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Background: There is no definition of what constitutes a lie when working with people with moderate to severe dementia. Lies are often defined as therapeutic with no evidence of how therapeutic value is gauged. There is no previous research that observes lies being told or the impact the lies have on people with dementia., Aim: The aim was to develop a taxonomy of lies for use when supporting people with moderate to severe dementia and then use this to develop a model, which could be used to explore the impact of lie telling., Research Design: Ethnography was used, with the researcher observing and recording lies told to people with moderate to severe dementia, by professional caregivers. Data analysis was based on Burnard's thematic analysis., Ethical Consideration: Ethical approval for the study was obtained from Northumbria University, the Research Ethics Committee (REC) and the Health Research Authority (HRA) in the United Kingdom. Study number 227508., Findings: Six categories of lie were identified; blatant, avoidance, familiarity, props, banter and going along with. Spontaneous and planned lies were observed. Motivation, validation and genuineness were key in terms of how the person with dementia responded. These affective domains were used to develop the Lie ARM (affective reflective model)., Discussion: Planned and spontaneous lies are an effective intervention for people with moderate to severe dementia. Healthcare professionals need to be aware of their motivation for using lies, as well as the impact they have on patients., Conclusion: The taxonomy is an objective way to categorise lies. It supports increased reflection, particularly if used in conjunction with the Lie ARM. The Lie ARM is a useful tool to help staff reflect on practice or to predict whether a proposed lie is likely to be therapeutic., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: A 12-week randomized controlled trial demonstrated that brexpiprazole is efficacious for treating agitation in patients with dementia due to Alzheimer's disease., Objective: To assess the long-term safety and tolerability of brexpiprazole for the treatment of agitation associated with dementia due to Alzheimer's disease., Methods: This 12-week, active-treatment (oral brexpiprazole 2 or 3 mg/day) extension trial ran from October 2018-September 2022 at 66 sites in Europe/US. Patients with agitation in dementia due to Alzheimer's disease in a care facility/community-based setting who completed the randomized trial were eligible (N = 259 enrolled/analyzed for safety; 88.4% completed). Stable Alzheimer's disease medications were permitted. The primary safety endpoint was the frequency and severity of treatment-emergent adverse events (TEAEs). Change in Cohen-Mansfield Agitation Inventory (CMAI) total score was an exploratory efficacy endpoint., Results: Mean (SD) age was 74.3 (7.6) years, 145 patients (56.0%) were female, and 248 (95.8%) were White. TEAEs were reported by 67 patients (25.9%), most commonly headache (3.5%) and fall (2.3%). Most TEAEs were mild or moderate in severity; 5 patients (1.9%) reported a severe TEAE, including 3 severe falls attributed to tripping, misjudging sitting, or dehydration. Twelve patients (4.6%) discontinued due to TEAEs. No patients died. Mean CMAI total score improved by 9.1 points over 12 weeks., Conclusions: Considering the randomized and extension trials together, brexpiprazole 2 or 3 mg was generally well tolerated for up to 24 weeks in elderly patients with agitation associated with dementia due to Alzheimer's disease. Patients showed continued improvement in agitation., Clinicaltrials.gov Identifier: NCT03594123 (registration date: July 11, 2018)., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Saloni Behl, Daniel Lee, and Alvin Estilo were full-time employees of Otsuka Pharmaceutical Development & Commercialization Inc. at the time of this work. Mary Slomkowski, Dalei Chen, Denise Chang, Alpesh Shah, and Mary Hobart are full-time employees of Otsuka Pharmaceutical Development & Commercialization Inc. Nanco Hefting is a full-time employee of H. Lundbeck A/S. Uwa Kalu is a full-time employee of Lundbeck LLC.

Background: Dignity, an abstract and complex concept, is an essential part of humanity and an underlying guiding principle in healthcare. Previous literature indicates dignity is compromised in people with dementia (PwD), but those PwD maintain the capacity to live with dignity with appropriate external support. Alzheimer's disease and related dementias (ADRDs) lead to progressive functional decline and increased vulnerability and dependence, leading to heightened risks of PwD receiving inappropriate or insufficient care that diminishes dignity. Considering the increased disease prevalence and the continuously escalating costs of dementia care, establishing a productive value-based guideline may prevent suffering, maximize dignity, and thus promote quality of life (QoL). Aim: The goal of this project is to identify actionable targets for integrating dignity harmoniously and practically into care planning and management for PwD. Research Design: We conducted a concept analysis using Walker and Avant's eight-step process. A comprehensive literature search was conducted (PubMed and CINAHL) with the keywords "dignity," "dementia," "Alzheimer's disease," and "dementia care." Results: A total of 42 out of 4910 publications were included. The concept of dignity in PwD is operationalized as the promotion of worthiness and the accordance of respect that allows the presence and expression of a person's sense of self, regardless of physical, mental, or cognitive health. The concept has two subdimensions: absolute dignity which encompasses the inherent self and relative dignity characterized by its dynamic reflective nature. Worthiness and respect are the two main attributes, while autonomy is an underlying component of dignity. Specific antecedents of dignity in PwD are empowerment, non-maleficence, and adaptive environmental scaffolding. As a consequence of facilitating dignity in PwD, QoL may be enhanced. Conclusion: As a foundational and necessary humanistic value, incorporating dignity into dementia care can lead to efficient and effective care that optimizes QoL in PwD throughout their disease progression., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Pre-existing dementia was related to poor functional outcome after intracerebral hemorrhage (ICH), and its commonly underlying pathologies were considered as cerebral amyloid angiopathy. But the impact of pre-existing dementia on in-hospital mortality in Chinese ICH patients has not been well characterized., Objective: To investigate the association between pre-existing dementia and in-hospital mortality after ICH., Methods: Data were extracted from the China Stroke Center Alliance database. Information about the existence of prior to stroke dementia was obtained from next of kin informants and registered in clinical charts. Patients' characteristics, in-hospital mortality, home discharge and complications were compared between ICH patients with and without pre-existing dementia., Results: Out of the 72,318 ICH patients, we identified 328 patients with pre-existing dementia. Patients with pre-existing dementia were more likely to experience greater stroke severity as measured by the National Institute of Health Stroke Scale and Glasgow Coma Scale. In the adjusted models, the presence of pre-existing dementia was associated with an increased risk of in-hospital mortality (OR 2.31, 95% CI 1.12-4.77), more frequent in-hospital complications of pulmonary embolism (OR 5.41, 95% CI 1.16-25.14), pneumonia (OR 1.58, 95% CI 1.08-2.33), urinary tract infection (OR 2.37, 95% CI 1.21-4.64), gastrointestinal bleeding (OR 2.39, 95% CI 1.27-4.49) and lower home discharge (OR 0.59, 95% CI 0.38∼0.93)., Conclusions: ICH patients with pre-existing dementia are more likely to suffer from greater stroke severity, poorer outcomes and lower home discharge. Future studies should evaluate the value of intensive risk factor control among individuals with pre-existing dementia for stroke prevention., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Endovascular thrombectomy (EVT) and intravenous thrombolysis (IVT) have an unclear benefit in those with pre-stroke dementia or cognitive impairment, as these patients were often excluded from landmark stroke trials. We performed a systematic review and meta-analysis to assess the outcomes of IVT and EVT in these populations., Aims: Our systematic review, conforming to the Meta-Analysis of Observational Studies in Epidemiology guidelines, investigated studies on acute ischemic stroke patients with pre-stroke dementia or cognitive impairment treated with IVT or EVT. Primary outcome was favorable 90-day outcome (mRS 0-2). Secondary outcomes included 90-day mortality, symptomatic intracranial hemorrhage (SICH), and radiographic intracranial hemorrhage (ICH)., Summary of Review: Nine articles were identified, with five observational studies of IVT use in patients with (n = 1078) and without dementia (n = 2805) being selected for the meta-analysis. There were no significant differences in favorable outcome (adjusted OR: 0.61, 95% CI 0.24-1.59), mortality (unadjusted OR: 1.19, 95% CI 0.86-1.64), ICH (unadjusted OR: 1.32, 95% CI 0.79-2.19), and symptomatic ICH (unadjusted OR: 0.94, 95% CI 0.70-1.25) for patients undergoing IVT with pre-stroke dementia versus those without. One EVT study (n = 615 with dementia vs n = 9600 without) found no significant differences in outcomes apart from an increased odds of ICH for those with pre-existing dementia (adjusted OR: 1.57, 95% CI 1.03-2.40). A pooled analysis of three IVT studies showed no significant association of cognitive impairment (n = 93 vs n = 211 without) with all assessed outcomes, whereas a study of EVT found that pre-stroke cognitive impairment was associated with poor 90-day outcomes (mRS 3-6)., Conclusion: These results suggest no substantial safety issues in the use of IVT or EVT for patients with pre-existing dementia or cognitive impairment compared to those without. However, the efficacy of these therapies in this demographic remains uncertain. Further rigorous studies that include a more nuanced outcome measurement approach are warranted., Registration: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42021240499., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: W.B., F.B., and B.B report no disclosures. J.S.M. reports research grants with GE Healthcare independent of the current study and is the scientific advisor and consultant for GE Healthcare independent of the current study. Dr A.G. reports membership in the editorial boards of Stroke, Neurology, and Neurology Clinical Practice; consulting fees and honoraria from Atheneum, AlphaSights, MD Analytics, Figure 1, My Medical Panel, Creative Research Designs, CTC Communications Corp, Alexion, Biogen, and Servier Canada; research support from Alberta Innovates, Campus Alberta Neuroscience, Brain Canada, the Canadian Cardiovascular Society, Panmure House, the Government of Canada INOVAIT and New Frontiers in Research programs, and the Canadian Institutes of Health Research; stock/stock options from SnapDx; and a patent application for a system for patient monitoring and cuff-based therapies—all outside the scope of the published work.

Objective: To develop an individualized method for detecting cognitive adverse events (CAEs) in the context of an ongoing trial of electroconvulsive therapy for refractory agitation and aggression for advanced dementia (ECT-AD study)., Methods: Literature search aimed at identifying (a) cognitive measures appropriate for patients with advanced dementia, (b) functional scales to use as a proxy for cognitive status in patients with floor effects on baseline cognitive testing, and (c) statistical approaches for defining a CAE, to develop CAEs monitoring plan specifically for the ECT-AD study., Results: Using the Severe Impairment Battery-8 (SIB-8), baseline floor effects are defined as a score of ≤5/16. For patients without floor effects, a decline of ≥6 points is considered a CAE. For patients with floor effects, a decline of ≥30 points from baseline on the Barthel Index is considered a CAE. These values were derived using the standard deviation index (SDI) approach to measuring reliable change., Conclusions: The proposed plan accounts for practical and statistical challenges in detecting CAEs in patients with advanced dementia. While this protocol was developed in the context of the ECT-AD study, the general approach can potentially be applied to other interventional neuropsychiatric studies that carry the risk of CAEs in patients with advanced dementia., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Patients with chronic limb-threatening ischemia (CLTI) have high mortality rates after revascularization. Risk stratification for short-term outcomes is challenging. We aimed to develop machine-learning models to rank predictive variables for 30-day and 90-day all-cause mortality after peripheral vascular intervention (PVI)., Methods: Patients undergoing PVI for CLTI in the Medicare-linked Vascular Quality Initiative were included. Sixty-six preprocedural variables were included. Random survival forest (RSF) models were constructed for 30-day and 90-day all-cause mortality in the training sample and evaluated in the testing sample. Predictive variables were ranked based on the frequency that they caused branch splitting nearest the root node by importance-weighted relative importance plots. Model performance was assessed by the Brier score, continuous ranked probability score, out-of-bag error rate, and Harrell's C-index., Results: A total of 10,114 patients were included. The crude mortality rate was 4.4% at 30 days and 10.6% at 90 days. RSF models commonly identified stage 5 chronic kidney disease (CKD), dementia, congestive heart failure (CHF), age, urgent procedures, and need for assisted care as the most predictive variables. For both models, eight of the top 10 variables were either medical comorbidities or functional status variables. Models showed good discrimination (C-statistic 0.72 and 0.73) and calibration (Brier score 0.03 and 0.10)., Conclusion: RSF models for 30-day and 90-day all-cause mortality commonly identified CKD, dementia, CHF, need for assisted care at home, urgent procedures, and age as the most predictive variables as critical factors in CLTI. Results may help guide individualized risk-benefit treatment conversations regarding PVI., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Mena-Hurtado reports unrestricted research grants from Philips and Shockwave, and is a consultant for Abbott Vascular, Cook, Medtronic, and Optum Labs; Dr Smolderen reports unrestricted research grants from Philips, Merck, Shockwave, and Johnson & Johnson; she is a consultant for Optum Labs, Cook, Tegus, Twill Inc., and Abbott Vascular. The other authors report no competing interests.

Objectives: To compare the etiology, phenomenology and motor subtype of delirium in patients with and without an underlying dementia., Methods: A combined dataset (n = 992) was collated from two databases of older adults (>65 years) from liaison psychiatry and palliative care populations in Ireland and India. Phenomenology and severity of delirium were analysed using the Delirium Symptom Rating Scale Revised (DRS-R98) and contributory etiologies for the delirium groups were ascertained using the Delirium Etiology Checklist (DEC). Delirium motor subtype was documented using the abbreviated version of the Delirium Motor Subtype Scale (DMSS4)., Results: Delirium superimposed on dementia (DSD) showed greater impairment in short term memory, long term memory and visuospatial ability than the delirium group but showed significantly less perceptual disturbance, temporal onset and fluctuation. Systemic infection, cerebrovascular and other Central nervous system etiology were associated with DSD while metabolic disturbance, organ insufficiency and intracranial neoplasm were associated with the delirium only group., Conclusion: The etiology and phenomenology of delirium differs when it occurs in the patient with an underlying dementia. We discuss the implications in terms of identification and management of this complex condition., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Enlarged perivascular spaces (EPVS) of the brain may be involved in dementia, such as Alzheimer's disease and cerebral small vessel disease (CSVD). Hypertension has been reported to be a risk factor for dementia and CSVD, but the association between blood pressure (BP) and perivascular spaces is still unclear. The aim of this study was to determine the association between BP and EPVS volumes and to examine the interactions of relevant factors., Methods: A total of 9296 community-dwelling subjects aged ≥65 years participated in a brain magnetic resonance imaging and health status screening examination. Perivascular volume was measured using a software package based on deep learning that was developed in-house. The associations between BP and EPVS volumes were examined by analysis of covariance and multiple regression analysis., Results: Mean EPVS volumes increased significantly with rising systolic and diastolic BP levels ( P for trend = .003, P for trend<.001, respectively). In addition, mean EPVS volumes increased significantly for every 1-mmHg-increment in systolic and diastolic BPs (both P values <.001). These significant associations were still observed in the sensitivity analysis after excluding subjects with dementia., Conclusions: The present data suggest that higher systolic and diastolic BP levels are associated with greater EPVS volumes in cognitively normal older people., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Toshiharu Ninomiya received funds from the Japan Agency for Medical Research and Development and Suntory Holdings Limited (Osaka, Japan). The other authors assert that they have no competing interests.

Objectives: To assess clinicians' prescribing practices for anticoagulation in older adults with atrial fibrillation or atrial flutter (AF/F) and determine factors common among those without anticoagulation., Methods: We performed a community-based retrospective cohort study of adults aged 65 years and older with a history of nonvalvular AF/F to determine the rate of oral anticoagulation utilization. We also assessed for associations between anticoagulation use and comorbid conditions and common geriatric syndromes., Results: A total of 3832 patients with a diagnosis of nonvalvular AF/F were included (mean [SD] age, 79.9 [8.4] years), 2693 (70.3%) of whom were receiving anticoagulation (51.7%, a vitamin K antagonist; 48.1%, a direct-acting oral anticoagulant). Patients with higher Elderly Risk Assessment index (ERA) scores, a surrogate for health vulnerability, received anticoagulation less often than patients with lower scores. The percentage of patients with a history of falling was higher among those who did not receive anticoagulation than among those who did (44.4% vs 32.8%; P  < .001). Similarly, a diagnosis of dementia was more common in the no-anticoagulation group than the anticoagulation group (18.5% vs 12.7%; P  < .001)., Conclusions: A substantial proportion of older adults with AF/F do not receive anticoagulation. Those without anticoagulation had higher risk of health deterioration based on higher ERA scores and had a higher incidence of dementia and fall history. This suggests that the presence of geriatric syndromes may influence the decision to withhold anticoagulation., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Among the older adults, hearing impairment is a common problem and may contribute to dementia., Objective: Therefore, we aimed to examine the association between hearing impairment and the risk of dementia among older adults in South Korea., Methods: Using the Korean National Health Insurance Service-Senior Cohort from 2005 to 2019, we collected data of 44,728 patients. Hearing impairment was determined using the national disability registry. Propensity score matching (1:1) was performed to match patients with and without hearing impairment (case: 22,364, control: 22,364). A Cox proportional hazards regression model was built to analyze the association between hearing impairment and dementia., Results: Patients with hearing impairment had a higher risk of dementia than those without hearing impairment (hazard ratio [HR] = 1.28, 95% confidence interval [CI] = 1.23-1.34). Assessing the degree of disability, both severe (HR = 1.25, 95% CI = 1.16-1.35) and mild conditions (HR = 1.29, 95% CI = 1.23-1.35) had an increased risk of dementia, respectively., Conclusions: Older patients with hearing impairment exhibit an increased risk of dementia, thereby warranting a new approach to dementia care among these patients regardless of the degree of hearing impairment.

Background: The relationship between young-onset dementia and peripheral vestibular disorders remained largely unknown although this association was observed in the older population., Objective: This case-control study aims to investigate the association of young-onset dementia with a pre-existing diagnosis of peripheral vestibular disorders using a population-based data from Taiwan's Longitudinal Health Insurance Database 2010., Methods: This study included 989 patients with young-onset dementia and 2967 propensity-score-matching controls. Differences in baseline characteristic between patients with young-onset dementia and controls were investigated using chi-square tests or t-tests. Multiple logistic regression models were employed to assess the association of young-onset dementia (outcome) with pre-existing peripheral vestibular disorders (predictor)., Results: Compared to patients without young-onset dementia, those affected by this condition exhibited a statistically significantly higher rate of peripheral vestibular disorders (18.3% versus 8.2%, p < 0.001). Furthermore, our analysis found notable between-group disparities in the rates of Meniere's Disease (3.5% versus 2.0%, p= 0.015), benign paroxysmal positional vertigo (2.4% versus 1.1%, p= 0.006), and vestibular neuritis (2.4% versus 1.1%, p= 0.003). Multiple logistic regression analysis showed that the presence of prior peripheral vestibular disorders increased the odds of young-onset dementia [2.603 (95% CI = 2.105∼3.220)] after adjusting for age, sex, monthly income, geographic location, urbanization level, hyperlipidemia, diabetes, coronary heart disease, hearing loss, and hypertension., Conclusions: The study findings demonstrate a notable association between young-onset dementia and pre-existing peripheral vestibular disorders, suggesting that vestibular malfunction could play a role in the development of young-onset dementia.

Background: Dementia is prevalent among the elderly, also representing a risk for seizures/epilepsy. Estimations of epilepsy risk in dementia patients are not widely available., Objective: Our research aims to ascertain the incidence of epilepsy and its associated risk factors in subjects with dementia in the Umbria region, based on data from healthcare databases., Methods: In this retrospective study based on the healthcare administrative database of Umbria, we identified all patients diagnosed with dementia from 2013 to 2017, based on ICD-9-CM codes. For epilepsy ascertainment, we used a validated algorithm that required an EEG and the prescription of one or more anti-seizure medications post-dementia diagnosis. A case-control analysis was conducted, matching five non-dementia subjects by gender and age to each dementia patient. Cox proportional hazards models were then utilized in the analysis., Results: We identified 7,314 dementia cases, also including 35,280 age- and sex-matched control subjects. Out of patients with dementia, 148 individuals (2.02%) were diagnosed with epilepsy. We observed a progressive increase in the cumulative incidence of seizures over time, registering 1.45% in the first year following the diagnosis, and rising to 1.96% after three years. Analysis using Cox regression revealed a significant association between the development of epilepsy and dementia (HR = 4.58, 95% CI = 3.67-5.72). Additional risk factors were male gender (HR = 1.35, 95% CI = 1.07-1.69) and a younger age at dementia onset (HR = 1.03, 95% CI=1.02-1.04)., Conclusions: Dementia increases epilepsy risk, especially with early onset and male gender. Clinicians should have a low threshold to suspect seizures in dementia cases.

Objectives: Dance as a non-pharmacological therapy is commonly used in dementia care, although the evidence of its effects remains unclear. This study systematically reviewed the effects of dance interventions on neuropsychiatric symptoms (NPS) in people living with dementia. To systematically identify and evaluate dance interventions, a standardized terminology for Dance-Specific Activity (DSA) is proposed., Methods: Literature search was conducted on electronic databases until April 30 th 2021. Studies were included when they quantified the effects of DSA on NPS in people with clinical diagnosis of dementia. Included studies were analyzed in detail for NPS. Study quality was assessed by PEDro scale (German version)., Results: 4 studies were included. The studies differed in study design, intervention protocols, dance styles, or measurement tools, and were generally of low study quality. Two trials showed improvements in NPS and 2 trials showed no exacerbation of NPS after DSA., Conclusions: The results of the 4 available trials indicate a positive tendency towards the effects of DSA, but considering the limitations of the few available studies, a clear statement about the effects of DSA is not possible yet. Based on the included trials, the following implications for clinical research and routine care can be derived: (1) DSA seems to be a practical terminology for identifying dance interventions (2) DSA seems to be a safe intervention for people living with dementia. (3) Different dance styles can be used. (4) DSA approaches should be better structured by differentiating between the domains type, content, intention, and protocol of the intervention.

Background: The existing literature on sexuality and intimacy in residential care tends to focus on either the question of rights, or the value of autonomy. Where the literature does reference values other than autonomy, such values are considered in the context of being a guide to whether or not a resident is autonomous, rather than being important values in their own right., Objective: This paper draws on qualitative data gathered as part of a larger study in order to inform practice on how care workers respond to intimacy issues that arise with residents with dementia and to inform a general ethics of sex and sexuality, demonstrating that an approach which permits value pluralism can be appropriate in certain contexts., Research Design: The qualitative data referred to in this paper was gathered from semi-structured interviews undertaken as part of a larger mixed-method research project. The interview text was analysed using Thorne's methodological approach, interpretive description., Participants and Research Context: The qualitative arm of the project consisted of semi-structured interviews conducted between October 2018 and October 2019 with participants (staff, residents and family members) recruited from 35 residential care homes in Aotearoa New Zealand., Ethical Considerations: Participation was informed, voluntary and written consent was gained before interviews. The project was approved by the Massey University Human Ethics Committee (Northern), number NOR 18/25., Findings: Analysis of the scenarios presented in this paper shows that decision-making around sexual intimacy involving people with dementia in a residential care setting is complex and requires recognizing and weighing the different values that may be a in play., Conclusion: A focus on safety and consent to the exclusion of other values which matter morally in this context is a mistake which prevents care workers from providing appropriately person-centred care to residents, as policies which focus on the goal of care allow space for critical examination of issues which are likely to be highly context-sensitive.

Cognitive and behavioral aspects may mask posttraumatic stress disorder (PTSD) in people with dementia. PTSD severely lowers quality of life in people with dementia. Proper recognition of PTSD is essential to ensure adequate treatment. However, a valid diagnostic tool for PTSD in dementia is lacking. A Delphi study was conducted among 20 Dutch and 6 international experts in the field of PTSD and dementia care or research. The aim was to reach consensus in 3 rounds on the added value, form, content, and application for developing such an instrument. The first round confirmed the need for a new diagnostic tool for research and clinical practice. Consensus was reached on 23 statements regarding the support base and 19 related to content of the instrument. In the third round, opinions on several conceptual problems were gathered. Based on the experts' opinions, a draft version of an instrument, the TRAuma and DEmentia-interview (TRADE-interview), was developed. Clinical and research implications of this new measure are discussed.

Background: Depression and dementia confer substantial global health burdens, particularly in women. Understanding the association between depression and dementia may inform new targets for prevention and/or early intervention., Objective: To investigate the association between depression in mid- and later-life and dementia (all-cause, Alzheimer's disease (AD) or vascular dementia (VaD)) in women., Methods: A prospective study design. Nurses were followed from age 60 years or entry into the cohort, whichever came last, until date of dementia, death, emigration, or end of follow-up, whichever came first. Cox regression models with age as the underlying timeline were used to estimate the associations between time-varying depression and incident dementia., Results: The study included 25,651 female Danish nurses (≥45 years) participating in the Danish Nurse Cohort. During an average of 23 years of follow-up, 1,232 (4.8%) nurses developed dementia and 8,086 (31.5%) were identified with at least two episodes of treated depression. In adjusted analyses, nurses with depression were at a statistically significant 5.23-fold higher risk of all-cause dementia (aHR 5.23:95% CI, 4.64-5.91) compared to those with no history of depression. The differential effects of depression were greater for VaD (aHR 7.96:95% CI, 5.26-12.0) than AD (aHR 4.64:95% CI, 3.97-5.42). Later life depression (>60 years) (aHR 5.85:95% CI, 5.17-6.64) and recurrent depression (aHR 3.51:95% CI, 2.67-4.61) elevated dementia risk. Severe depression tripled the risk of all cause dementia (aHR 3.14:95% CI, 2.62-3.76)., Conclusion: Both later life and severe depression substantially increase dementia risk in women, particularly VaD.

Objective: To evaluate the effects of light therapy on the alleviation of sleep disturbances, agitation and depression in people with dementia., Methods: A search was performed in PubMed, Medline, SCOPUS, Web of Science, EMBASE, CINAHL, Cochrane Library, for studies published between 2000 and 2021., Results: A total of 4315 articles were screened. Sixteen articles were eligible for this review and 11 randomized controlled studies were included in the meta-analysis. Light therapy had a significant effect on reducing the number of awakenings in sleep ( n = 4; 95% CI = -.56, -.05; I 2 = 0%; SMD = -.31) but was not significant in reducing the wake after sleep onset ( n = 3; 95% CI = -.14, .59; I 2 = 0%; SMD = .23), agitation ( n = 4; 95% CI = -1.02, .45; I 2 = 87%; SMD = -.28) and depression ( n = 6; 95% CI = -.80, .40, I 2 = 85%; SMD = -.20)., Conclusion: Light therapy appeared to be more effective in terms of alleviating sleep disturbances, rather than reducing agitation and depression, but its long-term effects remain unclear.

Background: Cerebral ischemic stroke is caused due to neurovascular damage or thrombosis, leading to neuronal dysfunction, neuroinflammation, neurodegeneration, and regenerative failure responsible for neurological deficits and dementia. The valid therapeutic targets against cerebral stroke remain obscure. Thus, insight into neuropathomechanisms resulting from the aberrant expression of genes appears to be crucial., Objective: In this study, we have elucidated how neurogenesis-related genes are altered in experimental stroke brains from the available transcriptome profiles in correlation with transcriptome profiles of human postmortem stroke brain tissues., Methods: The transcriptome datasets available on the middle cerebral artery occlusion (MCAo) rat brains were obtained from the Gene Expression Omnibus, National Center for Biotechnology Information. Of the available datasets, 97 samples were subjected to the meta-analysis using the network analyst tool followed by Cytoscape-based enrichment mapping analysis. The key differentially expressed genes (DEGs) were validated and compared with transcriptome profiling of human stroke brains., Results: Results revealed 939 genes are differently expressed in the brains of the MCAo rat model of stroke, in which 30 genes are key markers of neural stem cells, and regulators of neurogenic processes. Its convergence with DEGs from human stroke brains has revealed common targets., Conclusion: This study has established a panel of highly important DEGs to signify the potential therapeutic targets for neuroregenerative strategy against pathogenic events associated with cerebral stroke. The outcome of the findings can be translated to mitigate neuroregeneration failure seen in various neurological and metabolic disease manifestations with neurocognitive impairments.

Background: Sleep disturbances have been linked with cognitive decline and a higher risk of dementia. However, there is a lack of studies with sufficient follow-up duration, a detailed neuropsychological assessment and adequate control of main confounders., Objective: To investigate the relation between self-reported sleep quality and cognitive decline over 12 years in cognitively healthy individuals from the general population., Methods: We used data from the Maastricht Aging Study (MAAS), a Dutch population-based prospective cohort study of 1,823 community-dwelling adults aged 24 to 82 years at baseline. Cognitive performance was measured at baseline, 6 and 12 years on verbal memory, executive functions, and information processing speed. Sleep quality was assessed at baseline using the sleep subscale score of the 90-item Symptom Checklist (SCL-90). Additional modifiable dementia risk factors were summarized in the LIfestyle for BRAin health (LIBRA) risk score. Weighted linear mixed models tested the association between continuous scores and tertiles of subjective sleep quality and change in cognitive performances over time. Models were adjusted for age, gender, educational level, LIBRA, and use of hypnotic (sleep) medication., Results: Worse sleep quality was associated with faster decline in processing speed. At older age (≥65 years), it was also associated with faster decline in verbal memory. Association were independent of other modifiable dementia risk factors and use of hypnotic medication. Directionally similar but non-significant associations were found between worse sleep quality and executive functions., Conclusions: In this population-based study across the adult age range, poor self-reported sleep was associated with accelerated cognitive decline.

Background: Hearing loss is common in people with dementia (PwD) and a modifiable risk factor for cognitive decline. Recent studies revealed that hearing loss could cause social isolation and depression, which is associated with health-related quality of life (HRQoL). However, there is a lack of knowledge about the impact of the utilization of hearing aids on these outcomes., Objective: To assess whether hearing aids use might be positively associated with the progression of cognitive function, depression, and HRQoL among PwD., Methods: We analyzed two-year follow-up data from 258 PwD (≥70 years, living at home). Cognitive decline was measured with Mini-Mental Status Examination (MMSE), depression using Geriatric Depression Scale (GDS), and HRQoL with Quality of Life in Alzheimer's Disease Scale (QoL-AD). The impact of hearing aid utilization on the progression of outcomes was assessed using multivariate regression models., Results: 123 patients had hearing loss (47.7%), from which n = 54 (43.9%) used hearing aids. Patients with hearing loss were older and had a lower HRQoL than those without hearing loss. Use of hearing aids in patients with hearing loss was associated with a lower increase in depressive symptoms (b = -0.74, CI95 -1.48 --0.01, p = 0.047) over time as compared to those not using hearing aids. There was no effect on PwD's cognition, and the association with higher HRQoL was significant after one, but not consistently over two years., Conclusion: Early detection and intervention of presbycusis using hearing aids might improve mental health and HRQoL in dementia.

Background: The association between body mass index (BMI) and dementia risk is heterogeneous across age groups and might be influenced by sex., Objective: This study aimed to clarify sex differences in the association between BMI and dementia risk in community-dwelling people., Methods: This cohort study with an 8-year follow-up targeted 13,802 participants aged 40-74 years at baseline in 2011-2013. A self-administered questionnaire requested information on body size, including height, weight, and waist circumference (the values of which were validated by direct measurement), socio-demographics, lifestyle, and disease history. BMI was calculated and categorized as < 18.5 (underweight), 18.5-20.6 (low-normal), 20.7-22.6 (mid-normal), 22.7-24.9 (high-normal), 25.0-29.9 (overweight), and≥30.0 kg/m2 (obese). Incident cases of dementia were obtained from the long-term care insurance database. A Cox proportional hazards model was used to calculate multivariable-adjusted hazard ratios (HRs)., Results: The mean age of participants was 59.0 years. In men, higher BMI was associated with lower dementia risk (fully-adjusted p for trend = 0.0086). In women, the association between BMI and dementia risk was U-shaped; the "underweight," "low-normal," and "overweight" groups had a significantly higher risk (fully-adjusted HR = 2.12, 2.08, and 1.78, respectively) than the reference ("high-normal" group). These findings did not change after excluding dementia cases which occurred within the first four years of the follow-up period., Conclusion: Overweight/obese women, but not men, had an increased risk of dementia, suggesting that sex differences in adiposity might be involved in the development of dementia.

Background: Many health systems are interested in increasing the number of uncomplicated and typical dementia diagnoses that are made in primary care, but the comparative accuracy of tests is unknown., Objective: Calculate diagnostic accuracy of brief cognitive tests in primary care., Methods: We did a diagnostic test accuracy study in general practice, in people over 70 years who had consulted their GP with cognitive symptoms but had no prior diagnosis of dementia. The reference standard was specialist assessment, adjudicated for difficult cases, according to ICD-10. We assessed 16 index tests at a research clinic, and additionally analyzed referring GPs clinical judgement., Results: 240 participants had a median age of 80 years, of whom 126 were men and 132 had dementia. Sensitivity of individual tests at the recommended thresholds ranged from 56% for GP judgement (specificity 89%) to 100% for MoCA (specificity 16%). Specificity of individual tests ranged from 4% for Sniffin' sticks (sensitivity 100%) to 91% for Timed Up and Go (sensitivity 23%). The 95% centile of test duration in people with dementia ranged from 3 minutes for 6CIT and Time and Change, to 16 minutes for MoCA. Combining tests with GP judgement increased test specificity and decreased sensitivity: e.g., MoCA with GP Judgement had specificity 87% and sensitivity 55%., Conclusions: Using GP judgement to inform selection of tests was an efficient strategy. Using IQCODE in people who GPs judge as having dementia and 6CIT in people who GPs judge as having no dementia, would be a time-efficient and accurate diagnostic assessment.The original protocol for the study is available at https://bmcfampract.biomedcentral.com/articles/10.1186/s12875-016-0475-2.

Existing interventions for family carers of people with dementia tend to be less effective for anxiety than for depression. Therefore, identifying factors affecting carer anxiety is important to inform future interventions. This study conducted 2 multiple regression analyses using a sample of 91 family carers. The first regression model ( ∆R 2 = .24), exploring the impact of demographic variables and carer stressors, demonstrated that hours of caring ( β = .33) and overall sleep quality ( β = .28) were significant predictors of anxiety. To further investigate the impact of sleep quality, the second model ( ∆R 2 = .24) focussed on exploring the differential impact of various components of sleep quality on anxiety. Findings demonstrated that subjective sleep quality ( β = .33) and sleep disturbances ( β = .22) were significant predictors. Hours of caring per week, subjective sleep quality and sleep disturbances seem to be critical for treating anxiety in family carers. Future studies should investigate whether targeting these variables could improve carer anxiety.

Background: Alzheimer's disease (AD) is associated with EEG changes across the sleep-wake cycle. As the brain is a non-linear system, non-linear EEG features across behavioral states may provide an informative physiologic biomarker of AD. Multiscale fluctuation dispersion entropy (MFDE) provides a sensitive non-linear measure of EEG information content across a range of biologically relevant time-scales., Objective: To evaluate MFDE in awake and sleep EEGs as a potential biomarker for AD., Methods: We analyzed overnight scalp EEGs from 35 cognitively normal healthy controls, 23 participants with mild cognitive impairment (MCI), and 19 participants with mild dementia due to AD. We examined measures of entropy in wake and sleep states, including a slow-to-fast-activity ratio of entropy (SFAR-entropy). We compared SFAR-entropy to linear EEG measures including a slow-to-fast-activity ratio of power spectral density (SFAR-PSD) and relative alpha power, as well as to cognitive function., Results: SFAR-entropy differentiated dementia from MCI and controls. This effect was greatest in REM sleep, a state associated with high cholinergic activity. Differentiation was evident in the whole brain EEG and was most prominent in temporal and occipital regions. Five minutes of REM sleep was sufficient to distinguish dementia from MCI and controls. Higher SFAR-entropy during REM sleep was associated with worse performance on the Montreal Cognitive Assessment. Classifiers based on REM sleep SFAR-entropy distinguished dementia from MCI and controls with high accuracy, and outperformed classifiers based on SFAR-PSD and relative alpha power., Conclusion: SFAR-entropy measured in REM sleep robustly discriminates dementia in AD from MCI and healthy controls.

Background: Persons with dementia are at risk of developing nutritional problems. Theoretical models on nutritional problems have been developed, but have not been evaluated with healthcare professionals., Objective: This study aimed to explore the comprehensiveness and applicability of a theoretical model of nutritional problems in persons with dementia for daily nursing home practice., Methods: A qualitative design employing a combined deductive and inductive approach was used. Healthcare professionals were eligible to participate if they 1) had expert knowledge of and experience with nutritional problems related to dementia, and 2) worked in a nursing home affiliated with an academic network covering the east and south of the Netherlands. Three focus group interviews with 20 healthcare professionals from seven professions were held. We conducted thematic analysis and we compared themes with existing theoretical models from the literature., Results: We identified six themes, four of which corresponded with the existing models (observing and analysing nutritional problems; consequences of nutritional problems; functioning of the person with dementia; environmental factors). Interprofessional collaboration and ethical factors were identified as new themes. The analyses indicated interactions within each theme, between themes, and a bidirectional connection between themes., Conclusions: This study demonstrated the relevance of interprofessional collaboration and ethical considerations in nutritional problems related to dementia. It uncovered complex bidirectional relations within and between factors regarding nutritional problems. All aspects should be taken into account to minimize the consequences of nutritional problems for persons with dementia.

Background: Diabetes is a major risk factor for the development of dementia, which has been proven to be associated with systemic inflammation. Acute pancreatitis, also a local and systemic inflammatory disease, is the most common gastrointestinal disease requiring acute hospitalization., Objective: The effect of acute pancreatitis on dementia was investigated in type 2 diabetic patients., Methods: Data was collected from the Korean National Health Insurance Service. The study sample included type 2 diabetes patients who received general health examination from 2009 to 2012. Cox proportional hazard regression analysis was used to evaluate the association between acute pancreatitis and dementia with adjustment of confounders. Stratified subgroup analysis by age, sex, smoking, alcohol consumption, hypertension, dyslipidemia, and body mass index was conducted., Results: Among the 2,328,671 participants in total, 4,463 patients had a history of acute pancreatitis before the health examination. During a median follow-up of 8.1 (IQR, 6.7-9.0) years, 194,023 participants (8.3%) developed all-cause dementia. Previous history of acute pancreatitis was a significant risk factor for dementia after adjustment of confounding variables (HR 1.39 [95% CI 1.26-1.53]). In the subgroup analysis, patient characteristics such as age under 65 years, male, current smoker, and alcohol consumption were significant risk factors for dementia in patients with a history of acute pancreatitis., Conclusion: The history of acute pancreatitis was associated with the development of dementia in patients with diabetes. Because the risk of dementia increases with alcohol consumption and smoking in diabetic patients with history of acute pancreatitis, abstinence from alcohol and smoking should be recommended.

Background: The assessment of language changes associated with visual search impairment can be an important diagnostic tool in the Alzheimer's disease (AD) continuum., Objective: Investigate the performance of an eye-tracking assisted visual inference language task in differentiating subjects with mild cognitive impairment (MCI) or AD dementia from cognitively unimpaired older adults (controls)., Methods: We assessed a group of 95 older adults (49 MCI, 18 mild dementia due to AD, and 28 controls). The subjects performed the same task under multiple experimental conditions which generate correlated responses that need to be taken into account. Thus, we performed a non-parametric repeated measures ANOVA model for verbal answers, and a linear mixed model (LMM) or its generalized version for the analysis of eye tracking variables., Results: Significant differences were found in verbal answers across all diagnostic groups independently of type of inference, i.e., logic or pragmatic. Also, eye-tracking parameters were able to discriminate AD from MCI and controls. AD patients did more visits to challenge stimulus (Control-AD, -0.622, SE = 0.190, p = 0.004; MCI-AD, -0.514, SE = 0.173, p = 0.011), more visits to the correct response stimulus (Control-AD, -1.363, SE = 0.383, p = 0.002; MCI-AD, -0.946, SE = 0.349, p = 0.022), more fixations on distractors (Control-AD, -4.580, SE = 1.172, p = 0.001; MCI-AD, -2.940, SE = 1.070, p = 0.020), and a longer time to first fixation on the correct response stimulus (Control-AD, -0.622, SE = 0.190, p = 0.004; MCI-AD, -0.514, SE = 0.173, p = 0.011)., Conclusion: The analysis of oculomotor behavior along with language assessment protocols may increase the sensitivity for detection of subtle deficits in the MCI-AD continuum, representing an important diagnostic tool.

Background: The Boston Naming Test (BNT) is the most widely used measure to assess anomia. However, it has been criticized for failing to differentiate the underlying cognitive process of anomia., Objective: We validated the color-picture version of BNT (CP-BNT) in a sample with diverse neurodegenerative dementia diseases (NDDs). We also verified the differential ability of the composite indices of CP-BNT across NDDs groups., Methods: The present study included Alzheimer's disease (n = 132), semantic variant primary progressive aphasia (svPPA, n = 53), non-svPPA (n = 33), posterior cortical atrophy (PCA, n = 35), and normal controls (n = 110). We evaluated psychometric properties of CP-BNT for the spontaneous naming (SN), the percentage of correct responses on semantic cuing and word recognition cuing (% SC, % WR). Receiver operating characteristic analysis was used to examine the discriminatory power of SN alone and the composite indices (SN, % SC, and % WR)., Results: The CP-BNT had sufficient internal consistency, good convergent, divergent validity, and criterion validity. Different indices of CP-BNT demonstrated distinct cognitive underpinnings. Category fluency was the strongest predictor of SN (β= 0.46, p < 0.001). Auditory comprehension tests highly associated with % WR (Sentence comprehension: β= 0.22, p = 0.001; Word comprehension: β= 0.20, p = 0.001), whereas a lower visuospatial score predicted % SC (β= -0.2, p = 0.001). Composite indices had better predictability than the SN alone when differentiating between NDDs, especially for PCA versus non-svPPA (area under the curve increased from 63.9% to 81.2%)., Conclusion: The CP-BNT is a highly linguistically relevant test with sufficient reliability and validity. Composite indices could provide more differential information beyond SN and should be used in clinical practice.

Background: Hyperuricemia in patients with gout is associated with a low risk of neurodegenerative diseases, including dementia. However, the prevalence of dementia in patients with gout has not yet been reported., Objective: To analyze the prevalence of dementia among patients diagnosed with gout by utilizing the Health Insurance and Review Assessment database, a nationwide registry of the South Korean population., Methods: Data from the Health Insurance and Review Assessment database of patients diagnosed with gout between 2011 and 2018 were extracted. The annual prevalence of dementia according to age and sex was analyzed. We investigated whether there was an association between comorbidities and gout medication in patients with both gout and dementia and in patients with only gout., Results: Between 2011 and 2018, the age-adjusted prevalence of dementia per 100,000 persons ranged from 54.0 (95% confidence interval: 47.7-60.2) to 69.9 (95% confidence interval: 65.3-74.5). Compared to previous studies, the prevalence of dementia was lower in patients with gout than in the general population. Patients with both gout and dementia were more likely to be women, have a wide range of comorbidities, and be prescribed gout-related drugs, including allopurinol, febuxostat, nonsteroidal anti-inflammatory drugs, and steroids than patients with gout without dementia., Conclusions: This study demonstrated a relatively low prevalence of dementia in patients with gout. Gout, characterized by hyperuricemia, might be associated with a reduced risk of dementia.

Background: Loneliness has been highlighted as a risk factor for dementia. However, the nature of the relationship between loneliness and cognitive function prior to onset of dementia is unclear., Objective: The aim of this systematic review and meta-analysis was to examine the relationship between loneliness and cognitive function in samples screened for dementia at study commencement., Methods: Five electronic databases (PubMed, PsycNET, Web of Science, EBSCOhost, Scopus) were searched from inception to August 31, 2021. A narrative review and random-effects meta-analysis were conducted on studies meeting search criteria. PROSPERO registration number: CRD42020155539., Results: The sixteen studies that met inclusion criteria involved 30,267 individuals, with mean age ranging from 63.0 to 84.9 years. Studies varied in dementia screening criteria, measurement of loneliness and cognitive function, and statistical modeling approach. The narrative review indicated that loneliness was associated with poorer global cognition, episodic memory, working memory, visuospatial function, processing speed, and semantic verbal fluency. Results of the meta-analysis indicated that loneliness was negatively associated with global cognitive function (overall r = -0.08; 95% CI = -0.14, -0.02; n = 6). Due to lack of sufficient data and heterogeneity between studies, we were unable to explore associations with other cognitive domains or longitudinal associations., Conclusion: Loneliness is associated with subtle impairment across multiple cognitive domains in older adults who were screened for dementia. Better characterization of this relationship will provide important information about how loneliness contributes to the clinical and pathological sequalae of AD and be informative for risk reduction and early detection strategies.

The purpose of this study was to consider gender differences in depressive symptoms, agitation, resistiveness to care, physical function, and use of psychotropic medications in older adults with moderate to severe dementia in nursing homes. Sixty-seven nursing homes and 889 residents from two states were included. The majority of the participants were female (n = 640, 72%) and White (n = 618, 70%) with a mean age of 86.58 years ( SD  = 10.31). Differences by gender with regard to age, physical function, depressive symptoms, agitation/aggression, and resistiveness to care were tested using multivariate analysis of variance. Older females with moderate to severe dementia present with more depressive symptoms (anxiety, sadness, and somatic complaints) than males. Males present with more aggressive behavior and are more likely to receive anticonvulsants. Caregivers should focus on preventing and managing depressive symptoms including anxiety, sadness, and somatic complaints among older females and aggressive behavior in older males with dementia.

Background: There is limited information on new onset poststroke dementia (NPSD) in sub-Saharan Africa (SSA). We estimated incidence, cumulative incidence, risk factors and outcome of NPSD at 1 year in Nigerian survivors of a first-ever stroke., Methods: Hospital-based prospective observational study. Assessments for global cognition, learning, memory, executive and activities of daily life (ADL) functioning were conducted at 3 poststroke timepoints (Baseline, 3- and 12 months). NPSD was ascertained according to the "National Institute of Neurological Disorders and Stroke and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) criteria." Outcomes were assessed using the modified Rankin Scale (mRS), center for epidemiologic studies depression scale (CES-D 10), health related quality of life in stroke patients (HRQOLISP-26) and caregivers strain index (CSI)., Results: Among 144 stroke survivors who were free of dementia at baseline, we found a 1-year cumulative incidence of 4.52% (95% C.I = 3.20, 6.39). In multivariate Cox regression analyses, diabetes was associated with NPSD (Hazard Ratio = 2.10, 95% CI = 1.02, 4.35). NPSD at 3 months was independently associated with motor decline [Mean difference (MD) in mRS = 1.6, 95% C.I = 0.9, 2.3)], depression (MD in CES-D = 2.9, 95% C.I = 0.3, 5.4), caregivers burden (MD in CSI = 1.2, 95% C.I = 0.5, 1.8), and poor quality of life (MD in HRQOLISP-26 = -11.2, 95% C.I = -15.7, -6.8) at 1 year., Conclusion: Approximately 4.5% of stroke survivors in Nigeria had NPSD at 1 year. Diabetes, which can be prevented, represent a primary prevention target for NPSD and its consequences in SSA.

Objective: Both posttraumatic stress disorder (PTSD) and dementia have been associated with a variety of behavioral changes; however, little is known about the behavioral consequences of comorbid PTSD and dementia. An integrative review was conducted to identify and examine studies reporting on behavioral disturbances in Veterans with PTSD and dementia., Methods: PubMed and PsychINFO databases were searched for articles on behavioral disturbances in Veterans with comorbid PTSD and dementia., Results: Seven studies met inclusion for this review, sampling a total of 822 Veterans. Preliminary findings suggest that though Veterans with dementia and comorbid PTSD may present with more difficult behavioral symptoms, they do not typically display increased levels of aggression., Conclusion: Given the limited study inventory, the key finding from this review highlights the lack of methodologically rigorous empirical studies on this topic. A research agenda is proposed to encourage future studies to address gaps in the literature.

Poor sleep is prevalent among caregivers of persons living with dementia and increases their risk for cognitive impairment and decline. In this cross-sectional, correlational study, we compared the cognitive function scores of caregivers with poor sleep with the demographically adjusted normed scores of the National Institutes of Health Toolbox Cognition Battery. Caregivers completed a 14-day sleep diary. On average, caregivers (n = 28) were 65.14 (±10.08) years, female, and White. Their average crystallized cognitive function composite score was significantly higher and their average fluid cognitive function composite score was significantly lower than the normative scores. Caregivers performed significantly worse on the processing speed domain measure. Poor sleep may affect how caregivers, including highly educated caregivers, process and respond to information, thus can influence how they safely perform complex caregiving tasks. Health care providers should consistently assess caregivers' sleep and cognitive abilities to promptly identify changes and provide timely interventions.

Background: It is unclear whether the main antihypertensive medication classes (diuretics, calcium channel blockers, beta-blockers, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers (ARBs)) are associated with different risks of cognitive decline. Published evidence is conflicting and stems mainly from observational studies., Objective: To investigate the differential effects of antihypertensives on the risks of developing dementia and cognitive decline, with a specific focus on the vascular component of the mechanisms underlying these interactions., Methods: Older adults with a history of hypertension and without dementia were drawn from the population-based HELIAD cohort. Age-, gender-, education-, and antihypertensive medication- (five dichotomous exposures) adjusted Cox proportional-hazards models and generalized estimating equations were performed to appraise the associations of baseline antihypertensive therapy with dementia incidence and cognitive decline (quantified using a comprehensive neuropsychological battery). Analyses were subsequently adjusted for clinical vascular risk (dyslipidemia, diabetes mellitus, smoking, cardiovascular, and cerebrovascular history) and genetic susceptibility to stroke (using polygenic risk scores generated according to the MEGASTROKE consortium GWAS findings)., Results: A total of 776 predominantly female participants (73.61±4.94 years) with hypertension and a mean follow-up of 3.02±0.82 years were analyzed. Baseline treatment was not associated with the risk of incident dementia. ARB users experienced a slower yearly global cognitive [2.5% of a SD, 95% CI = (0.1, 4.9)] and language [4.4% of a SD, 95% CI = (1.4, 7.4)] decline compared to non-users. The fully adjusted model reproduced similar associations for both global cognitive [β= 0.027, 95% CI =  (-0.003, 0.057)], and language decline [β= 0.063, 95% CI = (0.023, 0.104)]., Conclusion: ARBs may be superior to other antihypertensive agents in the preservation of cognition, an association probably mediated by vascular-independent mechanisms.

Background: The established link between cardiovascular disease (CVD) and dementia may provide new insights into dementia prevention., Objective: It aims to quantify the burden of dementia attributable to people with CVD., Methods: A Markov microsimulation model was developed to simulate the lifetime cost and quality-adjusted life-years (QALYs) related to people with and without CVD in Australia. A de-novo systematic review was undertaken to identify all evidence around the association between CVD [i.e., stroke, myocardial infarction (MI), atrial fibrillation (AF), and heart failure (HF)] and the risk of developing dementia. Incremental costs and QALY losses were estimated for people by type of CVD compared to the general Australian population without CVD., Results: Of the comprehensive literature search, 19 observational studies were included in the qualitative synthesis. Patients who had CVD incurred both higher healthcare costs over their lifetime (ranging from $73,131 for patients with AF to $127,396 for patients with HF) and fewer QALYs gains (from -1.099 for patients with MI to -5.163 for patients with stroke), compared to people who did not have CVD. The total incremental economic burden of dementia from patients aged 65 years and over with CVD was $6.45 billion (stroke), $11.89 billion (AF), $17.57 billion (MI), or $7.95 billion (HF) over their remaining life expectancy., Conclusion: The results highlighted the importance of CVD prevention to reduce the CVD burden and decrease the prevalence of dementia. Interventions that target patients with dementia risk factors like CVD may prove to be effective and cost-effective strategies.

Background: Epidemiological studies examining associations between traumatic brain injury (TBI) and Alzheimer's disease and related dementias (ADRD) have yielded conflicting results, which may be due to methodological differences., Objective: To examine the relationship between the presence and severity of TBI and risk of ADRD using a population-based cohort with medical record abstraction for confirmation of TBI and ADRD., Methods: All TBI events among Olmsted County, Minnesota residents aged > 40 years from 1985-1999 were confirmed by manual review and classified by severity. Each TBI case was randomly matched to two age-, sex-, and non-head injury population-based referents without TBI. For TBI events with non-head trauma, the Trauma Mortality Prediction Model was applied to assign an overall measure of non-head injury severity and corresponding referents were matched on this variable. Medical records were manually abstracted to confirm ADRD diagnosis. Cox proportional hazards models examined the relationship between TBI and severity with risk of ADRD., Results: A total of 1,418 residents had a confirmed TBI (865 Possible, 450 Probable, and 103 Definite) and were matched to 2,836 referents. When combining all TBI severities, the risk of any ADRD was significantly higher for those with a confirmed TBI compared to referents (HR = 1.32, 95% CI: 1.11, 1.58). Stratifying by TBI severity, Probable (HR = 1.42, 95% CI: 1.05, 1.92) and Possible (HR = 1.29, 95% CI: 1.02-1.62) TBI was associated with an increased risk of ADRD, but not Definite TBI (HR = 1.22, 95% CI: 0.68, 2.18)., Conclusion: Our analyses support including TBI as a potential risk factor for developing ADRD.

Background: No study on the long-term incidence of Alzheimer's disease (AD) and related dementias (ADRD) has been reported in women with breast cancer by vascular diseases., Objective: To determine the risk of ADRD in association with cardiovascular diseases (CVD), stroke, hypertension, and diabetes in women with breast cancer., Methods: Study identified 246,686 women diagnosed with breast cancer at age≥65 years in 1991-2015 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Women were free of ADRD at the time of cancer diagnosis and followed from 1991 to 2016., Results: Cumulative incidence of AD over 26 years of follow-up varied from 10.7% to 13.6% by CVD, stroke, hypertension, and diabetes. Cumulative incidence of ADRD was higher in those with CVD (40.75%) versus no-CVD (31.32%), stroke (40.24%) versus no-stroke (31.34%), hypertension (33.06%) versus no-hypertension (30.47%), and diabetes (33.38%) versus no-diabetes (31.77%). After adjusting for confounders, those with CVD (hazard ratio:1.30, 95% CI: 1.27-1.33), stroke (1.50,1.47-1.54), hypertension (1.08,1.06-1.09), and diabetes (1.26,1.24-1.29) had significantly higher risks of developing ADRD. Women aged 80-84, and≥85 had 5- and 7-fold higher risks of AD than those aged 65-69. As compared to white women, black women had a significantly higher risk of AD (1.21, 1.16-1.27), whereas Asians/Pacific-Islanders had a significantly lower risk of AD (0.77, 0.71-0.83)., Conclusion: In women with breast cancer, CVD, stroke, hypertension, and diabetes were associated with a significantly higher risk of developing any ADRD combined. The risk of ADRD was higher in black women and lower in Asian/Pacific-Islanders than white women.

Background: Long term risk of Alzheimer's disease (AD) and related dementias (ADRD) associated with vascular diseases in people with colorectal cancer is unknown., Objective: To determine the risk of ADRD in association with cardiovascular diseases (CVD), stroke, hypertension, and diabetes in a cohort of patients with colorectal cancer., Methods: This retrospective cohort study consisted of 210,809 patients diagnosed with colorectal cancer at age≥65 years in 1991-2015 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database with follow-up from 1991-2016, who were free of any ADRD at the baseline (<12 months prior to or < 30 days after the date of cancer diagnosis)., Results: The crude 26-year cumulative incidence of total ADRD in men and women with colorectal cancer was higher in those with versus without CVD (31.92% versus 28.12%), with versus without stroke (39.82% versus 26.39%), with versus without hypertension (31.88% versus 24.88%), and with versus without diabetes (32.01% versus 27.66%). After adjusting for socio-demographic and tumor factors, the risk of developing ADRD was significantly higher in patients with CVD (adjusted hazard ratio: 1.17, 95% confidence intervals: 1.14-1.20), stroke (1.65, 1.62-1.68), hypertension (1.07, 1.05-1.09), and diabetes (1.26, 1.24-1.29) versus persons without. For those with 1, 2, 3 and 4 vascular diseases present versus absent, the risk of AD increased from 1.12 (1.07-1.16) to 1.31 (1.25-1.36), 1.66 (1.57-1.75), and 2.03 (1.82-2.27)., Conclusion: In older patients with colorectal cancer, a significant dose-response relationship was observed between an increasing number of these vascular diseases and the risk of all types of dementia.

Background: Cognitive decline is classically attributed to organic causes such as dementia; however, depression can play a role in cognitive decline., Objective: To evaluate cognitive screening tools and the 4-item Geriatric Depression Scale (GDS-4) for use in primary care to distinguish cognitive decline secondary to depression., Method: Clinical data collected over 2.5 years for assessed patients in a secondary clinical service for younger adults. Cognitive screening tools (General Practitioner Assessment of Cognition, Addenbrooke's Cognitive Examination-III, Rowland Universal Dementia Assessment Scale, Salzburg Dementia Test Prediction) and GDS-4 were analyzed for their accuracy to differentiate patients with cognitive decline due to depression from those with subjective cognitive complaints., Results: 180 young adults seen in a memory clinic setting (< 65 years) were included. These individuals either had a diagnosis of depression (n = 46) or no cognitive impairment on assessment (n = 134) despite having subjective cognitive complaints. All used cognitive tools had poor accuracy in differentiating cognitive decline secondary to depression from subjective cognitive complaints. The GDS-4 alone, however, was able to differentiate with high accuracy (AUC = 0.818) individuals who had cognitive problems secondary to depression., Conclusion: Cognitive screening tools used alone are ineffective in discriminating cognitive decline secondary to depression. Incorporating the GDS-4 into the screening process by primary practitioners could facilitate early identification and treatment of depression in younger people, avoiding unnecessary referrals memory services.

Background: Lewy body dementia is the second most common neurodegenerative dementia, but data concerning the onset age and clinical features in the prodromal stage remain limited in China., Objective: To investigate the associations between onset age and clinical manifestations of cognitive impairment with Lewy bodies in a large-sample cohort., Methods: We included 74 patients with mild cognitive impairment with Lewy bodies (MCI-LB), 533 patients with dementia with Lewy bodies (DLB), 118 patients with Parkinson's disease with MCI (PD-MCI), and 313 patients with Parkinson's disease dementia (PDD) in this multicenter cohort from 22 memory clinics of China from 1 January 2018 to 31 March 2022. The onset age, clinical manifestations, and neuropsychological assessments were recorded and analyzed after reviewing the medical records., Results: The average onset age of memory loss was 68.28 (±7.00) years, and parkinsonism happened 2.00 (±1.24) years later for patients with MCI-LB. The average onset age of parkinsonism was 60.56 (±8.96) years, and the memory loss happened 3.49 (±3.02) years later for patients with PD-MCI. Rapid eye movement sleep behavior disorder and visual hallucinations were frequently reported in MCI-LB, DLB, and PDD, while visual hallucinations were least frequently reported in PD-MCI. Lower scores of MMSE and depression, and higher scores of activities of daily living and delusions, were independently associated with older onset age in DLB., Conclusion: The onset of PD-MCI precedes MCI-LB, and memory loss occurs 3 years after parkinsonism. The onset age is associated with cognition and neuropsychiatric symptoms in process.

Background: Negative impacts of the COVID-19 pandemic on people with dementia have been widely-documented, but most studies have relied on carer reports and few have compared responses to information collected before the pandemic., Objective: We aimed to explore the impact of the pandemic on community-dwelling individuals with mild-to-moderate dementia and compare responses with pre-pandemic data., Methods: During the second wave of the pandemic, we conducted structured telephone interviews with 173 people with dementia and 242 carers acting as informants, all of whom had previously participated in the IDEAL cohort. Where possible, we benchmarked responses against pre-pandemic data., Results: Significant perceived negative impacts were identified in cognitive and functional skills and ability to engage in self-care and manage everyday activities, along with increased levels of loneliness and discontinuity in sense of self and a decline in perceived capability to 'live well'. Compared to pre-pandemic data, there were lower levels of pain, depression, and anxiety, higher levels of optimism, and better satisfaction with family support. There was little impact on physical health, mood, social connections and relationships, or perceptions of neighborhood characteristics., Conclusion: Efforts to mitigate negative impacts of pandemic-related restrictions and restore quality of life could focus on reablement to address the effects on participation in everyday activities, creating opportunities for social contact to reduce loneliness, and personalized planning to reconnect people with their pre-COVID selves. Such efforts may build on the resilience demonstrated by people with dementia and carers in coping with the pandemic.

Background: Air pollution particulate matter (PM) is strongly associated with risks of accelerated cognitive decline, dementia and Alzheimer's disease. Ambient PM batches have variable neurotoxicity by collection site and season, which limits replicability of findings within and between research groups for analysis of mechanisms and interventions. Diesel exhaust particles (DEP) offer a replicable model that we define in further detail., Objective: Define dose- and time course neurotoxic responses of mice to DEP from the National Institute of Science and Technology (NIST) for neurotoxic responses shared by DEP and ambient PM., Methods: For dose-response, adult C57BL/6 male mice were exposed to 0, 25, 50, and 100μg/m3 of re-aerosolized DEP (NIST SRM 2975) for 5 h. Then, mice were exposed to 100μg/m3 DEP for 5, 100, and 200 h and assayed for amyloid-β peptides, inflammation, oxidative damage, and microglial activity and morphology., Results: DEP exposure at 100μg/m3 for 5 h, but not lower doses, caused oxidative damage, complement and microglia activation in cerebral cortex and corpus callosum. Longer DEP exposure for 8 weeks/200 h caused further oxidative damage, increased soluble Aβ, white matter injury, and microglial soma enlargement that differed by cortical layer., Conclusion: Exposure to 100μg/m3 DEP NIST SRM 2975 caused robust neurotoxic responses that are shared with prior studies using DEP or ambient PM0.2. DEP provides a replicable model to study neurotoxic mechanisms of ambient PM and interventions relevant to cognitive decline and dementia.

Background: Little is known about the sex differences in the association between body mass index (BMI) and dementia in late life., Objective: Therefore, this retrospective cohort study aimed to analyze associations between BMI and dementia in older women and men separately in general practices in Germany., Methods: This study included patients followed in one of 832 general practices in Germany between 2006 and 2019 (index date: first visit date). Study variables included dementia (dependent variable), BMI (independent variable), age, sex, and comorbidities (control variables). Kaplan-Meier curves and adjusted Cox regression analyses were conducted to analyze associations between BMI and the 10-year incidence of dementia in women and men, separately., Results: There were 296,767 patients included in this study (mean [standard deviation] age 70.2 [5.9] years; 54.3% women). The proportion of underweight, normal weight, overweight, and obesity was 0.9%, 25.5%, 41.5%, and 32.1%, respectively. The 10-year incidence of dementia significantly decreased with increasing BMI, from 11.5% in women with underweight to 9.1% in those with obesity (log-rank p < 0.001). Respective figures in men were 12.0% and 8.2% (log-rank p < 0.001). In women, only overweight (versus normal weight) was significantly associated with dementia (HR = 0.93, 95% CI = 0.88-0.97). In contrast, in men, the only BMI category significantly associated with the incidence of dementia was underweight (HR = 1.58, 95% CI = 1.11-2.25)., Conclusion: In this study conducted in Germany, overweight was negatively associated with dementia in women, whereas there was a positive underweight-dementia relationship in men. More data are needed to confirm or refute these findings in other settings.

Psychotic phenomena are among the most severe and disruptive symptoms of dementias and appear in 30% to 50% of patients. They are associated with a worse evolution and great suffering to patients and caregivers. Their current treatments obtain limited results and are not free of adverse effects, which are sometimes serious. It is therefore crucial to develop new treatments that can improve this situation. We review available data that could enlighten the future design of clinical trials with psychosis in dementia as main target. Along with an explanation of its prevalence in the common diseases that cause dementia, we present proposals aimed at improving the definition of symptoms and what should be included and excluded in clinical trials. A review of the available information regarding the neurobiological basis of symptoms, in terms of pathology, neuroimaging, and genomics, is provided as a guide towards new therapeutic targets. The correct evaluation of symptoms is transcendental in any therapeutic trial and these aspects are extensively addressed. Finally, a critical overview of existing pharmacological and non-pharmacological treatments is made, revealing the unmet needs, in terms of efficacy and safety. Our work emphasizes the need for better definition and measurement of psychotic symptoms in dementias in order to highlight their differences with symptoms that appear in non-dementing diseases such as schizophrenia. Advances in neurobiology should illuminate the development of new, more effective and safer molecules for which this review can serve as a roadmap in the design of future clinical trials.

Introduction: The objective of this study was to examine the relationship between dementia severity and early discharge from home health., Methods: This was a retrospective study of 100% national Medicare home health da ta files (2016-2017). Multilevel logistic regression was used to study the relationship of dementia severity, caregiver support, and medication assistance with early discharge from home health., Results: The final cohort consisted of 91 302 Medicare beneficiaries with an ADRD diagnosis. A pattern of early discharge rates across dementia severity levels was not demonstrated. The relative risk for early discharge was lower for individuals who needed assistance with medication and for those with unmet caregiver needs., Discussion: The findings of this study do not support the hypothesis that dementia severity contributes to early discharge from home health. Further research is needed to fully understand key factors contributing to early discharge from home health.

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: Behavioral and psychological symptoms of dementia (BPSD) have a large impact on the quality of life of patients with Alzheimer's disease (AD). Few studies have compared BPSD between early-onset (EOAD) and late-onset (LOAD) patients, finding conflicting results., Objective: The aims of this study were to: 1) characterize the presence, overall prevalence, and time of occurrence of BPSD in EOAD versus LOAD; 2) estimate the prevalence over time and severity of each BPSD in EOAD versus LOAD in three stages: pre-T0 (before the onset of the disease), T0 (from onset to 5 years), and T1 (from 5 years onwards); 3) track the manifestation of BPSD sub-syndromes (i.e., hyperactivity, psychosis, affective, and apathy) in EOAD versus LOAD at T0 and T1., Methods: The sample includes 1,538 LOAD and 387 EOAD diagnosed from 1996 to 2018. Comprehensive assessment batteries, including the Neuropsychiatric Inventory (NPI), were administered at the first medical assessment and at different follow-up period., Results: The overall prevalence for the most of BPSD was significantly higher in EOAD compared to LOAD whereas most BPSD appeared significantly later in EOAD patients. Between the two groups, from pre-T0 to T1 we recorded a different pattern of BPSD prevalence over time as well as for BPSD sub-syndromes at T0 and T1. Results on severity of BPSD did not show significant differences., Conclusion: EOAD and LOAD represent two different forms of a single entity not only from a neuropathological, cognitive, and functional level but also from a psychiatric point of view.

Background: A negative association between cancer and Alzheimer's disease (AD) was revealed., Objective: We aimed to further explore the dementia risk among cancer survivors and then among cancer survivors who received cancer treatment in subsequent subgroup analyses., Methods: Databases of PubMed, Embase, and Cochrane Library were systematically searched from inception to April 1, 2021, following PRISMA and MOOSE guidelines. Relative risks (RR) of dementia were pooled by a random-effects model stratifying the data by potential confounding factors to explore the heterogeneity. This study is registered with PROSPERO, number CRD42021250654., Results: A total of 36 studies were included in this meta-analysis, of which 16 studies were about the risk of dementia in cancer survivors, and 20 studies were about the risk of dementia in survivors who accepted cancer treatment. The pooled RR reached 0.89 ([95% CI = 0.82-0.97], I2 = 97.9%) for dementia and 0.89 ([0.83-0.95], I2 = 92.6%) for AD in cancer survivors compared with non-cancer controls. Notably, both dementia risk and AD risk significantly decreased in survivors of colon, leukemia, small intestine, and thyroid cancers (RR ranged from 0.64 to 0.92). Furthermore, prostate cancer patients treated with androgen deprivation therapy exhibited a significantly increased risk of dementia (RR:1.18 [1.09-1.27], I2 = 89.5%) and AD (RR:1.17 [1.08-1.25], I2 = 81.3%), with evidence of between-study heterogeneity., Conclusion: Currently, available evidence suggests that the risk of dementia among cancer survivors is decreased. However, large-scale prospective cohort studies are warranted to further prove the association.