Assessing the effect of anthocyanins through diet and supplementation on cognitive function in older adults at risk for dementia: protocol for a randomised controlled trial.

INTRODUCTION: Promising evidence is emerging for the procognitive, anti-inflammatory and neuroprotective properties of dietary flavonoids, particularly anthocyanins that provide red, purple and blue plant pigments. METHODS AND ANALYSIS: The 'Food for Thought' study is a multicentre, 6-month randomised, parallel 3-arm clinical trial. Its primary aim is to investigate whether anthocyanin consumption, either through diet or supplementation, can prevent memory loss progression and improve inflammatory and cardiovascular health in older adults at risk for dementia. Eligible participants will include those aged 60-85 years with a diagnosis of amnestic mild cognitive impairment or with a self-referral of memory concerns and scoring ≤13 on the Memory Index Score within the Telephone Montreal Cognitive Assessment screening test. Participants will be randomised to one of three arms: High anthocyanin ('purple foods') diet (aiming for a target of 250 mg anthocyanins/day); freeze-dried product derived from blackcurrants (250 mg anthocyanins/day); or control (coloured maltose powder). The primary outcome is auditory anterograde memory functioning assessed by the Buschke and Grober Free and Cued Selective Reminding Test-Immediate Recall. Secondary outcomes are additional cognitive functions including processing speed, working memory, aspects of executive functioning (attentional shifting and word generativity) and premorbid estimate as well as subjective memory problems and self-reported depression symptoms. Additional secondary outcomes are blood pressure, inflammatory biomarkers, brain-derived neurotrophic factor, fatty acid profile, apolipoprotein E and polyphenol metabolites, gut microbiota composition and function and vascular and microvascular endothelial function tests. Repeated measures analysis of variance and/or mixed linear modelling will evaluate changes over time, with the inclusion of covariates. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the Greater Western Human Research Ethics Committee (2021/ETH12083). A Consumer Advisory Group was established to guide and review the protocol and dissemination strategy. The results of this trial are intended to be published in a peer-reviewed journal. TRIAL SPONSOR: National Health and Medical Research Centre Dementia Collaborative Research Centre.Start date of clinical trial: 02 September 2022.Expected end date: 11 October 2024. TRIAL REGISTRATION NUMBER: ACTRN12622000065796.

Lifetime history of gestational diabetes and cognitive function in parous women in midlife.

AIMS/HYPOTHESIS: We aimed to determine whether a history of gestational diabetes mellitus (GDM) is associated with cognitive function in midlife. METHODS: We conducted a secondary data analysis of the prospective Nurses' Health Study II. From 1989 to 2001, and then in 2009, participants reported their history of GDM. A subset participated in a cognition sub-study in 2014-2019 (wave 1) or 2018-2022 (wave 2). We included 15,906 parous participants (≥1 birth at ≥18 years) who completed a cognitive assessment and were free of CVD, cancer and diabetes before their first birth. The primary exposure was a history of GDM. Additionally, we studied exposure to GDM and subsequent type 2 diabetes mellitus (neither GDM nor type 2 diabetes, GDM only, type 2 diabetes only or GDM followed by type 2 diabetes) and conducted mediation analysis by type 2 diabetes. The outcomes were composite z scores measuring psychomotor speed/attention, learning/working memory and global cognition obtained with the Cogstate brief battery. Mean differences (ß and 95% CI) in cognitive function by GDM were estimated using linear regression. RESULTS: The 15,906 participants were a mean of 62.0 years (SD 4.9) at cognitive assessment, and 4.7% (n=749) had a history of GDM. In models adjusted for age at cognitive assessment, race and ethnicity, education, wave of enrolment in the cognition sub-study, socioeconomic status and pre-pregnancy characteristics, women with a history of GDM had lower performance in psychomotor speed/attention (ß -0.08; 95% CI -0.14, -0.01) and global cognition (ß -0.06; 95% CI -0.11, -0.01) than those without a history of GDM. The lower cognitive performance in women with GDM was only partially explained by the development of type 2 diabetes. CONCLUSIONS/INTERPRETATION: Women with a history of GDM had poorer cognition than those without GDM. If replicated, our findings support future research on early risk modification strategies for women with a history of GDM as a potential avenue to decrease their risk of cognitive impairment.

Patients with dementia or frailty undergoing major limb amputation have poor outcomes.

OBJECTIVE: Major lower limb amputation is a disfiguring operation associated with impaired mobility and high near-term mortality. Informed decision-making regarding amputation requires outcomes data. Despite the co-occurrence of both chronic limb-threatening ischemia (CLTI) and Alzheimer's Disease and related dementias (ADRD), there is sparse data on the outcomes of major limb amputation in this population and the impact of frailty. We sought to determine mortality, complications, readmissions, revisions, intensive interventions (e.g., cardiopulmonary resuscitation), and other outcomes after amputation for CLTI in patients living with ADRD looking at the modifying effects of frailty. METHODS: We examined Medicare fee-for-service claims data from January 1, 2016 to December 31, 2020. Patients with CLTI undergoing amputation at or proximal to the ankle were included. Along with demographic information, dementia status, and comorbid conditions, we measured frailty using a claims-based frailty index. We dichotomized dementia and frailty (pre-frail/robust = "non-frail" vs moderate/severe frailty = "frail") to create four groups: non-frail/non-ADRD, frail/non-ADRD, non-frail/ADRD, and frail/ADRD. We used linear and logistic regression via generalized estimating equations in addition to performing selected outcomes analyses with death as a competing risk to understand the association between dementia status, frailty status, and one-year mortality as our primary outcome in addition to the postoperative outcomes outlined above. RESULTS: Among 46,930 patients undergoing major limb amputation, 11,465 (24.4%) had ADRD and 24,790 (52.8%) had frailty. Overall, 55.9% of amputations were below-knee. Selected outcomes among frail/ADRD patients undergoing amputation (N=10,153) were: 55.3% one-year mortality 29.6% readmissions at 30 days, and 32.3% amputation revision/reoperation within one year. Of all four groups, those in the frail/ADRD had the worst outcomes only for 1-year mortality. CONCLUSIONS: First, patients with ADRDw or moderate/severe frailty suffer an array of very poor outcomes after major limb amputation for CLTI including high mortality, readmissions, revision, and risks of discharge to higher levels of care. Second, there is a complex relationship between outcome severity and ADRD/frailty status. Specifically, frailty is more often than ADRD associated with the poorest results for any given outcome. These data provide important outcomes data to help align decision-making with healthcare values and goals.

Characteristics of people diagnosed with dementia vs lung cancer and cardiovascular disease at commencement of community palliative care: a population-based study.

BACKGROUND: Most people diagnosed with dementia live and die in community settings. This study aimed to: (i) describe the palliative care needs of patients with dementia at commencement of community palliative care; (ii) compare palliative care needs between patients with dementia and those with lung cancer and cardiovascular disease (CVD). METHODS: This is a population-based descriptive study that involved 8,727, 7,539 and 25,279 patients who accessed community palliative care across Australia principally because of dementia, CVD and lung cancer. Patients' functional abilities, symptom burden and clinical condition were assessed at commencement of community alliative care using five validated instruments: Resource Utilisation Groups-Activities of Daily Living, Australia-modified Karnofsky Performance Status, Symptoms Assessment Scale, Palliative Care Problem Severity Score and Palliative Care Phase. We fitted ordinal logistic regression models to examine the differences in these assessments for dementia versus CVD and lung cancer, respectively. RESULTS: Overall, patients with dementia generally had low levels of distress from symptoms but poor functional problems. Compared to the other two diagnostic groups, palliative care for dementia was often initiated later and with shorter contacts. Also, patients with dementia presented with poorer functional performance (adjusted OR (aOR) = 4.02, Confidence Interval (CI): 3.68 - 4.38 for dementia vs CVD; aOR = 17.59, CI: 15.92 - 19.44 for dementia vs lung cancer) and dependency (aOR = 5.68, CI: 5.28 - 6.12 for dementia vs CVD; aOR = 24.97, CI: 22.77 - 27.39 for dementia vs lung cancer), but experienced lower levels of distress and problem severity for the majority of symptoms. CONCLUSION: Community palliative care is often an ideal care option for many patients, particularly for those with dementia. We call for expansion of the palliative care workforce and options for home care support to optimize accessibility of community palliative care for dementia.

Effect of Deep Brain Stimulation on Parkinson Disease Dementia: A Systematic Review and Meta-analysis.

Introduction: Patients in the early stages of Parkinson disease (PD) may have subtle cognitive deficits, while overt cognitive deficits are usually manifestations of late-stage PD. There is still a debate on the outcome of deep brain stimulation (DBS) on the cognitive function of PD patients. This study aimed to investigate the effect of subthalamic nucleus (STN)-DBS on the dementia of PD patients after surgery compared to medical therapy and other procedures. Methods: We searched PubMed, Scopus, Cochrane Library, and Web of Science database on October 2020, with keywords: "Deep brain stimulation," "Parkinson disease," "dementia," and "memory." Reviews, abstracts, case presentations, and letters were excluded. Results: In total, 491 studies were screened after removing the duplicates. The screening results yielded 81 articles to be screened for eligibility. Finally, 6 studies were included in this meta-analysis for synthesis. Overall, 800 patients were included in this meta-analysis, using the Mattis dementia rating scale (MDRS) and descriptive data from the articles extracted to assess global dementia. Conclusion: Our results suggest that the STN-DBS group showed a larger cognitive decline than the patients receiving the best medical treatment (BMT). However, comparing STN-DBS with globus pallidus interna stimulation and pallidotomy could not demonstrate a significant statistical effect on the global dementia of patients. More long-term studies with larger sample sizes are needed to validate current findings.

Experiences of patients with advanced chronic diseases and their associates with a structured palliative care nurse visit followed by an interprofessional case conference in primary care - a deductive-inductive content analysis based on qualitative interviews (KOPAL-Study).

BACKGROUND: Chronic, non-malignant diseases (CNMD) like chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF) and dementia in advanced stages are very burdensome for patients. Timely palliative care with strong collaboration between general practitioners (GPs) and specialist palliative home care (SPHC) teams can reduce symptom burden, hospitalization rates, hospitalization costs and overall healthcare costs. The KOPAL-study on strengthening interprofessional collaboration for patients with palliative care needs tested the effect of an intervention comprising of a SPHC nurse assessment and an interprofessional case conference. This qualitative evaluative study explores patients', proxies' and their associates' motivation to participate in the KOPAL-study and views on the (benefits of the) intervention. METHODS: We interviewed 13 male and 10 female patients as well as 14 proxies of patients with dementia and six associates of study participants using a semi-structured interview guide. All interviews were digitally recorded, transcribed verbatim and analysed with deductive-inductive qualitative content analysis. RESULTS: Motivation for participation was driven by curiosity, the aim to please the GP or to support research, respectively to help other patients. Few interviewees pointed out to have expected positive effects for themselves. The nurse visit was evaluated very positively. Positive changes concerning health care or quality of life were reported sparsely. Most study participants did not prepare for the SPHC nurse assessment. They had no expectations concerning potential benefits of such an assessment, the interdisciplinary case conference and an early integration of palliative care. The majority of interviewees reported that they did not talk about the nurse visit and the interprofessional case conference with their GPs. CONCLUSION: Our results lead to the conclusion that SPHC nurses can serve as an advocate for the patient and thereby support the patients' autonomy. GPs should actively discuss the results of the interdisciplinary case conference with patients and collaboratively decide on further actions. Patient participation in the interdisciplinary case conference could be another way to increase the effects of the intervention by empowering patients to not just passively receive the intervention. TRIAL REGISTRATION: DRKS00017795 German Clinical Trials Register, 17Nov2021, version 05.

Mortality in people living with dementia who self-harmed: An Australian data linkage study.

OBJECTIVES: This study aimed to examine mortality for people living with dementia/mild cognitive impairment who self-harmed. METHODS: We conducted a retrospective cohort study in New South Wales, Australia, using data ranging from 2001 to 2015. From people who accessed hospital services in the study period, we identified 154,811 people living with dementia/mild cognitive impairment, 28,972 who self-harmed and 1511 who had a record of both dementia/mild cognitive impairment and self-harm. We examined rates, causes and predictors of death for people with dementia/mild cognitive impairment and/or self-harm diagnoses using flexible parametric survival analyses. We explored rates of repeat self-harm in people living with dementia who self-harmed. RESULTS: Circulatory disorders accounted for 32.0% of deaths in people with a living with dementia who self-harmed, followed by neoplasms (14.7%), and mental and behavioural disorders (9.6%). Death was more likely for someone who had self-harmed if they developed dementia/mild cognitive impairment. Predictors of death included male sex, greater physical comorbidity, a history of delirium, more previous emergency department presentations and fewer previous mental health ambulatory service days. Greater engagement with outpatient mental health services predicted a decreased likelihood of repeat self-harm. DISCUSSION: We found that mortality increases when people who self-harm develop dementia. We argue post-diagnosis support offers a potential opportunity to reduce mortality rates in people with both dementia and self-harm diagnoses.

Increasing Identification and Follow-Up of Cognitive Impairment in Primary Care: A Quality Improvement Pilot Study.

INTRODUCTION: Beyond our population growing older and living longer, there is an increased risk of developing a cognitive disorder. Standardized screening during a routine visit in primary care may be ideal for early detection of mild cognitive impairment (MCI) and follow-up for cognitive changes. AIM: This quality improvement (QI) project aimed to determine the impact of implementing the Mini-Cog© quick screening for early dementia detection to identify and follow up on the cognitive impairment of older adults in a primary care clinic setting. METHODS: Implementation started in February 2024 in a primary care clinic in Southern California. Data was collected for this project over a total of 16 weeks. This QI project implemented a routine cognitive screening using the Mini-Cog©. Cognitive impairment was identified, and if indicated by the Mini-Cog© scores, follow-up for a cognitive assessment and care plan services were initiated. Data were obtained from the project site's electronic medical record on a total sample size of 471 participants (n = 382 in the pre-implementation group and n = 89 in the post-implementation group). RESULTS: Pearson's chi-square test indicated a statistically significant improvement in the identification rate of cognitive impairment, increasing from 11.8% (n = 45 out of 382) at pre-implementation to 34.8% (n = 31 out of 89) at post-implementation, and specifically, mild cognitive impairment increased from zero identified in pre-implementation to 12.4% (n = 11 out of 89) post-implementation. Lastly, follow-up rates improved from 91.1% (n = 41 out of 45) to 100% (n = 31 out of 31) in post-implementation, and clinical significance was evident based on the phi-coefficient (φ = 0.196), indicating a small effect size and a 100% follow-up rate. CONCLUSIONS: The findings of this project suggest older adults should receive cognitive screenings to help identify early cognitive impairment and increase follow-up for further evaluation, treatment, and advanced care planning.

Breaking barriers: addressing inequities in Alzheimer's disease diagnosis and treatment in Africa.

Introduction: Alzheimer's disease represents a substantial and escalating public health threat across Africa. Alzheimer's disease leads to substantial cognitive impairment and memory loss, placing a heavy burden on the affected individuals and their families, friends, and caregivers. It affects 2.67 million people in Africa, the majority of whom live in sub-Saharan Africa. The prevalence of this disease is expected to rise drastically to approximately 150 million individuals worldwide by 2050, as estimated by the WHO. Aim: This paper offers an integrative profile of Alzheimer's disease in Africa, spanning known genetic and modifiable risks, discusses the existing challenges in diagnosis and treatment, projections on prevalence and disability-adjusted life year burden through 2050, and priority policy responses needed to rebalance the equation. Methods: This paper examines available literature to summarize current knowledge on risk factors, diagnosis, treatments, and burden of Alzheimer's disease in Africa. Gather epidemiological assessments, clinical guidelines, and commentary related to Alzheimer's disease in Africa. Results: The data reveals concerning realities regarding Alzheimer's disease diagnosis and care in Africa. Diagnostic infrastructure shortcomings, resource limitations, and knowledge gaps emerge as recurring barriers. Positron emission tomography scans, cerebrospinal fluid assays, and other mainstay detection modalities common in developed countries show restricted availability. Conclusion: Addressing Africa's Alzheimer's disease crisis demands a multipronged strategy to uplift diagnostic capacities, treatment availability, specialist training, public awareness, and coordinated policymaking. Prioritizing biomarkers and imaging to confirm early neurodegeneration is foundational, alongside drug access expansion.

QBT improved cognitive dysfunction in rats with vascular dementia by regulating the Nrf2/xCT/GPX4 and NLRP3/Caspase-1/GSDMD pathways to inhibit ferroptosis and pyroptosis of neurons.

BACKGROUND: The novel phthalein component QBT, extracted from Ligusticum chuanxiong, shows promising biological activity against cerebrovascular diseases. This study focused on ferroptosis and pyroptosis to explore the effects of QBT on nerve injury, cognitive dysfunction, and related mechanisms in a rat model of vascular dementia (VaD). METHODS: We established a rat model of VaD and administered QBT as a treatment. Cognitive dysfunction in VaD rats was evaluated using novel object recognition and Morris water maze tests. Neuronal damage and loss in the brain tissues of VaD rats were assessed with Nissl staining and immunofluorescence. Furthermore, we investigated the neuroprotective mechanisms of QBT by modulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/cystine-glutamate antiporter (xCT)/glutathione peroxidase 4 (GPX4) and Nod-like receptor family pyrin domain-containing 3 (NLRP3)/cysteine-requiring aspartate protease-1 (Caspase-1)/Gasdermin D (GSDMD) pathways to inhibit ferroptosis and pyroptosis both in vivo and in vitro. RESULTS: Our findings indicated that QBT significantly ameliorated neuronal damage and cognitive dysfunction in VaD rats. Additionally, QBT reversed abnormal changes associated with ferroptosis and pyroptosis in the brains of VaD rats, concurrently up-regulating the Nrf2/xCT/GPX4 pathway and down-regulating the NLRP3/Caspase-1/GSDMD pathway to inhibit ferroptosis and pyroptosis in neuronal cells, thereby exerting a neuroprotective role. CONCLUSION: In summary, QBT effectively mitigated neuronal damage and cognitive dysfunction in VaD rats, demonstrating a neuroprotective effect by inhibiting ferroptosis and pyroptosis in neuronal cells. This study offers a novel perspective and theoretical foundation for the future development of drugs targeting VaD.

Guardians of memory: The urgency of early dementia screening in an aging society.

The global aging population has led to a significant rise in the prevalence of age-related non-communicable diseases such as dementia and other cognitive disorders. In 2019, there were 57.4 million people with dementia worldwide, and this number is projected to triple by 2050. Intervening in and managing 12 potentially modifiable dementia risk factors can prevent or delay the onset and progression of about 40% of dementia cases. Neuroimaging, biomarkers, and advanced neuropsychological testing offer promising pathways for the early detection of dementia. Emphasis should be placed on educating the public about the importance of brain health and the early signs of cognitive impairment, as well as promoting dementia prevention measures. Adopting a healthy lifestyle - including a balanced diet, regular physical exercise, active social engagement, cognitive activities, and avoiding smoking and excessive alcohol consumption - can help reduce the risk of cognitive decline and prevent cognitive disorders. Government policies on dementia prevention and health care, along with early and regular dementia screening programs, can enhance the early identification and management of individuals at risk. In addition, integrating cognitive health assessments into routine medical check-ups is essential for the early screening and management of dementia.

Comparison of the Effect of Pump Flow Type (Pulsatile or Non-Pulsatile) on Postoperative Neurocognitive Functions in Coronary Artery Surgery.

INTRODUCTION: The effect of pump flow type on perfusion in coronary surgery using cardiopulmonary bypass (CPB) is discussed. We aimed to evaluate the effect of pump flow type on cognitive functions with neurocognitive function tests. METHODS: One hundred patients who underwent isolated coronary artery bypass surgery between November 2020 and July 2021 were divided into two equa groups. Groups were formed according to pump flow type pulsatile (Group 1) and non-pulsatile (Group 2). Clock drawing test (CDT) and standardized mini mental test (SMMT) were performed on the patients in both groups in the preoperative period, on the 1st preoperative day, and on the day before discharge. Neurocognitive effects were compared with all follow-up parameters. RESULTS: There was no difference between the groups in terms of demographic data and in terms of neurocognitive tests performed before the operation. SMMT on postoperative day 1 (Group I: 27.64 ± 1.05; Group II: 24.44 ± 1.64; P=0.001) and CDT (Group I: 5.4 ± 0.54; Group II: 4 .66 ± 0.52; P=0.001), and SMMT on the day before discharge (Group I: 27.92 ± 1.16; Group II: 24.66 ± 1.22; P=0.001) and CDT (Group I: 5 It was calculated as .66 ± 0.48; Group II: 5.44 ± 0.5; P=0.001). The duration of intensive care and hospitalization were higher in the non-pulsatile group. CONCLUSION: We think that the type of pump flow used in coronary artery bypass surgery using CPB is effective in terms of neurocognitive functions and that pulsatile flow makes positive contributions to this issue.

Global burden of young-onset Alzheimer's disease and other dementias: a secondary analysis of the global burden of disease study, 2019.

The aging of the world population has led to an increase in the epidemiology and burden of Alzheimer's disease and other dementias. Objective: To describe the global burden of young-onset Alzheimer's disease and other dementias by world region and income through a secondary analysis of the Global Burden of Disease Study 2019. Methods: This is a descriptive cross-sectional ecological study. Data by sex and five-year age groups from 40 to 64 years were extracted from the Global Burden of Disease Study results tool. We performed a descriptive analysis of prevalence, incidence, deaths, disability-adjusted life years, years of life lost, and years lived with disability. Results: In 2019, young-onset Alzheimer's disease and other dementias presented a prevalence of 2.67 cases and an incidence of 0.44 per 1,000 inhabitants globally. It carried a significant burden, resulting in 1.16 disability-adjusted life years per 1,000 inhabitants, primarily due to years of life lost, and to a lesser extent due to years lived with disability. East Asia & the Pacific, Latin America & the Caribbean, and North America are the most affected regions. Burden rates are consistently higher among women; no gradient was observed by country income. Smoking was the most relevant risk factor, presenting a broad difference by country income level. Conclusion: The global burden of young-onset Alzheimer's disease and other dementias may reshape healthcare requirements and the societal impact of dementias, and its understanding is relevant to inform decisions related to service offerings and research agendas.

O envelhecimento da população mundial tem levado a um aumento da epidemiologia e da carga da Doença de Alzheimer e outras Demências. Objetivo: Descrever a Carga Global da Doença de Alzheimer de Início Precoce e outras Demências (DAIPoD) por região do mundo e nível de renda por meio de uma análise secundária do Estudo Global de Carga de Doenças (Global Burden of Disease Study ­ GBD), 2019. Métodos: Estudo ecológico transversal descritivo. Os dados de cinco anos por sexo e faixa etária de 40 a 64 anos foram extraídos da ferramenta de resultados do GBD. Realizou-se uma análise descritiva de prevalência, incidência, óbitos, Anos de Vida Ajustados por Incapacidade (Disability Adjusted Life Years ­ DALY), Anos de Vida Perdidos (Years of Life Lost ­ YLL) e Anos Vividos com Incapacidade (Years Lived with Disability ­ YLD). Resultados: Em 2019, a DAIPoD apresentou uma prevalência de 2,67 casos e uma incidência de 0,44 casos por 1.000. Foi observada uma carga significativa, resultando em 1,16 DALY por 1.000, principalmente devido aos YLL e, em menor grau, aos YLDs. As regiões mais afetadas foram o Leste Asiático e Pacífico, a América Latina e Caribe, e a América do Norte. As taxas de carga são consistentemente mais elevadas entre as mulheres; não foi observado um gradiente por nível de renda dos países. O tabagismo foi o fator de risco mais relevante, apresentando uma ampla diferença por nível de renda do país. Conclusão: A carga global do DAIPoD pode remodelar as necessidades de saúde e o impacto social das demências, e sua compreensão é relevante para informar decisões relacionadas à oferta de serviços e agendas de pesquisa.

Establishing and evaluating the gradient of item naming difficulty in post-stroke aphasia and semantic dementia.

Anomia is a common consequence following brain damage and a central symptom in semantic dementia (SD) and post-stroke aphasia (PSA), for instance. Picture naming tests are often used in clinical assessments and experience suggests that items vary systematically in their difficulty. Despite clinical intuitions and theoretical accounts, however, the existence and determinants of such a naming difficulty gradient remain to be empirically established and evaluated. Seizing the unique opportunity of two large-scale datasets of semantic dementia and post-stroke aphasia patients assessed with the same picture naming test, we applied an Item Response Theory (IRT) approach and we (a) established that an item naming difficulty gradient exists, which (b) partly differs between patient groups, and is (c) related in part to a limited number of psycholinguistic properties - frequency and familiarity for SD, frequency and word length for PSA. Our findings offer exciting future avenues for new, adaptive, time-efficient, and patient-tailored approaches to naming assessment and therapy.

Risk of Dementia in Different Types of Cancer Survivors: A Nationwide Cohort Study.

OBJECTIVES: The association between specific types of malignancies and the subsequent risk of dementia remains unknown. DESIGN: A retrospective population-based cohort study based on data from Taiwan National Health Insurance Research Database. SETTING AND PARTICIPANTS: We recruited 32,250 patients who survived malignancies and 322,500 controls between 1998 and 2011 and followed them up until the end of 2013. MEASUREMENTS: Diagnoses of dementia (including Alzheimer's disease (AD), vascular dementia (VaD), and unspecified dementia) was made during the follow-up period. Cox regression analyses were performed after adjusting for potential confounders. A sensitivity analysis was conducted to exclude patients with prodromal dementia. RESULTS: Cancer survivors were more likely to develop AD (hazard ratio [HR]: 1.68, 95% confidence interval [CI]: 1.38-2.06), unspecified dementia (HR: 1.19, 95% CI: 1.07-1.32), and any dementia (HR: 1.26, 95% CI: 1.16-1.37) compared with controls after adjusting for potential confounders. Importantly, cancers of the digestive and genitourinary organs seem to be associated with AD, unspecified dementia, and any dementia, whereas only malignant neoplasms of the brain are more likely to develop into VaD. Sensitivity analyses after exclusion of the first three or five years of observation and after exclusion of case enrollment before 2009 or 2007 showed consistent findings. CONCLUSION: Cancer survivors are at higher risk of subsequent dementia. Different types of cancer survivors may contribute to variable risks of specific dementias. Further studies are necessary to investigate the underlying mechanisms in cancer survivors and patients with dementia.

General practitioners' perspectives on lifestyle interventions for cognitive preservation in dementia prevention.

BACKGROUND: General practitioners (GPs) play a crucial role in identifying cognitive impairment and dementia and providing post-diagnostic care. This study investigates (1) how promising GP consider lifestyle changes to maintain cognitive performance in general, (2) GP beliefs about the power of modifiable health and lifestyle factors to maintain cognitive performance, and (3) whether those beliefs vary by GP age. METHODS: As part of the AgeWell.de trial, GPs (n = 72) completed a process evaluation questionnaire assessing their perspectives on lifestyle changes to preserve cognitive performance in elderly patients. In greater detail, their perceived efficacy of established risk and protective factors was investigated using a 5-point Likert scale. Descriptive statistical analyses were performed for research question (1) and (2). Spearman´s rank correlations and ordinal logistic regressions were used to answer research question (3). All results were interpreted exploratively. RESULTS: GPs rated the overall chance of lifestyle changes maintaining cognitive performance quite neutral with a median score of 3.0 (IQR = 2.0). They rated the efficacy of all the modifiable health and lifestyle factors high, with increase in physical and social activity ((Mdn = 5.0, IQR = 1.0) receiving the highest ratings with the narrowest range. Spearman's rank correlation indicated a significant positive relationship between age and the belief in "Optimization of nutrition" for preventing cognitive decline and dementia (ρ = .255, p = .041). However, ordinal logistic regressions showed no significant relationships between age and GP ratings of lifestyle change efficacy. CONCLUSION: These findings highlight the positive perception of GPs on the efficacy of modifiable health and lifestyle factors for preventing cognitive decline and dementia. TRIAL REGISTRATION: The AgeWell.de trial is registered in the German Clinical Trials Register (DRKS; trial identifier: DRKS00013555, Registration Date 07 December 2017).

Patient and public involvement in international research: Perspectives of a team of researchers from six countries on collaborating with people with lived experiences of dementia and end-of-life.

BACKGROUND: Patient and public involvement (PPI) is a critical priority in research, policy, academia and advocacy organizations. PPI in dementia research is gaining momentum. However, these efforts are missing in international projects aimed at those living with advanced dementia in long-term care (LTC) homes. Additional complexities can arise in enacting PPI within the context of integration of a palliative approach to care and experiences around end-of-life in (EOL) dementia. The mySupport study involved implementing the Family Carer Decision Support (FCDS) intervention for care partners of those living with advanced dementia in LTC in six countries. RESEARCH DESIGN AND OBJECTIVE: An interpretive description study was conducted to explore the perspectives of international researchers from six countries on engaging people with lived experiences of dementia and EOL care in research processes. The findings from this study informed the development of a PPI strategy and a subsequent toolkit for the FCDS intervention. FINDINGS: Thirty-eight interviews were completed with project researchers: 12 from the United Kingdom, 8 from Canada, 7 from Ireland, 4 each from Italy and The Netherlands and 3 from the Czech Republic. Four broad themes describe international researchers' perspectives on advancing methods of engagement for people with lived experiences of dementia and EOL in international PPI activities: (1) Groundwork to engage in research; (2) planning for research activities is key; (3) focus on meaningful engagement and (4) having foresight for practical issues shaping PPI. DISCUSSION AND IMPLICATIONS: International projects that involve PPI can present many sources of challenges. The findings in this study highlight important considerations for foundational work for incorporating PPI in international projects. Learning from world leaders and those with lived experiences in various regions can be insightful and help share tools and resources. PATIENT OR PUBLIC CONTRIBUTION: PPI was envisioned as a critical part of conducting the mySupport study. The findings from this study informed the development of a PPI strategy and an international Strategic Guiding Council that included family carers of those living with advanced dementia in LTC homes in six countries. This manuscript focused on the perspectives of researchers on their engagement with people with lived experiences of dementia and EOL. The perspectives of persons with lived experiences on engaging in the mySupport research study will be reported in a forthcoming manuscript.

A need to integrate pharmacological management for multimorbidity into dementia guidelines in Australia.

Introduction: Pharmacological management is a vital aspect of dementia care. Suboptimal medication prescribing and adverse drug reactions are major causes for ongoing concerns for the quality of care. This review aims to investigate the existence and comprehensiveness of Australian guidelines dedicated to supporting dementia care in the context of pharmacological management. Methods: Guideline registries and databases (EMBASE and CINAHL) were searched to identify Australian guidelines addressing pharmacological management in dementia care and to uncover barriers and considerations associated with guideline implementation. Results: Seven Australian guidelines were identified. Barriers to effective implementation were identified at individual, provider, and system levels. None of the identified guidelines provided comprehensive guidance on management of multimorbidity and polypharmacy. Discussion: Although Australian guidelines are available to guide pharmacological management in dementia, several barriers impede their effective implementation. There is an urgent need for updated guidelines that address the management of multimorbidity and polypharmacy in people living with dementia.

Osteoarthritis, osteoarthritis treatment and risk of incident dementia: a prospective cohort study based on UK Biobank.

BACKGROUND: We aimed to investigate the association between OA and treatment with dementia risk and structural brain abnormalities. METHODS: We recruited a total of 466,460 individuals from the UK Biobank to investigate the impact of OA on the incidence of dementia. Among the total population, there were 63,081 participants diagnosed with OA. We subsequently categorised the OA patients into medication and surgery groups based on treatment routes. Cox regression models explored the associations between OA/OA treatment and dementia risk, with the results represented as hazard ratios (HRs) and 95% confidence intervals (95% CI). Linear regression models assessed the associations of OA/OA therapy with alterations in cortical structure. RESULTS: During an average of 11.90 (± 1.01) years of follow-up, 5,627 individuals were diagnosed with all-cause dementia (ACD), including 2,438 AD (Alzheimer's disease), and 1,312 VaD (vascular dementia) cases. Results revealed that OA was associated with the elevated risk of ACD (HR: 1.116; 95% CI: 1.039-1.199) and AD (HR: 1.127; 95% CI: 1.013-1.254). OA therapy lowered the risk of dementia in both medication group (HR: 0.746; 95% CI: 0.652-0.854) and surgery group (HR: 0.841; 95% CI: 0.736-0.960). OA was negatively associated with cortical area, especially precentral, postcentral and temporal regions. CONCLUSIONS: Osteoarthritis increased the likelihood of developing dementia, and had an association with regional brain atrophy. OA treatment lowered the dementia risk. OA is a promising modifiable risk factor for dementia.

Deep learning assisted quantitative analysis of Aß and microglia in patients with idiopathic normal pressure hydrocephalus in relation to cognitive outcome.

Neuropathologic changes of Alzheimer disease (AD) including Aß accumulation and neuroinflammation are frequently observed in the cerebral cortex of patients with idiopathic normal pressure hydrocephalus (iNPH). We created an automated analysis platform to quantify Aß load and reactive microglia in the vicinity of Aß plaques and to evaluate their association with cognitive outcome in cortical biopsies of patients with iNPH obtained at the time of shunting. Aiforia Create deep learning software was used on whole slide images of Iba1/4G8 double immunostained frontal cortical biopsies of 120 shunted iNPH patients to identify Iba1-positive microglia somas and Aß areas, respectively. Dementia, AD clinical syndrome (ACS), and Clinical Dementia Rating Global score (CDR-GS) were evaluated retrospectively after a median follow-up of 4.4 years. Deep learning artificial intelligence yielded excellent (>95%) precision for tissue, Aß, and microglia somas. Using an age-adjusted model, higher Aß coverage predicted the development of dementia, the diagnosis of ACS, and more severe memory impairment by CDR-GS whereas measured microglial densities and Aß-related microglia did not correlate with cognitive outcome in these patients. Therefore, cognitive outcome seems to be hampered by higher Aß coverage in cortical biopsies in shunted iNPH patients but is not correlated with densities of surrounding microglia.