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Introduction: Choroid plexus (CP)-related mechanisms have been implicated in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease. In this pilot study, we aimed to elucidate the association between longitudinal changes in CP volume, sex and cognitive impairment., Methods: We assessed longitudinal changes in CP volume in a cohort of n  = 613 subjects across n  = 2,334 datapoints from ADNI 2 and ADNI-GO, belonging to cognitively unimpaired (CN), stable mild cognitive impairment (MCI), clinically diagnosed Alzheimer's disease dementia (AD) or convertor (to either AD or MCI) subgroups. CP volume was automatically segmented and used as a response variable in linear mixed effect models with random intercept clustered by patient identity. Temporal effects of select variables were assessed by interactions and subgroup analyses., Results: We found an overall significant increase of CP volume in time (14.92 mm 3 per year, 95% confidence interval, CI (11.05, 18.77), p  < 0.001). Sex-disaggregated results showed an annual rate of increase 9.48 mm 3 in males [95% CI (4.08, 14.87), p  < 0.001], and 20.43 mm 3 in females [95% CI (14.91, 25.93), p  < 0.001], indicating more than double the rate of increase in females, which appeared independent of other temporal variables. The only diagnostic group with a significant CP increase as compared to CN was the convertors group, with an increase of 24.88 mm 3 /year [95% CI (14, 35.82), p  < 0.001]. ApoE exhibited a significant temporal effect, with the E4 homozygote group's CP increasing at more than triple the rate of non-carrier or heterozygote groups [40.72, 95% CI (25.97, 55.46), p  < 0.001 vs. 12.52, 95% CI (8.02, 17.02), p  < 0.001 for ApoE E4 homozygotes and E4 non-carriers, respectively], and may have modified the diagnostic group relationship., Conclusion: Our results contribute to potential mechanisms for sex differences in cognitive impairment with a novel finding of twice the annual choroid plexus enlargement in females and provide putative support for CP-related mechanisms of cognitive deterioration and its relationship to ApoE E4., Competing Interests: MF is the Cofounder and CSO of the Women’s Brain Project. She has received personal fees for consulting from Lilly, Roche, and Lundbeck, not related to the present project. AF was employed by Women’s Brain Project. JH received consultancy and lecture fees from Biogen, Schwabe, Zentiva and holds share options in Alzheon company. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Novakova Martinkova, Ferretti, Ferrari, Lerch, Matuskova, Secnik and Hort.)

Background: Dementia and psychotropic medications are discussed as risk factors for severe/lethal outcome of the coronavirus disease 2019 (COVID-19). We aimed to explore the associations between the presence of dementia and medication use with mortality in the hospitalized and discharged patients who suffered from COVID-19., Methods: We conducted an open-cohort observational study based on electronic patient records from nine geriatric care clinics in the larger Stockholm area, Sweden, between February 28, 2020, and November 22, 2021. In total, we identified 5122 hospitalized patients diagnosed with COVID-19, out of which 762 (14.9%) patients had concurrent dementia and 4360 (85.1%) were dementia-free. Patients' age, sex, baseline oxygen saturation, comorbidities, and medication prescription (cardiovascular and psychotropic medication) were registered at admission. The hazard ratios (HRs) with 95% confidence intervals (CIs) of in-hospital, 30-day, 90-day, 365-day post-discharge, and overall mortality during the follow-up were obtained. Then, the associations of dementia and medication use with mortality were determined using proportional hazards regression with time since entry as a time scale., Results: After adjustment, dementia was independently associated with 68% higher in-hospital mortality among COVID-19 patients compared to patients who were dementia-free at admission [HRs (95% CI) 1.68 (1.37-2.06)]. The increase was consistent post-discharge, and the overall mortality of dementia patients was increased by 59% [1.59 (1.40-1.81)]. In addition, the prescription of antipsychotic medication at hospital admission was associated with a 70% higher total mortality risk [1.70 (1.47-1.97)]., Conclusions: The clinical co-occurence of dementia and COVID-19 increases the short- and long-term risk of death, and the antipsychotics seem to further the risk increase. Our results may help identify high-risk patients in need of more specialized care when infected with COVID-19., (© 2023. The Author(s).)

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.

Background: The effectiveness of glucose-lowering drugs (GLDs) is unknown among patients with dementia., Objective: To analyze all-cause mortality among users of six GLDs in dementia and dementia-free subjects, respectively., Methods: This was a longitudinal open-cohort registry-based study using data from the Swedish Dementia Registry, Total Population Register, and four supplemental registers providing data on dementia status, drug usage, confounders, and mortality. The cohort comprised 132,402 subjects with diabetes at baseline, of which 11,401 (8.6%) had dementia and 121,001 (91.4%) were dementia-free. Subsequently, comparable dementia - dementia-free pairs were sampled. Then, as-treated and intention-to-treat exposures to metformin, insulin, sulfonylurea, dipeptidyl-peptidase-4 inhibitors, glucagon-like peptide-1 analogues (GLP-1a), and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) were analyzed in the parallel dementia and dementia-free cohorts. Confounding was addressed using inverse-probability weighting and propensity-score matching, and flexible parametric survival models were used to produce hazard ratios (HR) and 95% confidence intervals (CI) of the association between GLDs and all-cause mortality., Results: In the as-treated models, increased mortality was observed among insulin users with dementia (HR 1.34 [95%CI 1.24-1.45]) as well as in dementia-free subjects (1.54 [1.10-1.55]). Conversely, sulfonylurea was associated with higher mortality only in dementia subjects (1.19 [1.01-1.42]). GLP-1a (0.44 [0.25-0.78]) and SGLT-2i users with dementia (0.43 [0.23-0.80]) experienced lower mortality compared to non-users., Conclusion: Insulin and sulfonylurea carried higher mortality risk among dementia patients, while GLP-1a and SGLT-2i were associated with lower risk. GLD-associated mortality varied between dementia and comparable dementia-free subjects. Further studies are needed to optimize GLD use in dementia patients.

Background: The effect of antidiabetic medication on cognitive function is unclear. We analyzed the association between five antidiabetic drugs and change in Mini-Mental State Examination (MMSE) scores in patients with diabetes and dementia., Methods: Using the Swedish Dementia Registry and four supplementary Swedish registers/databases, we identified 1873 patients (4732 observations) with diagnosis of type 2 diabetes (diabetes) and Alzheimer's disease or mixed-pathology dementia who were followed up at least once after dementia diagnosis. Use of metformin, insulin, sulfonylurea, thiazolidinediones (TZD), and dipeptidyl-peptidase-4 inhibitors (DPP-4i) was identified at baseline. Prevalent-user, incident-user, and drug-drug cohorts were sampled, and propensity-score matching was used to analyze comparable subjects. Beta coefficients with 95% confidence intervals (CI) from the random intercept and slope linear mixed-effects models determined the association between the use of antidiabetic medications and decline in MMSE score points between the follow-ups. Inverse-probability weighting was used to account for patient dropout., Results: Compared to non-users, prevalent users of metformin (beta 0.89, 95% CI 0.44; 1.33) and DPP-4i (0.72, 0.06; 1.37) experienced a slower cognitive decline with time. Secondly, compared to DPP-4i, the use of insulin (-1.00, -1.95; -0.04) and sulfonylureas (-1.19; -2.33; -0.04) was associated with larger point-wise decrements in MMSE with annual intervals., Conclusions: In this large cohort of patients with diabetes and dementia, the use of metformin and DPP-4i was associated with a slower decline in MMSE scores. Further examination of the cognitive effects of metformin and incretin-based medications is warranted., (© 2021. The Author(s).)

Objective: To explore the dementia diagnostic process and drug prescription for persons with dementia (PWD) with different socioeconomic status (SES)., Design: Register-based cohort study., Setting and Participants: This study included 74,414 PWD aged ≥65 years from the Swedish Dementia Register (2007-2018). Their data were linked with the Swedish Longitudinal Integrated Database for Health Insurance and Labor Market Studies (2006-2017) to acquire the SES information 1 year before dementia diagnosis., Methods: Education and income-2 traditional SES indicators-were divided into 5 levels. Outcomes comprised the dementia diagnostic examinations, types of dementia diagnosis, diagnostic unit, and prescription of antidementia drugs. Binary logistic regression was performed to evaluate socioeconomic inequalities., Results: Compared to PWD with the lowest educational level, PWD with the highest educational level had a higher probability of receiving the basic diagnostic workup [odds ratio (OR) 1.19, 95% confidence interval (CI) 1.10-1.29], clock test (OR 1.12, 95% CI 1.02-1.24) and neuroimaging (OR 1.23, 95% CI 1.09-1.39). Compared with PWD in the lowest income quintile, PWD in the highest income quintile presented a higher chance of receiving the basic diagnostic workup (OR 1.35, 95% CI 1.26-1.46), clock test (OR 1.40, 95% CI 1.28-1.52), blood analysis (OR 1.21, 95% CI 1.06-1.39), Mini-Mental State Examination (OR 1.47, 95% CI 1.26-1.70), and neuroimaging (OR 1.30, 95% CI 1.18-1.44). PWD with higher education or income had a higher likelihood of obtaining a specified dementia diagnosis or being diagnosed at a memory clinic. SES presented no association with prescription of antidementia medication, except for the association between education and the use of memantine., Conclusions and Implications: Higher education or income was significantly associated with higher chance of receiving dementia diagnostic examinations, a specified dementia diagnosis, being diagnosed at a memory clinic, and using memantine. Socioeconomic inequalities in dementia diagnostic process and prescription of memantine occurred among PWD with different education or income levels., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Evidence is lacking on how treatment of comorbidities improves outcomes in patients with dementia. In this study, we evaluated temporal changes in the management of comorbidities in relation to survival rates in incident dementia over a 10-year period in Sweden., Design: Observational cohort study., Setting and Participants: A total of 40,219 patients with recently diagnosed dementia in memory clinics from the Swedish Dementia Registry (SveDem) from 2008 to 2017., Methods: In 1-year blocks, pharmacological treatment of dementia and comorbidities in relationship to risk for fractures, major cardiovascular events (MACE), and death were analyzed using Cox models. Standardized Incidence Ratios (SIR) of death are presented., Results: After standardization for demographics and comorbidities, the risk of fracture, MACE, and mortality decreased by 16%, 23%, and 28%, respectively, between 2008 and 2016. Each year decreased the risk of fracture by 3% (hazard ratio 0.97, 95% confidence interval 0.96-0.99), MACE by 4% (0.96, 0.95-0.97), and death by 5% (0.95, 0.93-0.97). Adjustment for changes in medication use attenuated these associations. Compared with the general population, the risk of death declined by 11%, corresponding to standardized incidence rate ratio, between 2008 and 2016., Conclusions and Implications: Over 10 years, a reduction in the short-term risks of fracture, MACE, and death in patients with dementia was associated with changes in drug prescribing practices. These improvements seem to be partly explained by progressive implementation of dementia diagnostic, treatment guidelines, and general management of comorbidities., (Copyright © 2020 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: The effect of calcium channel blockers (CCB) on mortality and ischaemic stroke risk in dementia patients is understudied., Objectives: To calculate the risk of death and ischaemic stroke in dementia patients treated with CCBs, considering individual agents and dose response., Methods: Longitudinal cohort study with 18 906 hypertensive dementia patients from the Swedish Dementia Registry (SveDem), 2008-2014. Other Swedish national registries contributed information on comorbidities, dispensed medication and outcomes. Individual CCB agents and cumulative defined daily doses (cDDD) were considered., Results: In patients with hypertension and dementia, nifedipine was associated with increased mortality risk (aHR 1.32; CI 1.01-1.73; P < 0.05) compared to non-CCB users. Patients diagnosed with Alzheimer's dementia (AD) or dementia with Lewy bodies/Parkinson's disease dementia (DLB-PDD) taking amlodipine had lower mortality risk (aHR, 0.89; CI, 0.80-0.98; P < 0.05 and aHR 0.58; CI, 0.38-0.86; P < 0.01, respectively), than those taking other CCBs. Amlodipine was associated with lower stroke risk in patients with Alzheimer's dementia compared to other CCBs (aHR 0.63; CI, 0.44-0.89; P < 0.05). Sensitivity analyses with propensity score-matched cohorts repeated the results for nifedipine (aHR 1.35; 95% CI, 1.02-1.78; P < 0.05) and amlodipine in AD (aHR, 0.87; CI, 0.78-0.97; P < 0.05) and DLB-PDD (aHR, 0.56, 95%CI, 0.37-0.85; P < 0.05)., Conclusion: Amlodipine was associated with reduced mortality risk in dementia patients diagnosed with AD and DLB-PDD. AD patients using amlodipine had a lower risk of ischaemic stroke compared to other CCB users., (© 2020 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

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.

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.

Background: Recurrent ischemic stroke (IS) increases the risk of cognitive decline. To lower the risk of recurrent IS, secondary prevention is essential., Objective: Our aim was to compare post-discharge secondary IS prevention and its maintenance up to 3 years after first IS in patients with and without Alzheimer's disease and other dementia disorders., Methods: Prospective open-cohort study 2007-2014 from the Swedish national dementia registry (SveDem) and the Swedish national stroke registry (Riksstroke). Patients with dementia who experienced an IS (n = 1410; 332 [23.5%] with Alzheimer's disease) were compared with matched non-dementia IS patients (n = 7150). We analyzed antiplatelet, anticoagulant, blood pressure lowering, and statin treatment as planned medication initiation at discharge and actual dispensation of medications at first, second, and third year post-stroke., Results: At discharge, planned initiation of medication was higher in patients with dementia compared to non-dementia patients for antiplatelets (OR with 95% CI for fully adjusted models 1.23 [1.02-1.48]) and lower for blood pressure lowering medication (BPLM; 0.57 [0.49-0.67]), statins (0.57 [0.50-0.66]), and anticoagulants (in patients with atrial fibrillation - AF; 0.41 [0.32-0.53]). When analysis for antiplatelets was stratified according to the presence of AF, ORs for receiving antiplatelets remained significant only in the presence of AF (in the presence of AF 1.56 [1.21-2.01], in patients without AF 0.99 [0.75-1.33]). Similar trends were observed in 1st, 2nd, and 3rd year post-stroke., Conclusions: Dementia was a predictor of lower statin and BPLM use. Patients with dementia and AF were more likely to be prescribed antiplatelets and less likely to receive anticoagulants.

Objective: Cholinesterase inhibitors (ChEIs) and memantine are the only approved pharmacological treatments for Alzheimer's disease (AD). Recent literature suggests reductions in cardiovascular burden and risk of stroke in ChEI users. However, the clinical effectiveness of these drugs in patients with diabetes mellitus (DM) and dementia has not been evaluated., Research Design and Methods: We conducted a registry-based open-cohort study of 22 660 patients diagnosed with AD and mixed-pathology dementia registered in the Swedish Dementia Registry until December 2015. Information on drug use, comorbidity and mortality was extracted using the linkage with the National Patient Registry, the Prescribed Drug Registry and the Cause of Death Registry. In total, 3176 (14%) patients with DM and 19 484 patients without DM were identified. Propensity-score matching, Cox-regression and competing-risk regression models were applied to produce HRs with 95% CIs for differences in all-cause, cardiovascular and diabetes-related mortality rates in ChEI users and non-users., Results: After matching the ChEI use in patients with DM was associated with 24% all-cause mortality reduction (HR 0.76 (95% CI 0.67 to 0.86)), compared with 20% reduction (0.80 (0.75 to 0.84)) in non-DM users. Donepezil and galantamine use were associated with a reduced mortality in both patients with DM (0.84 (0.74 to 0.96); 0.80 (0.66 to 0.97)) and patients without DM (0.85 (0.80 to 0.90); 0.93 (0.86 to 0.99)). Donepezil was further associated with reduction in cardiovascular mortality, however only in patients without DM (0.84 (0.75 to 0.94)). Rivastigmine lowered mortality only in the whole-cohort analysis and in patients without DM (0.82 (0.75 to 0.89)). Moreover, ChEI use was associated with 48% reduction in diabetes-related mortality (HR 0.52 (0.32 to 0.87)) in the whole-cohort analysis. Last, low and high doses were associated with similar benefit., Conclusions: We found reductions in mortality in patients with DM and AD or mixed-pathology dementia treated with ChEIs, specifically donepezil and galantamine were associated with largest benefit. Future studies should evaluate whether ChEIs help maintain self-management of diabetes in patients with dementia., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Care individualization dominates in clinical guidelines for cognitively impaired patients with diabetes; however, few studies examined such adaptations., Objective: Describe long-term pharmacological changes in diabetes treatment in subjects with and without dementia., Methods: We performed a registry-based cohort study on 133,318 Swedish subjects (12,284 [9.2%] with dementia) with type 2 or other/unspecified diabetes. Dementia status originated from the Swedish Dementia Registry, while the National Patient Register, Prescribed Drug Register, and Cause of Death Register provided data on diabetes, comorbidities, drug dispensation, and mortality. Drug dispensation interval comprised years between 2005 and 2018 and the dispensation was assessed relative to index date (dementia diagnosis) in full cohort and propensity-score (PS) matched cohorts. Annual changes of drug dispensation were analyzed by linear regression, while Cox and competing-risk regression were used to determine the probability of drug dispensation after index date in naïve subjects. Studied medications included insulin, metformin, sulfonylureas, thiazolidinediones, dipeptidyl-peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 agonists (GLP-1a), and sodium-glucose cotransporter-2 inhibitors (SGLT-2i)., Results: Dementia patients had higher probability of insulin dispensation (hazard ratio 1.21 [95% CI 1.11-1.31] and lower probability of DPP-4i (0.72 [0.66-0.79]), GLP-1a (0.51 [0.41-0.63]), and SGLT-2i dispensation (0.44 [0.36-0.54]) after index date. PS-matched analyses showed increased annual insulin dispensation (β difference 0.97%) and lower increase in DPP-4i (-0.58%), GLP-1a (-0.13%), and SGLT-2i (-0.21%) dispensation in dementia patients compared to dementia-free controls., Conclusion: Dementia patients had lower probability of receiving newer antidiabetic drugs, with simultaneous higher insulin dispensation compared to dementia-free subjects.

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., (Copyright © 2018. Published by Elsevier Inc.)

Background: Previous studies have shown that patients with dementia receive less testing and treatment for stroke., Objectives: Our aim was to investigate hospital management of acute ischemic stroke in patients with and without dementia., Methods: Retrospective analysis of prospectively collected data 2010-2014 from the Swedish national dementia registry (SveDem) and the Swedish national stroke registry (Riksstroke). Patients with dementia who suffered an acute ischemic stroke (AIS) (n = 1,356) were compared with matched non-dementia AIS patients (n = 6,755). Outcomes included length of stay in a stroke unit, total length of hospitalization, and utilization of diagnostic tests and assessments., Results: The median age at stroke onset was 83 years. While patients with dementia were equally likely to be directly admitted to a stroke unit as their non-dementia counterparts, their stroke unit and total hospitalization length were shorter (10.5 versus 11.2 days and 11.6 versus 13.5, respectively, p < 0.001). Dementia patients were less likely to receive carotid ultrasound (OR 0.36, 95% CI [0.30-0.42]) or undergo assessments by the interdisciplinary team members (physiotherapists, speech therapists, occupational therapists; p < 0.05 for all adjusted models). However, a similar proportion of patients received CT imaging (97.4% versus 98.6%, p = 0.001) and a swallowing assessment (90.7% versus 91.8%, p = 0.218)., Conclusions: Patients with dementia who suffer an ischemic stroke have equal access to direct stroke unit care compared to non-dementia patients; however, on average, their stay in a stroke unit and total hospitalization are shorter. Dementia patients are also less likely to receive specific diagnostic tests and assessments by the interdisciplinary stroke team.

Objective: We aimed to investigate the differences in clinical characteristics and pharmacological treatment associated with the presence of diabetes in a large cohort of patients with dementia., Research Design and Methods: A cross-sectional registry-based study was conducted using data from the Swedish Dementia Registry (SveDem). Data on dementia diagnosis, dementia type, and demographic determinants were extracted from SveDem. Data from the Swedish Patient Register and Prescribed Drug Register were combined for the diagnosis of diabetes. Data on antidiabetic, dementia, cardiovascular, and psychotropic medications were extracted from the Swedish Prescribed Drug Register. Logistic regression was used to determine whether the variables were associated with diabetes after adjustment for confounders. In total, 29,630 patients were included in the study, and 4,881 (16.5%) of them received a diagnosis of diabetes., Results: In the fully adjusted model, diabetes was associated with lower age at dementia diagnosis (odds ratio [OR] 0.97 [99% CI 0.97-0.98]), male sex (1.41 [1.27-1.55]), vascular dementia (1.17 [1.01-1.36]), and mixed dementia (1.21 [1.06-1.39]). Dementia with Lewy bodies (0.64 [0.44-0.94]), Parkinson disease dementia (0.46 [0.28-0.75]), and treatment with antidepressants (0.85 [0.77-0.95]) were less common among patients with diabetes. Patients with diabetes who had Alzheimer disease obtained significantly less treatment with cholinesterase inhibitors (0.78 [0.63-0.95]) and memantine (0.68 [0.54-0.85])., Conclusions: Patients with diabetes were younger at dementia diagnosis and obtained less dementia medication for Alzheimer disease, suggesting less optimal dementia treatment. Future research should evaluate survival and differences in metabolic profile in patients with diabetes and different dementia disorders., (© 2017 by the American Diabetes Association.)

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.

The interaction of the retroviral nucleocapsid protein (NC) with nucleic acids forms the basis of its varied roles in the replication cycle, which include binding and condensing the viral RNA within the virion, stimulation of the early steps in reverse transcription, and dissociation from RNA in the replication complex. As part of an investigation of the NC binding site and of the forces that drive its interaction with nucleic acids, the relative affinities of NC from avian myeloblastosis virus were determined for a series of mononucleotides and mononucleotide components using a competitive displacement assay utilizing the extrinsic fluorescent probe bis-ANS [Secnik, J., Wang, Q., Chang, C.-M., & Jentoft, J.E. (1990) Biochemistry 29, 7991-7997]. The estimated binding affinities were unexpectedly similar for nucleotides, nucleosides, and bases (Ka greater than 10(6) M-1). AMP, UMP, GMP, and CMP bound to NC with essentially equal affinity, indicating that NC does not discriminate between bases. This is consistent with its role in coating, condensing, and packaging the RNA within virions. Nucleosides, bases, riboses, and ribose phosphate bind to NC with 1000-fold higher affinity than inorganic phosphate, indicating that the NC binding site includes elements that recognize nucleotide base and ribose components in addition to phosphate ions. However, the binding affinities of components are not additive, i.e., the Kapp values for adenine and deoxyribose are very similar to that for deoxyadenosine, indicating that the interaction between the NC subsite and the base and the sugar components is complex. The stoichiometry of the complex between bis-ANS and NC was established to be NC.(bis-ANS)3.(ABSTRACT TRUNCATED AT 250 WORDS)

The structural and functional properties of the nucleocapsid (NC) protein of the avian myeloblastosis virus were examined by steady-state fluorescence and fluorescence anisotropy measurements of the complex between the NC and the extrinsic fluorophore 4,4'-bis(phenylamino)(1,1'-binaphthalene)-5,5'-disulfonic acid (bis-ANS). The intrinsic fluorescence of bis-ANS is enhanced many fold upon forming a complex with the NC. Between 2 and 10 molecules of bis-ANS bind strongly to the NC, with an overall Kd of less than 10(-6) M. The emission of bis-ANS in the complex can also be induced by excitation at 298 nm, indicating that energy is transferred from Trp 80, the sole tryptophan in the NC protein, to bis-ANS. The energy transferred between the Trp 80 and bis-ANS was analyzed to yield a calculated distance of separation between these fluorophores of 28 +/- 3 A; thus, Trp 80 is well removed from the nearest bound bis-ANS. The fluorescence emission of bis-ANS in the NC.bis-ANS complex is efficiently quenched by added salts and by poly(A), suggesting that salt (presumably anions), nucleic acid, and bis-ANS bind to the same, positively charged region on the NC protein. A site size of six nucleotides was determined for nucleic acid binding to the NC protein, with an estimated Kd of less than 10(-6) M. Salt (anion) binding is strong, but nonspecific, with a Kapp of 4 mM, raising the possibility that anion binding to the NC protein might regulate the interaction of the NC with viral RNA inside the host cell.