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Introduction: Clinical research with remote monitoring technologies (RMTs) has multiple advantages over standard paper-pencil tests, but also raises several ethical concerns. While several studies have addressed the issue of governance of big data in clinical research from the legal or ethical perspectives, the viewpoint of local research ethics committee (REC) members is underrepresented in the current literature. The aim of this study is therefore to find which specific ethical challenges are raised by RECs in the context of a large European study on remote monitoring in all syndromic stages of Alzheimer's disease, and what gaps remain. Methods: Documents describing the REC review process at 10 sites in 9 European countries from the project Remote Assessment of Disease and Relapse–Alzheimer's Disease (RADAR-AD) were collected and translated. Main themes emerging in the documents were identified using a qualitative analysis approach. Results: Four main themes emerged after analysis: data management, participant's wellbeing, methodological issues, and the issue of defining the regulatory category of RMTs. Review processes differed across sites: process duration varied from 71 to 423 days, some RECs did not raise any issues, whereas others raised up to 35 concerns, and the approval of a data protection officer was needed in half of the sites. Discussion: The differences in the ethics review process of the same study protocol across different local settings suggest that a multi-site study would benefit from a harmonization in research ethics governance processes. More specifically, some best practices could be included in ethical reviews across institutional and national contexts, such as the opinion of an institutional data protection officer, patient advisory board reviews of the protocol and plans for how ethical reflection is embedded within the study. [ABSTRACT FROM AUTHOR]

Background: The majority of individuals with dementia will suffer from behavioral and psychological symptoms of dementia (BPSD). These symptoms contribute to functional impairment and caregiver burden.Objective: To characterize BPSD in Alzheimer's disease (AD), vascular dementia (VaD), mixed (Mixed) dementia, Parkinson's disease dementia (PDD), dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and unspecified dementia in individuals residing in long-term care facilities.Methods: We included 10,405 individuals with dementia living in long-term care facilities from the Swedish registry for cognitive/dementia disorders (SveDem) and the Swedish BPSD registry. BPSD was assessed with the Neuropsychiatric Inventory - Nursing Home Version (NPI-NH). Multivariate logistic regression models were used to evaluate the associations between dementia diagnoses and different BPSDs.Results: The most common symptoms were aberrant motor behavior, agitation, and irritability. Compared to AD, we found a lower risk of delusions (in FTD, unspecified dementia), hallucinations (FTD), agitation (VaD, PDD, unspecified dementia), elation/euphoria (DLB), anxiety (Mixed, VaD, unspecified dementia), disinhibition (in PDD), irritability (in DLB, FTD, unspecified dementia), aberrant motor behavior (Mixed, VaD, unspecified dementia), and sleep and night-time behavior changes (unspecified dementia). Higher risk of delusions (DLB), hallucinations (DLB, PDD), apathy (VaD, FTD), disinhibition (FTD), and appetite and eating abnormalities (FTD) were also found in comparison to AD.Conclusion: Although individuals in our sample were diagnosed with different dementia disorders, they all exhibited aberrant motor behavior, agitation, and irritability. This suggests common underlying psychosocial or biological mechanisms. We recommend prioritizing these symptoms while planning interventions in long-term care facilities. [ABSTRACT FROM AUTHOR]

Background: Stroke and dementia are interrelated diseases and risk for both increases with age. Even though stroke incidence and age-standardized death rates have decreased due to prevention of stroke risk factors, increased utilization of reperfusion therapies, and other changes in healthcare, the absolute numbers are increasing due to population growth and aging.Objective: To analyze predictors of death after stroke in patients with dementia and investigate possible time and treatment trends.Methods: A national longitudinal cohort study 2007-2017 using Swedish national registries. We compared 12,629 ischemic stroke events in patients with dementia with matched 57,954 stroke events in non-dementia controls in different aspects of patient care and mortality. Relationship between dementia status and dementia type (Alzheimer's disease and mixed dementia, vascular dementia, other dementias) and death was analyzed using Cox regressions.Results: Differences in receiving intravenous thrombolysis between patients with and without dementia disappeared after the year 2015 (administered to 11.1% dementia versus 12.3% non-dementia patients, p = 0.117). One year after stroke, nearly 50% dementia and 30% non-dementia patients had died. After adjustment for demographics, mobility, nursing home placement, and comorbidity index, dementia was an independent predictor of death compared with non-dementia patients (HR 1.26 [1.23-1.29]).Conclusion: Dementia before ischemic stroke is an independent predictor of death. Over time, early and delayed mortality in patients with dementia remained increased, regardless of dementia type. Patients with≤80 years with prior Alzheimer's disease or mixed dementia had higher mortality rates after stroke compared to patients with prior vascular dementia. [ABSTRACT FROM AUTHOR]

Background: In Sweden, 2,296,000 firearms were legally owned by private persons in 2017 and there were 150,000 persons living with a dementia diagnosis. A proportion of these persons owning a firearm may pose safety concerns.Objective: The aim was to describe firearm ownership in persons with dementia in Sweden and examine which characteristics are explaining physicians' decision to report a person to the police as unsuitable to possess a firearm.Methods: This was a registry-based observational study. 65,717 persons with dementia registered in the Swedish Dementia Registry were included in the study. Logistic regression was used to evaluate which of the persons' characteristics were most important in predicting the likelihood of being reported as unsuitable to possess a firearm. Relative importance of predictors was quantified using standardized coefficients (SC) and dominance analysis (DA).Results: Out of 53,384 persons with dementia, 1,823 owned a firearm and 419 were reported to the police as unsuitable owners. Firearm owners were predominantly younger, males, living alone, and without assistance of homecare. The most important predictors of being reported to the police were: living with another person (SC = 0.23), frontotemporal dementia (SC = 0.18), antipsychotics prescription (SC = 0.18), being diagnosed in a memory/cognitive clinic (SC = -0.27), female gender (SC = 0.18), mild (SC = -0.25) and moderate (SC = -0.21) dementia, and hypnotics prescription (SC = 0.17).Conclusion: Firearm owners with dementia were mostly younger males who were still living more independent lives. The decision to remove a weapon was not solely based on a diagnosis of dementia but a combination of factors was considered. [ABSTRACT FROM AUTHOR]

Background: Functional decline in Alzheimer's disease (AD) is typically measured using single-time point subjective rating scales, which rely on direct observation or (caregiver) recall. Remote monitoring technologies (RMTs), such as smartphone applications, wearables, and home-based sensors, can change these periodic subjective assessments to more frequent, or even continuous, objective monitoring. The aim of the RADAR-AD study is to assess the accuracy and validity of RMTs in measuring functional decline in a real-world environment across preclinical-to-moderate stages of AD compared to standard clinical rating scales. Methods: This study includes three tiers. For the main study, we will include participants (n = 220) with preclinical AD, prodromal AD, mild-to-moderate AD, and healthy controls, classified by MMSE and CDR score, from clinical sites equally distributed over 13 European countries. Participants will undergo extensive neuropsychological testing and physical examination. The RMT assessments, performed over an 8-week period, include walk tests, financial management tasks, an augmented reality game, two activity trackers, and two smartphone applications installed on the participants' phone. In the first sub-study, fixed sensors will be installed in the homes of a representative sub-sample of 40 participants. In the second sub-study, 10 participants will stay in a smart home for 1 week. The primary outcome of this study is the difference in functional domain profiles assessed using RMTs between the four study groups. The four participant groups will be compared for each RMT outcome measure separately. Each RMT outcome will be compared to a standard clinical test which measures the same functional or cognitive domain. Finally, multivariate prediction models will be developed. Data collection and privacy are important aspects of the project, which will be managed using the RADAR-base data platform running on specifically designed biomedical research computing infrastructure. Results: First results are expected to be disseminated in 2022. Conclusion: Our study is well placed to evaluate the clinical utility of RMT assessments. Leveraging modern-day technology may deliver new and improved methods for accurately monitoring functional decline in all stages of AD. It is greatly anticipated that these methods could lead to objective and real-life functional endpoints with increased sensitivity to pharmacological agent signal detection. [ABSTRACT FROM AUTHOR]

Objective: To investigate the factors that increase the risk of discontinuing dental care utilisation after dementia is diagnosed in a population in Stockholm County, Sweden.Background: As the progression of dementia results in a deteriorating ability to maintain good oral health, it is important to identify people at risk of discontinued dental care after being diagnosed with dementia.Materials and Methods: This study is a register-based longitudinal study. Data were extracted from the Swedish Dementia Registry (SveDem), the Swedish National Patient Register, the Dental Health Register and the Municipal Dental Care Register (Stockholm County Council). The data included people using both general public dental services and care-dependent individuals. Dental visits three years before and after dementia had been diagnosed were analysed.Results: In total, 10 444 people were included in the analysis, of which 19% did not have dental visits recorded after they were diagnosed with dementia. A logistic regression model, adjusted for relevant factors, showed that the factors associated with a greater risk for discontinued dental attendance were fewer remaining teeth (OR = 0.96, 95% CI = 0.95, 0.97) and living alone compared to living with another adult (OR = 1.23, 95% CI = 1.05, 1.43). People with Parkinson's disease dementia had a lower risk (OR = 0.40, 95% CI = 0.19, 0.84) than people with Alzheimer's disease.Conclusion: Patients, dental and healthcare personnel, and family members should all be aware of these risk factors so that appropriate support and oral care for people with dementia can be delivered. [ABSTRACT FROM AUTHOR]

Introduction: Dementia may be associated with discontinuation of regular dental checkups, which in turn results in poorer oral health. Methods: We investigated the trend of change in dental care utilization and the number of teeth before and after being diagnosed with dementia. Longitudinal cognitive‐ and dental health‐related information were merged using data on 58,037 newly diagnosed individuals from the Swedish Dementia Registry and Swedish Dental Health Register during 2007 to 2015. Results: Following dementia diagnosis, rate of dental care visits significantly declined. Individuals with mixed dementia, dementia with parkinsonism, and those with more severe and faster cognitive impairment had significantly higher rate of decline in dental care utilization. Vascular dementia and lower baseline Mini–Mental State Examination score were significant predictors of faster loss of teeth. Discussion: Dental care utilization markedly declines following dementia diagnosis. The reduction is more prominent in those with rapid progressive cognitive impairment and the ones with extra frailty burden. [ABSTRACT FROM AUTHOR]

Background: Many people with Alzheimer's disease (AD) live alone in their own homes. There is a lack of knowledge about whether these individuals receive the same quality of diagnostics and treatment for AD as patients who are cohabiting.Objectives: To investigate the diagnostic work-up and treatment of community-dwelling AD patients who live alone.Methods: We performed a cross-sectional cohort study based on data from the Swedish Dementia Registry (SveDem). We studied patients diagnosed with AD between 2007 and 2015 (n = 26,163). Information about drugs and comorbidities was acquired from the Swedish Prescribed Drug Register and the Swedish Patient Register.Results: 11,878 (46%) patients lived alone, primarily older women. After adjusting for confounders, living alone was inversely associated with receiving computed tomography (OR 0.90; 95% CI 0.82-0.99), magnetic resonance imaging (OR 0.91; 95% CI 0.83-0.99), and lumbar puncture (OR 0.86; 95% CI 0.80-0.92). Living alone was also negatively associated with the use of cholinesterase inhibitors (OR 0.81; 95% CI 0.76; 0.87), memantine (OR 0.77; 95% CI 0.72; 0.83), and cardiovascular medication (OR 0.92; 0.86; 0.99). On the other hand, living alone was positively associated with the use of antidepressants (OR 1.15; 95% CI 1.08; 1.22), antipsychotics (OR 1.41; 95% CI 1.25; 1.58), and hypnotics and sedatives (OR 1.09; 95% CI 1.02; 1.17).Conclusions: Solitary living AD patients do not receive the same extent of care as those who are cohabiting. [ABSTRACT FROM AUTHOR]

Background: the increasing prevalence of Alzheimer's dementia (AD) has shifted the burden of management towards primary care (PC). Our aim is to compare diagnostic process and management of AD in PC and specialist care (SC). Design: cross-sectional study. Subjects: a total of, 9,625 patients diagnosed with AD registered 2011-14 in SveDem, the Swedish Dementia Registry. Methods: descriptive statistics are shown. Odds ratios are presented for test performance and treatment in PC compared to SC, adjusted for age, sex, Mini-Mental State Examination (MMSE) and number of medication. Results: a total of, 5,734 (60%) AD patients from SC and 3,891 (40%) from PC. In both, 64% of patients were women. PC patients were older (mean age 81 vs. 76; P < 0.001), had lower MMSE (median 21 vs. 22; P < 0.001) and more likely to receive home care (31% vs. 20%; P < 0.001) or day care (5% vs. 3%; P < 0.001). Fewer diagnostic tests were performed in PC and diagnostic time was shorter. Basic testing was less likely to be complete in PC. The greatest differences were found for neuroimaging (82% in PC vs. 98% in SC) and clock tests (84% vs. 93%). These differences remained statistically significant after adjusting for MMSE and demographic characteristics. PC patients received less antipsychotic medication and more anxiolytics and hypnotics, but there were no significant differences in use of cholinesterase inhibitors between PC and SC. Conclusion: primary and specialist AD patients differ in background characteristics, and this can influence diagnostic work-up and treatment. PC excels in restriction of antipsychotic use. Use of head CT and clock test in PC are areas for improvement in Sweden. [ABSTRACT FROM AUTHOR]

Objectives The causes of death in dementia are not established, particularly in rarer dementias. The aim of this study is to calculate risk of death from specific causes for a broader spectrum of dementia diagnoses. Design Cohort study. Setting Swedish Dementia Registry (SveDem), 2007-2012. Participants Individuals with incident dementia registered in SveDem (N = 28,609); median follow-up 741 days. Observed deaths were 5,368 (19%). Measurements Information on number of deaths and causes of mortality was obtained from death certificates. Odds ratios for the presence of dementia on death certificates were calculated. Hazard ratios ( HRs) and 95% confidence intervals ( CIs) were calculated using Cox hazards regression for cause-specific mortality, using Alzheimer's dementia ( AD) as reference. Hazard ratios for death for each specific cause of death were compared with hazard ratios of death from all causes ( P-values from t-tests). Results The most frequent underlying cause of death in this cohort was cardiovascular (37%), followed by dementia (30%). Dementia and cardiovascular causes appeared as main or contributory causes on 63% of certificates, followed by respiratory (26%). Dementia was mentioned less in vascular dementia (VaD; 57%). Compared to AD, cardiovascular mortality was higher in individuals with VaD than in those with AD ( HR = 1.82, 95% CI = 1.64-2.02). Respiratory death was higher in individuals with Lewy body dementia ( LBD, including Parkinson's disease dementia and dementia with Lewy bodies, HR = 2.16, 95% CI = 1.71-2.71), and the risk of respiratory death was higher than expected from the risk for all-cause mortality. Participants with frontotemporal dementia were more likely to die from external causes of death than those with AD ( HR = 2.86, 95% CI = 1.53-5.32). Conclusion Dementia is underreported on death certificates as main and contributory causes. Individuals with LBD had a higher risk of respiratory death than those with AD. [ABSTRACT FROM AUTHOR]

Background: Driving constitutes a very important aspect of daily life and is dependent on cognitive functions such as attention, visuo-spatial skills and memory, which are often compromised in dementia. Therefore, the driving fitness of patients with dementia needs to be addressed by physicians and those that are deemed unfit should not be allowed to continue driving.Objective: We aimed at investigating to what extent physicians assess driving fitness in dementia patients and determinant factors for revoking of their licenses.Methods: This study includes 15113 patients with newly diagnosed dementia and driver's license registered in the Swedish Dementia Registry (SveDem). The main outcomes were reporting to the licensing authority and making an agreement about driving eligibility with the patients.Results: Physicians had not taken any action in 16% of dementia patients, whereas 9% were reported to the authority to have their licenses revoked. Males (OR = 3.04), those with an MMSE score between 20-24 (OR = 1.35) and 10-19 (OR = 1.50), patients with frontotemporal (OR = 3.09) and vascular dementia (OR = 1.26) were more likely to be reported to the authority.Conclusion: For the majority of patients with dementia, driving fitness was assessed. Nevertheless, physicians did not address the issue in a sizeable proportion of dementia patients. Type of dementia, cognitive status, age, sex and burden of comorbidities are independent factors associated with the assessment of driving fitness in patients with dementia. Increased knowledge on how these factors relate to road safety may pave the way for more specific guidelines addressing the issue of driving in patients with dementia. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction New research guidelines for the diagnosis of Alzheimer's disease (AD) include biomarker evidence of amyloid-β (Aβ) and tau pathology. The aim of this study was to investigate what proportion of AD patients diagnosed in clinical routine in Sweden that had an AD-indicative cerebrospinal fluid (CSF) biomarker profile. Methods By cross-referencing a laboratory database with the Swedish Dementia Registry (SveDem), 2357 patients with data on CSF Aβ and tau biomarkers and a clinical diagnosis of AD with dementia were acquired. Results Altogether, 77.2% had pathologic Aβ 42 and total tau or phosphorylated tau in CSF. These results were stable across age groups. Female sex and low mini-mental state examination score increased the likelihood of pathologic biomarkers. Discussion About a quarter of clinically diagnosed AD patients did not have an AD-indicative CSF biomarker profile. This discrepancy may partly reflect incorrect (false positive) clinical diagnosis or a lack in sensitivity of the biomarker assays. [ABSTRACT FROM AUTHOR]

Progressive cognitive decline in combination with a cerebrospinal fluid biomarker pattern of low levels of amyloid-β1-42 and high levels of total tau and phosphorylated tau is typical of Alzheimer's disease. However, several neurodegenerative disorders may overlap with Alzheimer's disease both in regards to clinical symptoms and neuropathology. In a uniquely large cohort of dementia patients, we examined the associations of cerebrospinal fluid biomarkers for Alzheimer's disease molecular pathology with clinical dementia diagnoses and disease severity. We cross-referenced the Swedish Dementia Registry with the clinical laboratory database at the Sahlgrenska University Hospital. The final data set consisted of 5676 unique subjects with a clinical dementia diagnosis and a complete set of measurements for cerebrospinal fluid amyloid-β1-42, total tau and phosphorylated tau. In cluster analysis, disregarding clinical diagnosis, the optimal natural separation of this data set was into two clusters, with the majority of patients with early onset Alzheimer's disease (75%) and late onset Alzheimer's disease (73%) assigned to one cluster and the patients with vascular dementia (91%), frontotemporal dementia (94%), Parkinson's disease dementia (94%) and dementia with Lewy bodies (87%) to the other cluster. Frontotemporal dementia had the highest cerebrospinal fluid levels of amyloid-β1-42 and the lowest levels of total tau and phosphorylated tau. The highest levels of total tau and phosphorylated tau and the lowest levels of amyloid-β1-42 and amyloid-β1-42:phosphorylated tau ratios were found in Alzheimer's disease. Low amyloid-β1-42, high total tau and high phosphorylated tau correlated with low Mini-Mental State Examination scores in Alzheimer's disease. In Parkinson's disease dementia and vascular dementia low cerebrospinal fluid amyloid-β1-42 was associated with low Mini-Mental State Examination score. In the vascular dementia, frontotemporal dementia, dementia with Lewy bodies and Parkinson's disease dementia groups 53%, 34%, 67% and 53% of the subjects, respectively had abnormal amyloid-β1-42 levels, 41%, 41%, 28% and 28% had abnormal total tau levels, and 29%, 28%, 25% and 19% had abnormal phosphorylated tau levels. Cerebrospinal fluid biomarkers were strongly associated with specific clinical dementia diagnoses with Alzheimer's disease and frontotemporal dementia showing the greatest difference in biomarker levels. In addition, cerebrospinal fluid amyloid-β1-42, total tau, phosphorylated tau and the amyloid-β1-42:phosphorylated tau ratio all correlated with poor cognitive performance in Alzheimer's disease, as did cerebrospinal fluid amyloid-β1-42 in Parkinson's disease dementia and vascular dementia. The results support the use of cerebrospinal fluid biomarkers to differentiate between dementias in clinical practice, and to estimate disease severity. [ABSTRACT FROM AUTHOR]

Background/Aims: The use of structural brain imaging [computed tomography (CT)/magnetic resonance imaging (MRI)] and the analysis of cerebrospinal fluid biomarkers are included in the guidelines for the diagnosis of dementia. The influence of variables such as age, gender and disease severity on the use of MRI, CT and lumbar puncture (LP) for the differential diagnosis of dementia and the consonance with the recommendations of the Swedish national guidelines were investigated. Methods: From the National Swedish Dementia Registry (SveDem), 17,057 newly diagnosed dementia patients were included in our study, with the majority from specialist care units (90%). Results: In the diagnostic workup, a CT was performed in 87%, MRI in 16% and LP in 40% of the cases. Age (p < 0.001) and cognitive status (p < 0.001) significantly influenced the use of MRI, CT or LP. Older patients with severe dementia were often investigated with CT. LP and MRI were used more often when less common dementia disorders were suspected. Conclusion: Our findings indicate that age, severity of cognitive impairment and the type of dementia disorder suspected are determinants for the choice of CT, MRI or LP. The majority of the dementia workups in specialist care units follow the recommendations of the Swedish national guidelines where CT is performed as a basic workup, and MRI and LP are chosen when extended workup is needed. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Introduction Compared to Alzheimer's disease (AD), dementia with Lewy bodies (DLB) is usually associated with a more complex clinical picture and higher burden of care. Yet, few investigations have been performed on comorbidities and risk factors of DLB. Therefore, we aimed to compare clinical risk factors and comorbidity profile in DLB and AD patients using two nationwide registries. Methods This is a linkage study between the Swedish dementia registry (SveDem) and the Swedish National Patient Registry conducted on 634 subjects with DLB and 9161 individuals with AD registered during the years 2007-2012. Comorbidity profile has been coded according to the International Classification of Diseases version 10 (ICD 10) in addition to the date of each event. The main chapters of the ICD-10, the Charlson score of comorbidities and a selected number of neuropsychiatric diseases were compared between the DLB and AD groups. Comorbidity was registered before and after the dementia diagnosis. Results "Mental and behavioral disorders", "diseases of the nervous system", "diseases of the eye and adnexa", diseases of the "circulatory", "respiratory", and "genitourinary" systems, "diseases of the skin and subcutaneous tissue" and "diseases of the musculoskeletal system and connective tissue" occurred more frequently in the DLB group after multivariate adjustment. Depression [adjusted OR = 2.12 (95%CI 1.49 to 3.03)] and migraine [adjusted OR = 3.65 (95%CI 1.48 to 9.0)] were more commonly recorded before the diagnosis of dementia in the DLB group. Following dementia diagnosis, ischemic stroke [adjusted OR = 1.89 (95%CI 1.21 to 2.96)] was more likely to happen among the DLB patients compared to the AD population. Conclusions Our study indicated a worse comorbidity profile in DLB patients with higher occurrence of depression, stroke and migraine compared with the AD group. Deeper knowledge about the underlying mechanisms of these associations is needed to explore possible reasons for the different pattern of comorbidity profile in DLB compared to AD and their prognostic significance. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The functional impact of amyloid peptides (Aβs) on the vascular system is less understood despite these pathologic peptides are substantially deposited in the brain vasculature of Alzheimer's patients. Here we show substantial accumulation of Abs 40 and 42 in the brain arterioles of Alzheimer's patients and of transgenic Alzheimer's mice. PurifiedAbs 1-40 and 1-42 exhibited vascular regression activity in the in vivo animal models and vessel density was reversely correlated with numbers and sizes of amyloid plaques in human patients. A significant high number of vascular cells underwent cellular apoptosis in the brain vasculature of Alzheimer's patients. VEGF significantly prevented Aβ-induced endothelial apoptosis in vitro. Neuronal expression of VEGF in transgenic mice restored memory behavior of Alzheimer's. These findings provide conceptual implication of improvement of vascular functions as a novel therapeutic approach for the treatment of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Background/Aims: We aimed to study whether there are differences between dementia disorders and the use of anti-dementia drugs and antipsychotics (neuroleptics) in a large population of dementia patients. Methods: Information about dementia disorders was obtained from the national Swedish Dementia Registry (SveDem) 2007-2010 (n = 7,570). Multivariate logistic regression analysis was performed to investigate the association between dementia disorders and the use of anti-dementia drugs and antipsychotics, after adjustment for age, sex, residential setting, living alone, MMSE score and number of other drugs (a proxy for overall co-morbidity). Results: More than 80% of the Alzheimer's disease (AD) and 86% of dementia with Lewy bodies (DLB) patients used anti-dementia drugs. Women were more likely than men to be treated with cholinesterase inhibitors. A higher MMSE score was positively associated with the use of cholinesterase inhibitors, but negatively associated with NMDA receptor antagonists and antipsychotics. Use of antipsychotics was 6% overall; however, it was 16% in DLB patients with an adjusted odds ratio of 4.2 compared to AD patients. Conclusion: Use of anti-dementia drugs in AD was in agreement with Swedish guidelines. However, use of antipsychotics in DLB patients was high, which might be worrying given the susceptibility of DLB patients to antipsychotics. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aims: We examine the dementia assessment with focus on age and gender differences. Methods: Data from the national quality database, Swedish Dementia Registry (SveDem), including 6,937 dementia patients diagnosed during 2007-2009 at memory clinics were used. We have studied the use of investigations for dementia diagnostics such as cognitive tests, blood and cerebrospinal fluid analyses, electroencephalography, radiological examinations and assessments of functions. Severity of cognitive impairment was assessed with the Mini Mental State Examination (MMSE). Results: There was a significant decrease in the number of total tests used in the elderly group (>75 years) when compared with the middle-aged group (65-75 years) and younger patients (<65 years). The oldest group was examined with 4 of 11 possible tests, the middle-aged group had 5/11 tests performed and the youngest age group 6/11 tests. There was also a significant gender difference in the diagnostic workup, however, mostly attributable to age. The number of tests positively correlated with the level of cognition assessed by the MMSE. Conclusion: We show here for the first time the impact of age, gender and MMSE score on the dementia diagnostic workup in a large memory clinic patient population in one country. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

One of the cardinal neuropathological findings in brains from Alzheimer’s disease (AD) patients is the occurrence of amyloid β-peptide (Aβ) deposits. The γ-secretase-mediated intramembrane proteolysis event generating Aβ also results in the release of the APP intracellular domain (AICD), which may mediate nuclear signaling. It was recently shown that AICD starts at a position distal to the site predicted from γ-secretase cleavage within the membrane. This novel site, the &epsiv; site, is located close to the inner leaflet of the membrane bilayer. The relationship between proteolysis at the γ and &epsiv; sites has not been fully characterized. Here we studied AICD signaling in intact cells using a chimeric C99 molecule and a luciferase reporter system. We show that the release of AICD from the membrane takes place in a compartment downstream of the endoplasmic reticulum, is dependent on presenilin proteins, and can be inhibited by treatment with established γ-secretase inhibitors. Moreover, we find that AICD signaling remains unaltered from C99 derivatives containing mutations associated with increased Aβ42 production and familial AD. These findings indicate that there are very similar routes for Aβ and AICD formation but that FAD-linked mutations in APP primarily affect γ-secretase-mediated Aβ42 formation, and not AICD signaling. [Copyright &y& Elsevier]

As Alzheimer''s disease (AD) is a complex disease, we decided to estimate how previously reported genetic polymorphisms interact to increase the risk for the disease. Five candidate genes were chosen: apolipoprotein E (APOE), α2-macroglobulin, cathepsin D, myeloperoxidase and nitric oxide synthase. Genotyping was performed in 100 cases of late-onset AD and 100 healthy controls. We found a highly significant difference in APOE &epsiv;4 distribution between groups (P<0.005). However, no evidence of association for other studied loci was found. Cumulative analysis of five genetic polymorphisms was performed, but it also failed to reveal any synergistic effect of candidate genes greater than that caused by APOE itself. Our results suggest that the APOE &epsiv;4 allele is the only known genetic risk factor for late-onset, sporadic AD. [Copyright &y& Elsevier]

Objective: Severe cognitive impairment is common in elderly patients with schizophrenia. Alzheimer's disease is the main cause of dementia among the elderly. Biochemical and genetic studies suggest that amyloid β-peptide is central in Alzheimer's disease. The authors examined the possible involvement of amyloid β-peptide in cognitive impairment in schizophrenia. Method: Specific antibodies against two major forms of amyloid β-peptide, Aβx-40 and Aβx-42, were used in sandwich enzyme-linked immunosorbent assays to determine the levels of amyloid β-peptide in postmortem brain samples from Alzheimer's disease patients (N = 10), normal elderly comparison subjects (N = 11), and schizophrenia patients with (N = 7) or without (N = 26) Alzheimer's disease. Results: The levels of amyloid β-peptide were highest in the Alzheimer's disease patients, followed by the patients with schizophrenia and comparison subjects. The mean Aβx-42 level in the schizophrenia patients without Alzheimer's disease was similar to that in the comparison subjects, but the level in the schizophrenia patients with Alzheimer's disease was significantly higher than in those without Alzheimer's disease or the comparison subjects. The Aβx-42 level in the schizophrenia patients with Alzheimer's disease was significantly lower than the level in the Alzheimer's disease cohort. Conclusions: In contrast to elderly schizophrenia patients with Alzheimer's disease pathology, those without Alzheimer's disease had amyloid β-peptide levels that were not significantly different from those of normal subjects; hence amyloid β-peptide does not account for the cognitive deficits in this group. These results suggest that the causes of cognitive impairment in "pure" schizophrenia are different from those in Alzheimer's disease. [ABSTRACT FROM AUTHOR]

The saitohin (STH) gene is located in intron 9 of the tau protein gene. It has been postulated that the R allele of Q7R polymorphism at the Saitohin gene is over-represented in the homozygous state in sporadic Alzheimer''s disease (AD). Tau protein was implicated in AD pathophysiology and the tau gene haplotype is probably connected with sporadic late-onset Parkinson''s disease (PD). We analyzed the STH polymorphism and tau gene haplotype in 100 clinically diagnosed AD cases, 100 PD cases and 100 age-matched healthy controls. We found that the R allele of the STH gene is associated with the H2 haplotype of tau in all cases. Additionally we observed no correlation between R allele frequency and AD or PD. [Copyright &y& Elsevier]

Abstract: Excess cholesterol is removed from the brain via hydroxylation mediated by cholesterol 24S-hydroxylase (CYP46). Although serum and cerebrospinal fluid (CSF) concentrations of 24S-hydroxycholesterol are altered during the progress of Alzheimer''s disease, studies carried out to date in different populations on the association of CYP46 gene polymorphisms and risk of AD have been inconclusive. In this report, we analyzed CYP46 polymorphisms in 215 Polish AD cases and 173 healthy individuals. A fragment of CYP46 intron 2 was amplified by PCR reaction and sequenced. We discovered a new single nucleotide substitution in CYP46 intron 2, but found no difference in particular genotype or allele frequencies between AD patients and controls. However, the GG genotype of the known rs754203 polymorphic site might be a risk factor for AD, especially in APOE ɛ4 carriers. Interestingly, in AD patients the rs754203 G allele was more frequent in males than in females. However, considering the extreme divergence of results obtained by different authors, a clear connection between the CYP46 gene and AD is questionable. [Copyright &y& Elsevier]

Mutations in the presenilin 1 (PSEN1) gene are known to cause nearly 50% of early-onset, familial Alzheimer''s disease (AD) cases. To determine whether E318G mutation is related causally to AD in the Polish population E318G mutation frequency was assessed using PCR-RFLP method in a total of 659 subjects: 256 AD patients, 210 healthy, age-matched control subjects, 100 Parkinson''s disease patients and 93 centenarians. When the mutation frequencies were compared to healthy controls, no significant differences between the groups were found. It could be concluded that E318G mutation is not related causally to AD in the Polish population, either as a risk factor or a disease causing mutation. [Copyright &y& Elsevier]

Mutations in three causative genes have been identified in patients with an autosomal-dominant form of early-onset Alzheimer''s disease (EOAD). To determine the spectrum of mutations in a group consisting of 40 Polish patients with clinically diagnosed familial EOAD and 1 patient with mild cognitive impairment (MCI) and family history of AD, we performed a screening for mutations in the presenilin 1 (PSEN1), presenilin 2 (PSEN2) and amyloid precursor protein (APP) genes. Four previously recognized pathogenic mutations in PSEN1 gene (H163R, M139V) and APP gene (T714A, V715A), and three novel putative mutations in PSEN1 gene (P117R and I213F) and PSEN2 gene (Q228L) were identified. The 34 patients with no mutations detected were older than the patients with mutations. A frequency of APOE4 allele was higher in this group. Frequency of mutations is relatively low (17%), possibly due to used operational definition of a patient with familial EOAD (a patient having at least one relative with early-onset dementia). It could be concluded that screening for mutations in the three genes could be included in a diagnostic program directed at patients with a positive family history or age of onset before 55 years. [Copyright &y& Elsevier]

Abstract Objective To assess all-cause mortality patients with dementia treated with typical and atypical antipsychotic drugs (APDs). Design Registry-based cohort study. Setting and participants A total of 58,412 patients diagnosed with dementia and registered in the Swedish Dementia Registry were included in the study. Of the study sample, 2526 of the patients were prescribed APDs. Of these, 602 patients were prescribed typical APDs and 1833 patients were prescribed atypical APDs. Ninety-one patients were prescribed both typical and atypical APDs. Measurements All-cause mortality based on Swedish Cause of Death Register. Adjusted hazard ratios of mortality were calculated according to class of APDs (typical or atypical) prescribed. Final models were adjusted for age at dementia diagnosis, sex, Charlson comorbidity index, living arrangement, and Mini-Mental State Examination. Results In the adjusted models, use of APDs at the time of dementia diagnosis was associated with increased mortality risk in the total cohort (hazard ratio = 1.4; 95% confidence interval 1.3–1.5). After stratifying for dementia types, increased mortality risks associated with APDs were found in patients with Alzheimer's disease, mixed dementia, unspecified dementia, and vascular dementia. Higher risk for mortality was found with typical APDs in patients with mixed and vascular dementia and with atypical APDs in patients with Alzheimer's disease, mixed, unspecified, and vascular dementia. Furthermore, in patients with Alzheimer's disease who had typical APDs, use lower risk of death emerged in comparison with patients with atypical APDs. Conclusions/Implications Both the use of atypical and typical APDs increased the risk of death in patients with dementia even after adjusting for differences in basic characteristics between groups. Although we cannot rule out the influence of residual confounding, these results would seem to add to studies suggesting caution in APD prescription for patients with dementia. [ABSTRACT FROM AUTHOR]