COVID-19 Pandemic and Stroke Care in Patients with Dementia Compared to Other Stroke Patients.

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 patients with strokes, 1357 had documented preexisting dementia, and 20,438 had stroke without a dementia diagnosis. Throughout all study periods, a significantly lower proportion of patients with stroke 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.

Immigration and access to dementia diagnostics and treatment: A nationwide study in Sweden.

•Compared to Swedish-born people, foreign-born people were less likely to receive dementia diagnostic tests.•Being born in Africa or Europe was associated with lower chance of receiving cholinesterase inhibitors.•Asian-born people had higher chance of receiving cholinesterase inhibitors, but were less likely to receive memantine.•Disparities existed in dementia diagnostics and treatment between Swedish-born and foreign-born people, but were not consistent after adjusting for MMSE scores.

Statins and cognitive decline in patients with Alzheimer's and mixed dementia: a longitudinal registry-based cohort study.

BACKGROUND: Disturbances in brain cholesterol homeostasis may be involved in the pathogenesis of Alzheimer's disease (AD). Lipid-lowering medications could interfere with neurodegenerative processes in AD through cholesterol metabolism or other mechanisms. OBJECTIVE: To explore the association between the use of lipid-lowering medications and cognitive decline over time in a cohort of patients with AD or mixed dementia with indication for lipid-lowering treatment. METHODS: A longitudinal cohort study using the Swedish Registry for Cognitive/Dementia Disorders, linked with other Swedish national registries. Cognitive trajectories evaluated with mini-mental state examination (MMSE) were compared between statin users and non-users, individual statin users, groups of statins and non-statin lipid-lowering medications using mixed-effect regression models with inverse probability of drop out weighting. A dose-response analysis included statin users compared to non-users. RESULTS: Our cohort consisted of 15,586 patients with mean age of 79.5 years at diagnosis and a majority of women (59.2 %). A dose-response effect was demonstrated: taking one defined daily dose of statins on average was associated with 0.63 more MMSE points after 3 years compared to no use of statins (95% CI: 0.33;0.94). Simvastatin users showed 1.01 more MMSE points (95% CI: 0.06;1.97) after 3 years compared to atorvastatin users. Younger (< 79.5 years at index date) simvastatin users had 0.80 more MMSE points compared to younger atorvastatin users (95% CI: 0.05;1.55) after 3 years. Simvastatin users had 1.03 more MMSE points (95% CI: 0.26;1.80) compared to rosuvastatin users after 3 years. No differences regarding statin lipophilicity were observed. The results of sensitivity analysis restricted to incident users were not consistent. CONCLUSIONS: Some patients with AD or mixed dementia with indication for lipid-lowering medication may benefit cognitively from statin treatment; however, further research is needed to clarify the findings of sensitivity analyses.

Psychiatric Disorders Before and After Dementia Diagnosis.

Importance: Little is known about the specific timing and sequence of incident psychiatric comorbidities at different stages of dementia diagnosis. Objectives: To examine the temporal risk patterns of psychiatric disorders, including depression, anxiety, stress-related disorders, substance use disorders, sleep disorders, somatoform/conversion disorders, and psychotic disorders, among patients with dementia before, at the time of, and after receipt of a diagnosis. Design, Setting, and Participants: This population-based, nationwide cohort study analyzed data from 796 505 participants obtained from 6 registers between January 1, 2000, and December 31, 2017, including the Swedish registry for cognitive/dementia disorders. Patients with dementia were matched on year of birth (±3 years), sex, and region of residence with up to 4 controls. Data were analyzed between March 1, 2023, and August 31, 2023. Exposures: Any cause of dementia and dementia subtypes. Main Outcomes and Measures: Flexible parametric survival models to determine the time-dependent risk of initial diagnosis of psychiatric disorders, from 7 years prior to dementia diagnosis to 10 years after diagnosis. Subgroup analysis was conducted for psychiatric drug use among persons receiving a diagnosis of dementia from January 1, 2011, to December 31, 2012. Results: Of 796 505 patients included in the study (mean [SD] age at diagnosis, 80.2 [8.3] years; 448 869 (56.4%) female), 209 245 had dementia, whereas 587 260 did not, across 7 824 616 person-years. The relative risk of psychiatric disorders was consistently higher among patients with dementia compared with control participants and began to increase from 3 years before diagnosis (hazard ratio, [HR], 1.72; 95% CI, 1.67-1.76), peaked during the week after diagnosis (HR, 4.74; 95% CI, 4.21-5.34), and decreased rapidly thereafter. Decreased risk relative to controls was observed from 5 years after diagnosis (HR, 0.93; 95% CI, 0.87-0.98). The results were similar for Alzheimer disease, mixed dementia, vascular dementia and unspecified dementia. Among patients with dementia, markedly elevated use of psychiatric medications was observed in the year leading up to the dementia diagnosis and peaked 6 months after diagnosis. For example, antidepressant use was persistently higher among patients with dementia compared with controls, and the difference increased from 2 years before dementia diagnosis (15.9% vs 7.9%, P < .001), peaked approximately 6 months after dementia diagnosis (29.1% vs 9.7%, P < .001), and then decreased slowly from 3 years after diagnosis but remained higher than controls 5 years after diagnosis (16.4% vs 6.9%, P < .001). Conclusions and Relevance: The findings of this cohort study that patients with dementia had markedly increased risks of psychiatric disorders both before and after dementia diagnosis highlight the significance of incorporating psychiatric preventative and management interventions for individuals with dementia across various diagnostic stages.

The Impact of Educational Attainment and Income on Long-Term Care for Persons with Alzheimer's Disease and Other Dementias: A Swedish Nationwide Study.

BACKGROUND: Long-term care improves independence and quality of life of persons with dementia (PWD). The influence of socioeconomic status on access to long-term care was understudied. OBJECTIVE: To explore the socioeconomic disparity in long-term care for PWD. METHODS: This registry-based study included 14,786 PWD, registered in the Swedish registry for cognitive and dementia disorders (2014-2016). Education and income, two traditional socioeconomic indicators, were the main exposure. Outcomes were any kind of long-term care, specific types of long-term care (home care, institutional care), and the monthly average hours of home care. The association between outcomes and socioeconomic status was examined with zero-inflated negative binomial regression and binary logistic regression. RESULTS: PWD with compulsory education had lower likelihood of receiving any kind of long-term care (OR 0.80, 95% CI 0.68-0.93), or home care (OR 0.83, 95% CI 0.70-0.97), compared to individuals with university degrees. Their monthly average hours of home care were 0.70 times (95% CI 0.59-0.82) lower than those of persons with university degrees. There was no significant association between education and the receipt of institutional care. Stratifying on persons with Alzheimer's disease showed significant association between lower education and any kind of long-term care, and between income and the hours of home care. CONCLUSIONS: Socioeconomic inequalities in long-term care existed in this study population. Lower-educated PWD were less likely to acquire general long-term care, home care and had lower hours of home care, compared to their higher-educated counterparts. Income was not significantly associated with the receipt of long-term care.

Temporal trends in hospitalizations and 30-day mortality in older patients during the COVID pandemic from March 2020 to July 2021.

BACKGROUND: A reduction in mortality risk of COVID-19 throughout the first wave of the pandemic has been reported, but less is known about later waves. This study aimed to describe changes in hospitalizations and mortality of patients receiving inpatient geriatric care for COVID-19 or other causes during the pandemic. METHODS: Patients 70 years and older hospitalized in geriatric hospitals in Stockholm for COVID-19 or other causes between March 2020-July 2021 were included. Data on the incidence of COVID-positive cases and 30-day mortality of the total ≥ 70-year-old population, in relation to weekly hospitalizations and mortality after hospital admissions were analyzed. Findings The total number of hospitalizations was 5,320 for COVID-19 and 32,243 for non-COVID-cases. In COVID-patients, the 30-day mortality rate was highest at the beginning of the first wave (29% in March-April 2020), reached 17% at the second wave peak (November-December) followed by 11-13% in the third wave (March-July 2021). The mortality in non-COVID geriatric patients showed a similar trend, but of lower magnitude (5-10%). During the incidence peaks, COVID-19 hospitalizations displaced non-COVID geriatric patients. INTERPRETATION: Hospital admissions and 30-day mortality after hospitalizations for COVID-19 increased in periods of high community transmission, albeit with decreasing mortality rates from wave 1 to 3, with a probable vaccination effect in wave 3. Thus, the healthcare system could not compensate for the high community spread of COVID-19 during the pandemic peaks, which also led to displacing care for non-COVID geriatric patients.

External Causes of Death From Death Certificates in Patients With Dementia.

OBJECTIVES: We aim to analyze the risk of death from specific external causes, including falls, complications of medical and surgical care, unintentional injuries, and suicide, in dementia patients. DESIGN: Swedish nationwide cohort study integrating 6 registers from May 1, 2007, through December 31, 2018, including the Swedish Registry for Cognitive/Dementia Disorders (SveDem). SETTING AND PARTICIPANTS: Population-based study. Patients diagnosed with dementia from 2007 to 2018 and up to 4 controls matched on year of birth (±3 years), sex, and region of residence. METHODS: The exposures of this study were diagnosis of dementia and dementia subtypes. Number of deaths and causes of mortality were obtained from death certificates compiled into the Cause of Death Register. Hazard ratios (HRs) and 95% CIs were estimated using Cox and flexible models, adjusted for sociodemographics, medical and psychiatric disorders. RESULTS: The study population included 235,085 patients with dementia [96,760 men (41.2%); mean age 81.5 (SD 8.5) years] and 771,019 control participants [341,994 men (44.4%); mean age 79.9 (SD 8.6) years], over 3,721,687 person-years. Compared with control participants, patients with dementia presented increased risk for unintentional injuries (HR 3.30, 95% CI 3.19-3.40) and falls (HR 2.67, 95% CI 2.54-2.80) during old age (≥75 y), and suicide (HR 1.56, 95% CI 1.02-2.39) in middle age (<65 y). Suicide risk was 5.04 times higher (HR 6.04, 95% CI 4.22-8.66) in patients with both dementia and 2 or more psychiatric disorders relative to controls (incidence rate per person-years, 1.6 vs 0.3). For dementia subtypes, frontotemporal dementia had the highest risks of unintentional injuries (HR 4.28, 95% CI 2.80-6.52) and falls (HR 3.83, 95% CI 1.98-7.41), whereas subjects with mixed dementia were less likely to die from suicide (HR 0.11, 95% CI 0.03-0.46) and complications of medical and surgical care (HR 0.53, 95% CI 0.40-0.70) compared to controls. CONCLUSIONS AND IMPLICATIONS: Suicide risk screening and psychiatric disorders management in early-onset dementia and early interventions for unintentional injuries and falls prevention in older dementia patients should be provided.

Machine learning algorithms for identifying predictive variables of mortality risk following dementia diagnosis: a longitudinal cohort study.

Machine learning (ML) could have advantages over traditional statistical models in identifying risk factors. Using ML algorithms, our objective was to identify the most important variables associated with mortality after dementia diagnosis in the Swedish Registry for Cognitive/Dementia Disorders (SveDem). From SveDem, a longitudinal cohort of 28,023 dementia-diagnosed patients was selected for this study. Sixty variables were considered as potential predictors of mortality risk, such as age at dementia diagnosis, dementia type, sex, body mass index (BMI), mini-mental state examination (MMSE) score, time from referral to initiation of work-up, time from initiation of work-up to diagnosis, dementia medications, comorbidities, and some specific medications for chronic comorbidities (e.g., cardiovascular disease). We applied sparsity-inducing penalties for three ML algorithms and identified twenty important variables for the binary classification task in mortality risk prediction and fifteen variables to predict time to death. Area-under-ROC curve (AUC) measure was used to evaluate the classification algorithms. Then, an unsupervised clustering algorithm was applied on the set of twenty-selected variables to find two main clusters which accurately matched surviving and dead patient clusters. A support-vector-machines with an appropriate sparsity penalty provided the classification of mortality risk with accuracy = 0.7077, AUROC = 0.7375, sensitivity = 0.6436, and specificity = 0.740. Across three ML algorithms, the majority of the identified twenty variables were compatible with literature and with our previous studies on SveDem. We also found new variables which were not previously reported in literature as associated with mortality in dementia. Performance of basic dementia diagnostic work-up, time from referral to initiation of work-up, and time from initiation of work-up to diagnosis were found to be elements of the diagnostic process identified by the ML algorithms. The median follow-up time was 1053 (IQR = 516-1771) days in surviving and 1125 (IQR = 605-1770) days in dead patients. For prediction of time to death, the CoxBoost model identified 15 variables and classified them in order of importance. These highly important variables were age at diagnosis, MMSE score, sex, BMI, and Charlson Comorbidity Index with selection scores of 23%, 15%, 14%, 12% and 10%, respectively. This study demonstrates the potential of sparsity-inducing ML algorithms in improving our understanding of mortality risk factors in dementia patients and their application in clinical settings. Moreover, ML methods can be used as a complement to traditional statistical methods.

Mobile health to promote physical activity in people post stroke or transient ischemic attack - study protocol for a feasibility randomised controlled trial.

BACKGROUND: Physical activity is essential to improve health and reduce the risk of recurrence of stroke or transient ischemic attack (TIA). Still, people post stroke or TIA are often physically inactive and the availability of physical activity promotion services are often limited. This study builds on an existing Australian telehealth-delivered programme (i-REBOUND- Let's get moving) which provides support for home-based physical activity for people post stroke or TIA. The aim of this study is to test the feasibility, acceptability, and preliminary effects of a mobile Health (mHealth) version of the i-REBOUND programme for the promotion of physical activity in people post stroke or TIA living in Sweden. METHODS: One hundred and twenty participants with stroke or TIA will be recruited via advertisement. A parallel-group feasibility randomised controlled trial design with a 1:1 allocation ratio to 1) i-REBOUND programme receiving physical exercise and support for sustained engagement in physical activity through behavioural change techniques, or 2) behavioural change techniques for physical activity. Both interventions will proceed for six months and be delivered digitally through a mobile app. The feasibility outcomes (i.e., reach, adherence, safety and fidelity) will be monitored throughout the study. Acceptability will be assessed using the Telehealth Usability Questionnaire and further explored through qualitative interviews with a subset of both study participants and the physiotherapists delivering the intervention. Clinical outcomes on preliminary effects of the intervention will include blood pressure, engagement in physical activity, self-perceived exercise self-efficacy, fatigue, depression, anxiety, stress and health-related quality of life and will be measured at baseline and at 3, 6 and 12 months after the baseline assessments. DISCUSSION: We hypothesise that the mHealth delivery of the i-REBOUND programme will be feasible and acceptable in people post stroke/TIA living in rural and urban regions of Sweden. The results of this feasibility trial will inform the development of full-scale and appropriately powered trial to test the effects and costs of mHealth delivered physical activity for people after stroke or TIA. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05111951. Registered November 8, 2021.

Association between cholinesterase inhibitors and kidney function decline in patients with Alzheimer's dementia.

Preclinical evidence shows that activation of the cholinergic anti-inflammatory pathway (CAP) may have direct and indirect beneficial effects on the kidney. Cholinesterase inhibitors (ChEIs) are specific Alzheimer's dementia (AD) therapies that block the action of cholinesterases and activate CAP. Here, we explored a plausible effect of ChEIs on slowing kidney function decline by comparing the risk of CKD progression among patients with newly diagnosed AD that initiated ChEI or not within 90 days. Using complete information of routine serum creatinine tests, we evaluated changes in estimated glomerular filtration rate (eGFR) and defined the outcome of chronic kidney disease (CKD) progression as the composite of an eGFR decline of over 30%, initiation of dialysis/transplant or death attributed to CKD. A secondary outcome was death. Inverse probability of treatment-weighted Cox regression was used to estimate hazard ratios. Among 11, 898 patients, 6,803 started on ChEIs and 5,095 did not. Mean age was 80 years (64% women) and the mean eGFR was 68 ml/min/1.73m2. During a median 3.0 years of follow-up, and compared to non-use, ChEI use was associated with 18% lower risk of CKD progression (1,231 events, adjusted hazard ratio 0.82; 95% confidence interval 0.71-0.96) and a 21% lower risk of death (0.79; 0.72-0.86). Results were consistent across subgroups, ChEI subclasses and after accounting for competing risks. Thus, in patients with AD undergoing routine care, use of ChEI (vs no-use) was associated with lower risk of CKD progression.

Conversion Between the Mini-Mental State Examination and the Montreal Cognitive Assessment for Patients With Different Forms of Dementia.

OBJECTIVES: The Mini-Mental Status Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) are 2 frequently used brief cognitive screening tasks. Here, we provide a conversion method from MMSE to MoCA for patients with Alzheimer's dementia, frontotemporal dementia, and Parkinson dementia/Lewy body dementia, as well as for patients with dementia and with or without previous stroke. This conversion is needed as everyday clinical practice varies in their use of the 2 scales, which makes comparisons between studies, meta-analysis, and patient cohorts difficult. DESIGN: Observational cohort study. SETTING AND PARTICIPANTS: A total of 387 patients with recently diagnosed dementia in memory clinics from the Swedish registry for cognitive/dementia disorders (SveDem) from 2007 to 2018. METHODS: Overall, 387 patients of the Swedish registry for cognitive/dementia disorders with both MMSE and MoCA scores were evaluated. An equipercentile equating method was used to convert MMSE to MoCA scores in the different patient populations. Furthermore, receiver operating curves were used to examine whether MMSE or MoCA scores can distinguish between patients with different dementia types. RESULTS: MMSE scores were converted to MoCA scores for all dementia types and depicted in a conversion table. Results show that the equipercentile equating method and log-linear smoothing allow the creation of a conversion table in which for each test score of the MMSE, the equivalent score of the MoCA for each investigated group can be looked up (and vice-versa). CONCLUSIONS AND IMPLICATIONS: This study reports a reliable and easy conversion for transforming MMSE to MoCA scores (and vice-versa) in patients with Alzheimer's dementia, frontotemporal dementia, Parkinson dementia or Lewy body dementia, as well as patients with dementia with and without previous stroke.

Glucose-Lowering Medications and Post-Dementia Survival in Patients with Diabetes and Dementia.

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.

Periodontal conditions and incident dementia: A nationwide Swedish cohort study.

BACKGROUND: Periodontal disease has been proposed as a putative etiological factor for dementia. The aim of this investigation was to compare the incidence of dementia in individuals with or without deep probing pocket depths (DPPD), serving as a proxy for periodontitis. METHODS: In this cohort study, conducted in Sweden, we identified 7992 individuals with DPPD and 29,182 matched individuals without DPPD (non-DPPD), using the Swedish Quality Registry for Caries and Periodontal Diseases (SKaPa). The two groups were followed for incident dementia (mean follow-up time was 7.6 years) based on data from the Swedish Dementia Registry (SveDem). The exposure-outcome relationship was explored by applying the Royston-Parmar (RP) flexible parametric survival model. RESULTS: The incidence of dementia in the two groups was similar. In the DPPD group 137 (1.7%) developed dementia and 470 (1.6%) in the non-DPPD group. The incidence rate of dementia was estimated to be 2.3 per 1000 person-years (95% confidence interval [CI] 1.9 to 2.7) in the DPPD group and 2.1 per 1000 person-years (95% CI 1.9 to 2.3) in the non-DPPD group. The RP model disclosed no association between DPPD and dementia incidence after controlling for potential confounders (the exponentiated coefficient was estimated to 1.13 [95% CI = 0.39 to 3.24]). CONCLUSION: In this sample, no association was revealed between deep probing pocket depths and the incidence of dementia.

The association of antidiabetic medications and Mini-Mental State Examination scores in patients with diabetes and dementia.

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.

Brain Renin-Angiotensin System as Novel and Potential Therapeutic Target for Alzheimer's Disease.

The activation of the brain renin-angiotensin system (RAS) plays a pivotal role in the pathophysiology of cognition. While the brain RAS has been studied before in the context of hypertension, little is known about its role and regulation in relation to neuronal function and its modulation. Adequate blood flow to the brain as well as proper clearing of metabolic byproducts become crucial in the presence of neurodegenerative disorders such as Alzheimer's disease (AD). RAS inhibition (RASi) drugs that can cross into the central nervous system have yielded unclear results in improving cognition in AD patients. Consequently, only one RASi therapy is under consideration in clinical trials to modify AD. Moreover, the role of non-genetic factors such as hypercholesterolemia in the pathophysiology of AD remains largely uncharacterized, even when evidence exists that it can lead to alteration of the RAS and cognition in animal models. Here we revise the evidence for the function of the brain RAS in cognition and AD pathogenesis and summarize the evidence that links it to hypercholesterolemia and other risk factors. We review existent medications for RASi therapy and show research on novel drugs, including small molecules and nanodelivery strategies that can target the brain RAS with potential high specificity. We hope that further research into the brain RAS function and modulation will lead to innovative therapies that can finally improve AD neurodegeneration.

Influence of Education and Income on Receipt of Dementia Care in Sweden.

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.

Potential for improved retention rate by personalized antiseizure medication selection: A register-based analysis.

OBJECTIVE: The first antiseizure medication (ASM) is ineffective or intolerable in 50% of epilepsy cases. Selection between more than 25 available ASMs is guided by epilepsy factors, but also age and comorbidities. Randomized evidence for particular patient subgroups is seldom available. We asked whether register data could be used for retention rate calculations based on demographics, comorbidities, and ASM history, and quantified the potential improvement in retention rates of the first ASM in several large epilepsy cohorts. We also describe retention rates in patients with epilepsy after traumatic brain injury and dementia, patient groups with little available evidence. METHODS: We used medical, demographic, and drug prescription data from epilepsy cohorts from comprehensive Swedish registers, containing 6380 observations. By analyzing 381 840 prescriptions, we studied retention rates of first- and second-line ASMs for patients with epilepsy in multiple sclerosis (MS), brain infection, dementia, traumatic brain injury, or stroke. The rank of retention rates of ASMs was validated by comparison to published randomized control trials. We identified the optimal stratification for each brain disease, and quantified the potential improvement if all patients had received the optimal ASM. RESULTS: Using optimal stratification for each brain disease, the potential improvement in retention rate (percentage points) was MS, 20%; brain infection, 21%; dementia, 14%; trauma, 21%; and stroke, 14%. In epilepsy after trauma, levetiracetam had the highest retention rate at 80% (95% confidence interval [CI] = 65-89), exceeding that of the most commonly prescribed ASM, carbamazepine (p = .04). In epilepsy after dementia, lamotrigine (77%, 95% CI = 68-84) and levetiracetam (74%, 95% CI = 68-79) had higher retention rates than carbamazepine (p = .006 and p = .01, respectively). SIGNIFICANCE: We conclude that personalized ASM selection could improve retention rates and that national registers have potential as big data sources for personalized medicine in epilepsy.

Decreased Mortality Over Time During the First Wave in Patients With COVID-19 in Geriatric Care: Data From the Stockholm GeroCovid Study.

OBJECTIVE: To describe temporal changes in treatment, care, and short-term mortality outcomes of geriatric patients during the first wave of the COVID-19 pandemic. DESIGN: Observational study. SETTING AND PARTICIPANTS: Altogether 1785 patients diagnosed with COVID-19 and 6744 hospitalized for non-COVID-19 causes at 7 geriatric clinics in Stockholm from March 6 to July 31, 2020, were included. METHODS: Across admission month, patient vital signs and pharmacological treatment in relationship to risk for in-hospital death were analyzed using the Poisson regression model. Incidence rates (IRs) and incidence rate ratios (IRRs) of death are presented. RESULTS: In patients with COVID-19, the IR of mortality were 27%, 17%, 10%, 8%, and 2% from March to July, respectively, after standardization for demographics and vital signs. Compared with patients admitted in March, the risk of in-hospital death decreased by 29% [IRR 0.71, 95% confidence interval (CI) 0.51-0.99] in April, 61% (0.39, 0.26-0.58) in May, 68% (0.32, 0.19-0.55) in June, and 86% (0.14, 0.03-0.58) in July. The proportion of patients admitted for geriatric care with oxygen saturation <90% decreased from 13% to 1%, which partly explains the improvement of COVID-19 patient survival. In non-COVID-19 patients during the pandemic, mortality rates remained relatively stable (IR 1.3%-2.3%). Compared with non-COVID-19 geriatric patients, the IRR of death declined from 11 times higher (IRR 11.7, 95% CI 6.11-22.3) to 1.6 times (2.61, 0.50-13.7) between March and July in patients with COVID-19. CONCLUSIONS AND IMPLICATIONS: Mortality risk in geriatric patients from the Stockholm region declined over time throughout the first pandemic wave of COVID-19. The improved survival rate over time was only partly related to improvement in saturation status at the admission of the patients hospitalized later throughout the pandemic. Lower incidence during the later months could have led to less severe hospitalized cases driving down mortality.