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.

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.

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.

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.

Metabolic patterns across core features in dementia with lewy bodies.

OBJECTIVE: To identify brain regions whose metabolic impairment contributes to dementia with Lewy bodies (DLB) clinical core features expression and to assess the influence of severity of global cognitive impairment on the DLB hypometabolic pattern. METHODS: Brain fluorodeoxyglucose positron emission tomography and information on core features were available in 171 patients belonging to the imaging repository of the European DLB Consortium. Principal component analysis was applied to identify brain regions relevant to the local data variance. A linear regression model was applied to generate core-feature-specific patterns controlling for the main confounding variables (Mini-Mental State Examination [MMSE], age, education, gender, and center). Regression analysis to the locally normalized intensities was performed to generate an MMSE-sensitive map. RESULTS: Parkinsonism negatively covaried with bilateral parietal, precuneus, and anterior cingulate metabolism; visual hallucinations (VH) with bilateral dorsolateral-frontal cortex, posterior cingulate, and parietal metabolism; and rapid eye movement sleep behavior disorder (RBD) with bilateral parieto-occipital cortex, precuneus, and ventrolateral-frontal metabolism. VH and RBD shared a positive covariance with metabolism in the medial temporal lobe, cerebellum, brainstem, basal ganglia, thalami, and orbitofrontal and sensorimotor cortex. Cognitive fluctuations negatively covaried with occipital metabolism and positively with parietal lobe metabolism. MMSE positively covaried with metabolism in the left superior frontal gyrus, bilateral-parietal cortex, and left precuneus, and negatively with metabolism in the insula, medial frontal gyrus, hippocampus in the left hemisphere, and right cerebellum. INTERPRETATION: Regions of more preserved metabolism are relatively consistent across the variegate DLB spectrum. By contrast, core features were associated with more prominent hypometabolism in specific regions, thus suggesting a close clinical-imaging correlation, reflecting the interplay between topography of neurodegeneration and clinical presentation in DLB patients. Ann Neurol 2019;85:715-725.

Metabolic Correlates of Dopaminergic Loss in Dementia with Lewy Bodies.

BACKGROUND: Striatal dopamine deficiency and metabolic changes are well-known phenomena in dementia with Lewy bodies and can be quantified in vivo by 123 I-Ioflupane brain single-photon emission computed tomography of dopamine transporter and 18 F-fluorodesoxyglucose PET. However, the linkage between both biomarkers is ill-understood. OBJECTIVE: We used the hitherto largest study cohort of combined imaging from the European consortium to elucidate the role of both biomarkers in the pathophysiological course of dementia with Lewy bodies. METHODS: We compared striatal dopamine deficiency and glucose metabolism of 84 dementia with Lewy body patients and comparable healthy controls. After normalization of data, we tested their correlation by region-of-interest-based and voxel-based methods, controlled for study center, age, sex, education, and current cognitive impairment. Metabolic connectivity was analyzed by inter-region coefficients stratified by dopamine deficiency and compared to healthy controls. RESULTS: There was an inverse relationship between striatal dopamine availability and relative glucose hypermetabolism, pronounced in the basal ganglia and in limbic regions. With increasing dopamine deficiency, metabolic connectivity showed strong deteriorations in distinct brain regions implicated in disease symptoms, with greatest disruptions in the basal ganglia and limbic system, coincident with the pattern of relative hypermetabolism. CONCLUSIONS: Relative glucose hypermetabolism and disturbed metabolic connectivity of limbic and basal ganglia circuits are metabolic correlates of dopamine deficiency in dementia with Lewy bodies. Identification of specific metabolic network alterations in patients with early dopamine deficiency may serve as an additional supporting biomarker for timely diagnosis of dementia with Lewy bodies. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Do Acetylcholinesterase Inhibitors Prevent or Delay Psychotropic Prescribing in People With Dementia? Analyses of the Swedish Dementia Registry.

OBJECTIVES: To investigate whether acetylcholinesterase inhibitor (AChEI) use prevents or delays subsequent initiation of psychotropic medications in people with Alzheimer's disease (AD) and Lewy body dementia (LBD). METHODS: Cohort study of 17,763 people with AD and LBD, without prior psychotropic use at time of dementia diagnosis, registered in the Swedish Dementia Registry from 2007 to 2015. Propensity score-matched regression models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between time-dependent AChEI use and risk of psychotropic initiation. RESULTS: Compared with matched comparators, AChEI users had a lower risk of antipsychotic (HR: 0.85, 95%CI: 0.75-0.95) and anxiolytic (HR: 0.76, 95%CI: 0.72-0.80) initiation. In subanalyses, this association remained significant at higher AChEI doses, and in AD but not LBD. There were no associations between AChEI use and initiation of antidepressants or hypnotics. CONCLUSION: AChEI use may be associated with lower risk of antipsychotic and anxiolytic initiation in AD, particularly at higher doses. Further investigation into aceytylcholinesterase inhibitors in behavioral and psychological symptoms of dementia management in LBD is warranted.

Controlling for selective dropout in longitudinal dementia data: Application to the SveDem registry.

INTRODUCTION: Loss to follow-up in dementia studies is common and related to cognition, which worsens over time. We aimed to (1) describe dropout and missing cognitive data in the Swedish dementia registry, SveDem; (2) identify factors associated with dropout; and (3) estimate propensity scores and use them to adjust for dropout. METHODS: Longitudinal cognitive data were obtained from 53,880 persons from the SveDem national quality dementia registry. Inverse probability of censoring weights (IPCWs) were estimated using a logistic regression model on dropout. RESULTS: The mean annualized rate of change in Mini-Mental State Examination (MMSE) in those with a low MMSE (0 to 10) was likely underestimated in the complete case analysis (+1.5 points/year) versus the IPCW analysis (-0.3 points/year). DISCUSSION: Handling dropout by IPCWs resulted in plausible estimates of cognitive decline. This method is likely of value to adjust for biased dropout in longitudinal cohorts of dementia.

The caregiving phenomenon and caregiver participation in dementia.

BACKGROUND: Dementia presents barriers to the collaboration between individuals and the healthcare system. Caregivers perform multiple functions helping patients with basic and instrumental activities but also communicating and mediating the dyads' needs within the broader social group. Interventions focusing on caregivers show that caregiver burden can be reduced, improving patient outcomes in a cost-effective way, but the generalisation of these findings is limited by several factors such as low participation rates of caregivers in studies. There is a global push to increase patient participation in health care, but this can be difficult for patients with dementia. Caregiver participation has arisen as a substitute, but there is a lack of standardised definitions, goals and outcome measurement tools for this participation. METHODS: In 2015, the Swedish Association of Local Authorities and Regions commissioned a study on possibilities of increasing caregiver participation within the Swedish Dementia Registry (SveDem). This discussion paper updates and adapts that report, aiming to broadly summarise the caregiving phenomenon in order to provide a backdrop for clinicians seeking to understand the legal, ethical and practical considerations of caregiver participation in dementia. Relevant literature on caregiver participation is presented, and its definition, extent and practical implementation are discussed. DISCUSSION: The Swedish legal framework compels care providers to facilitate patient and caregiver participation in dementia and provides support to caregivers through the local level of government, but further work is needed to clarify and define the extension and form that this participation must take in clinical practice. Advanced directives are one step in extending patient participation to the period of advanced dementia. CONCLUSION: Little research exists on caregiver participation. There is a need to develop a framework for caregiver and patient participation to determine the extent, type and form that such participation should take in health care, research and quality initiatives pertaining to persons with dementia.

Dental care utilization in patients with different types of dementia: A longitudinal nationwide study of 58,037 individuals.

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.

Acetylcholinesterase inhibitors and risk of stroke and death in people with dementia.

INTRODUCTION: The aim of this study was to investigate the association between acetylcholinesterase inhibitor (AChEI) use and risk of ischemic stroke and death in people with dementia. METHODS: A cohort study of 44,288 people with dementia registered in the Swedish Dementia Registry from 2007 to 2014. Propensity score-matched competing risk regression models were used to compute hazard ratios and 95% confidence intervals for the association between time-dependent AChEI use and risk of stroke and death. RESULTS: Compared with matched controls, AChEI users had a lower risk of stroke (hazard ratio: 0.85, 95% confidence interval: 0.75-0.95) and all-cause death (hazard ratio: 0.76, 95% confidence interval: 0.72-0.80). After considering competing risk of death, high doses (≥1.33 defined daily doses) of AChEI remained significantly associated with reduced stroke risk. DISCUSSION: The use of AChEIs in people with dementia may be associated with reduced risk of ischemic stroke and death. These results call for a closer examination of the cardiovascular effects of AChEIs.

Mortality and nursing home placement of dementia patients in rural and urban areas: a cohort study from the Swedish Dementia Registry.

BACKGROUND: Life in rural and urban areas differs in regard to social support and health care. Our aim was to examine the association between nursing home placement and survival of patients with dementia living in urban vs. rural areas. METHODS: We performed a longitudinal cohort study of patients with dementia at time of diagnosis (n = 58 154) and at first follow-up (n = 21 522) including patients registered from 2007 through 2014 in the Swedish Dementia Registry (SveDem). Descriptive statistics are shown. Odds ratios with 95% CI are presented for nursing home placement and hazard ratios for survival analysis. RESULTS: In age- and sex-adjusted analyses, patients living in urban areas were more likely to be in nursing homes at the time of dementia diagnosis than patients in rural areas (1.49, 95% CI: 1.29-1.73). However, there were no differences in rural vs urban areas in either survival after dementia diagnosis (urban: 0.99, 0.95-1.04, intermediate: 1.00, 0.96-1.04), or nursing home placement at first follow-up (urban: 1.00, 0.88-1.13; intermediate: 0.95, 0.85-1.06). CONCLUSION: Persons with dementia living in rural areas are less likely to live in a nursing home than their urban counterparts at the time of dementia diagnosis, but these differences disappear by the time of first follow-up. Differences in access to nursing homes between urban and rural settings could explain these findings. Results should be considered in the future healthcare decisions to ensure equality of health care across rural and urban areas.

Differences in diagnostic process, treatment and social Support for Alzheimer's dementia between primary and specialist care: resultss from the Swedish Dementia Registry.

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.

Parkinson Disease and Dementia.

Dementia is a frequent complication of Parkinson disease (PD) with a yearly incidence of around 10% of patients with PD. Lewy body pathology is the most important factor in the development of Parkinson disease dementia (PDD) and there is evidence for a synergistic effect with ß-amyloid. The clinical phenotype in PDD extends beyond the dysexecutive syndrome that is often present in early PD and encompasses deficits in recognition memory, attention, and visual perception. Sleep disturbances, hallucinations, neuroleptic sensitivity, and fluctuations are often present. This review provides an update on current knowledge of PDD including aspects of epidemiology, pathology, clinical presentation, management, and prognosis.

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.

Acute Kidney Injury and Its Association With Dementia and Specific Dementia Types: Findings From a Population-Based Study in Sweden.

BACKGROUND AND OBJECTIVES: Preclinical studies suggest that acute kidney injury (AKI) results in biochemical and pathologic changes in the brain. We aimed to explore the association between experiencing AKI and subsequent risks of developing dementia. METHODS: We conducted a study involving individuals aged 65 years and older in Stockholm from 2006 to 2019, who were free from dementia diagnosis and had data on kidney function. The exposure was an episode of AKI (time varying), ascertained by issued clinical diagnoses and transient creatinine elevations according to Kidney Disease Improving Global Outcomes criteria. The outcome was all-cause dementia and specific types of dementia, ascertained by clinically confirmed cases in the Swedish registry of cognitive/dementia disorders, the presence of 2 issued dementia diagnoses in outpatient care, or initiation of specific antidementia medications. We investigated associations with dementia through Cox proportional hazard regression by AKI, severity levels of AKI, AKI recurrence, and setting (community-acquired or hospital-acquired AKI). RESULTS: We included 305,122 individuals with a median age of 75 ± 8 years (56.6% women). During a median follow-up of 12.3 (interquartile range 8.7-13.3) years, there were 79,888 individuals (26%) suffering from at least 1 episode of AKI and 47,938 incident cases (16%) of dementia. The rate of dementia cases was 37.0 per 1,000 person-years (95% CI 36.2-37.8) after developing AKI, which was approximately 2 times higher than the rate observed during the periods before AKI (17.3, 95% CI 17.2-17.5). After multivariable adjustment, developing AKI was associated with a 49% higher rate of subsequent dementia (adjusted hazard ratio hazard ratio [HR] 1.49, 95% CI 1.45-1.53). This pattern was consistent across dementia types, with HRs of 1.88 (95% CI 1.53-2.32), 1.47 (1.38-1.56), and 1.31 (1.25-1.38) for dementia with Lewy bodies and Parkinson disease with dementia, vascular dementia, and Alzheimer dementia, respectively. Risk associations were stronger in magnitude across more severe AKIs and in hospital-acquired vs community-acquired AKI. DISCUSSION: Individuals who experienced an AKI were at increased risk of receiving a diagnosis of dementia.

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.

Cerebrovascular and Alzheimer's disease biomarkers in dementia with Lewy bodies and other dementias.

Co-pathologies are common in dementia with Lewy bodies and other dementia disorders. We investigated cerebrovascular and Alzheimer's disease co-pathologies in patients with dementia with Lewy bodies in comparison with patients with mild cognitive impairment, Alzheimer's disease, mixed dementia, vascular dementia or Parkinson's disease with dementia and cognitively unimpaired participants. We assessed the association of biomarkers of cerebrovascular and Alzheimer's disease co-pathologies with medial temporal atrophy and global cognitive performance. Additionally, we evaluated whether the findings were specific to dementia with Lewy bodies. We gathered a multi-cohort dataset of 4549 participants (dementia with Lewy bodies = 331, cognitively unimpaired = 1505, mild cognitive impairment = 1489, Alzheimer's disease = 708, mixed dementia = 268, vascular dementia = 148, Parkinson's disease with dementia = 120) from the MemClin Study, Karolinska Imaging in Dementia Study, Gothenburg H70 Birth Cohort Studies and the European DLB Consortium. Cerebrovascular co-pathology was assessed with visual ratings of white matter hyperintensities using the Fazekas scale through structural imaging. Alzheimer's disease biomarkers of ß-amyloid and phosphorylated tau were assessed in the cerebrospinal fluid for a subsample (N = 2191). Medial temporal atrophy was assessed with visual ratings and global cognition with the mini-mental state examination. Differences and associations were assessed through regression models, including interaction terms. In dementia with Lewy bodies, 43% had a high white matter hyperintensity load, which was significantly higher than that in cognitively unimpaired (14%), mild cognitive impairment (26%) and Alzheimer's disease (27%), but lower than that in vascular dementia (62%). In dementia with Lewy bodies, white matter hyperintensities were associated with medial temporal atrophy, and the interaction term showed that this association was stronger than that in cognitively unimpaired and mixed dementia. However, the association between white matter hyperintensities and medial temporal atrophy was non-significant when ß-amyloid was included in the model. Instead, ß-amyloid predicted medial temporal atrophy in dementia with Lewy bodies, in contrast to the findings in mild cognitive impairment where medial temporal atrophy scores were independent of ß-amyloid. Dementia with Lewy bodies had the lowest performance on global cognition, but this was not associated with white matter hyperintensities. In Alzheimer's disease, global cognitive performance was lower in patients with more white matter hyperintensities. We conclude that white matter hyperintensities are common in dementia with Lewy bodies and are associated with more atrophy in medial temporal lobes, but this association depended on ß-amyloid-related pathology in our cohort. The associations between biomarkers were overall stronger in dementia with Lewy bodies than in some of the other diagnostic groups.

Extreme delta brush in a patient with anti-NMDAR encephalitis.

Anti-N-methyl-D-aspartate receptor encephalitis is a severe, potentially treatable, disorder and prognosis depends on early recognition and prompt immunotherapy. We report a case of anti-N-methyl-D-aspartate receptor encephalitis with atypical age and gender, and a characteristic electroencephalographic pattern that supported the diagnosis. A 66-year-old male presented with psychiatric disturbances and focal seizures with alteration of consciousness, and progressed to a state of akinetic mutism. Auxiliary tests were negative or non-specific for anti-NMDAR encephalitis. Electroencephalographic monitoring revealed a unique pattern; the extreme delta brush. The patient improved with immunotherapy and was asymptomatic at six months of follow-up. Ancillary testing was positive for anti-N-methyl-D-aspartate receptor antibodies. Extreme delta brush is a recently described electroencephalographic pattern presenting in only one third of patients with anti-N-methyl-D-aspartate receptor encephalitis. The identification of this pattern, as in our case, may guide early diagnosis and treatment of anti-N-methyl-D-aspartate receptor encephalitis.

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.