The Paintings Reveal the Story: Case Study of a Well-Known Swedish Artist Suffering from Alzheimer's Disease.

Background: Creativity is a multifaceted, complex, activity, and as such is an overarching function of the brain rather than being confined to a specific structure or region.Alzheimer's disease effects several cognitive domains involved in the creative process of producing art. Objective: We analyze the art of a well-known Swedish visual artist who suffered from Alzheimer's disease to determine if, and in what way, his art and creative process might have been influenced by the disease. Methods: We compared his artistic process and artwork along with information from his spouse, medical r ecords, and cognitive tests as well as reviews of exhibitions written by art critics. Results: We show that not only did the artist continue to produce artwork well into a major decline in cognitive function, according to commonly used tests, but he could continue to do so for even longer with some assistance from his spouse. However, the artwork changed considerably as the disease progressed. We hypothesize that there is a substantial lack of representation of creative ability and function in cognitive tests. Conclusions: Signs of the Alzheimer's disease can be seen in the early artwork if viewed by critics and those with more specialized knowledge into the artist's production. Further analysis of the complex interaction between complex neural activities, such as artistic creativity, and cognitive diseases is warranted and might provide insight in the field of neurological degenerative disease.

Diagnostic Accuracy of the Swedish Version of the Multicultural Cognitive Examination for Cognitive Assessment in Swedish Memory Clinics.

BACKGROUND: Cognitive assessment for foreign-born individuals is suboptimal. The Multicultural Cognitive Examination (MCE) was developed for use in culturally, linguistically and educationally diverse populations. The MCE includes the Rowland Universal Dementia Assessment Scale (RUDAS) and performs assessment of memory, verbal fluency, and visuospatial function. OBJECTIVE: To compare the psychometric properties of the Swedish version of the Multicultural Cognitive Examination (MCE-S) with the Swedish versions of the RUDAS (RUDAS-S), the Mini-Mental State Examination (MMSE-SR), and the Clock Drawing Test (CDT), and to explore the ability of the MCE-S test to differentiate patients with and without dementia in a multicultural population. METHODS: 117 outpatients at four memory clinics were tested using the MCE-S to complement the routine cognitive assessment. RESULTS: Significant differences between patients with and without dementia were observed for all MCE-S components. There were significant differences between foreign-born and Swedish-born patients in the MMSE-SR, but not in the MCE-S or the RUDAS-S. The MCE-S, had good diagnostic performance for detecting dementia (AUC, 0.82), and was at least as good as the RUDAS-S alone (AUC, 0.79). The MCE-S also distinguished Alzheimer's disease (AD) from non-AD dementia. Contrary to expectations, the MCE-S was also at least as good as the MMSE-SR among the Swedish-born patients. CONCLUSIONS: The MCE-S is adequate for detecting dementia in both foreign-born and Swedish-born populations. Based on the cultural diversity of general society, adapted cognitive tests that can be used for everyone are practical and beneficial for both patients and health-care professionals. Further studies are needed within primary care.

Development of the Swedish anticholinergic burden scale (Swe-ABS).

BACKGROUND: Drugs with anticholinergic properties are associated with cognitive adverse effects, especially in patients vulnerable to central muscarinic antagonism. A variety of drugs show weak, moderate or strong anticholinergic effects. Therefore, the cumulative anticholinergic burden should be considered in patients with cognitive impairment. This study aimed to develop a Swedish Anticholinergic Burden Scale (Swe-ABS) to be used in health care and research. METHODS: A systematic literature review was conducted in PubMed and Ovid Embase to identify previously published tools quantifying anticholinergic drug burden (i.e., exposure). Drugs and grading scores (0-3, no to high anticholinergic activity) were extracted from identified lists. Enteral and parenteral drugs authorized in Sweden were included. Drugs with conflicting scores in the existing lists were assessed by an expert group. Two drugs that were not previously assessed were also added to the evaluation process. RESULTS: The systematic literature search identified the following nine anticholinergic burden scales: Anticholinergic Activity Scale, Anticholinergic Burden Classification, updated Anticholinergic Cognitive Burden scale, Anticholinergic Drug Scale, Anticholinergic Load Scale, Anticholinergic Risk Scale, updated Clinician-rated Anticholinergic Scale, German Anticholinergic Burden Scale and Korean Anticholinergic Burden Scale. A list of drugs with significant anticholinergic effects provided by The Swedish National Board of Health and Welfare was included in the process. The suggested Swe-ABS consists of 104 drugs scored as having weak, moderate or strong anticholinergic effects. Two hundred and fifty-six drugs were listed as having no anticholinergic effects based on evaluation in previous scales. In total, 62 drugs were assessed by the expert group. CONCLUSIONS: Swe-ABS is a simplified method to quantify the anticholinergic burden and is easy to use in clinical practice. Publication of this scale might make clinicians more aware of drugs with anticholinergic properties and patients' total anticholinergic burden. Further research is needed to validate the Swe-ABS and evaluate anticholinergic exposure versus clinically significant outcomes.

Exploring the prevalence of undetected bradyarrhythmia in dementia with Lewy bodies.

PURPOSE: To explore the prevalence of undetected bradyarrhythmia in a cohort of people with dementia with Lewy bodies. METHODS: Thirty participants diagnosed with dementia with Lewy bodies were enrolled from three memory clinics in southern Sweden between May 2021 and November 2022. None had a history of high-grade atrioventricular block or sick sinus syndrome. Each participant underwent orthostatic testing, cardiac [123I]metaiodobenzylguanidine scintigraphy and 24-h ambulatory electrocardiographic monitoring. Concluding bradyarrhythmia diagnosis was obtained until the end of December 2022. RESULTS: Thirteen participants (46.4%) had bradycardia at rest during orthostatic testing and four had an average heart rate < 60 beats per minute during ambulatory electrocardiographic monitoring. Three participants (10.7%) received a diagnosis of sick sinus syndrome, of whom two received pacemaker implants to manage associated symptoms. None received a diagnosis of second- or third-degree atrioventricular block. CONCLUSION: This report showed a high prevalence of sick sinus syndrome in a clinical cohort of people with dementia with Lewy bodies. Further research on the causes and consequences of sick sinus syndrome in dementia with Lewy bodies is thus warranted.

Pacemaker Implants and Their Influence on the Daily Life of Patients with Dementia with Lewy Bodies: A Qualitative Case Study.

INTRODUCTION: Dementia with Lewy bodies (DLB) is an incurable form of dementia associated with detriments to the daily life of patients and carers from their family. Symptoms of orthostatic hypotension, syncope, and falls are supportive of DLB diagnosis. These symptoms may also be present among people with sick sinus syndrome (SSS), and subsequent pacemaker treatment to manage bradyarrhythmia is associated with improved cognitive function. The prevalence of SSS seems to be higher among people with underlying Lewy body pathology compared to the general age-matched population (5.2% vs. 0.17%). To our knowledge, how people with DLB and their family carers may experience pacemaker treatment to manage bradyarrhythmia has not been previously reported. Therefore, the aim of this study was to explore how people with DLB experience daily life following a pacemaker implant to manage associated symptoms of bradyarrhythmia. METHODS: A qualitative case study design was used. Two men with DLB and their spouse carers were repeatedly interviewed as a dyad within 1 year following implant of a dual-chamber rate-adaptive (DDD-CLS) pacemaker to manage SSS in the men. Content analysis was used to assess the qualitative interview data collected. RESULTS: Three categories emerged: (1) gaining control, (2) maintaining a social life, and (3) being influenced by concurrent diseases. Less syncope/falls and remote pacemaker monitoring increased a sense of control in everyday life, while perceived physical and/or cognitive improvements influenced social participation. The men were still affected by concurrent diseases, which continuously influenced each couple's daily life. CONCLUSION: Identifying and managing concurrent bradyarrhythmia through a pacemaker implant could improve well-being for people with DLB.

A Retrospective Study on Clinical Assessment of Cognitive Impairment in a Swedish Cohort: Is There Inequality Between Natives and Foreign-Born?

BACKGROUND: People with a migration background are underrepresented in dementia research and disfavored in assessment and treatment, and many foreign-born individuals with dementia remain undiagnosed. OBJECTIVE: The aim of this study was to examine whether there is inequality in the clinical assessment of dementia between native and foreign-born individuals in Sweden. METHODS: Information was gathered retrospectively from a cohort of 91 native and 36 foreign-born patients attending four memory clinics in Skåne, Sweden. Data included information on cognitive test results, cerebrospinal fluid biomarkers, scores at structural imaging scales of global cortical atrophy (GCA), medial temporal lobe atrophy (MTA) and the Fazekas scale, laboratory measures of thyroid-stimulating hormone, calcium, albumin, homocysteine, hemoglobin, cobalamin (vitamin B12), and folate (vitamin B9), contact with health care, and treatment. RESULTS: Foreign-born patients had lower educational level and scored lower on Mini-Mental State Examination and Clock Drawing Test (p < 0.001-0.011). Relatives initiated contact with health care to a higher extent in the foreign-born group (p = 0.031). Foreign-born patients had less white matter lesions (p = 0.018). Additionally, Alzheimer's disease (AD) biomarkers were significantly less used in foreign-born patients to support an AD diagnosis (p = 0.001). No significant differences were found for scores on GCA and MTA, laboratory measures, or initiated treatment. CONCLUSION: Although native and foreign-born patients were predominantly homogenous regarding examined variables, differences in the diagnostic process and underlying biological correlates of dementia exist and need to be further investigated in a larger sample.

Diagnostic Accuracy of the Swedish Version of the Rowland Universal Dementia Assessment Scale (RUDAS-S) for Multicultural Cognitive Screening in Swedish Memory Clinics.

BACKGROUND: The number of people with a migration background and dementia is increasing in Europe. All patients with suspected dementia have the right to an appropriate cognitive assessment and correct diagnosis for optimal treatment and support. Rowland Universal Dementia Assessment Scale (RUDAS) cognitive screening instrument is less affected by language, culture, and educational background, and adapted for use in multicultural populations. OBJECTIVE: To compare the diagnostic accuracy of RUDAS-S to the Swedish version of Mini-Mental State Examination (MMSE-SR) for detecting dementia in a multicultural group of outpatients in Swedish memory clinics. METHODS: We tested 123 outpatients (36 nonnative Swedish), in 4 memory clinics in Southern Sweden with RUDAS-S to supplement the usual cognitive assessment. RESULTS: RUDAS-S had moderate to good diagnostic performance for detecting dementia in a multicultural population in Sweden, with an area under the receiver operating characteristic curve (AUC) of 0.81. At a cutoff score <25 its sensitivity was 0.92, specificity 0.60, and accuracy 76%. The AUC for the MMSE-SR was 0.79. At a cutoff score <23 its sensitivity was 0.65, specificity 0.81, and accuracy 73%. CONCLUSION: RUDAS-S is at least as accurate as MMSE-SR for detecting dementia in memory clinics in Sweden and can be used for all patients undergoing a cognitive assessment, irrespective of their cultural, language, and educational background. However, there is a need for other cross-cultural cognitive tests to complement RUDAS-S to extend cognitive examination.

"I Know Hyena. Do you Know Hyena?" Challenges in Interpreter-Mediated Dementia Assessment, Focusing on the Role of the Interpreter.

Dementia assessment requires functional communication and interaction between healthcare professionals and the patient being assessed. These can be affected by the requirement for an interpreter to communicate with the patient. The purpose of this study was to elucidate the interactions between patient, healthcare professionals and interpreter, focusing on the role of the interpreter and the challenges that may arise in interpreter-mediated dementia assessment. The study had an ethnographic design in which the data consisted of audio and video recordings of 19 dementia assessments conducted in the presence of an interpreter. The data were analyzed using the constant comparative method. The results showed that the interpreter could affect the patient's performance and results during the dementia assessment. The interpreter could alter the meaning and content of what was communicated, sometimes change information and instructions exchanged between the patient and healthcare professionals, could avoid interpreting everything being said, and occasionally made their own corrections to what was being communicated. This occurred mainly because of the interpreter's lack of linguistic skills and the interpreter failing to adhere to the ethical guidelines governing their profession. These challenges could also occur when the interpreter was not familiar with the context of dementia assessment. Alterations made by the interpreter to what was being communicated could lead to incorrect evaluation of the patient's cognitive abilities and health status. This, in turn, may lead to misjudgment of the patient's remaining resources and symptoms and their required treatment and support.

Choral Singing Enriches Everyday Life for People With Mild to Moderate Dementia and Their Family Caregivers.

Dementia causes substantial suffering for affected persons and their family caregivers. Because no cure is available, it is important to investigate how alternative therapies can improve life for these individuals. For the current study, persons with dementia (PwD) were recruited from a specialized Memory Clinic in Sweden to engage in a choral singing intervention for 1 hour per week for four semesters. PwD were encouraged to bring a family caregiver to the sessions; both were interviewed and data were analyzed using qualitative content analysis. The choral singing intervention appeared to become an important social context for PwD and family caregivers and had a positive impact on relationship, mental well-being, mood, and memory. The intervention appeared to act as an enriched environment for all participants. Choral singing interventions for PwD and their family caregivers is a simple means to create a social context and improve general well-being. [Journal of Psychosocial Nursing and Mental Health Services, 60(5), 29-36.].

Inter-modality assessment of medial temporal lobe atrophy in a non-demented population: application of a visual rating scale template across radiologists with varying clinical experience.

OBJECTIVES: To assess inter-modality agreement and accuracy for medial temporal lobe atrophy (MTA) ratings across radiologists with varying clinical experience in a non-demented population. METHODS: Four raters (two junior radiologists and two senior neuroradiologists) rated MTA on CT and MRI scans using Scheltens' MTA scale. Ratings were compared to a consensus rating by two experienced neuroradiologists for estimation of true positive and negative rates (TPR and TNR) and over- and underestimation of MTA. Inter-modality agreement expressed as Cohen's κ (dichotomized data), Cohen's κw, and two-way mixed, single measures, consistency ICC (ordinal data) were determined. Adequate agreement was defined as κ/κw ≥ 0.80 and ICC ≥ 0.80 (significance level at 95% CI ≥ 0.65). RESULTS: Forty-nine subjects (median age 72 years, 27% abnormal MTA) with cognitive impairment were included. Only junior radiologists achieved adequate agreement expressed as Cohen's κ. All raters achieved adequate agreement expressed as Cohen's κw and ICC. True positive rates varied from 69 to 100% and TNR varied from 85 to 100%. No under- or overestimation of MTA was observed. Ratings did not differ between radiologists. CONCLUSION: We conclude that radiologists with varying experience achieve adequate inter-modality agreement and similar accuracy when Scheltens' MTA scale is used to rate MTA on a non-demented population. However, TPR varied between radiologists which could be attributed to rating style differences. KEY POINTS: • Radiologists with varying experience achieve adequate inter-modality agreement with similar accuracy when Scheltens' MTA scale is used to rate MTA on a non-demented population. • Differences in rating styles might affect accuracy, this was most evident for senior neuroradiologists, and only junior radiologists achieved adequate agreement on dichotomized (abnormal/normal) ratings. • The use of an MTA scale template might compensate for varying clinical experience which could make it applicable for clinical use.

Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture.

The genetic basis of Lewy body dementia (LBD) is not well understood. Here, we performed whole-genome sequencing in large cohorts of LBD cases and neurologically healthy controls to study the genetic architecture of this understudied form of dementia, and to generate a resource for the scientific community. Genome-wide association analysis identified five independent risk loci, whereas genome-wide gene-aggregation tests implicated mutations in the gene GBA. Genetic risk scores demonstrate that LBD shares risk profiles and pathways with Alzheimer's disease and Parkinson's disease, providing a deeper molecular understanding of the complex genetic architecture of this age-related neurodegenerative condition.

Medications causing potential cognitive impairment are common in nursing home dementia units - A cross-sectional study.

Background: With advancing age the brain becomes more sensitive to centrally acting drugs thus increasing the risk of cognitive side-effects. The Swedish National Board of Health and Welfare developed indicators to measure and follow quality in older people's drug therapy, one being "Potentially Inappropriate Medications risking Cognitive impairment (PIMcogn)". Associations between anticholinergics and cognitive impairment are described, especially in persons with Alzheimer's disease or Lewy Body Dementia/Parkinson's disease dementia, due to degenerated cholinergic pathways. Objectives: To examine the prevalence of PIMcogn and if it differed between nursing home residents with and without a dementia diagnosis and between residents with different dementia aetiologias. Methods: Descriptive cross-sectional study, based on residents ≥65 years in nursing home dementia units in Malmö, Sweden, in 2012-2013 (N = 574). Results: The study population consisted of 76% women, the mean age was 86 years and a dementia diagnosis was registered in 92%. A total of 74% were prescribed at least one PIMcogn. Benzodiazepines were prevalent in 59%, opioids in 27%, antipsychotics in 20% and anticholinergics in 13%. Opioids used regularly and antiepileptics were more common in residents without a dementia diagnosis. The lowest proportion of anticholinergics was seen in the oldest age group, 11.0%. There was no difference seen in anticholinergics between dementia types with considerable cholinergic deficit and other dementia diagnoses. Conclusions: Treatment with at least one PIMcogn was common. Usage of benzodiazepines and antipsychotics was, despite the knowledge of alarming side-effects, high.An awareness of the inappropriateness in prescribing anticholinergics to the oldest old seems to be apparent, but not to persons with cholinergic deficit.

Reporting frequency of radiology findings increases after introducing visual rating scales in the primary care diagnostic work up of subjective and mild cognitive impairment.

OBJECTIVES: Study the effect of introducing a template for radiological reporting of non-enhanced computed tomography (NECT) in the primary care diagnostic work up of cognitive impairment using visual rating scales (VRS). METHODS: Radiology reports were assessed regarding compliance with a contextual report template and the reporting of the parameters medial temporal lobe atrophy (MTA), white matter changes (WMC), global cortical atrophy (GCA), and width of lateral ventricles (WLV) using established VRS in two age-matched groups examined with NECT before (n = 111) and after (n = 125) the introduction of contextual reporting at our department. True positive rate (TPR) and true negative rate (TNR) before and after were compared. RESULTS: We observed a significant increase in the percentage of radiology reports with mentioning of MTA from 29 to 76% (p < 0.001), WMC from 69 to 86% (p < 0.01), and GCA from 54 to 82% (p < 0.001). We observed a significant increase in the percentages of reports where all of the parameters were mentioned, from 6 to 29% (p < 0.001). There was a significant increase in TPR from 10 to 55% for MTA. CONCLUSION: This study suggests that contextual radiological assessment using VRS could increase the reporting frequency of radiology findings in the diagnostic work up of cognitive impairment but compliance with templates may be difficult to endorse. KEY POINTS: • Introducing visual rating scales in clinical practice increases the reporting frequency of MTA, WMC, and GCA in the diagnostic work up of subjective and mild cognitive impairment. • Introducing visual rating scales has an effect on the true positive rate of reported MTA. • Compliance with contextual radiology templates remains low when use of the template is not enforced by the department leadership.

Plasma Phospho-Tau Identifies Alzheimer's Co-Pathology in Patients with Lewy Body Disease.

BACKGROUND: Alzheimer's disease co-pathology is common in dementia with Lewy bodies and Parkinson's disease with dementia (Lewy body disease) and can reliably be detected with positron emission tomography (PET) or cerebrospinal fluid (CSF) biomarkers. Recently developed blood biomarkers are more accessible and less expensive alternatives. OBJECTIVE: To investigate if plasma phospho-tau217 and phospho-tau181 can detect Alzheimer's pathology in Lewy body disease with dementia. METHODS: In this cross-sectional study we investigated plasma phospho-tau217 and phospho-tau181 in 35 patients with Lewy body disease with dementia. Patients underwent tau-PET imaging (18 F-RO948). RESULTS: Plasma phospho-tau217 correlated with plasma phospho-tau181, CSF phospho-tau217 (rs = 0.68, P < 0.001), and negatively with CSF ß-amyloid42/40 (rs = -0.52, P = 0.001). Plasma phospho-tau217 and phospho-tau181 correlated with tau-PET signal in the temporal cortex (rs > 0.56, P < 0.001) and predicted abnormal tau-PET status and ß-amyloid status (area under the curve > 0.78 and > 0.81, respectively). CONCLUSION: Plasma phospho-tau might be a useful marker for Alzheimer's co-pathology in Lewy body disease with dementia. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

ß-Amyloid and tau biomarkers and clinical phenotype in dementia with Lewy bodies.

OBJECTIVE: In a multicenter cohort of probable dementia with Lewy bodies (DLB), we tested the hypothesis that ß-amyloid and tau biomarker positivity increases with age, which is modified by APOE genotype and sex, and that there are isolated and synergistic associations with the clinical phenotype. METHODS: We included 417 patients with DLB (age 45-93 years, 31% women). Positivity on ß-amyloid (A+) and tau (T+) biomarkers was determined by CSF ß-amyloid1-42 and phosphorylated tau in the European cohort and by Pittsburgh compound B and AV-1451 PET in the Mayo Clinic cohort. Patients were stratified into 4 groups: A-T-, A+T-, A-T+, and A+T+. RESULTS: A-T- was the largest group (39%), followed by A+T- (32%), A+T+ (15%), and A-T+ (13%). The percentage of A-T- decreased with age, and A+ and T+ increased with age in both women and men. A+ increased more in APOE ε4 carriers with age than in noncarriers. A+ was the main predictor of lower cognitive performance when considered together with T+. T+ was associated with a lower frequency of parkinsonism and probable REM sleep behavior disorder. There were no significant interactions between A+ and T+ in relation to the clinical phenotype. CONCLUSIONS: Alzheimer disease pathologic changes are common in DLB and are associated with the clinical phenotype. ß-Amyloid is associated with cognitive impairment, and tau pathology is associated with lower frequency of clinical features of DLB. These findings have important implications for diagnosis, prognosis, and disease monitoring, as well as for clinical trials targeting disease-specific proteins in DLB. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with probable DLB, ß-amyloid is associated with lower cognitive performance and tau pathology is associated with lower frequency of clinical features of DLB.

Analysis of neurodegenerative disease-causing genes in dementia with Lewy bodies.

Dementia with Lewy bodies (DLB) is a clinically heterogeneous disorder with a substantial burden on healthcare. Despite this, the genetic basis of the disorder is not well defined and its boundaries with other neurodegenerative diseases are unclear. Here, we performed whole exome sequencing of a cohort of 1118 Caucasian DLB patients, and focused on genes causative of monogenic neurodegenerative diseases. We analyzed variants in 60 genes implicated in DLB, Alzheimer's disease, Parkinson's disease, frontotemporal dementia, and atypical parkinsonian or dementia disorders, in order to determine their frequency in DLB. We focused on variants that have previously been reported as pathogenic, and also describe variants reported as pathogenic which remain of unknown clinical significance, as well as variants associated with strong risk. Rare missense variants of unknown significance were found in APP, CHCHD2, DCTN1, GRN, MAPT, NOTCH3, SQSTM1, TBK1 and TIA1. Additionally, we identified a pathogenic GRN p.Arg493* mutation, potentially adding to the diversity of phenotypes associated with this mutation. The rarity of previously reported pathogenic mutations in this cohort suggests that the genetic overlap of other neurodegenerative diseases with DLB is not substantial. Since it is now clear that genetics plays a role in DLB, these data suggest that other genetic loci play a role in this disease.

Author Correction: GBA and APOE ε4 associate with sporadic dementia with Lewy bodies in European genome wide association study.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Survival among the older adults with clinical signs of Lewy body dementia in 40 Swedish nursing homes: a 6-year follow-up study.

OBJECTIVES: To investigate survival among elderly residents of Swedish nursing homes (NHs), with specific focus on those with two or more signs of Lewy body dementia (LBD). DESIGN: Prospective observational study. SETTING: NHs in Malmö, the third largest city in Sweden. PARTICIPANTS: The study population was older adults (aged ≥65 years) living in the 40 NHs in Malmö. Clinical data were collected with a customised questionnaire assessing core clinical LBD signs. Patients were categorised based on 0-1 or 2-4 LBD signs. The head nurse at each NH collected the study data: LBD questionnaires, electronic medication lists and electronic medical records from 2012 to 2013. MAIN OUTCOME MEASURES: 80-month mortality. RESULTS: Five hundred and fifty-eight (96%) of the residents were deceased at follow-up; among these, mean (95% CI) overall survival time was 29 (28-31) months. Mean survival differed between the LBD groups; those with 0-1 LBD signs lived 8 months longer than those with 2-4 LBD signs. Mortality risk for residents in the LBD 2-4 group was also significantly higher. HR adjusted for age and sex was HR (95% CI) 1.60 (1.30 to 1.97). Mortality risk was also significantly higher in residents with signs of fluctuating cognition 1.36 (1.15 to 1.62), rapid eye movement sleep behaviour disorder 1.49 (1.11 to 1.98), balance problems 1.36 (1.14 to 1.61) or rigidity 1.41 (1.18 to 1.68). CONCLUSIONS: This large, longitudinal study shows the important survival effects of identifying and diagnosing older adults NH residents who have two or more LBD signs.

GBA and APOE ε4 associate with sporadic dementia with Lewy bodies in European genome wide association study.

Dementia with Lewy Bodies (DLB) is a common neurodegenerative disorder with poor prognosis and mainly unknown pathophysiology. Heritability estimates exceed 30% but few genetic risk variants have been identified. Here we investigated common genetic variants associated with DLB in a large European multisite sample. We performed a genome wide association study in Norwegian and European cohorts of 720 DLB cases and 6490 controls and included 19 top-associated single-nucleotide polymorphisms in an additional cohort of 108 DLB cases and 75545 controls from Iceland. Overall the study included 828 DLB cases and 82035 controls. Variants in the ASH1L/GBA (Chr1q22) and APOE ε4 (Chr19) loci were associated with DLB surpassing the genome-wide significance threshold (p < 5 × 10-8). One additional genetic locus previously linked to psychosis in Alzheimer's disease, ZFPM1 (Chr16q24.2), showed suggestive association with DLB at p-value < 1 × 10-6. We report two susceptibility loci for DLB at genome-wide significance, providing insight into etiological factors. These findings highlight the complex relationship between the genetic architecture of DLB and other neurodegenerative disorders.

Heritability and genetic variance of dementia with Lewy bodies.

Recent large-scale genetic studies have allowed for the first glimpse of the effects of common genetic variability in dementia with Lewy bodies (DLB), identifying risk variants with appreciable effect sizes. However, it is currently well established that a substantial portion of the genetic heritable component of complex traits is not captured by genome-wide significant SNPs. To overcome this issue, we have estimated the proportion of phenotypic variance explained by genetic variability (SNP heritability) in DLB using a method that is unbiased by allele frequency or linkage disequilibrium properties of the underlying variants. This shows that the heritability of DLB is nearly twice as high as previous estimates based on common variants only (31% vs 59.9%). We also determine the amount of phenotypic variance in DLB that can be explained by recent polygenic risk scores from either Parkinson's disease (PD) or Alzheimer's disease (AD), and show that, despite being highly significant, they explain a low amount of variance. Additionally, to identify pleiotropic events that might improve our understanding of the disease, we performed genetic correlation analyses of DLB with over 200 diseases and biomedically relevant traits. Our data shows that DLB has a positive correlation with education phenotypes, which is opposite to what occurs in AD. Overall, our data suggests that novel genetic risk factors for DLB should be identified by larger GWAS and these are likely to be independent from known AD and PD risk variants.