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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: 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 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

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 naive 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.

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.

The study aimed to investigate the link between physiological responses at encoding and subsequent memory of emotional stimuli, differing in two dimensions: valence and arousal. The participants (all male) freely viewed emotional images, while their pupil size and heart rate were recorded. Then, they were presented with a recognition task. Both pupil constriction and heart rate deceleration evoked by an image onset at the encoding predicted its later correct recognition. However, these effects interacted with valence and arousal. Increased pupillary constriction predicted correct recognition particularly well for low-arousing and negatively valenced images. Deeper heart rate deceleration was related to higher rate of correct recognition mainly in the case of negative images. The results show also an interaction between valence and arousal in their effect on memory. Higher arousal was linked to better recognition, but only when images were of neutral or positive valence. In contrast, negative images were remembered accurately, regardless of the level of arousal. This pattern of results supports the primacy of negative information in early memory consolidation. Overall, we demonstrate that physiological reactions at encoding - which can be linked to the depth of stimulus processing during memory formation - predict recognition accuracy. The emotional load of stimuli further modulates the prediction strength.

Changes that occur during the menstrual cycle affect various aspects of behavior, cognition, and emotion. Here, we focused on potential differences between early follicular and midluteal phases in the way women process images of behaviorally relevant content categories: children, threat, disgust, erotic scenes, low- and high-calorie food. Using eye-tracking, we examined women's engagement of attention in the key region of each image in a free-viewing condition. Specifically, we tested how quickly attention was attracted to these regions and for how long it was held there. Participants took part in two experimental sessions, one in the early follicular and one in the midluteal phase. The results showed that in the midluteal phase attention was attracted to the key region earlier than in the early follicular phase: the first fixation more often fell within the key region and there were fewer fixations preceding it. While the effect of the phase in terms of the capture of attention did not depend on the image category, the effect regarding the hold of attention was category-specific, concerning the disgust category only. Specifically, in the midluteal phase the duration of the exploration of the key region between reaching it for the first time and first exiting it was shorter, which might be due to heightened sensitivity to disgusting stimuli in this period. Overall, our results indicate the occurrence of changes in attentional processing of emotional scenes related to the menstrual cycle, which seem to differ depending on the aspect of attention deployment: in the midluteal phase the effect of enhancing orienting was general and concerned any important visual information, whereas the effect of the shortened hold of attention appeared to be limited to specific content.

BackgroundThe majority of individuals with dementia will suffer from psychological and behavioral symptoms of dementia (BPSD). There is limited number of studies investigating BPSD in different types of dementia.ObjectivesTo 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 (UNS) in individuals residing in long-term care facilities.MethodsWe 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.ResultsThe 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 (in FTD), agitation (VaD, in PDD, unspecified dementia), elation/euphoria (in DLB), anxiety (Mixed, VaD, unspecified dementia), disinhibition (in PDD); irritability (in DLB, FTD, unspecified dementia), aberrant motor behavior (in Mixed, VaD, unspecified dementia), sleep and night-time behavior changes (in unspecified dementia). Higher risk of delusions (in DLB), hallucinations (in DLB, PDD), apathy (VaD, FTD), disinhibition (in FTD) and appetite and eating abnormalities (in FTD) were also found in comparison to AD.ConclusionsBPSD was common in all types of dementia, with the most common symptoms being aberrant motor behavior, agitation, and irritability. Additionally, presentation of BPSD differ in different dementia types.

The core symptoms of different dementia subtypes are the behavioral and psychological symptoms of dementia (BPSD) and its neuropsychiatric symptoms (NPS). BPSD symptoms may occur at any stage in the case of dementia due to Alzheimer’s disease (AD), whereas they tend to occur early on in the case of its behavioral variant frontotemporal dementia or dementia with Lewy bodies and are essential for diagnosis. BPSD treatment consists of non-pharmacological as well as pharmacological interventions, with non-pharmacological interactions being suggested as first-line treatment. Agitation, psychotic features, apathy, depression, and anxiety may not respond to acetylcholinesterase inhibitors or memantine in AD cases; therefore, antipsychotics, antidepressants, sedative drugs or anxiolytics, and antiepileptic drugs are typically prescribed. However, such management of BPSD can be complicated by hypersensitivity to antipsychotic drugs, as observed in DLB, and a lack of effective pro-cognitive treatment in the case of frontotemporal dementia. The present paper reviews current knowledge of the management of BPSD and its limitations and discusses on-going clinical trials and future therapeutic options.

ObjectiveCholinesterase 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 methodsWe 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.ResultsAfter 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.ConclusionsWe 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.

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. Funding Agencies|Swedish Brain Power network; Swedish Associations of Local Authorities and Regions; Gun och Bertil Stohnes Stiftelse; CIMED grant; Alzheimerfonden; Swedish Research Council [Drn 2012-2291, Drn 2016-02317]; Stockholm County Council (ALF project)

Background: Behavioral and Psychological symptoms of Dementia (BPSD) are a heterogeneous group of clinical phenomena that is subjectively experienced by the patient and/or observable by an examiner (e.g., caregiver, physician) consisting in disturbed emotions, perception, thought, motor activity, and altered personality. There are recommendations to limit antipsychotic use in patients with dementia, and the big educational effort is made to follow them. In Sweden antipsychotics use changed from 10.1% in 2007-2008 to 5.2% in 2014-2015. Aims: The aim of the study is to analyze the actors associated with treatment and mortality of dementia patients, particularly those suffering from BPSD. Particularly we focus on assessing all-cause mortality patients with dementia treated with antipsychotic drugs (APDs). Methods: We have analyzed 58,412 patients newly diagnosed with dementia. We have found that 2526 of the patients were prescribed APDs (602 typical APDs and 1833 atypical APDs)- 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). We have also stratified the results. Conclusions: The risk of death in patients with dementia was increased in group that used atypical and typical APDs. Our study gives more evidence to advice caution in APD prescription for patients with dementia.