ABSTRACT
INTRODUCTION: There is concern about the use of anticholinergic medications in people living with dementia (PLWD). Such medicines may increase cognitive decline and may be associated with higher mortality in PLWD who take these medicines. The aim of this study was to analyse data from an online dementia discussion forum to explore the experiences and perspectives of PLWD and carers about the use of anticholinergic medicines in this population. METHODS: Following receipt of ethical approval, archived discussions (posts) from Dementia Talking Point, a fully public online forum for anyone affected by dementia, created and maintained by the Alzheimer's Society, were searched from the date of inception to January 2022 using a range of search terms including commonly used anticholinergic medicines. Posts, including any of the search terms, were assessed for relevance and analysed using inductive thematic analysis. RESULTS: Five hundred and fifty unique posts were analysed, all of which had been provided by carers, with no posts attributed to PLWD. The themes that encompassed carers' experiences were (1) motivators of prescribing, (2) perspectives on the process of prescribing and (3) the outcomes of prescribing. The dominant motivator of prescribing was the management of noncognitive symptoms, pre- and postdiagnosis of dementia. Carers' perspectives on the process of prescribing were informed by an assessment of the risk-benefit of starting a medication and shared decision-making between the carer and healthcare professional to a greater or lesser degree. The outcomes of prescribing were observing the effects of the medicines, which in turn influenced whether prescribing was reviewed and continued unchanged, continued but amended, reinitiated if the medicine had been previously stopped or discontinued (the process of deprescribing). CONCLUSION: This study has provided unique insights into carers' experiences and perspectives about the use of anticholinergic medications in PLWD, highlighting how commonly these medications are prescribed for PLWD and carers' concerns about their use. There is a clear need for carers and PLWD to receive information about these medicines and healthcare professionals to consider how to optimise the use of these medicines to avoid adverse effects. PATIENT OR PUBLIC CONTRIBUTION: This work was informed by findings from previous research studies focusing on optimising medicine use for people with dementia in primary care, in which interviews were conducted with PLWD, their carers and primary healthcare professionals. Although not strictly patient and public involvement, we utilised the feedback provided by key stakeholders to inform the research questions and aim/objectives of this study.
Subject(s)
Caregivers , Cholinergic Antagonists , Dementia , Humans , Caregivers/psychology , Dementia/drug therapy , Cholinergic Antagonists/therapeutic use , Female , Male , MotivationABSTRACT
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.
Subject(s)
Dementia , Multimorbidity , Polypharmacy , Practice Guidelines as Topic , Humans , Dementia/drug therapy , AustraliaABSTRACT
Psychosis is a distressing symptom commonly occurring in people with dementia. To treat Parkinson's disease psychosis, pimavanserin (1), a 5-HT2A receptor inverse agonist having minimal 5-HT2C receptor affinity and no dopamine D2 receptor affinity, was approved in the United States, but not for dementia-related psychosis due to limited efficacy issues. Herein, we report on the identification of a potent and dual 5-HT2A and 5-HT2C receptor inverse agonist 8 having minimal hERG inhibition, after having demonstrated the involvement of both 5-HT2A and 5-HT2C receptors to deliver antipsychotic efficacy in an MK-801-induced locomotor model and having conducted 5-HT2A and 5-HT2C occupancy studies including a surrogate method. The introduction of a spirocyclopropyl group boosting 5-HT2C affinity in 1 followed by further optimization to control lipophilicity resulted in balanced dual potency and metabolic stability, and mitigating hERG inhibition led to 8 that showed significant antipsychotic efficacy due to the involvement of both receptors.
Subject(s)
Antipsychotic Agents , Dementia , Psychotic Disorders , Receptor, Serotonin, 5-HT2A , Receptor, Serotonin, 5-HT2C , Serotonin 5-HT2 Receptor Agonists , Antipsychotic Agents/pharmacology , Antipsychotic Agents/therapeutic use , Antipsychotic Agents/chemistry , Antipsychotic Agents/chemical synthesis , Animals , Receptor, Serotonin, 5-HT2A/metabolism , Humans , Psychotic Disorders/drug therapy , Serotonin 5-HT2 Receptor Agonists/pharmacology , Serotonin 5-HT2 Receptor Agonists/therapeutic use , Serotonin 5-HT2 Receptor Agonists/chemistry , Receptor, Serotonin, 5-HT2C/metabolism , Dementia/drug therapy , Structure-Activity Relationship , Male , Drug Inverse Agonism , ERG1 Potassium Channel/metabolism , ERG1 Potassium Channel/antagonists & inhibitors , Rats , Mice , Piperidines/pharmacology , Piperidines/therapeutic use , Piperidines/chemistry , Rats, Sprague-Dawley , Ether-A-Go-Go Potassium Channels/antagonists & inhibitors , Ether-A-Go-Go Potassium Channels/metabolism , Urea/analogs & derivativesABSTRACT
BACKGROUND: Depression and dementia represent significant health challenges in older adults. Despite guidelines recommending antidepressants, their efficacy in depressed patients with dementia remains undetermined. OBJECTIVE: This review, in following a living systematic review approach, primarily aims to determine the effect of any-type antidepressant on the level of depressive symptoms in older adults with dementia and secondly if there is an effect of any-type antidepressants on cognitive state, quality of life, and functionality in the old-age population with dementia. METHODS: Systematic review and meta-analysis of RCTs from Medline, Embase, and Cochrane Register. Participants were ≥65 years, with both depression and any type of dementia. Certainty-of-Evidence was assessed through the Cochrane Risk-of-Bias tool and GRADE. Analysis involved standardized mean difference, with 95 % confidence-intervals (CIs). FINDINGS: Of the 27,771 screened articles, 8 studies (617 participants), treated with SSRI, SSNRI, atypical, and tricyclic antidepressants were retained for quantitative synthesis. No evidence for an effect was found (SMD -0.10 [-0.26, 0.07]), nor when subgrouped based on depression severity or dementia level, nor for secondary outcomes. INTERPRETATION: This review did not find evidence of a clinical effect of antidepressants for treating depression in older adults with dementia. Methodological challenges might contribute to this finding.
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Antidepressive Agents , Dementia , Depression , Humans , Dementia/drug therapy , Antidepressive Agents/therapeutic use , Depression/drug therapy , Aged , Aged, 80 and overABSTRACT
OBJECTIVES: The Action To promote brain HEalth iN Adults study aimed to determine the feasibility and applicability of recruitment using home blood pressure (BP) monitoring, routine blood biochemistry and videoconference measures of cognition, in adults at high risk of dementia. DESIGN: A decentralised double-blind, placebo-controlled, randomised feasibility trial with a four-stage screening process. SETTING: Conducted with participants online in the state of New South Wales, Australia. PARTICIPANTS: Participants were aged 50-70 years with moderately elevated BP (systolic >120 and <160 mm Hg or diastolic >80 and <95 mm Hg) and ≥1 additional enrichment risk factor of monotherapy treatment of hypertension, diabetes mellitus, elevated low-density lipoprotein cholesterol, obesity, current smoking or a first degree relative with dementia, which indicated an elevated risk for future cognitive decline. INTERVENTION: Triple Pill (active antihypertensive treatment of telmisartan 20 mg, amlodipine 2.5 mg and indapamide 1.25 mg) or placebo Triple Pill (blinded study capsules). PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was feasibility of the study expressed as the percentage of participants randomised from those who were screened. Secondary outcomes were the applicability of videoconference measures of cognition and the overall trial, tolerability of the Triple Pill, safety outcomes and medication adherence. RESULTS: The proportion (95% CI) of patients randomised to those screened was 5% (2%-10%). The applicability of the trial expressed as percentage of those who completed all remote assessments over the number of randomised participants was 67% (95% CI 05 to 22%). There were no serious adverse events or withdrawals from treatment. All participants adhered to study medication, except for one person who had two capsules left at the end of the study period. CONCLUSIONS: The feasibility of this decentralised trial on BP lowering in patients at high risk for dementia is low. However, the applicability of remote assessments of cognitive function is acceptable. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12621000121864.
Subject(s)
Antihypertensive Agents , Cognitive Dysfunction , Feasibility Studies , Hypertension , Humans , Middle Aged , Antihypertensive Agents/therapeutic use , Antihypertensive Agents/administration & dosage , Male , Female , Aged , Hypertension/drug therapy , Double-Blind Method , Cognitive Dysfunction/drug therapy , Telmisartan/therapeutic use , Telmisartan/administration & dosage , New South Wales , Amlodipine/administration & dosage , Amlodipine/therapeutic use , Blood Pressure Monitoring, Ambulatory , Benzimidazoles/therapeutic use , Benzimidazoles/administration & dosage , Dementia/drug therapy , Risk Factors , Drug Combinations , Blood Pressure/drug effectsSubject(s)
Dementia , Diabetes Mellitus, Type 2 , Sodium-Glucose Transporter 2 Inhibitors , Humans , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Dementia/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/therapeutic useSubject(s)
Antihypertensive Agents , Dementia , Hypertension , Humans , Dementia/epidemiology , Dementia/drug therapy , Antihypertensive Agents/adverse effects , Antihypertensive Agents/therapeutic use , Hypertension/drug therapy , Hypertension/complications , Aged , Risk Factors , Aging/drug effectsABSTRACT
BACKGROUND: Assisted living (AL) is an increasingly common residential setting for persons with dementia; yet concerns exist about sub-optimal care of this population in AL given its lower levels of staffing and services. Our objectives were to (i) examine associations between AL setting (dementia care vs. other), COVID-19 pandemic waves, and prevalent antipsychotic, antidepressant, anti-dementia, benzodiazepine, and anticonvulsant drug use among residents with dementia/cognitive impairment, and (ii) explore associations between resident and home characteristics and prevalent medication use. METHODS: We conducted a population-based, repeated cross-sectional study using linked clinical and health administrative databases for all publicly funded AL homes in Alberta, Canada, examined between January 2018 - December 2021. The quarterly proportion of residents dispensed a study medication was examined for each setting and period (pandemic vs. comparable historical [2018/2019 combined]) focusing on four pandemic waves (March-May 2020, September 2020-February 2021, March-May 2021, September-December 2021). Log-binomial GEE models estimated prevalence ratios (PR) for period (pandemic vs. historical periods), setting (dementia care vs. other) and period-setting interactions, adjusting for resident (age, sex) and home (COVID-19 cases, health region, ownership) characteristics. RESULTS: On March 1, 2020, there were 2,779 dementia care and 3,013 other AL residents (mean age 83, 69% female) with dementia/cognitive impairment. Antipsychotic use increased during waves 2-4 in both settings, but this was more pronounced in dementia care than other AL during waves 3 and 4 (e.g., adjusted [adj]PR 1.20, 95% CI 1.14-1.27 vs. adjPR 1.09, 95% CI 1.02-1.17, interaction p = 0.023, wave 3). Both settings showed a statistically significant but modest increase in antidepressant use and decrease in benzodiazepine use. For dementia care AL residents only, there was a statistically significant increase in gabapentinoid use during several waves (e.g., adjPR 1.32, 95% CI 1.10-1.59, wave 3). Other than a modest decrease in prevalent anti-dementia drug use for both settings in wave 2, no other significant pandemic effects were observed. CONCLUSIONS: The persistence of the pandemic-associated increase in antipsychotic and antidepressant use in AL residents coupled with a greater increase in antipsychotic and gabapentinoid use for dementia care settings raises concerns about the attendant risks for residents with cognitive impairment.
Subject(s)
Assisted Living Facilities , COVID-19 , Dementia , Humans , Cross-Sectional Studies , Dementia/epidemiology , Dementia/drug therapy , COVID-19/epidemiology , Assisted Living Facilities/trends , Male , Female , Aged , Aged, 80 and over , Alberta/epidemiology , Central Nervous System Agents/therapeutic useABSTRACT
OBJECTIVE: Sub-optimal care of people living with dementia has serious consequences for older populations. The 2021 Australian Royal Commission noted that a large proportion of older adults in aged care live with dementia, yet there are limitations in the knowledge and understanding of staff who care for them. In the pursuit of educating pharmacists, physicians, allied health care professionals, researchers, academics, people living with dementia and their carers, and the public, who are facing the challenges of dementia management, the 'Best Practice in Dementia Health Care' conference was held on November 10, 2022 at Western Health (Sunshine Hospital, Melbourne, Australia). METHODS: Sixteen experts presented on the current practice and challenges associated with delivering best practice dementia health care to older Australians, often highlighting how medication-related challenges impacted on their area of practice. RESULTS: Presenters highlighted the importance of individualised medication management plans, considerations of culture and Indigenous communities, the role of technology, and the impact of exercise and the physical environment on care of people living with dementia. Key clinical practice messages from each expert presenter fit into four main topics: 'navigating complexities of medication management'; 'enhancing wellbeing'; 'supportive settings and environments'; and 'programs and services improving care'. CONCLUSIONS: Pharmacists are crucial members of allied health care teams. They have the necessary medication and comorbidity expertise to review medication regimens, liaise with all health care providers, and provide holistic, pharmacological and non-pharmacological patient education. Towards providing best practice dementia health care, pharmacists can contribute in several ways, such as providing health practitioner education to increase understanding about medications and how they can impact on allied health practice, to ensure that medications are prescribed appropriately and safely. Further, pharmacists can make available resources to ensure people living with dementia receive culturally safe and appropriate care, while advocating for greater understanding of the history and experiences of people living with dementia to ensure care aligns with their day-to-day routines. Finally, pharmacists can provide peer-support to other health care professionals and care staff to ensure optimal management of behavioural and psychological symptoms of dementia. The information and insights shared at the conference can serve as a valuable resource for pharmacists and other health care professionals and researchers working to improve the lives of those living with dementia.
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Dementia , Humans , Dementia/drug therapy , Australia , Pharmacists/organization & administration , Pharmaceutical Services/organization & administration , Delivery of Health Care/organization & administration , Professional Role , Medication Therapy Management/organization & administrationABSTRACT
Various medicinal agents aimed at improving Alzheimer disease (AD) include cholinesterase inhibitors, memantine, aducanumab, and antioxidants. These medications are typically prescribed once AD is diagnosed in the clinical setting in order to slow progression. Though initiating treatment after being diagnosed with AD is important, significance should be placed on recognizing known acquired risk factors in order to potentially decrease the likelihood of developing dementia and perhaps specifically AD. This article summarizes the acquired factors that influence risk for dementia.
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Alzheimer Disease , Dementia , Humans , Alzheimer Disease/drug therapy , Alzheimer Disease/epidemiology , Alzheimer Disease/etiology , Antibodies, Monoclonal, Humanized/therapeutic use , Antioxidants/therapeutic use , Cholinesterase Inhibitors/therapeutic use , Dementia/drug therapy , Dementia/epidemiology , Dementia/etiology , Memantine/therapeutic use , Risk FactorsABSTRACT
Introduction: Studies have analyzed the effects of industrial installations on the environment and human health in Taranto, Southern Italy. Literature documented associations between different variables and dementia mortality among both women and men. The present study aims to investigate the associations between sex, environment, age, disease duration, pandemic years, anti-dementia drugs, and death rate. Methods: Data from the regional medication registry were used. All women and men with an anti-dementia medication between 2015 and 2021 were included and followed-up to 2021. Bayesian mixed effects logistic and Cox regression models with time varying exposures were fitted using integrated nested Laplace approximations and adjusting for patients and therapy characteristics. Results: A total of 7,961 person-years were observed. Variables associated with lower prevalence of acetylcholinesterase inhibitors (AChEIs) medication were male sex (OR 0.63, 95% CrI 0.42-0.96), age 70-79 years (OR 0.17, 95% CrI 0.06-0.47) and ≥ 80 years (OR 0.08, 95% CrI 0.03-0.23), disease duration of 2-3 years (OR 0.43, 95% CrI 0.32-0.56) and 4-6 years (OR 0.21, 95% CrI 0.13-0.33), and pandemic years 2020 (OR 0.50, 95% CrI 0.37-0.67) and 2021 (OR 0.47, 95% CrI 0.33-0.65). Variables associated with higher mortality were male sex (HR 2.14, 95% CrI 1.75-2.62), residence in the contaminated site of national interest (SIN) (HR 1.25, 95% CrI 1.02-1.53), age ≥ 80 years (HR 6.06, 95% CrI 1.94-18.95), disease duration of 1 year (HR 1.50, 95% CrI 1.12-2.01), 2-3 years (HR 1.90, 95% CrI 1.45-2.48) and 4-6 years (HR 2.21, 95% CrI 1.60-3.07), and pandemic years 2020 (HR 1.38, 95% CrI 1.06-1.80) and 2021 (HR 1.56, 95% CrI 1.21-2.02). Variables associated with lower mortality were therapy with AChEIs alone (HR 0.69, 95% CrI 0.56-0.86) and in combination with memantine (HR 0.54, 95% CrI 0.37-0.81). Discussion: Male sex, age, disease duration, and pandemic years appeared to be associated with lower AChEIs medications. Male sex, residence in the SIN of Taranto, age, disease duration, and pandemic years seemed to be associated with an increased death rate, while AChEIs medication seemed to be associated with improved survival rate.
Subject(s)
Bayes Theorem , Dementia , Humans , Male , Female , Italy/epidemiology , Aged , Dementia/mortality , Dementia/drug therapy , Aged, 80 and over , Sex Factors , Cholinesterase Inhibitors/therapeutic use , Survival Analysis , Cohort Studies , COVID-19/mortality , COVID-19/epidemiology , Middle Aged , RegistriesABSTRACT
BACKGROUND: Older adults with dementia often face the risk of potentially inappropriate medication (PIM) use. The quality of PIM evaluation is hindered by researchers' unfamiliarity with evaluation criteria for inappropriate drug use. While traditional machine learning algorithms can enhance evaluation quality, they struggle with the multilabel nature of prescription data. AIM: This study aimed to combine six machine learning algorithms and three multilabel classification models to identify correlations in prescription information and develop an optimal model to identify PIMs in older adults with dementia. METHOD: This study was conducted from January 1, 2020, to December 31, 2020. We used cluster sampling to obtain prescription data from patients 65 years and older with dementia. We assessed PIMs using the 2019 Beers criteria, the most authoritative and widely recognized standard for PIM detection. Our modeling process used three problem transformation methods (binary relevance, label powerset, and classifier chain) and six classification algorithms. RESULTS: We identified 18,338 older dementia patients and 36 PIMs types. The classifier chain + categorical boosting (CatBoost) model demonstrated superior performance, with the highest accuracy (97.93%), precision (95.39%), recall (94.07%), F1 score (95.69%), and subset accuracy values (97.41%), along with the lowest Hamming loss value (0.0011) and an acceptable duration of the operation (371s). CONCLUSION: This research introduces a pioneering CC + CatBoost warning model for PIMs in older dementia patients, utilizing machine-learning techniques. This model enables a quick and precise identification of PIMs, simplifying the manual evaluation process.
Subject(s)
Dementia , Machine Learning , Potentially Inappropriate Medication List , Humans , Aged , Dementia/drug therapy , Female , Male , Aged, 80 and over , Inappropriate Prescribing , AlgorithmsABSTRACT
BACKGROUND: Behavioural and psychological symptoms of dementia (BPSD) are highly prevalent in people living with dementia. Second-generation antipsychotics (SGAs) are commonly used to treat BPSD, but their comparative efficacy and acceptability are unknown. METHODS: The standard mean difference (SMD) was used to pool the fixed effects of continuous outcomes. We calculated ORs with corresponding 95% credible intervals (CI) for the categorical variable. Efficacy was defined as the scores improved on the standardised scales. Acceptability was defined as the all-cause dropout rate. Tolerability was defined as the discontinuation rate due to adverse effects (AEs). The relative treatment rankings were reported with the surface under the cumulative curve. The AE outcomes included mortality, cerebrovascular adverse events (CVAEs), falls, sedation, extrapyramidal symptoms and urinary symptoms. RESULTS: Twenty randomised controlled trials with a total of 6374 individuals containing 5 types of SGAs (quetiapine, olanzapine, risperidone, brexpiprazole and aripiprazole) with intervention lengths ranging from 6 weeks to 36 weeks were included in this network meta-analysis. For the efficacy outcome, compared with the placebo, brexpiprazole (SMD=-1.77, 95% CI -2.80 to -0.74) was more efficacious, and brexpiprazole was better than quetiapine, olanzapine and aripiprazole. Regarding acceptability, only aripiprazole (OR=0.72, 95% CI 0.54 to 0.96) was better than the placebo, and aripiprazole was also better than brexpiprazole (OR=0.61, 95% CI 0.37 to 0.99). In terms of tolerability, olanzapine was worse than placebo (OR=6.02, 95% CI 2.87 to 12.66), risperidone (OR=3.67, 95% CI 1.66 to 8.11) and quetiapine (OR=3.71, 95% CI 1.46 to 9.42), while aripiprazole was better than olanzapine (OR=0.25, 95% CI 0.08 to 0.78). Quetiapine presented good safety in CVAE. Brexpiprazole has better safety in terms of falls and showed related safety in sedation among included SGAs. CONCLUSION: Brexpiprazole showing great efficacy in the treatment of BPSD, with aripiprazole showing the highest acceptability and olanzapine showing the worst tolerability. The results of this study may be used to guide decision-making.
Subject(s)
Antipsychotic Agents , Dementia , Network Meta-Analysis , Humans , Antipsychotic Agents/therapeutic use , Antipsychotic Agents/adverse effects , Dementia/drug therapy , Randomized Controlled Trials as Topic , Treatment Outcome , Olanzapine/therapeutic use , Olanzapine/adverse effects , Aripiprazole/therapeutic use , Aripiprazole/adverse effects , Behavioral Symptoms/drug therapyABSTRACT
Anticancer drugs may affect the incidence of dementia by modulating the common pathophysiology between cancer and dementia. However, there is a paucity of research that focused on anticancer drugs with different mechanisms of action and their associations with subtypes of dementia. Therefore, we aimed to investigate the incidence of dementia according to various groups of anticancer drugs. From the Korea National Health Insurance Service database, our retrospective population-based cohort study enrolled 116,506 cancer patients aged 65 years and older who received anticancer drugs between January 1, 2008 and December 31, 2018. The hazard ratio was determined using Cox proportional hazards regression models, comparing each group of anticancer drugs to all other anticancer drugs, after adjusting for covariates. Antimetabolites (HR = 0.91; 95% CI 0.84-0.97) and molecular targeted therapies (HR = 0.60; 95% CI 0.49-0.74) were associated with a decreased incidence of dementia of the Alzheimer type (DAT), but not with vascular dementia. Among molecular targeted therapies, epidermal growth factor receptor inhibitors (HR = 0.60; 95% CI 0.46-0.79) and multikinase inhibitors (HR = 0.49; 95% CI 0.27-0.89) were associated with a low incidence of DAT only. Our findings highlight the potential for targeted repurposing of anticancer drugs to prevent dementia.
Subject(s)
Antineoplastic Agents , Dementia , Molecular Targeted Therapy , Neoplasms , Humans , Male , Aged , Female , Incidence , Antineoplastic Agents/therapeutic use , Retrospective Studies , Dementia/epidemiology , Dementia/drug therapy , Neoplasms/epidemiology , Neoplasms/drug therapy , Republic of Korea/epidemiology , Aged, 80 and over , Proportional Hazards Models , Alzheimer Disease/epidemiology , Alzheimer Disease/drug therapy , Cohort StudiesABSTRACT
Dementia is a growing problem around the globe as the world's population continues to age. Multiple studies have identified potentially modifiable risk factors for the development of dementia suggesting that addressing some or all of these risk factors might have a significant impact on the aging population worldwide. However, this is not always as straightforward as it seems since many of these risk factors are currently treated with drugs specific to the risk factor. Moreover, since people can have multiple risk factors, addressing each of them individually could be highly problematic as it would likely lead to negative outcomes associated with polypharmacy and, in the long term, could do significant harm. A potential alternative is to identify compounds that have shown efficacy against a number of these different risk factors. As discussed in this review, there is strong evidence that the flavonol fisetin is one such compound. In animal studies it has shown efficacy against many of the risk factors that have been associated with an increased risk of developing dementia and also exhibits direct neuroprotective effects. Thus, further human research on fisetin in the context of dementia risk factors is clearly warranted.
Subject(s)
Dementia , Flavonoids , Flavonols , Flavonols/therapeutic use , Flavonols/pharmacology , Humans , Dementia/prevention & control , Dementia/drug therapy , Dementia/epidemiology , Risk Factors , Animals , Flavonoids/pharmacology , Flavonoids/therapeutic use , Neuroprotective Agents/therapeutic use , Neuroprotective Agents/pharmacologyABSTRACT
Pharmacoepidemiologic studies using routinely collected data allow researchers to propose drugs for repurposing trials for dementia prevention or treatment. A recent cohort study reported a 54% lower dementia risk among users of sildenafil compared to users of certain cardiovascular medications. We caution that "confounding by indication" can arise when outcomes are compared between a drug of interest and an inappropriate comparator. Here, we emphasize important considerations in selecting an active comparator. We assess the implications of substantial risk of confounding by indication in pharmacoepidemiologic studies linking phosphodiesterase-5 inhibitors to lower dementia risk.
Subject(s)
Dementia , Phosphodiesterase 5 Inhibitors , Humans , Confounding Factors, Epidemiologic , Dementia/epidemiology , Dementia/drug therapy , Pharmacoepidemiology/methods , Phosphodiesterase 5 Inhibitors/adverse effects , Sildenafil Citrate/therapeutic use , Sildenafil Citrate/adverse effectsABSTRACT
BACKGROUND: Based on observational studies and randomised controlled trials (RCTs), the benefit-harm balance of antihypertensive treatment in older adults with dementia is unclear. OBJECTIVE: To assess whether discontinuing antihypertensive treatment reduces neuropsychiatric symptoms (NPSs) and maintains quality of life (QoL) in nursing home residents with dementia. DESIGN: Open-label, blinded-outcome RCT. Randomisation 1:1, stratified by nursing home organisation and baseline NPS. Trial registration: NL7365. SUBJECTS: Dutch long-term care residents with moderate-to-severe dementia and systolic blood pressure (SBP) ≤160 mmHg during antihypertensive treatment. Exclusion criteria included heart failure NYHA-class-III/IV, recent cardiovascular events/procedures or life expectancy <4 months (planned sample size n = 492). MEASUREMENTS: Co-primary outcomes NPS (Neuropsychiatric Inventory-Nursing Home [NPI-NH]) and QoL (Qualidem) at 16 weeks. RESULTS: From 9 November 2018 to 4 May 2021, 205 participants (median age 85.8 [IQR 79.6-89.5] years; 79.5% female; median SBP 134 [IQR 123-146] mmHg) were randomised to either antihypertensive treatment discontinuation (n = 101) or usual care (n = 104). Safety concerns, combined with lacking benefits, prompted the data safety and monitoring board to advice a premature cessation of randomisation. At 16-week follow-up, no significant differences were found between groups for NPI-NH (adjusted mean difference 1.6 [95% CI -2.3 to 5.6]; P = 0.42) or Qualidem (adjusted mean difference - 2.5 [95% CI -6.0 to 1.0]; P = 0.15). Serious adverse events (SAEs) occurred in 36% (discontinuation) and 24% (usual care) of the participants (adjusted hazard ratio 1.65 [95% CI 0.98-2.79]). All 32-week outcomes favoured usual care. CONCLUSION: Halfway through this study, a non-significant increased SAE risk associated with discontinuing antihypertensive treatment was observed, and an associated interim analysis showed that significant worthwhile health gain for discontinuation of antihypertensive treatment was unlikely. This unbeneficial benefit-harm balance shows that discontinuation of antihypertensive treatment in this context does not appear to be either safe or beneficial enough to be recommended in older adults with dementia.
Subject(s)
Antihypertensive Agents , Dementia , Homes for the Aged , Nursing Homes , Quality of Life , Humans , Female , Male , Dementia/psychology , Dementia/drug therapy , Dementia/diagnosis , Aged, 80 and over , Antihypertensive Agents/therapeutic use , Antihypertensive Agents/adverse effects , Aged , Netherlands , Withholding Treatment , Hypertension/drug therapy , Hypertension/psychology , Treatment Outcome , Blood Pressure/drug effectsABSTRACT
Neurolipids comprise a diverse class of bioactive lipids that include molecules capable of activating G proteincoupled receptors, thereby inducing systemic effects that contribute to the maintenance of homeostasis. Dementia, a nonspecific brain disorder characterized by a common set of signs and symptoms, usually arises subsequent to brain injuries or diseases and is often associated with the aging process. Individuals affected by dementia suffer from the disruption of several neurotransmitter and neuromodulatory systems, among which neurolipids play an important role, including the endocannabinoid, lysophosphatidic acid and sphingosine 1phosphate systems. In this review, we present an overview of the most recent and pertinent findings regarding the involvement of these neurolipidic systems in dementia, including data from a wide range of both in vitro and in vivo experiments as well as clinical trials.
Subject(s)
Dementia , Lysophospholipids , Humans , Dementia/drug therapy , Dementia/metabolism , Lysophospholipids/metabolism , Animals , Sphingosine/analogs & derivatives , Sphingosine/metabolism , Endocannabinoids/metabolism , Receptors, G-Protein-Coupled/metabolism , Brain/metabolism , Brain/drug effects , Neurotransmitter Agents/metabolismABSTRACT
OBJECTIVES: Previous research in the general population shows more potentially inappropriate medications (PIMs) among persons with a migration background compared with persons without a migration background. This study investigated the association between non-Western (nw) migration background (MB) and dementia-specific PIMs in older adults with dementia in the Netherlands. DESIGN: Cohort study using routinely recorded electronic health records and administrative data. SETTING AND PARTICIPANTS: Electronic health record data of general practitioners from the NIVEL-Primary Care Database, were linked to registries managed by Statistics Netherlands (2013-2014). A total of 9055 community-dwelling older adults with dementia were included, among whom 294 persons had an nw-MB from Africa, South America, or Asia, based on their country of birth. METHODS: We determined the presence of dementia-specific PIM prescriptions and compared this between persons with an nw-MB and without an MB, using logistic regression analysis adjusted for follow-up time, age, registered sex, and total number of prescriptions. Interaction effects of potentially relevant covariates were tested. The 3 largest nw-MB groups in the Netherlands were analyzed separately. RESULTS: Dementia-specific PIMs were less frequently prescribed to persons with an nw-MB compared to persons without an MB with a dementia diagnosis [30.6% vs 34.4%, odds ratio (OR) 0.71, 95% CI 0.54-0.92], with especially less often a benzodiazepine prescription in the group with an nw-MB, compared to persons without an MB (15.0% vs 19.3%, OR 0.61, 95% CI 0.43-0.84). Dementia duration, living alone, household income, and degree of urbanization did not influence the associations. CONCLUSIONS AND IMPLICATIONS: Among older adults with dementia in the Netherlands, persons with an nw-MB had less often a dementia-specific PIM prescription compared to persons without an MB. Whether this difference is a reflection of better quality of care, higher professional uncertainty, or less recognition of (mental) health problems in persons with an nw-MB and dementia, needs further investigation.
Subject(s)
Dementia , Potentially Inappropriate Medication List , Humans , Dementia/drug therapy , Male , Female , Netherlands , Aged , Potentially Inappropriate Medication List/statistics & numerical data , Aged, 80 and over , Cohort Studies , Inappropriate Prescribing/statistics & numerical data , Electronic Health RecordsABSTRACT
OBJECTIVES: Previous studies have examined the psychological burden of caregivers of patients with dementia. However, although many caregivers struggle to assist patients with dementia with medication management, the relationship between assisting such patients with taking their medicines and the caregiver psychological burden is understudied. Therefore, this study identified the association between caregivers' psychological burden and assisting patients with dementia with taking medication. METHODS: A cross-sectional survey was conducted among caregivers of patients with dementia in Japan. The survey questionnaire included questions that assessed the symptoms of patients with dementia, their status of taking medication through medication assistance from caregivers, and caregivers' psychological burden using the Kessler Psychological Distress Scale and the Japanese version of the Perceived Stress Scale. KEY FINDINGS: A total of 57 caregivers participated in the study. Higher Kessler Psychological Distress Scale scores were significantly associated with unsuccessful assistance with taking regular medication (ß = 0.35, 95% confidence interval [CI]: 2.23-12.0, P < .05), depressive symptoms (ß = 0.26, 95% CI: 0.10-8.53, P < .05), and irritability (ß = 0.38, 95% CI: 2.71-11.5, P < .05). Likewise, higher scores on the Japanese version of the Perceived Stress Scale were significantly associated with irritability (ß = 0.37, 95% CI: 1.87-12.5, P < .05) among patients with dementia. CONCLUSION: The findings suggest that caregiver psychological burden is associated with unsuccessful assistance with taking regular medication for patients with dementia.