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1.
  • Andersson, Christin, et al. (författare)
  • Differential CSF biomarker levels in APOE-epsilon4-positive and -negative patients with memory impairment.
  • 2007
  • Ingår i: Dementia and geriatric cognitive disorders. - Basel : S. Karger AG. - 1420-8008 .- 1421-9824. ; 23:2, s. 87-95
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To investigate the relationships between episodic memory, APOE genotype, CSF markers (total tau, T-tau; phospho-tau, P-tau; beta-amyloid, Abeta42) and longitudinal cognitive decline. METHODS: 124 memory clinic patients were retrospectively divided into 6 groups based on (i) episodic memory function (Rey Auditory Verbal Learning Test, RAVLT): severe, moderate or no impairment (SIM, MIM or NIM), and (ii) APOE genotype (epsilon4+ or epsilon4-). CSF marker levels and cognitive decline were compared across groups. RESULTS: Episodic memory function, according to RAVLT scores, was significantly correlated with CSF marker levels only among epsilon4+ subjects and not among epsilon4- subjects. When comparing the 6 subgroups, SIM epsilon4+ and MIM epsilon4+ groups showed significantly lower Abeta42 levels than the other groups. T-tau and P-tau levels were significantly increased in SIM epsilon4+ when compared to all the other groups, including the SIM epsilon4- group. However, both SIM epsilon4+ and SIM epsilon4- declined cognitively during the follow-up. CONCLUSION: It remains to be determined whether APOE genotype affects the expression of biomarkers in CSF, or whether the different biomarker patterns reflect different types of disease processes in patients with progressive cognitive dysfunction.
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2.
  • Andersson, Christin, et al. (författare)
  • Identifying patients at high and low risk of cognitive decline using Rey Auditory Verbal Learning Test among middle-aged memory clinic outpatients
  • 2006
  • Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 21:4, s. 251-259
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To investigate whether application of cutoff levels in an episodic memory test (Rey Auditory Verbal Learning Test, RAVLT) is a useful method for identifying patients at high and low risk of cognitive decline and subsequent dementia. METHODS: 224 patients with memory complaints (mean age = 60.7 years, mean MMSE = 28.2) followed-up at a memory clinic over approximately 3 years were assigned retrospectively to one of three memory groups from their baseline results in RAVLT [severe (SIM), moderate (MIM) or no impairment (NIM)]. These groups were investigated regarding cognitive decline. RESULTS: Patients assigned to SIM showed significant cognitive decline and progressed to dementia at a high rate, while a normal performance in RAVLT at baseline (NIM) predicted normal cognition after 3 years. Patients with MIM constituted a heterogeneous group; some patients deteriorated cognitively, while the majority remained stable or improved. CONCLUSIONS: The application of cutoff levels in RAVLT at baseline showed that patients with severely impaired RAVLT performance were at a high risk of cognitive decline and progression to dementia, while patients with normal RAVLT results did not show cognitive decline during 3 years. Furthermore, the initial degree of memory impairment was decisive in the cognitive prognosis 3 years later.
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3.
  • Andersson, Christin, et al. (författare)
  • Increasing CSF phospho-tau levels during cognitive decline and progression to dementia
  • 2008
  • Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 29:10, s. 1466-1473
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Little is known about longitudinal changes of cerebrospinal fluid (CSF) biomarkers during cognitive decline in neurodegenerative disease progression. OBJECTIVE: To investigate longitudinal changes in CSF biomarkers--total-tau (T-tau), phospho-tau (P-tau) and beta-amyloid (Abeta42)--during cognitive decline. METHODS: Forty memory clinic patients (47.5% females), aged 61.3+/-7.6 (S.D.) years, non-demented at baseline, underwent lumbar puncture and neuropsychological testing at two occasions. Baseline mean MMSE-score was 28.3+/-1.8. Patients were divided into three groups based on baseline memory functioning; severely impaired (SIM), moderately impaired (MIM) and no impairment (NIM). RESULTS: There was a significant increase in P-tau in the SIM-group during follow-up, while P-tau in MIM and NIM did not change. Eighty-three percent of the SIM-patients converted to dementia (80% AD), while most MIM- and NIM-patients remained non-demented. T-tau- and Abeta42-levels did not change in any of the memory groups during follow-up. CONCLUSION: Increasing P-tau levels during cognitive decline and conversion to dementia suggest that P-tau may be useful as a longitudinal marker of the neurodegenerative process.
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4.
  • Eriksdotter-Jönhagen, Maria, et al. (författare)
  • Encapsulated cell biodelivery of nerve growth factor to the Basal forebrain in patients with Alzheimer's disease.
  • 2012
  • Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 33:1, s. 18-28
  • Tidskriftsartikel (refereegranskat)abstract
    • Degeneration of cholinergic neurons in the basal forebrain correlates with cognitive decline in patients with Alzheimer's disease (AD). Targeted delivery of exogenous nerve growth factor (NGF) has emerged as a potential AD therapy due to its regenerative effects on the basal forebrain cholinergic neurons in AD animal models. Here we report the results of a first-in-man study of encapsulated cell (EC) biodelivery of NGF to the basal forebrain of AD patients with the primary objective to explore safety and tolerability.
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5.
  • Ferreira, Daniel, et al. (författare)
  • Brain changes in Alzheimer's disease patients with implanted encapsulated cells releasing nerve growth factor
  • 2015
  • Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 43, s. 1059-1072
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2015-IOS Press and the authors. New therapies with disease-modifying effects are urgently needed for treating Alzheimer's disease (AD). Nerve growth factor (NGF) protein has demonstrated regenerative and neuroprotective effects on basal forebrain cholinergic neurons in animal studies. In addition, AD patients treated with NGF have previously shown improved cognition, EEG activity, nicotinic binding, and glucose metabolism. However, no study to date has analyzed brain atrophy in patients treated with NGF producing cells. In this study we present MRI results of the first clinical trial in patients with AD using encapsulated NGF biodelivery to the basal forebrain. Six AD patients received the treatment during twelve months. Patients were grouped as responders and non-responders according to their twelve-months change in MMSE. Normative values were created from 131 AD patients from ADNI, selecting 36 age-and MMSE-matched patients for interpreting the longitudinal changes in MMSE and brain atrophy. Results at baseline indicated that responders showed better clinical status and less pathological levels of cerebrospinal fluid (CSF) Aβ1-42. However, they showed more brain atrophy, and neuronal degeneration as evidenced by higher CSF levels of T-tau and neurofilaments. At follow-up, responders showed less brain shrinkage and better progression in the clinical variables and CSF biomarkers. Noteworthy, two responders showed less brain shrinkage than the normative ADNI group. These results together with previous evidence supports the idea that encapsulated biodelivery of NGF might have the potential to become a new treatment strategy for AD with both symptomatic and disease-modifying effects.
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6.
  • Garcia-Ptacek, Sara, et al. (författare)
  • Body-Mass Index and Mortality in Incident Dementia : A Cohort Study on 11,398 Patients From SveDem, the Swedish Dementia Registry
  • 2014
  • Ingår i: Journal of the American Medical Directors Association. - : Elsevier BV. - 1525-8610 .- 1538-9375. ; 15:6, s. 447.e1-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Body mass index (BMI) is used worldwide as an indirect measure of nutritional status and has been shown to be associated with mortality. Controversy exists over the cut points associated with lowest mortality, particularly in older populations. In patients suffering from dementia, information on BMI and mortality could improve decisions about patient care. Objectives: The objective was to explore the association between BMI and mortality risk in an incident dementia cohort. Design: Cohort study based on SveDem, the Swedish Quality Dementia Registry; 2008-2011. Setting: Specialist memory clinics, Sweden. Participants: A total of 11,398 patients with incident dementia with data on BMI (28,190 person-years at risk for death). Main outcome measures: Hazard ratios and 95% confidence intervals for mortality associated with BMI were calculated, controlling for age, sex, dementia type, results from Mini-Mental State Examination, and number of medications. BMI categories and linear splines were used. Results: Higher BMI was associated with decreased mortality risk, with all higher BMI categories showing reduced risk relative to patients with BMI of 18.5 to 22.9 kg/m(2), whereas underweight patients (BMI <18.5 kg/m(2)) displayed excess risk. When explored as splines, increasing BMI was associated with decreased mortality risk up to BMI of 30.0 kg/m(2). Each point increase in BMI resulted in an 11% mortality risk reduction in patients with BMI less than 22.0 kg/m(2), 5% reduction when BMI was 22.0 to 24.9 kg/m(2), and 3% risk reduction among overweight patients. Results were not significant in the obese weight range. Separate examination by sex revealed a reduction in mortality with increased BMI up to BMI 29.9 kg/m(2) for men and 24.9 kg/m(2) for women. Conclusion: Higher BMI at the time of dementia diagnosis was associated with a reduction in mortality risk up to and including the overweight category for the whole cohort and for men, and up to the normal weight category for women.
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9.
  • Garcia-Ptacek, Sara, et al. (författare)
  • Mortality Risk after Dementia Diagnosis by Dementia Type and Underlying Factors : A Cohort of 15,209 Patients based on the Swedish Dementia Registry
  • 2014
  • Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 41:2, s. 467-477
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Knowledge on survival in dementia is crucial for patients and public health planning. Most studies comparing mortality risk included few different dementia diagnoses. Objectives: To compare mortality risk in the most frequent dementia disorders in a large cohort of patients with an incident diagnosis, adjusting for potential confounding factors. Methods: 15,209 patients with dementia from the national quality database, Swedish Dementia Registry (SveDem), diagnosed in memory clinics from 2008 to 2011, were included in this study. The impact of age, gender, dementia diagnosis, baseline Mini-Mental State Examination (MMSE), institutionalization, coresidency, and medication on survival after diagnosis were examined using adjusted hazard ratios (HR) with 95% confidence intervals (CI). Results: During a mean follow-up of 2.5 years, 4,287 deaths occurred, with 114 (95% CI 111-117) deaths/1,000 person-years. Adjusted HR of death for men was 1.56 (95% CI 1.46-1.66) compared to women. Low MMSE, institutionalization, and higher number of medications were associated with higher HR of death. All dementia diagnoses demonstrated higher HR compared to Alzheimer's disease, with vascular dementia presenting the highest crude HR. After adjusting, frontotemporal dementia had the highest risk with a HR of 1.91 (95% CI 1.52-2.39), followed by Lewy body dementia (HR 1.64; 95% CI 1.39-1.95), vascular dementia (HR 1.55; 95% CI 1.42-1.69), Parkinson's disease dementia (HR 1.47; 95% CI 1.17-1.84), and mixed Alzheimer's disease and vascular dementia (HR 1.32; 95% CI 1.22-1.44). Conclusion: Worse cognition, male gender, higher number of medications, institutionalization, and age were associated with increased death risk after dementia diagnosis. Adjusted risk was lowest in Alzheimer's disease patients and highest in frontotemporal dementia subjects.
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10.
  • Karami, Azadeh, et al. (författare)
  • Changes in CSF cholinergic biomarkers in response to cell therapy with NGF in patients with Alzheimer's disease
  • 2015
  • Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:11, s. 1316-1328
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: The extensive loss of central cholinergic functions in Alzheimer's disease (AD) brain is linked to impaired nerve growth factor (NGF) signaling. The cardinal cholinergic biomarker is the acetylcholine synthesizing enzyme, choline acetyltransferase (ChAT), which has recently been found in cerebrospinal fluid (CSF). The purpose of this study was to see if EC-NGF therapy will alter CSF levels of cholinergic biomarkers, ChAT, and acetylcholinesterase. Method: Encapsulated cell implants releasing NGF (EC-NGF) were surgically implanted bilaterally in the basal forebrain of six AD patients for 12 months and cholinergic markers in CSF were analyzed. Results: Activities of both enzymes were altered after 12 months. In particular, the activity of soluble ChAT showed high correlation with cognition, CSF tau and amyloid-beta, in vivo cerebral glucose utilization and nicotinic binding sites, and morphometric and volumetric magnetic resonance imaging measures. Discussion: A clear pattern of association is demonstrated showing a proof-of-principle effect on CSF cholinergic markers, suggestive of a beneficial EC-NGF implant therapy.
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11.
  • Mak, Jonathan K. L., et al. (författare)
  • Development of an Electronic Frailty Index for Hospitalized Older Adults in Sweden
  • 2022
  • Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press. - 1079-5006 .- 1758-535X. ; 77:11, s. 2311-2319
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Frailty assessment in the Swedish health system relies on the Clinical Frailty Scale (CFS), but it requires training, in-person evaluation, and is often missing in medical records. We aimed to develop an electronic frailty index (eFI) from routinely collected electronic health records (EHRs) and assess its association with adverse outcomes in hospitalized older adults. Methods EHRs were extracted for 18 225 patients with unplanned admissions between 1 March 2020 and 17 June 2021 from 9 geriatric clinics in Stockholm, Sweden. A 48-item eFI was constructed using diagnostic codes, functioning and other health indicators, and laboratory data. The CFS, Hospital Frailty Risk Score, and Charlson Comorbidity Index were used for comparative assessment of the eFI. We modeled in-hospital mortality and 30-day readmission using logistic regression; 30-day and 6-month mortality using Cox regression; and length of stay using linear regression. Results Thirteen thousand one hundred and eighty-eight patients were included in analyses (mean age 83.1 years). A 0.03 increment in the eFI was associated with higher risks of in-hospital (odds ratio: 1.65; 95% confidence interval: 1.54-1.78), 30-day (hazard ratio [HR]: 1.43; 1.38-1.48), and 6-month mortality (HR: 1.34; 1.31-1.37) adjusted for age and sex. Of the frailty and comorbidity measures, the eFI had the highest area under receiver operating characteristic curve for in-hospital mortality of 0.813. Higher eFI was associated with longer length of stay, but had a rather poor discrimination for 30-day readmission. Conclusions An EHR-based eFI has robust associations with adverse outcomes, suggesting that it can be used in risk stratification in hospitalized older adults.
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12.
  • Mak, Jonathan K. L., et al. (författare)
  • Two Years with COVID-19 : The Electronic Frailty Index Identifies High-Risk Patients in the Stockholm GeroCovid Study
  • 2023
  • Ingår i: Gerontology. - : S. Karger. - 0304-324X .- 1423-0003. ; 69:4, s. 396-405
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Frailty, a measure of biological aging, has been linked to worse COVID-19 outcomes. However, as the mortality differs across the COVID-19 waves, it is less clear whether a medical record-based electronic frailty index (eFI) that we have previously developed for older adults could be used for risk stratification in hospitalized COVID-19 patients. Objectives: The aim of the study was to examine the association of frailty with mortality, readmission, and length of stay in older COVID-19 patients and to compare the predictive accuracy of the eFI to other frailty and comorbidity measures. Methods: This was a retrospective cohort study using electronic health records (EHRs) from nine geriatric clinics in Stockholm, Sweden, comprising 3,980 COVID-19 patients (mean age 81.6 years) admitted between March 2020 and March 2022. Frailty was assessed using a 48-item eFI developed for Swedish geriatric patients, the Clinical Frailty Scale, and the Hospital Frailty Risk Score. Comorbidity was measured using the Charlson Comorbidity Index. We analyzed in-hospital mortality and 30-day readmission using logistic regression, 30-day and 6-month mortality using Cox regression, and the length of stay using linear regression. Predictive accuracy of the logistic regression and Cox models was evaluated by area under the receiver operating characteristic curve (AUC) and Harrell's C-statistic, respectively. Results: Across the study period, the in-hospital mortality rate decreased from 13.9% in the first wave to 3.6% in the latest (Omicron) wave. Controlling for age and sex, a 10% increment in the eFI was significantly associated with higher risks of in-hospital mortality (odds ratio = 2.95; 95% confidence interval = 2.42-3.62), 30-day mortality (hazard ratio [HR] = 2.39; 2.08-2.74), 6-month mortality (HR = 2.29; 2.04-2.56), and a longer length of stay (beta-coefficient = 2.00; 1.65-2.34) but not with 30-day readmission. The association between the eFI and in-hospital mortality remained robust across the waves, even after the vaccination rollout. Among all measures, the eFI had the best discrimination for in-hospital (AUC = 0.780), 30-day (Harrell's C = 0.733), and 6-month mortality (Harrell's C = 0.719). Conclusion: An eFI based on routinely collected EHRs can be applied in identifying high-risk older COVID-19 patients during the continuing pandemic.
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13.
  • Abzhandadze, Tamar, et al. (författare)
  • COVID-19 Pandemic and Stroke Care in Patients With Dementia Compared to Other Stroke Patients
  • 2024
  • Ingår i: Journal of the American Medical Directors Association. - : Lippincott Williams & Wilkins. - 1525-8610 .- 1538-9375. ; 25:7
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: The primary objective of this study was to examine the impact of the COVID-19 pandemic on the quality of stroke care for patients with preexisting dementia, compared with patients who had only stroke. The secondary aim was to investigate how the quality of stroke care changed during the pandemic and post-pandemic periods compared with the pre-pandemic period in patients with preexisting dementia.DESIGN: A registry-based, nationwide cohort study in Sweden.SETTING AND PARTICIPANTS: We included patients with a first stroke between 2019 and 2022, both with and without dementia. The study periods were defined as follows: pre-pandemic (January 1, 2019, to February 29, 2020), COVID-19 pandemic (March 1, 2020, to February 24, 2022), and post-COVID-19 pandemic period (February 25, 2022, to September 19, 2022). The outcomes examined were the following quality indicators of stroke care, suggested by the national guideline of stroke care in Sweden: stroke admission site, performance of swallowing assessment, reperfusion treatment, assessment for rehabilitation, and early supported discharge.METHODS: The associations were studied through group comparisons and binary logistic regressions.RESULTS: Of the 21,795 stroke patients, 1357 had documented preexisting dementia, and 20,438 had stroke without a dementia diagnosis. Throughout all study periods, a significantly lower proportion of stroke patients with preexisting dementia, compared with stroke-only patients, received reperfusion treatment, assessments for rehabilitation, and early supported discharge from stroke units. In the subgroup of stroke patients with preexisting dementia, no significant associations were found regarding the quality indicators of stroke care before, during, and after the pandemic.CONCLUSIONS AND IMPLICATIONS: Disparities in quality of stroke care were observed between stroke patients with preexisting dementia and those with only stroke during the COVID-19 pandemic. However, there were no statistically significant differences in stroke care for patients with dementia across the pandemic.
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14.
  • Axenhus, Michael, et al. (författare)
  • Changes in dementia diagnoses in Sweden during the COVID-19 pandemic
  • 2022
  • Ingår i: BMC Geriatrics. - : BioMed Central. - 1471-2318. ; 22:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: The COVID-19 pandemic has caused large disruptions to healthcare systems. Refocus on COVID-19 related care might have contributed to indirect effects on other healthcare areas. Care focused on acute conditions have been negatively affected although research into the effects on chronic and care intensive patient groups such as patients with dementia diseases is lacking. In this study we evaluated dementia diagnosis trends in Sweden during 2015–2020 according to International Classification of Disease version 10 coding of common dementia diseases.Methods: Regional and national statistics in the form of International Classification of Disease version 10 coding, COVID-19 incidence, mortality data, and population census data were collected from the National Institute of Health and Welfare. Logistic regression analysis was performed to identify trends of dementia diagnosis during 2015–2020. Correlation test was performed between COVID-19 incidence, mortality rates, and dementia coding.Results: Dementia diagnosis incidence has been declining since 2015 and further decline was noted in many regions in Sweden during 2020. As COVID-19 incidence increased, fewer cases of dementia were diagnosed, a decrease that differentially impacted women and those who were advanced in age.Conclusions: Dementia diagnosis incidence in Sweden has been on a decline since 2015. The COVID-19 pandemic caused a further larger decline in dementia diagnosis incidence during 2020. COVID-19 incidence, but not mortality, was associated with decrease in dementia diagnosis incidence. There might be a large number of undiagnosed patients with dementia and healthcare reforms should be enacted to address this. Women and elderly are particularly vulnerable groups.
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15.
  • Bergman, Mette, et al. (författare)
  • Overall and domain-specific life satisfaction when living with familial Alzheimer's disease risk : A quantitative approach.
  • 2017
  • Ingår i: Nursing and Health Sciences. - : Wiley. - 1441-0745 .- 1442-2018. ; 19:4, s. 452-458
  • Tidskriftsartikel (refereegranskat)abstract
    • In this study, we explored life satisfaction and sense of coherence in relation to biopsychosocial variables in individuals at risk for the development of familial Alzheimer's disease. Forty nine individuals (response rate: 96%) were interviewed. Life satisfaction was found to be high for the majority of participants. Those who were older than the expected age of onset of disease, those <6 years' inclusion in the Familial Alzheimer's disease biomarker study, and males tended to experience positive psychological health. Sense of coherence was positively associated with satisfaction with life as a whole, psychological health, vocation, and economy. Women seem to be more vulnerable than men, and attention should be given to those who have not passed the age of expected symptom onset. Early and recurrent counseling and psychosocial support were found to be essential. Issues related to vocation and economy are areas of concern, and are closely associated with sense of coherence, life satisfaction, and psychological health. This study emphasizes the importance of professional teams working together with the patient and their families.
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16.
  • Bergman, Mette, et al. (författare)
  • The meaning of living close to a person with Alzheimer disease
  • 2016
  • Ingår i: Medicine, Health care and Philosophy. - : Springer Science and Business Media LLC. - 1386-7423 .- 1572-8633. ; 19:3, s. 341-349
  • Tidskriftsartikel (refereegranskat)abstract
    • Only a few studies explore the lifeworld of the spouses of persons affected by early-onset Alzheimer disease (AD). The aim of this study is to explore the lifeworld of spouses when their partners are diagnosed with AD, focusing on spouses' lived experience. The study employs an interpretative phenomenological framework. Ten in-depth interviews are performed. The results show that spouses' lifeworld changes with the diagnosis. They experience an imprisoned existence in which added obligations, fear, and worry keep them trapped at home, both physically and mentally. In their longing for freedom, new strategies and attitudes helps the spouses to create an extended "lived space" with their partner. The findings stress the importance of paying attention to the lifeworld of spouses and making clinical recommendations on this basis. Most importantly, the lifeworld perspective has implications for how we understand what care is. We hope to challenge all different healthcare professionals and invite them to discuss the deep meaning of care and the definition of being professional in encounters with vulnerable others from a lifeworld perspective.
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17.
  • Bocchetta, Martina, et al. (författare)
  • The use of biomarkers for the etiologic diagnosis of MCI in Europe: An EADC survey.
  • 2015
  • Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5279 .- 1552-5260. ; 11:2, s. 195-206
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigated the use of Alzheimer's disease (AD) biomarkers in European Alzheimer's Disease Consortium centers and assessed their perceived usefulness for the etiologic diagnosis of mild cognitive impairment (MCI). We surveyed availability, frequency of use, and confidence in diagnostic usefulness of markers of brain amyloidosis (amyloid positron emission tomography [PET], cerebrospinal fluid [CSF] Aβ42) and neurodegeneration (medial temporal atrophy [MTA] on MR, fluorodeoxyglucose positron emission tomography [FDG-PET], CSF tau). The most frequently used biomarker is visually rated MTA (75% of the 37 responders reported using it "always/frequently") followed by CSF markers (22%), FDG-PET (16%), and amyloid-PET (3%). Only 45% of responders perceive MTA as contributing to diagnostic confidence, where the contribution was rated as "moderate". Seventy-nine percent of responders felt "very/extremely" comfortable delivering a diagnosis of MCI due to AD when both amyloid and neuronal injury biomarkers were abnormal (P < .02 versus any individual biomarker). Responders largely agreed that a combination of amyloidosis and neuronal injury biomarkers was a strongly indicative AD signature.
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18.
  • Cedres, Nira, et al. (författare)
  • Association of Cerebrovascular and Alzheimer Disease Biomarkers With Cholinergic White Matter Degeneration in Cognitively Unimpaired Individuals
  • 2022
  • Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 99:15, s. e1619-e1629
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Objectives Several pathologic processes might contribute to the degeneration of the cholinergic system in aging. We aimed to determine the contribution of amyloid, tau, and cerebrovascular biomarkers toward the degeneration of cholinergic white matter (WM) projections in cognitively unimpaired individuals.Methods The contribution of amyloid and tau pathology was assessed through CSF levels of the Aβ42/40 ratio and phosphorylated tau (p-tau). CSF Aβ38 levels were also measured. Cerebrovascular pathology was assessed using automatic segmentations of WM lesions (WMLs) on MRI. Cholinergic WM projections (i.e., cingulum and external capsule pathways) were modeled using tractography based on diffusion tensor imaging data. Sex and APOE ε4 carriership were also included in the analysis as variables of interest.Results We included 203 cognitively unimpaired individuals from the H70 Gothenburg Birth Cohort Studies (all individuals aged 70 years, 51% female). WM lesion burden was the most important contributor to the degeneration of both cholinergic pathways (increase in mean square error [IncMSE] = 98.8% in the external capsule pathway and IncMSE = 93.3% in the cingulum pathway). Levels of Aβ38 and p-tau also contributed to cholinergic WM degeneration, especially in the external capsule pathway (IncMSE = 28.4% and IncMSE = 23.4%, respectively). The Aβ42/40 ratio did not contribute notably to the models (IncMSE<3.0%). APOE ε4 carriers showed poorer integrity in the cingulum pathway (IncMSE = 21.33%). Women showed poorer integrity of the external capsule pathway (IncMSE = 21.55%), which was independent of amyloid status as reflected by the nonsignificant differences in integrity when comparing amyloid-positive vs amyloid-negative women participants (T201 = −1.55; p = 0.123).Discussion In cognitively unimpaired older individuals, WMLs play a central role in the degeneration of cholinergic pathways. Our findings highlight the importance of WM lesion burden in the elderly population, which should be considered in the development of prevention programs for neurodegeneration and cognitive impairment.
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19.
  • Cermakova, Pavla, et al. (författare)
  • Cardiovascular Diseases in similar to 30,000 Patients in the Swedish Dementia Registry
  • 2015
  • Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 48:4, s. 949-958
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Cardiovascular diseases are leading causes of death and patients with dementia are often affected by them. Objective: Investigate associations of cardiovascular diseases with different dementia disorders and determine their impact on mortality. Methods: This study included 29,630 patients from the Swedish Dementia Registry (mean age 79 years, 59% women) diagnosed with Alzheimer's disease (AD), mixed dementia, vascular dementia, dementia with Lewy bodies (DLB), Parkinson's disease dementia (PDD), frontotemporal dementia (FTD), or unspecified dementia. Records of cardiovascular diseases come from the Swedish National Patient Register. Multinomial logistic regression and cox proportional hazard models were applied. Results: Compared to AD, we found a higher burden of all cardiovascular diseases in mixed and vascular dementia. Cerebrovascular diseases were more associated with DLB than with AD. Diabetes mellitus was less associated with PDD and DLB than with AD. Ischemic heart disease was less associated with PDD and FTD than AD. All cardiovascular diseases predicted death in patients with AD, mixed, and vascular dementia. Only ischemic heart disease significantly predicted death in DLB patients (HR = 1.72; 95% CI = 1.16-2.55). In PDD patients, heart failure and diabetes mellitus were associated with a higher risk of death (HR = 3.06; 95% CI = 1.74-5.41 and HR = 3.44; 95% CI = 1.31-9.03). In FTD patients, ischemic heart disease and atrial fibrillation or flutter significantly predicted death (HR = 2.11; 95% CI = 1.08-4.14 and HR= 3.15; 95% CI = 1.60-6.22, respectively). Conclusion: Our study highlights differences in the occurrence and prognostic significance of cardiovascular diseases in several dementia disorders. This has implications for the care and treatment of the different dementia disorders.
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20.
  • Cermakova, Pavla, et al. (författare)
  • Cardiovascular medication burden in dementia disorders : a nationwide study of 19,743 dementia patients in the Swedish Dementia Registry
  • 2014
  • Ingår i: Alzheimer's research & therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 6:3, s. 34-
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Administration of several cardiovascular drugs has an effect on dementia. We aimed to investigate whether there are differences in the use of cardiovascular medication between different dementia disorders. Methods: We obtained information about dementia patients from the Swedish Dementia Registry. Patients were diagnosed with one of these dementia disorders: Alzheimer's disease (n = 8,139), mixed dementia (n = 5,203), vascular dementia (n = 4,982), Lewy body dementia (n = 605), frontotemporal dementia (n = 409) and Parkinson's disease dementia (n = 405). Multivariate logistic regression analysis was performed to investigate the association between use of cardiovascular medication and dementia disorders, after adjustment for age, gender, living alone, cognitive status and total number of drugs (a proxy for overall co-morbidity). Results: Seventy percent of all the dementia patients used cardiovascular medication. Use of cardiovascular drugs is common in patients with vascular and mixed dementia. Male gender, higher age, slightly better cognitive status and living with another person was associated with use of cardiovascular medication. Conclusions: Cardiovascular medication is used extensively across dementia disorders and particularly in vascular and mixed dementia. Future research should investigate the tolerability and effectiveness of these drugs in the different dementia disorders.
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21.
  • Cermakova, Pavla, et al. (författare)
  • Heart failure and dementia : survival in relation to types of heart failure and different dementia disorders
  • 2015
  • Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 17:6, s. 612-619
  • Tidskriftsartikel (refereegranskat)abstract
    • AimsHeart failure (HF) and dementia frequently coexist, but little is known about their types, relationships to each other and prognosis. The aims were to (i) describe patients with HF and dementia, assess (ii) the proportion of specific dementia disorders in types of HF based on ejection fraction and (iii) the prognostic role of types of HF and dementia disorders. Methods and resultsThe Swedish Heart Failure Registry (RiksSvikt) and The Swedish Dementia Registry (SveDem) were record-linked. Associations between dementia disorders and HF types were assessed with multinomial logistic regression and survival was investigated with Kaplan-Meier analysis and multivariable Cox regression. We studied 775 patients found in both registries (55% men, mean age 82years). Ejection fraction was preserved in 38% of patients, reduced in 34%, and missing in 28%. The proportions of dementia disorders were similar across HF types. Vascular dementia was the most common dementia disorder (36%), followed by other dementias (28%), mixed dementia (20%), and Alzheimer disease (16%). Over a mean follow-up of 1.5years, 76% of patients survived 1year. We observed no significant differences in survival with regard to HF type (P=0.2) or dementia disorder (P=0.5). After adjustment for baseline covariates, neither HF types nor dementia disorders were independently associated with survival. ConclusionsHeart failure with preserved ejection fraction was the most common HF type and vascular dementia was the most common dementia disorder. The proportions of dementia disorders were similar across HF types. Neither HF types nor specific dementia disorders were associated with survival.
  •  
22.
  • Cermakova, Pavla, et al. (författare)
  • Management of Acute Myocardial Infarction in Patients With Dementia : Data From SveDem, the Swedish Dementia Registry
  • 2017
  • Ingår i: Journal of the American Medical Directors Association. - : Elsevier BV. - 1525-8610 .- 1538-9375. ; 18:1, s. 19-23
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: We aimed to (1) study factors that determine the use of invasive procedures in the management of acute myocardial infarction (AMI) in patients with dementia and (2) determine whether the use of invasive procedures was associated with their better survival. Design: Cohort study based on patients registered in the Swedish Dementia Registry (SveDem), 20072012. Median follow-up time was 228 days. Setting: Patients diagnosed with dementia in specialist memory clinics and primary care units in Sweden. Participants: A total of 525 patients with dementia who suffered AMI (mean age 89 years, 54% women). Measurements: Information on AMI and use of invasive procedures (coronary angiography and percutaneous coronary intervention) was obtained from Swedish national health registers. Binary logistic regression was applied to study associations of patients characteristics with the use of invasive procedures; odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Survival was analyzed with Kaplan-Meier curves; log-rank test was used to compare survival of patients who received an invasive procedure versus those who did not receive it. Cox regression was applied to study association of the invasive procedures with all-cause mortality; hazard ratios (HRs) with 95% CIs were calculated. Results: One hundred ten patients (21%) with dementia received an invasive procedure in the management of AMI. After multivariate adjustment, lower age and higher global cognitive status were associated with the use of invasive procedures. The invasively managed patients survived longer (P = .001). The use of invasive procedures was associated with a lower risk of all-cause mortality, adjusting for type of AMI and dementia disorder, age, gender, registration unit, history of AMI and comorbidity score (HR 0.35, 95% CI 0.21-0.59), or total number of drugs (HR 0.34, 95% CI 0.20-0.58). Conclusion: Age and cognitive status determine the use of invasive procedures in patients with dementia. This study suggests that the invasive management of AMI has a benefit for survival of patients with dementia. (C) 2016 AMDA - The Society for Post-Acute and Long-Term Care Medicine.
  •  
23.
  • Ekman, Sirkka-Liisa, et al. (författare)
  • Alzheimer
  • 2011
  • Rapport (övrigt vetenskapligt/konstnärligt)
  •  
24.
  • Ekman, Urban, et al. (författare)
  • The MemClin project : a prospective multi memory clinics study targeting early stages of cognitive impairment
  • 2020
  • Ingår i: BMC Geriatrics. - : BMC. - 1471-2318. ; 20
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: There remains a lack of large-scale clinical studies of cognitive impairment that aim to increase diagnostic and prognostic accuracy as well as validate previous research findings. The MemClin project will amass large quantities of cross-disciplinary data allowing for the construction of robust models to improve diagnostic accuracy, expand our knowledge on differential diagnostics, strengthen longitudinal prognosis, and harmonise examination protocols across centres. The current article describes the Memory Clinic (MemClin) project's study-design, materials and methods, and patient characteristics. In addition, we present preliminary descriptive data from the ongoing data collection.Methods: Nine out of ten memory clinics in the greater Stockholm area, which largely use the same examination methods, are included. The data collection of patients with different stages of cognitive impairment and dementia is coordinated centrally allowing for efficient and secure large-scale database construction. The MemClin project rest directly on the memory clinics examinations with cognitive measures, health parameters, and biomarkers.Results: Currently, the MemClin project has informed consent from 1543 patients. Herein, we present preliminary data from 835 patients with confirmed cognitive diagnosis and neuropsychological test data available. Of those, 239 had dementia, 487 mild cognitive impairment (MCI), and 104 subjective cognitive impairment (SCI). In addition, we present descriptive data on visual ratings of brain atrophy and cerebrospinal fluid markers.Conclusions: Based on our current progress and preliminary data, the MemClin project has a high potential to provide a large-scale database of 1200-1500 new patients annually. This coordinated data collection will allow for the construction of improved diagnostic and prognostic models for neurodegenerative disorders and other cognitive conditions in their naturalistic setting.
  •  
25.
  • Enache, Daniela, et al. (författare)
  • CAIDE Dementia Risk Score and biomarkers of neurodegeneration in memory clinic patients without dementia
  • 2016
  • Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 42, s. 124-131
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to explore cross-sectional associations between Cardiovascular Risk Factors, Aging and Dementia Study (CAIDE) Dementia Risk Score and dementia-related cerebrospinal fluid and neuroimaging biomarkers in 724 patients without dementia from the Memory Clinic at Karolinska University Hospital, Huddinge, Sweden. We additionally evaluated the score's capacity to predict dementia. Two risk score versions were calculated: one including age, gender, obesity, hyperlipidemia, and hypertension; and one additionally including apolipoprotein E (APOE) ε4 carrier status. Cerebrospinal fluid was analyzed for amyloid β (Aβ), total tau, and phosphorylated tau. Visual assessments of medial temporal lobe atrophy (MTA), global cortical atrophy-frontal subscale, and Fazekas scale for white matter changes (WMC) were performed. Higher CAIDE Dementia Risk Score (version without APOE) was significantly associated with higher total tau, more severe MTA, WMC, and global cortical atrophy-frontal subscale. Higher CAIDE Dementia Risk Score (version with APOE) was associated with reduced Aβ, more severe MTA, and WMC. CAIDE Dementia Risk Score version with APOE seemed to predict dementia better in this memory clinic population with short follow-up than the version without APOE.
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