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This study aimed to evaluate the association between sacubitril/valsartan and dementia-related adverse events (AEs) in geographical subpopulations using subgroup disproportionality analysis. Cases from the FDA adverse event reporting system involving patients aged 60 or older with sacubitril/valsartan or angiotensin receptor blockers (ARBs) were analyzed. The adjusted reporting odds ratios (RORs) for dementia-related AEs were calculated for each continent. A total of 61,518 AEs associated with sacubitril/valsartan or ARBs were identified. Among these, 1441 were dementia-related AEs. In Asia, Europe, and Africa, the reporting risk of dementia-related AEs associated with sacubitril/valsartan was lower compared to ARBs (adjusted ROR, 0.57 [95% CI 0.31-1.01]; adjusted ROR, 0.89 [95% CI 0.69-1.14]; adjusted ROR, 0.40 [95% CI 0.27-0.61], respectively). In Latin America and Oceania, the reporting risk of dementia-related AEs associated with sacubitril/valsartan was similar to that associated with ARBs (adjusted ROR, 1.04 [95% CI 0.75-1.44]; adjusted ROR, 1.02 [95% CI 0.31-3.37], respectively). On the contrary, in North America, the reporting risk associated with sacubitril/valsartan was higher compared to ARBs (adjusted ROR, 1.29 [95% CI 1.10-1.53]). Although the ROR value did not meet the criteria for signal detection, the significantly greater than 1 ROR observed in North America suggests that caution may be warranted regarding potential dementia-related adverse events associated with sacubitril/valsartan., (© 2024. The Author(s).)

Background: Prostate cancer is a prevalent disease that urgently needs to address its treatment-related complications. By examining existing evidence on the association between Androgen Deprivation Therapy (ADT) and dementia, this study contributes to the understanding of potential risks. We sought to analyze the currently available evidence regarding the risk of dementia, Alzheimer's disease (AD), vascular dementia, and Parkinson's disease (PD) in patients undergoing ADT., Methods: A systematic search of PubMed, EMBASE, Scopus, and Google Scholar was performed to identify studies published from the databases' inception to April 2023. Studies were identified through systematic review to facilitate comparisons between studies with and without some degree of controls for biases affecting distinctions between ADT receivers and non-ADT receivers. This review identified 305 studies, with 28 meeting the inclusion criteria. Heterogeneity was assessed using Higgins I2%. Variables with an I2 over 50% were considered heterogeneous and analyzed using a Random-Effects model. Otherwise, a Fixed-Effects model was employed., Results: A total of 28 studies were included for analysis. Out of these, only 1 study did not report the number of patients. From the remaining 27 studies, there were a total of 2,543,483 patients, including 900,994 with prostate cancer who received ADT, 1,262,905 with prostate cancer who did not receive ADT, and 334,682 patients without prostate cancer who did not receive ADT. This analysis revealed significantly increased Hazard Ratios (HR) of 1.20 [1.11, 1.29], p < 0.00001 for dementia, HR 1.26 [1.10, 1.43], p = 0.0007 for Alzheimer's Disease, HR 1.66 [1.40, 1.97], p < 0.00001 for depression, and HR 1.57 [1.31, 1.88], p < 0.00001 for Parkinson's Disease. The risk of vascular dementia was HR 1.30 [0.97, 1.73], p < 0.00001., Conclusion: Based on the analysis of the currently available evidence, it suggests that ADT significantly increases the risk of dementia, AD, PD, and depression., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Study Objective: To explore the association between gabapentin use and the risk of dementia in patients with chronic pain, considering the rising concerns of dementia in an aging population and the potential cognitive impacts of chronic pain management., Design: A nested case-control study utilizing data from a longitudinal health insurance database., Setting: The study is based on a longitudinal health insurance database spanning 2000-2019 in Taiwan., Patients: A total of 201,492 patients aged 50 years and older diagnosed with chronic pain between 2001 and 2017 were included. The study focused on individuals with chronic pain, excluding those diagnosed with dementia a year before or after their chronic pain diagnosis., Intervention: Analysis of gabapentin prescription history was conducted, considering the cumulative dose from the chronic pain diagnosis date to the dementia diagnosis date or equivalent period for controls., Measurement: Data included demographics, gabapentin prescription history, and comorbidities. Logistic regression was used to estimate odds ratios for dementia risk., Main Results: No significant difference in the risk of dementia was found between low and high cumulative doses of gabapentin. The adjusted odds ratio for dementia risk associated with gabapentin use was 0.91 (95 % C.I. 0.83-1.01), indicating no substantial increase in risk., Conclusion: Long-term Gabapentin therapy for chronic pain is not associated with a differential risk of dementia across dosage levels, irrespective of age or gender. Further study into its potential cognitive impacts is essential., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Dementia is an important disease burden among the elderly, and its occurrence may be profoundly affected by environmental factors. Evidence of the relationship between air pollution and dementia is emerging, but the extent to which this can be offset by lifestyle factors remains ambiguous., Methods: This study comprised 155,828 elder adults aged 60 years and above in the UK Biobank who were dementia-free at baseline. Cox proportional hazard models were conducted to examine the associations of annual average levels of air pollutants in 2010, including nitrogen dioxide (NO 2 ), nitrogen oxides (NO X ), particulate matter (PM 2.5 , PM 10 , and PM coarse ) and lifestyle factors recorded at baseline [physical activity (PA), sleep patterns, or smoking status] with incident risk of dementia, and their interactions on both multiplicative and additive scales., Results: During a 12-year period of follow-up, 4,389 incidents of all-cause dementia were identified. For each standarddeviationincrease in ambient NO 2 , NO X or PM 2.5 , all-cause dementia risk increases by 1.07-fold [hazard ratio (HR) and 95 % confidence interval (CI) = 1.07 (1.04, 1.10)], 1.05-fold (95 % CI: 1.02, 1.08) and 1.07-fold (95 % CI: 1.04, 1.10), whereas low levels of PA, poor sleep patterns, and smoking are associated with an elevated risk of dementia [HR (95 % CI) = 1.17 (1.09, 1.26), 1.13 (1.00, 1.27), and 1.14 (1.07, 1.21), respectively]. Furthermore, these air pollutants show joint effects with low PA, poor sleep patterns, and smoking on the onset of dementia. The moderate to high levels of PA could significantly or marginally significantly modify the associations between NO 2 , NO X or PM 2.5 (P-int = 0.067, 0.036, and 0.067, respectively) and Alzheimer's disease (AD), but no significant modification effects are found for sleep patterns or smoking status., Conclusion: The increased exposures of NO 2 , NO X , or PM 2.5 are associated with elevated risk of dementia among elderly UK Biobank population. These air pollutants take joint effects with low PA, poor sleep patterns, and smoking on the development of dementia. In addition, moderate to high levels of PA could attenuate the incident risk of AD caused by air pollution. Further prospective researches among other cohort populations are warranted to validate these findings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Long-term exposure to high-level ambient PM 2.5 was associated with increased risks of brain disorders, while the associations remain uncertain when the exposure is lower than current air quality standards in numerous countries. This study aimed to assess the effects of PM 2.5 exposure on the brain system in the population with annual mean concentrations ≤15 μg/m 3 . We analyzed data from 260,922 participants without preexisting brain diseases at baseline in the UK Biobank. The geographical distribution of PM 2.5 in 2010 was estimated by a land use regression model and linked with individual residential address. We investigated associations of ambient PM 2.5 with incident neurological (dementia, Parkinson's diseases [PD], epilepsy, and migraine) and psychiatric (major depressive disorder [MDD] and anxiety disorder) diseases through Cox proportional hazard models. We further estimated the links with brain imaging phenotypes by neuroimaging analysis. Results showed that in the population with PM 2.5 concentrations ≤15 μg/m 3 , each interquartile range (IQR, 1.28 μg/m 3 ) increment in PM 2.5 was related to incidence risks of dementia, epilepsy, migraine, MDD, and anxiety disorder with hazard ratios of 1.08 (95% confidence interval [CI]: 1.03, 1.13), 1.12 (1.05, 1.20), 1.07 (1.00, 1.13), 1.06 (1.03, 1.09), and 1.05 (1.02, 1.08), respectively. We did not observe a significant association with PD. The association with dementia was stronger among the population with poor cardiovascular health (measured by Life's Essential 8) than the counterpart (P for interaction = 0.037). Likewise, per IQR increase was associated with specific brain imaging phenotypes, including volumes of total brain (β = -0.036; 95% CI: -0.050, -0.022), white matter (-0.030; -0.046, -0.014), grey matter (-0.030; -0.042, -0.017), respectively. The findings suggest long-term exposure to ambient PM 2.5 at low-level still has an adverse impact on the neuro-psychiatric systems. The brain-relevant epidemiological assessment suggests that each country should update the standard for ambient PM 2.5 following the World Health Organization Air Quality Guidelines 2021., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Benzodiazepine use is common, particularly in older adults. Benzodiazepines have well-established acute adverse effects on cognition, but long-term effects on neurodegeneration and dementia risk remain uncertain., Methods: We included 5443 cognitively healthy (MMSE ≥ 26) participants from the population-based Rotterdam Study (57.4% women, mean age 70.6 years). Benzodiazepine use from 1991 until baseline (2005-2008) was derived from pharmacy dispensing records, from which we determined drug type and cumulative dose. Benzodiazepine use was defined as prescription of anxiolytics (ATC-code: N05BA) or sedative-hypnotics (ATC-code: N05CD) between inception of pharmacy records and study baseline. Cumulative dose was calculated as the sum of the defined daily doses for all prescriptions. We determined the association with dementia risk until 2020 using Cox regression. Among 4836 participants with repeated brain MRI, we further determined the association of benzodiazepine use with changes in neuroimaging markers using linear mixed models., Results: Of all 5443 participants, 2697 (49.5%) had used benzodiazepines at any time in the 15 years preceding baseline, of whom 1263 (46.8%) used anxiolytics, 530 (19.7%) sedative-hypnotics, and 904 (33.5%) used both; 345 (12.8%) participants were still using at baseline assessment. During a mean follow-up of 11.2 years, 726 participants (13.3%) developed dementia. Overall, use of benzodiazepines was not associated with dementia risk compared to never use (HR [95% CI]: 1.06 [0.90-1.25]), irrespective of cumulative dose. Risk estimates were somewhat higher for any use of anxiolytics than for sedative-hypnotics (HR 1.17 [0.96-1.41] vs 0.92 [0.70-1.21]), with strongest associations for high cumulative dose of anxiolytics (HR [95% CI] 1.33 [1.04-1.71]). In imaging analyses, current use of benzodiazepine was associated cross-sectionally with lower brain volumes of the hippocampus, amygdala, and thalamus and longitudinally with accelerated volume loss of the hippocampus and to a lesser extent amygdala. However, imaging findings did not differ by type of benzodiazepines or cumulative dose., Conclusions: In this population-based sample of cognitively healthy adults, overall use of benzodiazepines was not associated with increased dementia risk, but potential class-dependent adverse effects and associations with subclinical markers of neurodegeneration may warrant further investigation., (© 2024. The Author(s).)

Background: The pathways by which air pollution affects cognition remain to be explored. This study aimed to explore how single air pollutants [including nitrogen oxide (NOX), nitrogen dioxide (NO2), particulate matter with a diameter of 2.5 micrometers (PM2.5), PM10, and PM2.5-10], and air pollution mixture could affect cognitive function and the incidence of dementia, and determine whether pulmonary function (PF) could play a mediating role in the relationship., Methods: Multiple statistical methods were employed to evaluate association of 5 air pollutants (NOX, NO2, PM2.5, PM10, and PM2.5-10) with cognitive function. Bootstrap method was used to estimate mediating role of PF in the association of air pollutants with cognition or the incidence of dementia., Results: A mixture of air pollutants was associated with performance on 5 cognitive tests, and global cognition (p < .05). Significantly negative association was also identified between mixture of air pollutants and PF (β= -0.020, 95% confidence interval (CI) = -0.029 to -0.011). In addition, as PF scores increase, performance on all cognitive tests significantly improve, although the risk of dementia correspondingly decreases. It was noted that PF was shown to mediate the effects of air pollution mixtures on all cognitive tests as well as global cognition. For global cognition, PF mediated 6.08% of the association. PF was also found to have a mediating role in the association between NOX, NO2, PM2.5, and the risk of dementia., Conclusions: Mixed air pollution may impact cognitive function, with PF potentially mediating this relationship., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Aluminum (Al) overexposure damages various organ systems, especially the nervous system. Regularly administered aluminum chloride (AlCl 3 ) to rats causes dementia and pathophysiological alterations linked to Alzheimer's disease (AD). Taxifolin's neuroprotective effects against AlCl 3 -induced neurotoxicity in vitro and in vivo studies were studied. Taxifolin (0.1, 0.3, 1, 3, and 10 μM) was tested against AlCl 3 (5 mM)-induced neurotoxicity in C6 and SH-SY5Y cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. Additionally, neural morphology was examined by confocal microscopy. Additionally, taxifolin's mode of binding with the co-receptor of toll-like receptor 4 (TLR4), human myeloid differentiation-2 ( h MD-2) was investigated. AlCl 3 (25 mg/kg/d, i.p. ) was administered to rats for 14 d, and from the eighth day, taxifolin (1, 2, and 5 mg/kg/d, i.p. ) was given along with AlCl 3 . This study assessed memory impairment using the Morris water maze, plus maze, and pole tests. This study also performed measurement of oxidant (malondialdehyde [MDA] and nitrite), antioxidant (reduced glutathione), and inflammatory (myeloperoxidase [MPO] activity, TLR4 expression) parameters in rats' brain in addition to histopathology. The docking score for taxifolin with h MD-2 was found to be -4.38 kcal/mol. Taxifolin treatment reduced the neurotoxicity brought on by AlCl 3 in both C6 and SH-SY5Y cells. Treatment with 10 μM taxifolin restored AlCl 3 -induced altered cell morphology. AlCl 3 administration caused memory loss, oxidative stress, inflammation (increased MPO activity and TLR4 expression), and brain atrophy. Taxifolin treatment significantly improved the AlCl 3 -induced memory impairment. Taxifolin treatment also mitigated the histopathological and neurochemical consequences of repeated AlCl 3 administration in rats. Thus, taxifolin may protect the brain against AD.

Introduction: Adverse effects of opioids are common among older individuals, and undertreatment as well as overuse can be an issue. Epidemiological data on opioid use in older individuals are available, but scarce in hospitalized patients. Aims: The aim of this study is to examine the one-day prevalence of opioid use among older inpatients and identify the factors associated with both opioid use and dosage. Materials and methods: One-day cross-sectional study with data collected from geriatric units across 14 Belgian hospitals. The primary focus of the study is to assess the prevalence of opioid use and dosage, along with identifying associated factors. To achieve this, a multiple binary logistic regression model was fitted for opioid use, and a multiple linear regression model for opioid dose. Results: Opioids were used in 24.4% of 784 patients, of which 57.9% was treated with tramadol, 13.2% with oxycodone or morphine and 28.9% with transdermal buprenorphine or fentanyl. The odds for opioid use were 4.2 times higher in patients in orthogeriatric units compared to other patients (OR=4.2, 95% CI=2.50-7.05). The prevalence of opioid use was 34% higher in patients without dementia compared to patients with dementia (OR=0.66, 95% CI=0.46-0.95). The overall mean daily dosage was 14.07mg subcutaneous morphine equivalent. After adjustment for age, gender and dementia, dosage was only associated with type of opioid: the estimated mean opioid dose was 70% lower with tramadol (mean ratio=0,30,95% CI=0,23-0,39) and 67% lower with oxycodone and morphine (mean ratio=0,33, 95% CI=0,22-0,48) compared to transdermal buprenorphine and transdermal fentanyl. Conclusions: One in four patients received opioid treatment. It is not clear whether this reflects under- or overtreatment, but these results can serve as a benchmark for geriatric units to guide future pain management practices. The utilization of transdermal fentanyl and buprenorphine, resulting in higher doses of morphine equivalent, poses significant risks for side effects.

Social cohesion can reduce stress, increase social interaction, and improve cognitive reserve. These social mechanisms may modify the effects of air pollution on dementia risk. This cohort study examines the potential moderating effect of social cohesion on associations between joint air pollution exposure and incident dementia leveraging data from 5112 community-dwelling adults ≥65 years of age enrolled in the National Health and Aging Trends Study (NHATS). Study participants were enrolled in 2011 and followed through 2018. We assigned 2010 residential census tract-level exposures to five air pollutants, particulate matter (PM) ≤ 10 μm in diameter, PM ≤ 2.5 μm in diameter, carbon monoxide, nitric oxide, and nitrogen dioxide, using the US Environmental Protection Agency's Community Multiscale Air Quality Modeling System. Dementia status was determined based on self- or proxy-reported dementia diagnosis or "probable dementia" according to NHATS cognitive screening tools. Participants' self-rated neighborhood social cohesion was evaluated based on three questions: neighbors knowing each other, being helpful, and being trustworthy. Social cohesion was dichotomized at the median into high vs low social cohesion. Associations between air pollutants and incident dementia were assessed using quantile g-computation Cox proportional hazard models and stratified by high vs low social cohesion, adjusting for age, sex, education, partner status, urbanicity, annual income, race and ethnicity, years lived at current residence, neighborhood disadvantage index, and tract segregation. High social cohesion (HR = 1.20, 95 % CI = 0.98, 1.47) and air pollution (HR = 1.08, 95 % CI = 0.92, 1.28) were not associated with incident dementia alone. However, when stratified, greater joint air pollution exposure increased dementia risk among participants at low (HR = 1.34, 95 % CI = 1.04, 1.72), but not high (HR = 1.00, 95 % CI = 0.93, 1.06) social cohesion. Air pollution was a risk factor for dementia only when reported social cohesion was low, suggesting that social interaction may play a protective role, mitigating dementia risk via air pollution exposure., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Cavin Ward-Caviness reports a relationship with Clock Foundation that includes: board membership. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Increasing evidence links higher air pollution exposures to increased risk of cognitive impairment. While midlife risk factors are often most strongly linked to dementia risk, few studies have considered associations between midlife roadway proximity or ambient air pollution exposure and incident dementia decades later, in late life., Objectives: Our objective was to determine if midlife exposures to ambient air pollution or roadway proximity are associated with increased risk of dementia in the Atherosclerosis Risk in Communities (ARIC) study over up to 29 years of follow-up., Methods: Our eligible sample included Black and White ARIC participants without dementia at Visit 2 (1990-1992). Participants were followed through Visit 7 (2018-2019), with dementia status and onset date defined based on formal dementia ascertainment at study visits, informant interviews, and surveillance efforts. We used adjusted Weibull survival models to assess the associations of midlife ambient air pollution and road proximity with incident dementia., Results: The median age at baseline (1990-1992, Visit 2) of the 12,700 eligible ARIC participants was 57.0 years; 56.0% were female, 24.2% were Black, and 78.9% had at least a high school education. Over up to 29 years of follow-up, 2511 (19.8%) persons developed dementia. No associations were found between ambient air pollutants and proximity to major roadways with risk of incident dementia. In exploratory analyses, living closer to roadways in midlife increased dementia risk in individuals younger at baseline and those without midlife hypertension, and there was evidence of increased risk of dementia with increased midlife exposure to NO x , several PM 2.5 components, and trace metals among those with diabetes in midlife., Conclusions: Midlife exposure to ambient air pollution and midlife roadway proximity was not associated with dementia risk over decades of follow-up. Further investigation to explore potential for greater susceptibility among specific subgroups identified here is needed., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Melinda C. Power reports a relationship with Biogen Healthy Lives, Healthy Climate that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Co-exposure to air pollution and neighborhood disadvantage may influence cognition decline. We tested these associations in the context of dementia risk., Methods: We leveraged a cohort of adults ≥65 years (n = 5397) enrolled from 2011 to 2018 in the National Health and Aging Trends Study (NHATS). Particulate matter (PM) ≤ 10 μm in diameter, PM ≤ 2.5 μm in diameter, carbon monoxide, nitric oxide, and nitrogen dioxide - and neighborhood disadvantage were tested for joint associations with dementia risk. Pollutant concentrations at the 2010 census tract level were assigned using the US Environmental Protection Agency's Community Multiscale Air Quality Modeling System. Neighborhood disadvantage was defined using the tract Social Deprivation Index (SDI). Dementia was determined through self- or proxy-report or scores indicative of "probable dementia" according to NHATS screening tools. Joint effects of air pollutants and SDI were tested using quantile g-computation Cox proportional hazards models. We also stratified joint air pollution effects across SDI tertiles. Analyses adjusted for age at enrollment, sex, education, partner status, urbanicity, income, race and ethnicity, years at residence, census segregation, and census region., Results: SDI score (aHR = 1.08; 95% CI 0.96, 1.22), joint air pollution (aHR = 1.03, 95% CI 0.92, 1.16) and joint SDI with air pollution (aHR = 1.04, 95% CI 0.89, 1.22) were not associated with dementia risk. After accounting for competing risk of death, joint SDI with air pollution was not associated with dementia risk (aHR = 1.06; 95% CI 0.87, 1.29). In stratified models, joint air pollution was associated with greater risk of dementia at high (aHR = 1.19; 95% CI 0.87, 1.63), but not at medium or low SDI., Conclusion: Air pollution was associated with greater dementia risk in disadvantaged areas after accounting for competing risks. Air pollution associations with dementia incidence may be attenuated when other risk factors are more prominent in disadvantaged neighborhoods., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Aisha S. Dickerson reports financial support was provided by National Institute of Environmental Health Sciences. Aisha S. Dickerson reports financial support was provided by Bloomberg American Health Initiative. Roland J. Thorpe, Jr. reports financial support was provided by National Institute on Aging. Roland J. Thorpe, Jr. reports financial support was provided by National Institute on Minority Health and Health Disparities. Cavin Ward-Caviness reports a relationship with Clock Foundation that includes: board membership. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

This study examines the effectiveness of lupeol and metformin in a mouse model of dementia generated by intracerebroventricular streptozotocin (i.c.v., STZ). Dementia was induced in Swiss mice with the i.c.v. administration of STZ at a dosage of 3 mg/kg on the first and third day. The assessment of dementia involved an examination of the Morris Water Maze (MWM) performance, as well as a number of biochemical and histological studies. STZ treatment resulted in significant decrease in MWM performance; various biochemical alterations (increase in brain acetyl cholinesterase (AChE) activity, thiobarbituric acid reactive species (TBARS), nitrite/nitrate, and reduction in nuclear factor erythroid 2 related factor-2 (Nrf-2), reduced glutathione (GSH) levels) and neuroinflammation [increased myeloperoxidase (MPO) activity & neutrophil infiltration]. The administration of Lupeol (50 mg/kg & 100 mg/kg; p.o.) and Metformin (150 mg/kg & 300 mg/kg; p.o.) demonstrated a considerable reduction in the behavioral, biochemical, and histological alterations produced by STZ. Low dose combination of lupeol (50 mg/kg; p.o.) and Metformin (150 mg/kg; p.o.) produced more pronounced effect than that of high doses of either agent alone. It is concluded that Lupeol and Metformin has shown efficacy in dementia with possible synergism between the two and can be explored as potential therapeutic agents for managing dementia of Alzheimer's disease (AD) type., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: The effects on the brain of hormone therapy after the onset of menopause remain uncertain. The effects may be beneficial, neutral, or harmful. We provide a conceptual review of the evidence., Methods: We 1) provide a brief history of the evidence, 2) discuss some of the interpretations of the evidence, 3) discuss the importance of age at menopause, type of menopause, and presence of vasomotor symptoms, and 4) provide some clinical recommendations., Results: The evidence and the beliefs about hormone therapy and dementia have changed over the last 30 years or more. Five recent observation studies suggested that hormone therapy is associated with an increased risk of dementia, and the association appears not to change with the timing of initiation of therapy. These harmful associations may be explained by a causal effect of hormone therapy on the brain or by several confounding mechanisms. We suggest that the use of hormone therapy should be customized for different subgroups of women. It may be important to subgroup women based on age at onset of menopause, type of menopause, and presence or absence of vasomotor symptoms. In addition, the effects may vary by type, dose, route, and duration of administration of estrogens and by the concurrent use of progestogens., Discussion: The relation of hormone therapy with the risk of dementia is complex. Hormone therapy may have beneficial, neutral, or harmful effects on the brain. Hormone therapy should be guided by the clinical characteristics of the women being treated., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2023. Published by Elsevier B.V.)

Background: Air pollution has been recognised as a potential risk factor for dementia. Yet recent epidemiological research shows mixed evidence. The aim of this study is to investigate the longitudinal associations between ambient air pollution exposure and dementia in older people across five urban and rural areas in the UK., Methods: This study was based on two population-based cohort studies of 11329 people aged ≥ 65 in the Cognitive Function and Ageing Study II (2008-2011) and Wales (2011-2013). An algorithmic diagnosis method was used to identify dementia cases. Annual concentrations of four air pollutants (NO 2 , O 3 , PM 10 , PM 2.5 ) were modelled for the year 2012 and linked via the participants' postcodes. Multistate modelling was used to examine the effects of exposure to air pollutants on incident dementia incorporating death and adjusting for sociodemographic factors and area deprivation. A random-effect meta-analysis was carried out to summarise results from the current and nine existing cohort studies., Results: Higher exposure levels of NO 2 (HR: 1.04; 95% CI: 0.94, 1.14), O 3 (HR: 0.90; 95% CI: 0.70, 1.15), PM 10 (HR: 1.17; 95% CI: 0.86, 1.58), PM 2.5 (HR: 1.41; 95% CI: 0.71, 2.79) were not strongly associated with dementia in the two UK-based cohorts. Inconsistent directions and strengths of the associations were observed across the two cohorts, five areas, and nine existing studies., Conclusions: In contrast to the literature, this study did not find clear associations between air pollution and dementia. Future research needs to investigate how methodological and contextual factors can affect evidence in this field and clarity the influence of air pollution exposure on cognitive health over the lifecourse., (© 2024. The Author(s).)

Background: Recent findings suggest a link between gout and the development of dementia. Early treatment with colchicine is recommended as a first-line therapy for gout flares. Animal studies demonstrate that colchicine could induce cognitive impairment. This cohort study aimed to investigate the association between colchicine use and the risk of developing dementia., Methods: In this nationwide cohort study, we performed comparative analysis on 6147 patients ≥40 years, with gout and colchicine new users against 6147 controls to assess subsequent dementia risk. The colchicine group and the control group (urate lowering therapy group) were matched on the bases of age, sex, index year, and comorbidities. All participants were followed for up to 14 years for a diagnosis of dementia considering medical records were retrospectively checked over this period. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Sensitivity analyses were performed to validate our findings., Results: The adjusted hazard ratio (aHR) of dementia for colchicine users was 1.45 (95% CI = 1.05, 1.99) relative to comparison group after adjusting for sex, age, and comorbidities. Sensitivity analysis aiming to minimize underdiagnosed occult dementia at the time of index year yielded consistent positive association. In higher accumulative dose colchicine group (cumulative defined daily dose [cDDD] >30), the aHR of dementia risk for colchicine users was 1.42 (95% CI = 1.03, 1.97) compared with nonusers. For those duration of colchicine use >30 days, the aHR was 1.53 (95% CI = 1.01-2.32) compared to the nonuser group., Conclusions: A significant risk of dementia was observed in this study in patients with gout using colchicine at higher cDDD and for a longer period. Further research is needed to elucidate the relationship between colchicine, gout, and dementia., (© 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Objective: Eradication of hepatitis C virus (HCV) infection has been linked with improvement in neurocognitive function, but few studies have evaluated the effect of antiviral treatment/ response on risk of dementia. Using data from the Chronic Hepatitis Cohort Study (CHeCS), we investigated how antiviral therapy impacts the risk of developing dementia among patients with HCV., Methods: A total of 17,485 HCV patients were followed until incidence of dementia, death, or last follow-up. We used an extended landmark modeling approach, which included time-varying covariates and propensity score justification for treatment selection bias, as well as generalized estimating equations (GEE) with a link function as multinominal distribution for a discrete time-to-event data. Death was considered a competing risk., Results: After 15 years of follow-up, 342 patients were diagnosed with incident dementia. Patients who achieved sustained virological response (SVR) had significantly decreased risk of dementia compared to untreated patients, with hazard ratios (HRs) of 0.32 (95% CI 0.22-0.46) among patients who received direct-acting antiviral (DAA) treatment and 0.41 (95% CI 0.26-0.60) for interferon-based (IFN) treatment. Risk reduction remained even when patients failed antiviral treatment (HR 0.38, 95% CI 0.38-0.51). Patients with cirrhosis, Black/African American patients, and those without private insurance were at significantly higher risk of dementia., Conclusion: Antiviral treatment independently reduced the risk of dementia among HCV patients, regardless of cirrhosis. Our findings support the importance of initiation antiviral therapy in chronic HCV-infected patients., (Copyright © 2023 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background and Objective: Preliminary evidence suggests a possible preventive effect of tumor necrosis factor-α inhibitors (TNFi) on incident dementia. The objective of the analysis was to investigate the association between TNFi and the risk of incident dementia in a population undergoing treatment for rheumatological disorders., Methods: We followed patients aged ≥ 65 years with dementia and rheumatological conditions in two cohort studies, DANBIO (N = 21,538), a Danish clinical database, and AOK PLUS (N = 7112), a German health insurance database. We defined incident dementia using diagnostic codes and/or medication use and used Cox regression to compare the associations of TNFi with other rheumatological therapies on the risk of dementia. To ensure that the patients were receiving long-term medication, we included patients with rheumatic diseases and systemic therapies., Results: We observed similar trends towards a lower risk of dementia associated with TNFi versus other anti-inflammatory agents in both cohorts (hazard ratios were 0.92 [95% confidence interval 0.76, 1.10] in DANBIO and 0.89 [95% confidence interval 0.63, 1.24] in AOK PLUS, respectively)., Conclusions: Tumor necrosis factor-α inhibitors may decrease the risk of incident dementia although the association did not reach statistical significance in this analysis. Further research, ideally with randomization, is needed to gauge the potential of repurposing TNFi for dementia prevention and/or treatment., (© 2024. The Author(s).)

Drug-associated bullous pemphigoid has been shown to follow long-term gliptin (dipeptidyl-peptidase 4 inhibitors) intake. This study aimed at identifying risk factors for gliptin-associated bullous pemphigoid among patients with type 2 diabetes. A retrospective study was conducted in a tertiary centre among diabetic patients exposed to gliptins between the years 2008-2021. Data including demographics, comorbidities, medications, and laboratory results were collected using the MDClone platform. Seventy-six patients with type 2 diabetes treated with dipeptidyl-peptidase 4 inhibitors who subsequently developed bullous pemphigoid were compared with a cohort of 8,060 diabetic patients exposed to dipeptidyl-peptidase 4 inhibitors who did not develop bullous pemphigoid. Based on a multivariable analysis adjusted for age and other covariates, Alzheimer's disease and other dementias were significantly more prevalent in patients with bullous pemphigoid (p = 0.0013). Concomitant use of either thiazide or loop diuretics and gliptin therapy was associated with drug-associated bullous pemphigoid (p < 0.0001 for both). While compared with sitagliptin, exposure to linagliptin and vildagliptin were associated with bullous pemphigoid with an odds ratio of 5.68 and 6.61 (p < 0.0001 for both), respectively. These results suggest gliptins should be prescribed with caution to patients with type 2 diabetes with coexisting Alzheimer's and other dementias, or patients receiving long-term use of thiazides and loop diuretics. The use of sitagliptin over linagliptin and vildagliptin should be preferred in these patients.

The use of antidepressants with anticholinergic effects has been associated with an increased risk of dementia. However, the results published are contradictory. The aim of the study is to compare the risk of developing dementia in elderly who were prescribed tricyclic antidepressants (TCA) versus those who were prescribed selective serotonin reuptake inhibitors (SSRIs) and other antidepressants (OA). A prospective population-based cohort study was performed using the Spanish Database for Pharmacoepidemiological Research in Primary Care (BIFAP) data (from 2005 to 2018). The cohort study included 62,928 patients age ≥ 60 without dementia and with antidepressant long-term monotherapy. Patients were divided into exposure antidepressant groups based on ATC system [TCA, SSRIs users and OAs users]. The risk of dementia was calculated by Cox regression models, providing hazard ratios (HR) and 95 % confidence intervals. The Kaplan-Meier model was used for survival analysis. Chi2 test was used as association test. The results showed SSRI users had higher dementia risk than TCA users (HR = 1.864; 95%CI = 1.624-2.140). Moreover, OA users had also significant risk of dementia (HR = 2.103; 95%CI = 1.818-2.431). Several limitations are the variation of the trend in the prescription of antidepressants, the small number of patients that use some antidepressants, the lack of information related to the dose, or socioeconomic characteristics, the use of antidepressant drugs for other indications, or the therapeutic compliance. Our findings showed that older users of SSRI and OA have more risk of developing dementia than TCA elderly users. However, additional studies would be needed., Competing Interests: Declaration of competing interest The corresponding author Elena González-Burgos, on behalf of all authors listed in the paper “Risk of dementia among antidepressant elderly users: a population-based cohort analysis in Spain” certify that there is no actual or potential of interest in relation to this article., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Several observational studies have suggested that oral anticoagulants (OACs) might reduce the risk of dementia in the elderly, but the evidence is inconclusive. And the consistency of this relationship across different OAC classes and dementia subtypes is still uncertain., Methods: To comprehensively evaluate this association, we applied Mendelian randomization (MR) combined with pharmacovigilance analysis. MR was used to assess the associations between genetic proxies for three target genes of OACs (VKORC1, F2, and F10) and dementia, including Alzheimer's disease (AD) and vascular dementia (VaD). This genetic analysis was supplemented with real-world pharmacovigilance data, employing disproportionality analysis for more reliable causal inference., Results: Increased expression of the VKORC1 gene was strongly associated with increased risk of dementia, especially for AD (OR = 1.28, 95% CI = 1.14-1.43; p value < 0.001). Based on pharmacovigilance data, vitamin K antagonists (VKAs, inhibitors targeting VKORC1) exhibited a protective effect against dementia risk (ROR = 0.43, 95% CI = 0.28-0.67). Additional sensitivity analyses, including different MR models and cohorts, supported these results. Conversely, no strong causal associations of genetically proxied F2 and F10 target genes with dementia and its subtypes were found., Conclusions: This study reveals that the inhibition of genetically proxied VKORC1 expression or VKAs exposure is associated with a reduced risk of Alzheimer's dementia. However, there is little evidence to support similar associations with direct oral anticoagulants (F2 inhibitors and F10 inhibitors). Further research is warranted to clinically validate our findings., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Sideritis scardica Griseb. and Clinopodium vulgare L., belonging to the Lamiaceae family, are rich in terpenoids and phenolics and exhibit various pharmacological effects, including antioxidant, anti-inflammatory and anti-cancer activities. While the memory-enhancing impacts of S. scardica are well documented, the cognitive benefits of C. vulgare remain unexplored. This study assessed the potential effect of C. vulgare on learning and memory in healthy and scopolamine (Sco)-induced memory-impaired male Wistar rats, comparing it with the effects of S. scardica . Over a 21-day period, rats orally received extracts of cultivated S. scardica (200 mg/kg) and C. vulgare (100 mg/kg), either individually or in combination, with administration starting 10 days before and continuing 11 days simultaneously with Sco injection at a dose of 2 mg/kg intraperitoneally. The results showed that both extracts effectively mitigated Sco-induced memory impairment. Their combination significantly improved recognition memory and maintained monoaminergic function. S. scardica excelled in preserving spatial working memory, while C. vulgare exhibited comparable retention of recognition memory, robust antioxidant activity and acetylcholinesterase inhibitory activity. The extracts alleviated Sco-induced downregulation of p-CREB/BDNF signaling, suggesting neuroprotective mechanisms. The extract combination positively affected most of the Sco-induced impairments, underscoring the potential for further investigation of these extracts for therapeutic development.

This study aimed to explore the association between household solid cooking fuel use and dementia prevalence and the mediating effect of depression on this association. A total of 3404 (2018) and 1379 (2015 to 2018) older participants (≥65) from the China Health and Retirement Longitudinal Study (CHARLS) were enrolled in the cross-sectional and retrospective longitudinal analyses, respectively. The results showed that solid cooking fuel use was associated with an increased dementia prevalence (adjusted OR = 1.44) from 2015 to 2018. The indirect effect of depression on this association explained 7.14% and 13.11% variances in the cross-sectional and longitudinal mediating model, respectively. Thus, household solid cooking fuel use is a risk factor for the development of dementia, and depressive symptoms partially accounted for this association. The use of improved cookstoves and clean fuel in households and air cleaners and early intervention in depression may reduce the incidence of dementia.

One of the reasons for the development or worsening of cognitive impairment (CI) may be the use of a number of drugs: non-steroidal anti-inflammatory drugs, antiarrhythmics, antidepressants, glucocorticosteroids, antitumor drugs and a number of others. The negative effect of drugs on cognitive functions is realized due to many pathophysiological mechanisms: disruption of hormonal regulation, decreased neuronal excitability, increased activity of gamma-aminobutyric acid receptors, decreased cerebral circulation, atrophic changes in the brain; many mechanisms have not been fully established. Risk factors for the development of drug-induced CIs are: old age or childhood, brain damage, chronic diseases, genetic factors, the patient's initial CI, polypharmacy, dose and duration of drug use, acute infectious diseases, metabolic disorders, dehydration, acute urinary retention, etc. To diagnose and differentially diagnose drug-induced CI, it is necessary to establish a connection between the start of taking a suspected drug-inducer and a decrease in cognitive functions. The first step in the treatment of drug-induced CI is the abolition of an inducer drug or a reduction in its dose, in cases where it is impossible to discontinue the drug and there is no replacement, special slow-release dosage forms can be considered. The main measures to prevent drug-induced CI include the use of drugs with the lowest risk of their development, assessment of drug interactions, and the use of modern scales to assess the risk of developing this side-effect (anticholinergic burden scale, etc.).

Introduction: Metformin has been suggested as a therapeutic agent for dementia, but the relevant evidence has been partial and inconsistent., Methods: We established a national cohort of 210,237 type 2 diabetes patients in the UK Clinical Practice Research Datalink. Risks of incident dementia were compared between metformin initiators and those who were not prescribed any anti-diabetes medication during follow-up., Results: Compared with metformin initiators (n = 114,628), patients who received no anti-diabetes medication (n = 95,609) had lower HbA1c and better cardiovascular health at baseline. Both Cox regression and propensity score weighting analysis showed metformin initiators had lower risk of dementia compared to those non-users (adjusted hazard ratio = 0.88 [95% confidence interval: 0.84-0.92] and 0.90 [0.84-0.96]). Patients on long-term metformin treatment had an even lower risk of dementia., Discussion: Metformin may act beyond its glycemic effect and reduce dementia risk to an even lower level than that of patients with milder diabetes and better health profiles., Highlights: Metformin initiators had a significantly lower risk of dementia compared with patients not receiving anti-diabetes medication. Compared with metformin initiators, diabetes patients not receiving pharmacological treatment had better glycemic profiles at baseline and during follow-up. Patients on long-term metformin treatment had an even lower risk of subsequent dementia incidence. Metformin may act beyond its effect on hyperglycemia and has the potential of being repurposed for dementia prevention., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Purpose: This study investigates the potential impact of cholinesterase inhibitors (ChEIs) on patients with heart failure (HF) and dementia. ChEIs are known to boost acetylcholine levels and benefit cognition in patients with dementia; however, their effect on patients with HF is uncertain. This study aimed to assess whether cardiovascular events and mortality among patients with HF and dementia are altered by ChEI therapy., Methods: Data from the National Health Insurance Research Database in Taiwan were retrospectively analyzed. Dementia patients diagnosed with HF were followed for 5 years until all-cause mortality, cardiovascular mortality, hospitalization for worsening HF, or the end of the study. Multivariable Cox models and inverse probability of treatment weighting (IPTW) were employed., Results: Out of 20,848 patients with dementia, 5138 had HF. Among them, 726 were ChEI users and 4412 were non-users. Based on IPTW, the ChEI users had significantly lower estimated risks of all-cause mortality [hazard ratio (HR) 0.43; 95% confidence interval (CI) 0.38-0.49, p < 0.001] and cardiovascular mortality (HR 0.41; 95% CI 0.33-0.53, p < 0.001) compared with the non-users, but there was no significant difference in hospitalization for worsening HF (HR 0.73; 95% CI 0.51-1.05, p = 0.091) after 5 years. The survival benefits of ChEIs were consistent across subgroups., Conclusions: The results of this retrospective cohort study suggest that ChEIs may be beneficial in reducing all-cause and cardiovascular mortality in patients with dementia with HF. Further research is needed to validate these findings and explore the potential benefits of ChEIs in all patients with HF, including those without dementia., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Medications with anticholinergic effects are commonly used in nursing homes, and their cumulative effect is of particular concern for the risk of adverse effects on cognition., Objective: The relation between cognitive function and anticholinergic burden measured with four scales, the Anticholinergic Cognitive Burden (ACB) Scale, the Anticholinergic Risk Scale, the German Anticholinergic Burden Scale, and the CRIDECO Anticholinergic Load Scale, is assessed according to the hypothesis that a higher anticholinergic burden is associated with reduced cognitive performance., Methods: This retrospective cross-sectional multicenter study was conducted in a sample of Italian long-term-care nursing homes (NH). Sociodemographic details, diagnosis, and drug treatments of each NH resident were collected using medical records four times during 2018 and 2019. Cognitive status was rated with the Mini-Mental State Examination (MMSE). The prevalence of anticholinergic use and its burden were calculated referring to the last time point for each patient. A longitudinal analysis was done on NH residents with at least two MMSE between 2018 and 2019 to assess the relation between the anticholinergic load and decline in MMSE. The relationship between drug-related anticholinergic burden and cognitive performance was analyzed using Poisson regression model theory. Multivariate analyses were adjusted according to the known risk factors of reduced cognitive performance available [age, sex, history of stroke or transient ischemic attack (TIA), and number of non-anticholinergic drugs] and for cholinesterase inhibitors. In view of the high number of subjects with an MMSE score = 0 among residents with dementia, for this group a zero-inflated Poisson regression model was used to give more consistent results. The association of anticholinergic burden with mortality was examined from each patient's last visit using a multivariate logistic model adjusted for age, sex, and Charlson Comorbidity Index (CCI)., Results: Among 1412 residents recruited, a clear direct relationship was found between higher anticholinergic burden and cognitive impairment only for the Anticholinergic Cognitive Burden Scale. Residents taking an anticholinergic who scored 5 or more had 2.5 points more decline than those not taking them (p < 0.001). Among residents without dementia there was a trend toward direct relationship for the Anticholinergic Cognitive Burden Scale and the Anticholinergic Risk Scale. Residents with higher scores had about 2 points more decline than residents not taking anticholinergic drugs. No relation was found between anticholinergic burden and cognitive decline or mortality., Conclusions: The cumulative effect of medications with modest antimuscarinic activity may influence the cognitive performance of NH residents. The anticholinergic burden measured with the ACB scale should help identify NH residents who may benefit from reducing the anticholinergic burden. A clear direct relationship between anticholinergic burden and cognitive impairment was found only for the ACB Scale., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Distressing behavioural symptoms, particularly agitation and aggressiveness, remain a difficult problem in everyday clinical practice in the treatment of multimorbid patients with dementia. Clozapine may be an effective therapeutic alternative in this context., Methods: In a retrospective study, patients who had a diagnosis of dementia and had been treated in a specialized geriatric psychiatry unit with clozapine between August 2018 and February 2022 were included, and medical records were systematically reviewed. The Clinical Global Impressions Scale was used to assess improvement, and the Pittsburgh Agitation Scale for symptom reduction. In addition, side effects and clinical features were documented in detail., Results: A total of 31 patients (median age 82 years) were identified with a mean clozapine dose of 47.2 (SD 35.6) mg. A total of 13 patients tolerated clozapine very well, 10 showed tolerable side effects, and in 10 patients side effects were the reason for stopping clozapine. Behavioural symptoms improved significantly, as indicated by the assessment scores., Conclusions: In summary, clozapine was effective and well tolerated in 23 patients, suggesting that low-dose clozapine may help to alleviate the suffering of difficult-to-treat multimorbid patients with advanced dementia and their caregivers. However, particular attention should be paid to adverse drug reactions, especially in patients with cardiovascular and pulmonary impairment., (© 2023 The Authors. Psychogeriatrics published by John Wiley & Sons Australia, Ltd on behalf of Japanese Psychogeriatric Society.)

The ageing population has been steadily increasing worldwide, leading to a higher risk of cognitive decline and dementia. Environmental toxicants, particularly metals, have been identified as modifiable risk factors for cognitive impairment. Continuous exposure to metals occurs mainly through dietary sources, with older adults being particularly vulnerable. However, imbalances in the gut microbiota, known as dysbiosis, have also been associated with dementia. A literature review was conducted to explore the potential role of metals in the development of cognitive decline and the most prevalent primary neurodegenerative dementias, as well as their interaction with the gut microbiota. High levels of iron (Fe) and copper (Cu) are associated with mild cognitive impairment (MCI) and Alzheimer's disease (AD), while low selenium (Se) levels are linked to poor cognitive status. Parkinson's disease dementia (PDD) is associated with elevated levels of iron (Fe), manganese (Mn), and zinc (Zn), but the role of copper (Cu) remains unclear. The relationship between metals and Lewy body dementia (LBD) requires further investigation. High aluminium (Al) exposure is associated with frontotemporal dementia (FTD), and elevated selenium (Se) levels may be linked to its onset. Challenges in comparing studies arise from the heterogeneity of metal analysis matrices and analytical techniques, as well as the limitations of small study cohorts. More research is needed to understand the influence of metals on cognition through the gut microbiota (GMB) and its potential relevance in the development of these diseases., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Margarita Torrente reports financial support was provided by Spain Ministry of Science and Innovation. David Mateo reports financial support was provided by Government of Catalonia Agency for Administration of University and Research Grants., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Studies on the association between proton pump inhibitor (PPI) use and dementia report mixed results and do not examine the impact of cumulative PPI use. We evaluated the associations between current and cumulative PPI use and risk of incident dementia in the Atherosclerosis Risk in Communities (ARIC) Study., Methods: These analyses used participants from a community-based cohort (ARIC) from the time of enrollment (1987-1989) through 2017. PPI use was assessed through visual medication inventory at clinic visits 1 (1987-1989) to 5 (2011-2013) and reported annually in study phone calls (2006-2011). This study uses ARIC visit 5 as baseline because this was the first visit in which PPI use was common. PPI use was examined 2 ways: current use at visit 5 and duration of use before visit 5 (from visit 1 to 2011, exposure categories: 0 day, 1 day-2.8 years, 2.8-4.4 years, >4.4 years). The outcome was incident dementia after visit 5. Cox proportional hazard models were used, adjusted for demographics, comorbid conditions, and other medication use., Results: A total of 5,712 dementia-free participants at visit 5 (mean age 75.4 ± 5.1 years; 22% Black race; 58% female) were included in our analysis. The median follow-up was 5.5 years. The minimum cumulative PPI use was 112 days, and the maximum use was 20.3 years. There were 585 cases of incident dementia identified during follow-up. Participants using PPIs at visit 5 were not at a significantly higher risk of developing dementia during subsequent follow-up than those not using PPIs (hazard ratio (HR): 1.1 [95% confidence interval (CI) 0.9-1.3]). Those who used PPIs for >4.4 cumulative years before visit 5 were at 33% higher risk of developing dementia during follow-up (HR: 1.3 [95% CI 1.0-1.8]) than those reporting no use. Associations were not significant for lesser durations of PPI use., Discussion: Future studies are needed to understand possible pathways between cumulative PPI use and the development of dementia., Classification of Evidence: This study provides Class III evidence that the use of prescribed PPIs for >4.4 years by individuals aged 45 years and older is associated with a higher incidence of newly diagnosed dementia., (Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Background: Despite significant warnings of adverse effects, antipsychotics continue to be prescribed for managing the behavioural and psychological symptoms of dementia (BPSD) in care homes. Information provided by staff working within care homes is a factor that can influence prescribing decisions in residents with BPSD., Aim: The review aimed to capture care home staff views towards antipsychotics for residents with BPSD and separately analyse tools utilized in the studies, mapping them onto the theory of planned behaviour (TPB)., Method: A comprehensive literature search published in ten databases was conducted between May and July 2020 and updated in July 2021. Studies published in full with no date restriction were included and quality assessed using CROSS checklist. A thematic framework approach was applied to extract data and study tools which were then mapped onto the TPB., Results: Fourteen studies (2059 participants) were included. Findings identified four overarching themes: attitudes toward antipsychotics (e.g. antipsychotics as an appropriate strategy and effectiveness); barriers to deprescribing (e.g. lower staff education, lack of resources and time, poor medication reviews); measures implemented (e.g. nonpharmacological interventions, medication reviews); and perceived needs of staff (e.g. need for training, financial or clinical support). Identified tools addressed seven but not all components of TPB namely, behavioural, normative and control beliefs, attitude, perceived behavioural control, intention and behaviour., Conclusion: The positive attitudes toward antipsychotics, the identified barriers to deprescribing and the existing tools not addressing all components of the TPB provide the impetus for further research., (© 2023. The Author(s).)