N-terminal-prosomatostatin are associated with increased incidence of vascular dementia. Our findings might be of importance for the understanding of dementia development in older adults.
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25.
  • Hölttä, Mikko, et al. (författare)
  • Evaluating amyloid-β oligomers in cerebrospinal fluid as a biomarker for Alzheimer's disease.
  • 2013
  • Ingår i: PloS one. - San Francisco, CA, United States : Public Library of Science (PLoS). - 1932-6203. ; 8:6
  • Tidskriftsartikel (refereegranskat)abstract
    • The current study evaluated amyloid-β oligomers (Aβo) in cerebrospinal fluid as a clinical biomarker for Alzheimer's disease (AD). We developed a highly sensitive Aβo ELISA using the same N-terminal monoclonal antibody (82E1) for capture and detection. CSF samples from patients with AD, mild cognitive impairment (MCI), and healthy controls were examined. The assay was specific for oligomerized Aβ with a lower limit of quantification of 200 fg/ml, and the assay signal showed a tight correlation with synthetic Aβo levels. Three clinical materials of well characterized AD patients (n=199) and cognitively healthy controls (n=148) from different clinical centers were included, together with a clinical material of patients with MCI (n=165). Aβo levels were elevated in the all three AD-control comparisons although with a large overlap and a separation from controls that was far from complete. Patients with MCI who later converted to AD had increased Aβo levels on a group level but several samples had undetectable levels. These results indicate that presence of high or measurable Aβo levels in CSF is clearly associated with AD, but the overlap is too large for the test to have any diagnostic potential on its own.
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26.
  • Janelidze, Shorena, et al. (författare)
  • Increased blood-brain barrier permeability is associated with dementia and diabetes but not amyloid pathology or APOE genotype
  • 2017
  • Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 51, s. 104-112
  • Tidskriftsartikel (refereegranskat)abstract
    • Blood-brain barrier (BBB) dysfunction might be an important component of many neurodegenerative disorders. In this study, we investigated its role in dementia using large clinical cohorts. The cerebrospinal fluid (CSF)/plasma albumin ratio (Qalb), an indicator of BBB (and blood-CSF barrier) permeability, was measured in a total of 1015 individuals. The ratio was increased in patients with Alzheimer's disease, dementia with Lewy bodies or Parkinson's disease dementia, subcortical vascular dementia, and frontotemporal dementia compared with controls. However, this measure was not changed during preclinical or prodromal Alzheimer's disease and was not associated with amyloid positron emission tomography or APOE genotype. The Qalb was increased in diabetes mellitus and correlated positively with CSF bio-markers of angiogenesis and endothelial dysfunction (vascular endothelial growth factor, intracellular adhesion molecule 1, and vascular cell adhesion molecule 1). In healthy elderly, high body mass index and waist-hip ratio predicted increased Qalb 20 years later. In summary, BBB permeability is increased in major dementia disorders but does not relate to amyloid pathology or APOE genotype. Instead, BBB impairment may be associated with diabetes and brain microvascular damage. (C) 2016 The Authors. Published by Elsevier Inc.
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27.
  • Jeppsson, Anna, et al. (författare)
  • CSF biomarkers distinguish idiopathic normal pressure hydrocephalus from its mimics
  • 2019
  • Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 90:10, s. 1117-1123
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To examine the differential diagnostic significance of cerebrospinal fluid (CSF) biomarkers reflecting Alzheimer's disease-related amyloid β (Aβ) production and aggregation, cortical neuronal damage, tau pathology, damage to long myelinated axons and astrocyte activation, which hypothetically separates patients with idiopathic normal pressure hydrocephalus (iNPH) from patients with other neurodegenerative disorders. Methods: The study included lumbar CSF samples from 82 patients with iNPH, 75 with vascular dementia, 70 with Parkinson's disease, 34 with multiple system atrophy, 34 with progressive supranuclear palsy, 15 with corticobasal degeneration, 50 with Alzheimer's disease, 19 with frontotemporal lobar degeneration and 54 healthy individuals (HIs). We analysed soluble amyloid precursor protein alpha (sAPPα) and beta (sAPPβ), Aβ species (Aβ38, Aβ40 and Aβ42), total tau (T-tau), phosphorylated tau, neurofilament light and monocyte chemoattractant protein 1 (MCP-1). Results: Patients with iNPH had lower concentrations of tau and APP-derived proteins in combination with elevated MCP-1 compared with HI and the non-iNPH disorders. T-tau, Aβ40 and MCP-1 together yielded an area under the curve of 0.86, differentiating iNPH from the other disorders. A prediction algorithm consisting of T-tau, Aβ40 and MCP-1 was designed as a diagnostic tool using CSF biomarkers. Conclusions: The combination of the CSF biomarkers T-tau, Aβ40 and MCP-1 separates iNPH from cognitive and movement disorders with good diagnostic sensitivity and specificity. This may have important implications for diagnosis and clinical research on disease mechanisms for iNPH. © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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28.
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29.
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30.
  • Kalldalen, Anette, et al. (författare)
  • Occupational Performance Problems in 85-Year-Old Women and Men in Sweden
  • 2012
  • Ingår i: OTJR (Thorofare, N.J.). - : Slack. - 1539-4492 .- 1938-2383. ; 32:2, s. 30-38
  • Tidskriftsartikel (refereegranskat)abstract
    • An area of concern for occupational therapy is to increase preventive interventions among relatively healthy elderly individuals. The purpose of this study was to explore occupational performance problems among 85-year-old women and men in relation to demographic data, mental health, and health-related quality of life. Participants completed a postal questionnaire including the EuroQoL health-related quality of life measurement. Instruments used during a home visit were the Canadian Occupational Performance Measure, the Mini-Mental State Examination, and the Geriatric Depression scale. The sample comprised 380 individuals. Women experienced poorer health and more occupational performance problems in community management, household management, and quiet leisure than men. Impaired cognitive function, lower self-rated health, and higher risk of depression correlated with a larger number of occupational performance problems. Intervention planning should be based on individual perceptions of meaningful occupations and environmental considerations.
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31.
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32.
  • Lindgren, Emma, et al. (författare)
  • Differences in Dementia Care Between Swedish-Born and Foreign-Born from Countries with Different Country Level Socioeconomic Position : A Nationwide Register-Based Study
  • 2021
  • Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 84:3, s. 1363-1371
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: With a growing elderly population worldwide, the prevalence of dementia is rapidly increasing. Studies from high income countries have shown that belonging to a minority ethnic group increases the risk of health disadvantages. Objective: The aim of the present registry-based study was to identify potential differences in diagnostics, treatment, and care of individuals with dementia focusing on foreign-born in Sweden and the impact of country level socioeconomic position (SEP). Methods: The study was based on a large dataset from the Swedish Dementia Registry (SveDem) and the Swedish Tax Agency's population registry. Data on demographic variables, cognitive tests, clinical assessments, medication, diagnosis, and interventions initiated at diagnosis were collected. Country level SEP was determined by country of birth as classified by World Bank Country and Lending groups. Results: Of 57,982 patients with dementia registered in SveDem, 7,171 (12.4%) were foreign-born. The foreign-born were significantly younger at diagnosis (p < 0.001), had a lower MMSE score (p < 0.001), lower odds of receiving a specific dementia diagnosis (p < 0.001), lower use of acetylcholinesterase inhibitors (p < 0.001), and overall a higher use of neuroleptics compared with the Swedish-born group. The lower SEP, the greater differences to Swedish-born were seen in many of the examined variables. Conclusion: There were significant differences in dementia diagnostics, treatment, and care between foreign-born and Swedish-born, a lower SEP indicating greater differences. Further research should focus on various socioeconomic aspects and health care outcomes for a more profound analysis of equity in dementia care.
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33.
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34.
  • Llorens, Franc, et al. (författare)
  • Cerebrospinal fluid lipocalin 2 as a novel biomarker for the differential diagnosis of vascular dementia
  • 2020
  • Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The clinical diagnosis of vascular dementia (VaD) is based on imaging criteria, and specific biochemical markers are not available. Here, we investigated the potential of cerebrospinal fluid (CSF) lipocalin 2 (LCN2), a secreted glycoprotein that has been suggested as mediating neuronal damage in vascular brain injuries. The study included four independent cohorts with a total n=472 samples. LCN2 was significantly elevated in VaD compared to controls, Alzheimers disease (AD), other neurodegenerative dementias, and cognitively unimpaired patients with cerebrovascular disease. LCN2 discriminated VaD from AD without coexisting VaD with high accuracy. The main findings were consistent over all cohorts. Neuropathology disclosed a high percentage of macrophages linked to subacute infarcts, reactive astrocytes, and damaged blood vessels in multi-infarct dementia when compared to AD. We conclude that CSF LCN2 is a promising candidate biochemical marker in the differential diagnosis of VaD and neurodegenerative dementias. Diagnosis of vascular dementia is hampered by the lack of biochemical markers for this disease. Here, the authors show that vascular dementia is associated with increased lipocalin-2 in cerebrospinal fluid, compared to controls and patients with other forms of dementia.
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35.
  • Lukkarinen, H., et al. (författare)
  • Cerebrospinal fluid biomarkers that reflect clinical symptoms in idiopathic normal pressure hydrocephalus patients
  • 2022
  • Ingår i: Fluids and Barriers of the Cns. - : Springer Science and Business Media LLC. - 2045-8118. ; 19:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The relationship between cerebrospinal fluid (CSF) biomarkers and the clinical features of idiopathic normal pressure hydrocephalus (iNPH) has been inconclusive. We aimed to evaluate CSF biomarkers reflecting Alzheimer’s disease (AD)-related amyloid β (Aβ) aggregation, tau pathology, neuroinflammation and axonal degeneration in relation to the clinical features of pre- and post-shunt surgery in iNPH patients. Methods: Mini Mental State Examination (MMSE) scores and gait velocity were evaluated pre- and postoperatively in cohorts of 65 Finnish (FIN) and 82 Swedish (SWE) iNPH patients. Lumbar CSF samples were obtained prior to shunt surgery and analysed for soluble amyloid precursor protein alpha (sAPPα) and beta (sAPPβ); amyloid-β isoforms of 42, 40 and 38 (Aβ42, Aβ40, Aβ38); total tau (T-tau); phosphorylated tau (P-tau181); neurofilament light (NfL) and monocyte chemoattractant protein 1 (MCP1). Results: Preoperative patient characteristics showed no significant differences between patients in the FIN and SWE cohorts. Patients in both cohorts had significantly improved gait velocity after shunt surgery (p < 0.0001). Low CSF T-tau and absence of apolipoprotein E ε4 predicted over 20% gait improvement postoperatively (p = 0.043 and p = 0.008). Preoperative CSF T-tau, P-tau181 and NfL correlated negatively with MMSE scores both pre- (p < 0.01) and post-surgery (p < 0.01). Furthermore, T-tau, NfL and Aβ42 correlated with MMSE outcomes (p < 0.05). Low preoperative CSF P-tau181 (p = 0.001) and T-tau with NfL (p < 0.001 and p = 0.049) best predicted pre- and postoperative MMSE scores greater than or equal to 26. Conclusions: CSF biomarkers of neurodegeneration appeared to correlate with pre- and postoperative cognition, providing a window into neuropathological processes. In addition, preoperative CSF neurodegeneration biomarkers may have potential in the prediction of gait and cognitive outcomes after shunt surgery. © 2022, The Author(s).
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36.
  • Mårdh, Selina, et al. (författare)
  • A longitudinal study of semantic memory impairment in patients with Alzheimer’s disease
  • 2013
  • Ingår i: Cortex. - : Elsevier. - 0010-9452 .- 1973-8102. ; 49:2, s. 528-533
  • Tidskriftsartikel (refereegranskat)abstract
    • The present study explored the nature of the semantic deterioration normally displayed in the course of Alzheimer’s disease (AD). The aim was to disentangle the extent to which semantic memory problems in patients with AD are best characterized as loss of semantic knowledge rather than difficulties in accessing semantic knowledge.A longitudinal approach was applied. The same semantic tests as well as same items were used across three test occasions a year apart. Twelve Alzheimer patients and 20 matched control subjects, out of a total of 25 cases in each group, remained at the final test occasion.Alzheimer patients were impaired in all the semantic tasks as compared to the matched comparison group. A progressing deterioration was evident during the study period. Our findings suggest that semantic impairment is mainly due to loss of information rather than problems in accessing semantic information.
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37.
  • Nakanishi, Miharu, et al. (författare)
  • Dementia behaviour management programme at home : impact of a palliative care approach on care managers and professional caregivers of home care services
  • 2018
  • Ingår i: Aging and Mental Health. - : Informa UK Limited. - 1360-7863 .- 1364-6915. ; 22:8, s. 1063-1068
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Care managers and professional caregivers of home care services are sometimes unaware of the psychosocial approaches to the challenging behaviour of dementia. Therefore, we developed a Behaviour Analytics & Support Enhancement (BASE) programme. We investigated the effects of the programme on the attitudes towards dementia care among professionals. Method: Forty-six participants in Japan received training in August 2016. The ongoing monitoring and assessment system was introduced to the participants for repeated measures of challenging behaviour. A 1-day follow-up meeting for debriefing was also performed after two months. A baseline and follow-up questionnaire survey was administered to the participating caregivers using a Japanese version of the Approaches to Dementia Questionnaire (ADQ) and the Zarit Burden Interview (ZBI). Results: A significant improvement was observed in the total ADQ score among the participating caregivers from baseline to follow-up assessment. There was no significant difference between the baseline and follow-up assessment in the ZBI scores. In the follow-up meeting, several participants reported challenges and suggested solutions in facilitating a discussion on an action plan among professionals from various organizations. Conclusion: The implementation of the programme resulted in enhanced attitudes towards dementia care among the participants without an increased burden of care. Future studies should examine the programme's effectiveness on the challenging behaviour of persons with dementia.
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38.
  • Nakanishi, Miharu, et al. (författare)
  • e-learning and web-based tools for psychosocial interventions addressing neuropsychiatric symptoms of dementia during the covid-19 pandemic in tokyo, japan : Quasi-experimental study
  • 2021
  • Ingår i: JMIR Medical Education. - : JMIR Publications Inc.. - 2369-3762. ; 7:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Concern has been raised that the COVID-19 pandemic and consequent social distancing measures may increase neuropsychiatric symptoms in people with dementia. Thus, we developed and delivered an e-learning training course to professional caregivers on using a web-based tool for psychosocial interventions for people with dementia. Objective: The aim of our study was to evaluate the feasibility and efficacy of an e-learning course in combination with a web-based tool in addressing neuropsychiatric symptoms of dementia. Methods: A quasi-experimental design was used in Tokyo, Japan. The e-learning course was delivered three times to professional caregivers between July and December 2020. Caregivers who completed the course assessed the level of neuropsychiatric symptoms in people with dementia using the total score from the Neuropsychiatric Inventory (NPI) via a web-based tool. The primary outcome measures were the number of caregivers who implemented follow-up NPI evaluations by March 2021 and the change in NPI scores from baseline to their most recent follow-up evaluations. As a control group, information was also obtained from professional caregivers who completed a face-to-face training course using the same web-based tool between July 2019 and March 2020. Results: A total of 268 caregivers completed the e-learning course in 2020. Of the 268 caregivers, 56 (20.9%) underwent follow-up evaluations with 63 persons with dementia. The average NPI score was significantly reduced from baseline (mean 20.4, SD 16.2) to the most recent follow-up evaluations (mean 14.3, SD 13.4). The effect size was assumed to be medium (Cohen drm [repeated measures]=0.40). The control group consisted of 252 caregivers who completed a face-to-face training course. Of the 252 caregivers, 114 (45.2%) underwent follow-up evaluations. Compared to the control group, caregivers who completed the e-learning course were significantly less likely to implement follow-up evaluations (χ2 1=52.0, P<.001). The change in NPI scores did not differ according to the type of training course (baseline-adjusted difference=-0.61, P=.69). Conclusions: The replacement of face-to-face training with e-learning may have provided professionals with an opportunity to participate in the dementia behavior analysis and support enhancement (DEMBASE) program who may not have participated in the program otherwise. Although the program showed equal efficacy in terms of the two training courses, the feasibility was suboptimal with lower implementation levels for those receiving e-learning training. Thus, further strategies should be developed to improve feasibility by providing motivational triggers for implementation and technical support for care professionals. Using online communities in the program should also be investigated.
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39.
  • Nakanishi, Miharu, et al. (författare)
  • Facilitators and barriers associated with the implementation of a Swedish psychosocial dementia care programme in Japan : a secondary analysis of qualitative and quantitative data
  • 2021
  • Ingår i: Scandinavian Journal of Caring Sciences. - : Wiley. - 0283-9318 .- 1471-6712. ; 35:2, s. 430-441
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: A psychosocial dementia care programme for challenging behaviour (DEMBASE®) was developed in collaboration with a Swedish BPSD-registry team for in-home care services use in Japan. The programme consisted of a web-based tool for the continued assessment of challenging behaviours and interdisciplinary discussion meetings. Effectiveness of the adapted programme was verified through a cluster-randomised controlled trial. The Tokyo Metropolitan Government provided municipal funding to introduce the programme into daily practice beginning in April 2018. Objectives: To investigate both facilitators and barriers associated with programme implementation. Design: A secondary analysis of qualitative and quantitative data. Settings: Data were collected in naturalistic long-term care settings from April 2018 to March 2019. Participants: A total of 138 professionals and 157 people with dementia participated in the programme. Methods: Challenging behaviour in persons with dementia was assessed by professionals using a total Neuropsychiatric Inventory score. Data on expected facilitators and barriers were extracted for qualitative analysis from a debriefing meeting between professionals. Results: Of the 157 persons with dementia, 81 (51.6%) received follow-up behavioural evaluations by March 2019. The average level of challenging behaviour was significantly reduced for 81 persons from baseline to their most recent follow-up evaluations. Facilitators included ‘programme available for care managers’, ‘visualised feedback on professionals’ work’, ‘affordable for providers and professionals’ and ‘media coverage’. Barriers included ‘professionals from different organisations’, ‘unpaid work’, ‘operation requirement for municipalities’ and ‘conflict with daily benefit-oriented framework’. Conclusions: A follow-up evaluation was not fully achieved. Further strategies to address barriers may include the development of a benefit-rewarding scheme for interdisciplinary discussion meetings, an e-learning system capable of substituting training course portions and a cross-municipality training course.
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40.
  • Nakanishi, Miharu, et al. (författare)
  • Psychosocial behaviour management programme for home-dwelling people with dementia : A cluster-randomized controlled trial
  • 2018
  • Ingår i: International Journal of Geriatric Psychiatry. - : Wiley. - 0885-6230 .- 1099-1166. ; 33:3, s. 495-503
  • Tidskriftsartikel (refereegranskat)abstract
    • Little is known about the effectiveness of a psychosocial behaviour management programme on home-dwelling people with dementia. We developed a Behaviour Analytics & Support Enhancement (BASE) programme for care managers and professional caregivers of home care services in Japan. We investigated the effects of BASE on challenging behaviour of home-dwelling people with dementia. Methods: A cluster-randomized controlled trial was conducted with home care providers from 3 different districts in Tokyo. Each provider recruited persons with dementia aged 65 years or older to receive home care in the BASE programme in August 2016. An online monitoring and assessment system was introduced to the intervention group for repeated measures of challenging behaviour with a total score of the Neuropsychiatric Inventory. Care professionals in both the intervention and control groups evaluated challenging behaviour of persons with dementia at baseline (September 2016) and follow-up (February 2017). Results: A majority of persons with dementia had Alzheimer disease (59.3%). One-hundred and forty-one persons with dementia were included in the intervention group and 142 in the control group. Multilevel modelling revealed a significant reduction in challenging behaviour in the intervention group after 6 months (mean score, 18.3 to 11.2) compared with that of the control group (11.6 to 10.8; P <.05). Conclusion: The implementation of the BASE programme resulted in a reduction of challenging behaviour of home-dwelling people with dementia. Future research should examine the long-term effects of behaviour management programmes on behaviour, nursing home placement, and hospital admission of home-dwelling people with dementia.
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41.
  • Nakanishi, Miharu, et al. (författare)
  • Time Investment for Program Implementation to Manage Neuropsychiatric Symptoms: An Observational Longitudinal Study in In-Home and Residential Care Settings
  • 2020
  • Ingår i: Journal of Alzheimer's Disease Reports. - : IOS Press. - 2542-4823. ; 4:1, s. 441-453
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: There are no studies on how the same psychosocial dementia care program is adapted to both in-home andresidential care settings.Objective: To evaluate the time investment required by professionals to implement a psychosocial dementia care programto manage neuropsychiatric symptoms.Methods: A prospective observational study design was used. The program consisted of 1) a one-day training course,2) three interdisciplinary discussion meetings in five months, and 3) a web-based tool for the continued assessment ofneuropsychiatric symptoms. Care professionals implemented the intervention in in-home (19 in-home care managementagencies and 14 multiple in-home service providers) and residential care settings (19 group homes and eight nursing homes)in Japan from October 2019 to February 2020. The level of neuropsychiatric symptoms for the participants was evaluatedusing the Neuropsychiatric Inventory (NPI: 0–144). The time investment was reported by participating professionals. A totalof 125 persons with dementia were included at baseline.Results: Neuropsychiatric symptoms were significantly decreased at the final follow-up in all types of providers (Cohen’sdrm = 0.44–0.61). The mean (SD) time required for the five-month implementation was 417.9 (219.8) minutes. There wasa mean (SD) decrease of 8.6 (14.0) points in the total NPI score among the 103 persons with completed interventions. The time investment was significantly lower in in-home care management agencies than in group homes, and lower infollow-ups than at baseline assessment.Conclusion: The program implementation may incur a substantial time investment regardless of setting. An additional benefitscheme to reward the time investment would be helpful to encourage implementation until the follow-ups.
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42.
  • Nielsen, Henrietta, et al. (författare)
  • Low levels of soluble NG2 in cerebrospinal fluid from patients with dementia with Lewy bodies
  • 2014
  • Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 40:2, s. 343-350
  • Tidskriftsartikel (refereegranskat)abstract
    • The proteoglycan NG2 plays a major role in proliferation, migration, and differentiation of pericytes and NG2 cells in the brain. We have previously reported decreased soluble NG2 (sNG2) levels in cerebrospinal fluid (CSF) from patients with Alzheimer's disease (AD) and a relationship between sNG2 and AD biomarkers in these patients. To further investigate whether alterations in sNG2 is specific to AD pathology, we measured levels of sNG2 in CSF from a patient cohort consisting of non-demented controls (n = 51), patients with Parkinson's disease (PD) (n = 61), and patients with dementia with Lewy bodies (DLB) (n = 37), two synucleinopathies whereof the latter disorder frequently coincides with amyloid-β pathology similar to AD. We found decreased sNG2 concentrations in DLB patients, but not in PD patients, compared to controls. Levels of sNG2 in controls and PD patients correlated to T-tau, P-tau, α-synuclein, and neurosin. Only one correlation, between sNG2 and neurosin, was found in DLB patients. Analysis of a second cohort consisting of controls (n = 23) and DLB patients (n = 31) showed that the result was reproducible, as lower levels of sNG2 again were found in DLB patients compared to controls. We conclude that lower levels of sNG2 levels indicate a DLB-related impact on NG2 expressing cells foremost associated with neuropathology linked to accumulation of amyloid-β and not α-synuclein.
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43.
  • Nilsson, Erik, et al. (författare)
  • Associations of central and brachial blood pressure with cognitive function : a population-based study
  • 2016
  • Ingår i: Journal of Human Hypertension. - : Nature Publishing Group. - 0950-9240 .- 1476-5527. ; 30:2, s. 95-99
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous observational studies on the association between brachial blood pressure (BP) and cognition have reported conflicting results. Central BP has been hypothesized to be more strongly related to cognition than brachial BP. The aim of this study was to assess the association between brachial as well as central BP and cognitive function, both cross-sectionally and with brachial BP measured 17 years before cognitive testing. The study population comprised 2548 individuals aged 61-85 years at follow-up (61.4% women). The cognitive tests administered were A Quick Test of cognitive speed and the Mini Mental State Examination. In fully adjusted linear regressions, small but significant cross-sectional associations were found between higher BP (systolic, diastolic and pulse pressure) and worse results on both of the cognitive tests (P-values <0.05). No significant prospective associations were found. Central BP did not show a stronger association than brachial BP did. After stratification, significant results were mainly found in the group taking BP-lowering drugs at follow-up. In summary, these findings add to existing evidence on the relationship between BP and cognition, but they do not support a superior role of central compared with brachial BP in the elderly.
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44.
  • Nilsson, Erik D., et al. (författare)
  • Copeptin, a Marker of Vasopressin, Predicts Vascular Dementia but not Alzheimer's Disease
  • 2016
  • Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 52:3, s. 1047-1053
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Copeptin is a reliable surrogate marker for the neurohypophyseal hormone vasopressin. Elevated plasma level of copeptin has been associated with cardiovascular and metabolic disease risk.OBJECTIVE: To investigate the association between copeptin and risk of dementia.METHODS: In all, 18,240 individuals from Malmö, Sweden, were examined between 2002 and 2006 (mean age 69.3 years, 69.8% men). Incident cases of dementia until 31 December 2009 were identified by linkage with the Swedish National Patient Register. To validate the dementia diagnoses, medical records as well as laboratory and neuroimaging data were carefully reviewed. Baseline level of copeptin was measured in frozen plasma in: (1) all participants who were diagnosed with dementia during follow-up, (2) a random sample of 5100 individuals of the cohort.RESULTS: During a median follow-up of 4.2 years, there were 374 incident dementia cases (age range 60-83 years at baseline): 120 were classified as Alzheimer's disease (AD), 84 as vascular dementia (VaD), and 102 as mixed dementia. In logistic regressions adjusted for cardiovascular risk factors, baseline level of copeptin predicted incident VaD (Odds ratio (OR) 1.30 per 1 SD increase in log copeptin, 95% CI 1.03-1.64). Copeptin did not predict incidence of all-cause dementia (OR 1.05, 95% CI 0.94-1.18), AD (OR 0.97, 95% CI 0.79-1.18), or mixed dementia (OR 0.85, 95% CI 0.68-1.05).CONCLUSION: Elevated plasma level of copeptin is a risk marker for incident VaD, but not for incident AD. This suggests that the vasopressin hormonal system might be involved in the development of VaD.
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45.
  • Nilsson, Erik D., et al. (författare)
  • No independent association between pulse wave velocity and dementia : a population-based, prospective study.
  • 2017
  • Ingår i: Journal of Hypertension. - : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598. ; 35:12, s. 2462-2467
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Carotid-femoral pulse wave velocity (CFPWV), a marker of aortic stiffness, has been associated with cognitive test results and markers of cerebral small vessel disease, but its association with dementia has not been studied in detail. Our aim was to assess the association of CFPWV with prevalent and incident dementia in a large population-based study.METHODS: In total, CFPWV was measured in 3056 participants of the Malmö Diet and Cancer study 2007-2012 (age range 61-85 years). Individuals scoring below preset cut-offs on cognitive screening tests were thoroughly evaluated for prevalent dementia. Also, dementia diagnoses were retrieved from the Swedish National Patient Register up until 31 December 2014, and then validated through medical records and neuroimaging findings.RESULTS: We identified 159 cases of dementia, of which 57 were classified as prevalent, and 102 as incident during a median follow-up of 4.6 years. In fully adjusted logistic regressions, CFPWV was not associated with prevalent all-cause dementia (odds ratio 0.95 per 1 m/s increase in CFPWV, 95% confidence interval 0.83-1.08), and it did not predict incident all-cause dementia (odds ratio 1.00, 95% confidence interval 0.91-1.09). Neither was CFPWV associated with subtypes of dementia (Alzheimer's disease, vascular dementia, mixed dementia), although the number of cases in subgroups were low.CONCLUSION: No independent association was found between CFPWV and dementia. It remains a matter of debate why CFPWV repeatedly has been associated with cognitive test results and markers of cerebral small vessel disease, but not with dementia.
  •  
46.
  • Nilsson, Erik, et al. (författare)
  • Nonlinear association between pulse wave velocity and cognitive function : a population-based study
  • 2014
  • Ingår i: Journal of Hypertension. - : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598. ; 32:11, s. 2152-2157
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Arterial stiffness has been hypothesized to contribute to cognitive decline. However, previous studies have reported inconsistent results. The aim of this cross-sectional study was to investigate the association between carotid-femoral pulse wave velocity (cfPWV), a marker of arterial stiffness, and cognitive function.METHODS: The study population comprised 2637 individuals from the population-based Malmö Diet and Cancer Study (mean age 72.1 years, 60.8% women). During the follow-up examinations between 2007 and 2012, cfPWV and results on the a quick test of cognitive speed (AQT) and Mini Mental State Examination (MMSE) cognitive tests were measured.RESULTS: After adjustments for demographics and traditional cardiovascular risk factors, a linear association was found between cfPWV and AQT (B = 0.37; P = 0.039). On the basis of hypothesis that individuals with high cfPWV values have worse cognitive function than can be inferred from a linear association, cfPWV was dichotomized at the 90th percentile (the binary variable denoted cfPWV >13.8). When cfPWV >13.8 was added to the model, the linear association between continuous cfPWV and AQT disappeared (B = -0.08; P = 0.72), but cfPWV >13.8 was highly significant (B = 4.81; P = 0.004). In the adjusted model with MMSE as outcome variable, cfPWV >13.8 also reached a statistically significant effect.CONCLUSION: Arterial stiffness was inversely associated with cognitive function in a nonlinear fashion, with individuals in the top decentile of cfPWV explaining the association. Results from linear regressions should thus be interpreted with caution because, even when statistical significance is reached, they can be explained by pronounced nonlinearity.
  •  
47.
  • Nutu, Magdalena, et al. (författare)
  • Evaluation of the Cerebrospinal Fluid Amyloid-beta(1-42)/Amyloid-beta(1-40) Ratio Measured by Alpha-LISA to Distinguish Alzheimer's Disease from Other Dementia Disorders
  • 2013
  • Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 36:1-2, s. 99-110
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The well-established core biomarkers used to identify Alzheimer's disease (AD) overlap with other dementia disorders such as dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD). This study aimed to evaluate whether the cerebrospinal fluid (CSF) amyloid-beta (A beta)(1-42)/A beta(1-40) ratio, measured by a novel method, could improve the differential diagnosis of AD, DLB and PDD. Method: CSF levels of A beta(1-40) and A beta(1-42) in patients with PDD, DLB, AD, Parkinson's disease and controls were analyzed using an amplified luminescent proximity homogenous immunoassay along with conventional immunoassays. Results: The CSF A beta(1-42)/A beta(1-40) ratio increased discrimination of AD from PDD and DLB compared with either of the two A beta biomarkers individually. Conclusion: The use of the A beta(1-42)/A beta(1-40) ratio could improve the differentiation of AD from PDD and DLB. (C) 2013 S. Karger AG, Basel
  •  
48.
  • Nutu, Magdalena, 1967, et al. (författare)
  • Evaluation of the Cerebrospinal Fluid Amyloid-β1-42/Amyloid-β1-40 Ratio Measured by Alpha-LISA to Distinguish Alzheimer's Disease from Other Dementia Disorders.
  • 2013
  • Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 36:1-2, s. 99-110
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The well-established core biomarkers used to identify Alzheimer's disease (AD) overlap with other dementia disorders such as dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD). This study aimed to evaluate whether the cerebrospinal fluid (CSF) amyloid-β (Aβ)1-42/Aβ1-40 ratio, measured by a novel method, could improve the differential diagnosis of AD, DLB and PDD. Method: CSF levels of Aβ1-40 and Aβ1-42 in patients with PDD, DLB, AD, Parkinson's disease and controls were analyzed using an amplified luminescent proximity homogenous immunoassay along with conventional immunoassays. Results: The CSF Aβ1-42/Aβ1-40 ratio increased discrimination of AD from PDD and DLB compared with either of the two Aβ biomarkers individually. Conclusion: The use of the Aβ1-42/Aβ1-40 ratio could improve the differentiation of AD from PDD and DLB. © 2013 S. Karger AG, Basel.
  •  
49.
  • Nägga, Katarina, 1962- (författare)
  • Aspects on clinical diagnosis of dementia, with focus on biological markers
  • 2004
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The clinical dementia diagnosis has become more complex with increasing knowledge of the heterogeneity of the disorder and its different aetiological aspects. A clinical dementia population and a control group were investigated with the following aims: I. To study the CSF levels of tau phosphorylated at threonine 181 (P-tau), total tau (T-tau) and ß-amyloid1-42 (Aß42) in the different diagnoses. II. To study associations between dementia disorder, cobalamin and/or folate deficiency, and gastritis. III. To study the presence and severity of CT brain changes in different dementia diagnoses. IV. To investigate to what extent different biomarkers and disease history contribute to the diagnostics of clinical dementia.I. CSF Levels of P-tau, T-tau and Aß42 were analysed with ELISA methods. Elevated CSF levels of P-tau were found in probable Alzheimer's disease (AD) patients compared with cognitively non-disturbed controls. Increased CSF T-tau, and decreased levels of Aß42 were found in both AD, mixed type of dementia, and vascular dementia (VaD) patients compared with the controls. Increased P-tau levels were more specific for AD pathology, but there was still an overlap with the controls, mixed dementia and VaD patients.II. Serological markers for cobalamin and folate deficiencies, and for gastritis were assessed in patients with different dementia diagnoses. Hyperhomocysteinaemia were commonly found in dementia without predominance in any of the investigated categories. Low levels of serum cobalamin or blood folate rarely reflected the elevated Hey levels. A lack of association between serological markers for cobalamin and folate deficiencies and for gastritis was demonstrated.III. A protocol for evaluation of the CT scans was used. Atrophy on the CT scans, although common in dementia, is an unspecific fmding in dementia of different backgrounds. White-matter changes and lacunes, indicating small-vessel disease, were common in dementia of different aetiologies. Dementia of mixed-type pathology was underestimated. More distinct criteria for this diagnostic category are warranted.IV. Partial Least Squares Discriminant Analysis (PLS-DA) was used on a large number of variables covering cognitive and biological markers and disease history. There were good discriminations of subgroups of dementia from the controls. However, the included variables were not able to distinguish between the investigated groups, indicating that several clinical parameters used in diagnosing dementia are in fact observed across different subtypes of dementia.It is concluded that there are no known biomarkers available that can provide a precise differential diagnosis of dementia. The clinical dementia diagnosis must still be based on a combination of a careful disease history, evaluation of risk factors, symptomatology, clinical findings, neurocognitive tests, blood analysis and other available methods such as CT and CSF markers.
  •  
50.
  • Nägga, Katarina, 1962-, et al. (författare)
  • 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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