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1.
Annu Rev Pharmacol Toxicol ; 64: 577-598, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-37788493

RESUMO

Seizures and other forms of neurovolatility are emerging as druggable prodromal mechanisms that link traumatic brain injury (TBI) to the progression of later dementias. TBI neurotrauma has both acute and long-term impacts on health, and TBI is a leading risk factor for dementias, including chronic traumatic encephalopathy and Alzheimer's disease. Treatment of TBI already considers acute management of posttraumatic seizures and epilepsy, and impressive efforts have optimized regimens of antiepileptic drugs (AEDs) toward that goal. Here we consider that expanding these management strategies could determine which AED regimens best prevent dementia progression in TBI patients. Challenges with this prophylactic strategy include the potential consequences of prolonged AED treatment and that a large subset of patients are refractory to available AEDs. Addressing these challenges is warranted because the management of seizure activity following TBI offers a rare opportunity to prevent the onset or progression of devastating dementias.


Assuntos
Lesões Encefálicas Traumáticas , Demência , Epilepsia Pós-Traumática , Humanos , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Epilepsia Pós-Traumática/complicações , Epilepsia Pós-Traumática/tratamento farmacológico , Epilepsia Pós-Traumática/prevenção & controle , Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/complicações , Convulsões/tratamento farmacológico , Convulsões/etiologia , Demência/tratamento farmacológico , Demência/prevenção & controle
2.
Ann Neurol ; 95(2): 237-248, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37782554

RESUMO

OBJECTIVE: To improve the timely recognition of patients with treatment-responsive causes of rapidly progressive dementia (RPD). METHODS: A total of 226 adult patients with suspected RPD were enrolled in a prospective observational study and followed for up to 2 years. Diseases associated with RPD were characterized as potentially treatment-responsive or non-responsive, referencing clinical literature. Disease progression was measured using Clinical Dementia Rating® Sum-of-Box scores. Clinical and paraclinical features associated with treatment responsiveness were assessed using multivariable logistic regression. Findings informed the development of a clinical criterion optimized to recognize patients with potentially treatment-responsive causes of RPD early in the diagnostic evaluation. RESULTS: A total of 155 patients met defined RPD criteria, of whom 86 patients (55.5%) had potentially treatment-responsive causes. The median (range) age-at-symptom onset in patients with RPD was 68.9 years (range 22.0-90.7 years), with a similar number of men and women. Seizures, tumor (disease-associated), magnetic resonance imaging suggestive of autoimmune encephalitis, mania, movement abnormalities, and pleocytosis (≥10 cells/mm3 ) in cerebrospinal fluid at presentation were independently associated with treatment-responsive causes of RPD after controlling for age and sex. Those features at presentation, as well as age-at-symptom onset <50 years (ie, STAM3 P), captured 82 of 86 (95.3%) cases of treatment-responsive RPD. The presence of ≥3 STAM3 P features had a positive predictive value of 100%. INTERPRETATION: Selected features at presentation reliably identified patients with potentially treatment-responsive causes of RPD. Adaptation of the STAM3 P screening score in clinical practice may minimize diagnostic delays and missed opportunities for treatment in patients with suspected RPD. ANN NEUROL 2024;95:237-248.


Assuntos
Demência , Encefalite , Adulto , Masculino , Humanos , Feminino , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Demência/diagnóstico , Demência/tratamento farmacológico , Demência/etiologia , Encefalite/complicações , Imageamento por Ressonância Magnética , Testes de Estado Mental e Demência , Progressão da Doença
3.
Eur J Neurosci ; 59(6): 1359-1385, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38154805

RESUMO

Candidate drugs targeting the central nervous system (CNS) demonstrate extremely low clinical success rates, with more than 98% of potential treatments being discontinued due to poor blood-brain barrier (BBB) permeability. Neurological conditions were shown to be the second leading cause of death globally in 2016, with the number of people currently affected by neurological disorders increasing rapidly. This increasing trend, along with an inability to develop BBB permeating drugs, is presenting a major hurdle in the treatment of CNS-related disorders, like dementia. To overcome this, it is necessary to understand the structure and function of the BBB, including the transport of molecules across its interface in both healthy and pathological conditions. The use of CNS drug carriers is rapidly gaining popularity in CNS research due to their ability to target BBB transport systems. Further research and development of drug delivery vehicles could provide essential information that can be used to develop novel treatments for neurological conditions. This review discusses the BBB and its transport systems and evaluates the potential of using nanoparticle-based delivery systems as drug carriers for CNS disease with a focus on dementia.


Assuntos
Doenças do Sistema Nervoso Central , Demência , Humanos , Barreira Hematoencefálica , Sistemas de Liberação de Medicamentos , Portadores de Fármacos/química , Portadores de Fármacos/uso terapêutico , Transporte Biológico , Demência/tratamento farmacológico
4.
N Engl J Med ; 385(4): 309-319, 2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34289275

RESUMO

BACKGROUND: Patients with dementia due to neurodegenerative disease can have dementia-related psychosis. The effects of the oral 5-HT2A inverse agonist and antagonist pimavanserin on psychosis related to various causes of dementia are not clear. METHODS: We conducted a phase 3, double-blind, randomized, placebo-controlled discontinuation trial involving patients with psychosis related to Alzheimer's disease, Parkinson's disease dementia, dementia with Lewy bodies, frontotemporal dementia, or vascular dementia. Patients received open-label pimavanserin for 12 weeks. Those who had a reduction from baseline of at least 30% in the score on the Scale for the Assessment of Positive Symptoms-Hallucinations and Delusions (SAPS-H+D, with higher scores indicating greater psychosis) and a Clinical Global Impression-Improvement (CGI-I) score of 1 (very much improved) or 2 (much improved) at weeks 8 and 12 were randomly assigned in a 1:1 ratio to continue receiving pimavanserin or to receive placebo for up to 26 weeks. The primary end point, assessed in a time-to-event analysis, was a relapse of psychosis as defined by any of the following: an increase of at least 30% in the SAPS-H+D score and a CGI-I score of 6 (much worse) or 7 (very much worse), hospitalization for dementia-related psychosis, stopping of the trial regimen or withdrawal from the trial for lack of efficacy, or use of antipsychotic agents for dementia-related psychosis. RESULTS: Of the 392 patients in the open-label phase, 41 were withdrawn for administrative reasons because the trial was stopped for efficacy; of the remaining 351 patients, 217 (61.8%) had a sustained response, of whom 105 were assigned to receive pimavanserin and 112 to receive placebo. A relapse occurred in 12 of 95 patients (13%) in the pimavanserin group and in 28 of 99 (28%) in the placebo group (hazard ratio, 0.35; 95% confidence interval, 0.17 to 0.73; P = 0.005). During the double-blind phase, adverse events occurred in 43 of 105 patients (41.0%) in the pimavanserin group and in 41 of 112 (36.6%) in the placebo group. Headache, constipation, urinary tract infection, and asymptomatic QT prolongation occurred with pimavanserin. CONCLUSIONS: In a trial that was stopped early for efficacy, patients with dementia-related psychosis who had a response to pimavanserin had a lower risk of relapse with continuation of the drug than with discontinuation. Longer and larger trials are required to determine the effects of pimavanserin in dementia-related psychosis. (Funded by Acadia Pharmaceuticals; HARMONY ClinicalTrials.gov number, NCT03325556.).


Assuntos
Antipsicóticos/uso terapêutico , Demência/psicologia , Alucinações/tratamento farmacológico , Piperidinas/uso terapêutico , Transtornos Psicóticos/tratamento farmacológico , Ureia/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Demência/tratamento farmacológico , Método Duplo-Cego , Feminino , Alucinações/etiologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/psicologia , Modelos de Riscos Proporcionais , Transtornos Psicóticos/etiologia , Recidiva , Ureia/uso terapêutico
5.
Osteoporos Int ; 35(4): 589-598, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37980284

RESUMO

Little is known about caregivers' perspectives on deprescribing bisphosphonates for older adults with dementia. Caregivers agreed that fracture prevention was important for maintaining functional independence but acknowledged that changing goals of care may justify deprescribing. Conversations grounded in "what matters most" can align fracture prevention treatment with goals of care. PURPOSE: The long-term fracture prevention benefits of bisphosphonates may begin to be overshadowed by the potential burden of adverse effects and polypharmacy for older adults living with dementia as the disease progresses. We characterized factors that influence caregiver decision-making for continuing versus deprescribing bisphosphonates for persons living with dementia. METHODS: We conducted 11 interviews with family or informal caregivers of older adults living with dementia in the community or in long-term care who had been treated with bisphosphonates. Interviews focused on experiences caring for someone who has experienced a fracture, perceived benefits and harms of bisphosphonates, and experiences with deprescribing. Analyses were conducted using a qualitative framework methodology guided by the Health Belief Model. RESULTS: Most caregivers were male (n = 8), younger than 65 (n = 8) and were an adult child caregiver (n = 8). Three caregivers were Black and five were Latino/a. Attempts to maintain functional independence despite high likelihood of falls was frequently discussed as contributing to fracture risk, in this population. Many caregivers perceived fracture prevention treatment as important, while several noted that it may become less important near the end of life. Perceived benefits of fracture prevention treatment for persons with dementia included improved quality of life and maintaining independence. Although most indicated that bisphosphonates were well tolerated, gastrointestinal adverse effects, preference for fewer treatments, and dementia-related behaviors that interfere with medication administration may be reasons for deprescribing. CONCLUSION: Conversations grounded in caregiver experiences and "what matters most" may help optimize fracture prevention treatment for older adults with dementia.


Assuntos
Demência , Desprescrições , Humanos , Masculino , Idoso , Feminino , Cuidadores , Difosfonatos/efeitos adversos , Qualidade de Vida , Demência/tratamento farmacológico
6.
Calcif Tissue Int ; 115(1): 14-22, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38744723

RESUMO

Increased ß-adrenergic receptor activity has been hypothesized to cause bone loss in those with dementia. We investigated the effect of long-term ß-blocker use on rate of bone loss in older adults with dementia. We used a linear mixed-effects model to estimate the relationship between long-term ß-blocker use and rate of bone loss in participants from the Health Aging and Body Composition study. Records of 1198 participants were analyzed, 44.7% were men. Among the men, 25.2% had dementia and 20.2% were on ß-blockers, while in the women, 22.5% had dementia and 16.6% received ß-blockers. In the 135 men with dementia, 23 were taking ß-blockers, while 15 of 149 women with dementia were using ß-blockers. In men with dementia, ß-blocker users had 0.00491 g/cm2 less bone mineral density (BMD) loss per year at the femoral neck (i.e., 0.63% less loss per year) than non-users (p < 0.05). No differences were detected in women with or without dementia and men without dementia. ß-blockers may be protective by slowing down bone loss in older men with dementia.


Assuntos
Antagonistas Adrenérgicos beta , Densidade Óssea , Demência , Humanos , Masculino , Feminino , Antagonistas Adrenérgicos beta/uso terapêutico , Antagonistas Adrenérgicos beta/farmacologia , Idoso , Densidade Óssea/efeitos dos fármacos , Demência/tratamento farmacológico , Idoso de 80 Anos ou mais , Osteoporose/tratamento farmacológico , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo
7.
Alzheimer Dis Assoc Disord ; 38(1): 59-64, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38300882

RESUMO

PURPOSE: The Carer Assessment of medicaTion management guidanCe for people with dementia at Hospital discharge (CATCH) tool was developed to examine the carer's experiences of medication management guidance delivery at discharge. This study explored its factor structure, characterized carers' experiences at discharge, and identified predictors of carer preparedness to manage medications at discharge. METHODS: A cross-sectional survey of carers across Australia was distributed. Survey responses were analyzed descriptively, and exploratory factor and regression analyses were performed. RESULTS: A total of 185 survey responses were completed. Exploratory factor analysis revealed 2 factors in the CATCH tool: (1) shared and supported decision-making in medication management (16 items loading 0.47 to 0.93); 2) provision of medication management guidance that is easy to understand (4 items loading (0.48 to 0.82). Internal consistency was acceptable (Cronbach alpha >0.8). Almost 18% of participants stated that they were not included in decisions about medications for people with dementia. The carer reported that the measure of how guidance is provided was positively related to their confidence in the management of medications postdischarge and satisfaction ( P < 0.05 for both). CONCLUSIONS: The CATCH tool can give the patient and carer an opportunity to provide feedback on key elements of medication management guidance delivered at discharge.


Assuntos
Demência , Alta do Paciente , Humanos , Cuidadores , Conduta do Tratamento Medicamentoso , Assistência ao Convalescente , Estudos Transversais , Demência/tratamento farmacológico , Hospitais
8.
Curr Psychiatry Rep ; 26(3): 73-77, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38381305

RESUMO

PURPOSE OF REVIEW: The purpose of this review is to identify key classes of medications that are used for the treatment of older adults with neurocognitive disorders. RECENT FINDINGS: Clinical factors play a critical role in the prescribing of these medication classes for the treatment of dementia. The variation in prescribing trends is determined by the presence of medical and psychiatric comorbidities commonly occurring in older adults and is based on the consideration of potential interactions between pharmacotherapies for the comorbidities and for the dementia. Six medication classes currently exist to address the neurocognitive aspect of dementia, with varying pharmacokinetic and pharmacodynamic profiles. We review these six classes in this report and provide a provision of clinical insights regarding the use of these agents. While literature exists on the safety and efficacy of individual medication options for the treatment of dementia in the older adult population, further research is needed to provide clearer guidance regarding the specific use of these agents in clinical practice.


Assuntos
Demência , Nootrópicos , Humanos , Idoso , Demência/tratamento farmacológico , Nootrópicos/uso terapêutico , Comorbidade
9.
Int J Geriatr Psychiatry ; 39(5): e6089, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38676658

RESUMO

OBJECTIVES: Dementia guidelines recommend antipsychotics are only used for behavioral and psychological symptoms when non-drug interventions fail, and to regularly review use. Population-level clinical quality indicators (CQIs) for dementia care in permanent residential aged care (PRAC) typically monitor prevalence of antipsychotic use but not prolonged use. This study aimed to develop a CQI for antipsychotic use >90 days and examine trends, associated factors, and variation in CQI incidence; and examine duration of the first episode of use among individuals with dementia accessing home care packages (HCPs) or PRAC. METHODS: Retrospective cohort study, including older individuals with dementia who accessed HCPs (n = 50,257) or PRAC (n = 250,196). Trends in annual CQI incidence (2011-12 to 2015-16) and associated factors were determined using Poisson regression. Funnel plots examined geographical and facility variation. Time to antipsychotic discontinuation was estimated among new antipsychotic users accessing HCP (n = 2367) and PRAC (n = 15,597) using the cumulative incidence function. RESULTS: Between 2011-12 and 2015-16, antipsychotic use for >90 days decreased in HCP recipients from 10.7% (95% CI 10.2-11.1) to 10.1% (95% CI 9.6-10.5, adjusted incidence rate ratio (aIRR) 0.97 (95% CI 0.95-0.98)), and in PRAC residents from 24.5% (95% CI 24.2-24.7) to 21.8% (95% CI 21.5-22.0, aIRR 0.97 (95% CI 0.96-0.98)). Prior antipsychotic use (both cohorts) and being male and greater socioeconomic disadvantage (PRAC cohort) were associated with higher CQI incidence. Little geographical/facility variation was observed. Median treatment duration in HCP and PRAC was 334 (interquartile range [IQR] 108-958) and 555 (IQR 197-1239) days, respectively. CONCLUSIONS: While small decreases in antipsychotic use >90 days were observed between 2011-12 and 2015-16, findings suggest antipsychotic use among aged care recipients with dementia can be further minimized.


Assuntos
Antipsicóticos , População Australasiana , Demência , Indicadores de Qualidade em Assistência à Saúde , Humanos , Antipsicóticos/uso terapêutico , Masculino , Feminino , Demência/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Austrália , Instituição de Longa Permanência para Idosos/estatística & dados numéricos , Instituição de Longa Permanência para Idosos/normas
10.
Int J Geriatr Psychiatry ; 39(5): e6097, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38782606

RESUMO

BACKGROUND: While some people with mild cognitive impairment (MCI) progress to dementia, many others show no progression. The aim of this study was to identify factors associated with risk of dementia development in this population. METHOD: A large naturalistic retrospective cohort study was assembled from mental healthcare records in a south London catchment. Patients were selected at first recorded diagnosis of MCI and subsequent dementia diagnosis was ascertained from case notes or death certificate, excluding those with dementia diagnoses and deaths within 6 months of MCI diagnosis. A range of demographic and clinical characteristics were ascertained around MCI diagnosis and Cox proportional hazards models were used to investigate independent predictors of dementia, focussing on neuropsychiatric symptoms, contextual factors, and antidepressant treatment. RESULTS: Of 2250 patients with MCI, 236 (10.5%) developed dementia at least 6 months after MCI diagnosis. Aside from older age, lower cognitive function, and activities of daily living impairment, impaired social relationships and recorded loneliness were associated with a higher risk of developing dementia. Patients of Black (compared to White) ethnicity were at a lower risk. For depression and antidepressant receipt, only tricyclic use compared to no antidepressant use was associated with an increased dementia risk. CONCLUSIONS: No evidence was found for co-morbid affective disorders or different antidepressant classes as risk factors for dementia development following MCI diagnosis, but loneliness and social impairment were independent predictors and would be worth evaluating as targets for interventions to delay progression.


Assuntos
Antidepressivos , Disfunção Cognitiva , Demência , Modelos de Riscos Proporcionais , Humanos , Disfunção Cognitiva/epidemiologia , Feminino , Masculino , Demência/epidemiologia , Demência/tratamento farmacológico , Idoso , Fatores de Risco , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Antidepressivos/uso terapêutico , Londres/epidemiologia , Atividades Cotidianas , Pessoa de Meia-Idade , Depressão/epidemiologia , Depressão/tratamento farmacológico , Solidão/psicologia
11.
Age Ageing ; 53(3)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38526026

RESUMO

BACKGROUND: There is a strong imperative to support people with dementia to live independently in their homes for as long as possible. A starting point is to understand how they manage medications on a daily basis. AIM: To understand how people with dementia and their informal carers manage medications within the home setting to inform the identification of opportunities to improve medication management. METHODS: A qualitative study using the Functional Resonance Analysis Method (FRAM). Interview data with people with dementia and informal carers were analysed to (i) Identify and describe key functions, (ii) identify and describe variability in performing key functions, and its potential consequences and (iii) map performance variability to Resilient Healthcare capacities. RESULTS AND DISCUSSION: A FRAM model was developed and consisted of 14 interdependent key functions. The interdependent nature of functions, and the different nature and sources of variability in how each key function was performed highlighted the level of complexity of the medication management system within the home setting. The medication system was managed almost entirely by the person with dementia and/or their informal carers. This shows the lack of system-level controls to support the safe functioning of the medication management system in the home setting. CONCLUSION: Future work will develop a comprehensive FRAM model that includes the perspectives of health and social care professionals and those from the third sectors to underpin the development of a range of system recommendations to strengthen resilience in the medication management system within the home setting.


Assuntos
Cuidadores , Demência , Humanos , Demência/tratamento farmacológico , Conduta do Tratamento Medicamentoso , Pesquisa Qualitativa
12.
Age Ageing ; 53(5)2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38783756

RESUMO

BACKGROUND: An updated time-trend analysis of anti-dementia drugs (ADDs) is lacking. The aim of this study is to assess the incident rate (IR) of ADD in individuals with dementia using real-world data. SETTING: Primary care data (country/database) from the UK/CPRD-GOLD (2007-20), Spain/SIDIAP (2010-20) and the Netherlands/IPCI (2008-20), standardised to a common data model. METHODS: Cohort study. Participants: dementia patients ≥40 years old with ≥1 year of previous data. Follow-up: until the end of the study period, transfer out of the catchment area, death or incident prescription of rivastigmine, galantamine, donepezil or memantine. Other variables: age/sex, type of dementia, comorbidities. Statistics: overall and yearly age/sex IR, with 95% confidence interval, per 100,000 person-years (IR per 105 PY (95%CI)). RESULTS: We identified a total of (incident anti-dementia users/dementia patients) 41,024/110,642 in UK/CPRD-GOLD, 51,667/134,927 in Spain/SIDIAP and 2,088/17,559 in the Netherlands/IPCI.In the UK, IR (per 105 PY (95%CI)) of ADD decreased from 2007 (30,829 (28,891-32,862)) to 2010 (17,793 (17,083-18,524)), then increased up to 2019 (31,601 (30,483 to 32,749)) and decrease in 2020 (24,067 (23,021-25,148)). In Spain, IR (per 105 PY (95%CI)) of ADD decreased by 72% from 2010 (51,003 (49,199-52,855)) to 2020 (14,571 (14,109-15,043)). In the Netherlands, IR (per 105 PY (95%CI)) of ADD decreased by 77% from 2009 (21,151 (14,967-29,031)) to 2020 (4763 (4176-5409)). Subjects aged ≥65-79 years and men (in the UK and the Netherlands) initiated more frequently an ADD. CONCLUSIONS: Treatment of dementia remains highly heterogeneous. Further consensus in the pharmacological management of patients living with dementia is urgently needed.


Assuntos
Demência , Humanos , Masculino , Feminino , Demência/tratamento farmacológico , Demência/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Bases de Dados Factuais , Fatores de Tempo , Nootrópicos/uso terapêutico , Espanha/epidemiologia , Reino Unido/epidemiologia , Padrões de Prática Médica/tendências , Fatores Etários , Uso de Medicamentos/tendências , Uso de Medicamentos/estatística & dados numéricos
13.
Acta Derm Venereol ; 104: adv26663, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38576104

RESUMO

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.


Assuntos
Demência , Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Penfigoide Bolhoso , Humanos , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Vildagliptina/efeitos adversos , Penfigoide Bolhoso/induzido quimicamente , Penfigoide Bolhoso/diagnóstico , Penfigoide Bolhoso/epidemiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Linagliptina/efeitos adversos , Estudos Retrospectivos , Inibidores de Simportadores de Cloreto de Sódio e Potássio/uso terapêutico , Fatores de Risco , Fosfato de Sitagliptina/efeitos adversos , Demência/induzido quimicamente , Demência/tratamento farmacológico
14.
Pharmacopsychiatry ; 57(3): 160-168, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38447959

RESUMO

Dementia, with loss of memory, cognitive abilities, and independent daily functioning, is increasing worldwide, related to an aging population. Currently, there is no curative treatment for dementia. Treatment of the frequently occurring behavioral and psychological symptoms of dementia (BPSD) is partially effective and associated with significant side effects. Cannabinoids are lipophilic molecules acting on the CB1 end CB2 receptors, essential for main biological processes such as sleep, appetite, memory, and pain. Cannabinoids might have a positive impact on amyloid formation in Alzheimer's disease, the main form of dementia, and on BPSD symptoms. Most knowledge currently concerns delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). In the context of dementia and BPSD, THC might be beneficial for associated spasticity and possible pain or lack of appetite and CBD probably works better on sleep, agitation, and anxiety. This overview of prospective clinical studies and randomized clinical trials, published between 2005 and April 2023, using cannabinoids for BPSD suggests that older studies using low-dose oral synthetic THC showed no positive results. Still, more recent studies using THC/CBD-based oral medication at higher doses show promising results and are feasible and safe in this elderly polymedicated population. Several RCTs are ongoing and planned worldwide, and we hope other trials will follow to establish clinical efficiency and optimal dosing, as well as other outcomes such as deprescribing other medications and facilitation of care. We suggest that researchers also address the more sociological aspects of prescribing cannabinoids for dementia and BPSD in their specific context.


Assuntos
Canabinoides , Demência , Humanos , Demência/tratamento farmacológico , Canabinoides/uso terapêutico , Sintomas Comportamentais/tratamento farmacológico , Canabidiol/uso terapêutico , Dronabinol/uso terapêutico
15.
Neurol Sci ; 45(1): 27-36, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37639023

RESUMO

PURPOSE: The relationship between varicella zoster virus (VZV) infection and the risk of dementia has not been previously studied specifically. Therefore, this study sought to determine the relationship between studying VZV infection and dementia occurring in the general population by conducting an extensive meta-analysis of published cases. METHOD: A systematic literature search was conducted in seven online databases by October 31, 2022. Heterogeneity was tested by the I2 index. Pooled HR and 95% CI were used to estimate the effect of VZV infection on dementia. Sensitivity analyses and publication bias were also performed. RESULT: Nine studies involving 3,326,673 subjects were included. VZV infection was associated with an increased risk of dementia (HR = 1.11, 95% CI: 1.02-1.21). The risk of dementia was reduced in those who received antiviral therapy compared to those who did not (HR = 0.84, 95% CI: 0.71-0.99). In addition, VZV infection was found to be associated with an increased risk of developing dementia in the pooled results of the moderate quality study (HR = 1.81,95% CI: 1.27-2.59), and this association persisted when subgroup analyses were performed based on region (Asia: HR = 1.18,95% CI: 1.04-1.33). CONCLUSIONS: Our results suggest that VZV infection might increase the risk of developing dementia, but there is no clear mechanism about the true relationship, and since there is no effective treatment for dementia, and our results suggest that some populations can benefit from antiviral therapy, it is at least arguable that patients who develop VZV infection should be treated with appropriate antiviral medications.


Assuntos
Demência , Herpes Zoster , Humanos , Antivirais/uso terapêutico , Demência/epidemiologia , Demência/etiologia , Demência/tratamento farmacológico , Herpes Zoster/complicações , Herpes Zoster/epidemiologia , Herpesvirus Humano 3
16.
Gerontology ; 70(6): 620-629, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38626732

RESUMO

INTRODUCTION: Dementia increases the risk of falls and fall-related injuries, which may be caused by inappropriate medication use. To date, there is little evidence on which medications are more likely to cause falls. We therefore investigated the effects of medication use and medication changes 48 h before falls in hospitalised patients with dementia. METHODS: This matched case-control study included 74 patients with a mean age of 83 years (38% women) who had been hospitalised for at least 7 days. Information on medications, diagnoses, disease severity, use of walking aids, falls, and demographics was collected from electronic medical records. The effects of the number of medications and psychotropics, equivalent daily doses of antidepressants, antipsychotics and benzodiazepines, anticholinergic burden, medication initiation, dose change, medication discontinuation, as-needed medications, opioid use and the presence of fall-increasing diseases were examined separately for the periods 0 h-24 h and 24 h-48 h before the falls using binomial logistic regression analyses. RESULTS: Falls increased significantly with higher daily antipsychotic doses 24 h before the fall. In addition, the rate of falls increased with higher anticholinergic burden and prevalence of medication discontinuation 24-48 h before the fall. Notably, the total number of medications and psychotropic medications had no effect on the incidence of falls. CONCLUSION: With regard to the short-term effects of medication on fall risk, particular attention should be paid to the daily dose of antipsychotics, anticholinergic burden and medication discontinuation. Further studies with larger samples are needed to confirm the results of this study.


Assuntos
Acidentes por Quedas , Antipsicóticos , Demência , Humanos , Acidentes por Quedas/estatística & dados numéricos , Feminino , Masculino , Idoso de 80 Anos ou mais , Demência/epidemiologia , Demência/tratamento farmacológico , Estudos de Casos e Controles , Idoso , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Fatores de Risco , Pacientes Internados , Polimedicação , Multimorbidade , Psicotrópicos/efeitos adversos , Antagonistas Colinérgicos/efeitos adversos , Hospitalização/estatística & dados numéricos
17.
Eur Neurol ; 87(2): 93-104, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38657568

RESUMO

INTRODUCTION: Dementia is a neurodegenerative disease with insidious onset and progressive progression, of which the most common type is Alzheimer's disease (AD). Lithium, a trace element in the body, has neuroprotective properties. However, whether lithium can treat dementia or AD remains a highly controversial topic. Therefore, we conducted a meta-analysis. METHODS: A systematic literature review was conducted on PubMed, Embase, and Web of Science. Comparison of the effects of lithium on AD or dementia in terms of use, duration, and dosage, and meta-analysis to test whether lithium therapy is beneficial in ameliorating the onset of dementia or AD. Sensitivity analyses were performed using a stepwise exclusion method. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of included studies. We determined the relative risk (RR) between patient groups using a random-effects model. RESULTS: A total of seven studies were included. The forest plot results showed that taking lithium therapy reduced the risk of AD (RR 0.59, 95% confidence interval [CI]: 0.44-0.78) and is also protective in reducing the risk of dementia (RR 0.66, 95% CI: 0.56-0.77). The duration of lithium therapy was able to affect dementia incidence (RR 0.70, 95% CI: 0.55-0.88); however, it is unclear how this effect might manifest in AD. It is also uncertain how many prescriptions for lithium treatment lower the chance of dementia development. CONCLUSION: The duration of treatment and the usage of lithium therapy seem to lower the risk of AD and postpone the onset of dementia.


Assuntos
Doença de Alzheimer , Demência , Humanos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/epidemiologia , Demência/epidemiologia , Demência/tratamento farmacológico , Compostos de Lítio/uso terapêutico , Prevalência , Lítio/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico
18.
BMC Geriatr ; 24(1): 279, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38519888

RESUMO

BACKGROUND: Pain medication may have an impact on the quality of life (QoL) in persons with dementia, but may also influence care dependency and daily functioning. The aim of this study is to investigate the effect of regularly scheduled paracetamol on care dependency and daily functioning in persons with advanced dementia with low QoL living in long-term care facilities. METHODS: The Quality of life and Paracetamol In advanced Dementia (Q-PID) study was a (block) randomized double-blind placebo-controlled crossover trial with paracetamol and placebo across seventeen long-term care facilities across 9 care organizations in the western region of the Netherlands. Participants were ≥ 65 years, had advanced dementia (Global Deterioration Scale 5-7), and low QoL (QUALIDEM-6D score ≤ 70). Measurements were performed by nursing staff at the start and at the end of each treatment period of six weeks. Repeated linear mixed models were used to compute differences between randomization groups, with adjustment for period and order effects, and psychotropic use. RESULTS: Ninety-five persons (mean age of 83.9 years, 57.4% female) were enrolled in the Q-PID study. The mean Care Dependency Scale total score was 37.8 (Standard Deviation [SD] 12.9) and the mean Katz-15 total score was 11.9 (SD 2.4). Repeated linear mixed models showed no difference in mean differences of care dependency (paracetamol - 1.0 [95% Confidence Interval (CI) -2.4-0.3], placebo + 0.1 [-1.3-1.5]), and daily functioning (paracetamol + 0.2 [95% CI -0.2-0.6], placebo + 0.1 [-0.3-0.4]). CONCLUSIONS: Compared to placebo, no effect of scheduled administration of paracetamol was found on care dependency and daily functioning in persons with advanced dementia with low QoL. Future research should focus on which specific items of care dependency need special attention to improve the care for persons with advanced dementia. A multi-domain approach is needed to enhance and/or maintain QoL of persons with advanced dementia. TRIAL REGISTRATION: Netherlands Trial Register (NTR6766); http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=6766 ; Trial registration date: 20/10/2017.


Assuntos
Acetaminofen , Demência , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Acetaminofen/uso terapêutico , Demência/tratamento farmacológico , Assistência de Longa Duração , Casas de Saúde , Qualidade de Vida , Idoso
19.
BMC Geriatr ; 24(1): 328, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600444

RESUMO

BACKGROUND: Studies have shown that potentially inappropriate prescribing (PIP) is highly prevalent among people with dementia (PwD) and linked to negative outcomes, such as hospitalisation and mortality. However, there are limited data on prescribing appropriateness for PwD in Saudi Arabia. Therefore, we aimed to estimate the prevalence of PIP and investigate associations between PIP and other patient characteristics among PwD in an ambulatory care setting. METHODS: A cross-sectional, retrospective analysis was conducted at a tertiary hospital in Saudi Arabia. Patients who were ≥ 65 years old, had dementia, and visited ambulatory care clinics between 01/01/2019 and 31/12/2021 were included. Prescribing appropriateness was evaluated by applying the Screening Tool of Older Persons Potentially Inappropriate Prescriptions (STOPP) criteria. Descriptive analyses were used to describe the study population. Prevalence of PIP and the prevalence per each STOPP criterion were calculated as a percentage of all eligible patients. Logistic regression analysis was used to investigate associations between PIP, polypharmacy, age and sex; odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Analyses were conducted using SPSS v27. RESULTS: A total of 287 PwD were identified; 56.0% (n = 161) were female. The mean number of medications prescribed was 9.0 [standard deviation (SD) ± 4.2]. The prevalence of PIP was 61.0% (n = 175). Common instances of PIP were drugs prescribed beyond the recommended duration (n = 90, 31.4%), drugs prescribed without an evidence-based clinical indication (n = 78, 27.2%), proton pump inhibitors (PPIs) for > 8 weeks (n = 75, 26.0%), and acetylcholinesterase inhibitors with concurrent drugs that reduce heart rate (n = 60, 21.0%). Polypharmacy was observed in 82.6% (n = 237) of patients and was strongly associated with PIP (adjusted OR 24.1, 95% CI 9.0-64.5). CONCLUSIONS: Findings have revealed a high prevalence of PIP among PwD in Saudi Arabia that is strongly associated with polypharmacy. Future research should aim to explore key stakeholders' experiences and perspectives of medicines management to optimise medication use for this vulnerable patient population.


Assuntos
Demência , Prescrição Inadequada , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Masculino , Prescrição Inadequada/prevenção & controle , Estudos Retrospectivos , Estudos Transversais , Acetilcolinesterase/uso terapêutico , Lista de Medicamentos Potencialmente Inapropriados , Polimedicação , Demência/diagnóstico , Demência/tratamento farmacológico , Demência/epidemiologia
20.
BMC Geriatr ; 24(1): 520, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877433

RESUMO

BACKGROUND: Dementia is a major global public health challenge, and with the growing elderly population, its prevalence is expected to increase in the coming years. In Sweden, municipalities are responsible for providing special housing for the elderly (SÄBO), which offers services and care for older individuals needing specific support. SÄBO is both the person´s home and a care environment and workplace. Polypharmacy in patients with dementia is common and increases the risk of medication interactions. Involving clinical pharmacists in medication reviews has been shown to enhance medication safety and improve prescribing practices. However, the views of the standard care team involved in medication prescribing, administration, monitoring and documentation on integrating pharmacist services have received less attention. Thus, this study aims to explore how pharmacists' contributions can enhance medication safety, improve patient care efficiency, and potentially alleviate the workload of general practitioners for people with dementia living in special housing. METHODS: This study has a descriptive qualitative study design using semi-structured interviews and qualitative content analysis. The study was conducted in a southern Swedish special housing and included nurses, assistant nurses, general practitioners (GPs), and a pharmacist. Due to the COVID-19 pandemic, interviews were conducted over the phone. The Swedish Ethical Review Authority approved the study. RESULTS: The analysis revealed three main categories, and eleven subcategories.: (1) Integrating multidisciplinary approaches for holistic dementia care, (2) Strengthening dementia care through effective medication management and (3) Advancing dementia care through pharmacist integration and role expansion. Nurses focused on non-pharmacological treatments, while GPs emphasized the importance of medication reviews in assessing the benefits and side-effects of prescribed medication. Pharmacists were valued for their reliable medication expertise, appreciated by GPs for saving time and providing recommendations prior to consultations with individuals with dementia and their next-of-kin. Although medication reviews were considered beneficial, there was skepticism about their ability to solve all medication-related problems associated with dementia care. CONCLUSIONS: This study highlights the critical role pharmacists play in enhancing medication safety and patient care efficiency in special housing for individuals with dementia. Despite the value of their contributions, communication barriers within healthcare teams pose significant challenges. Recognising potential pharmacist role expansion is essential to alleviate the workload of GPs and ensure effective collaborative practices for better patient outcomes.


Assuntos
Demência , Clínicos Gerais , Farmacêuticos , Humanos , Demência/tratamento farmacológico , Demência/terapia , Suécia/epidemiologia , Masculino , Feminino , Idoso , Enfermeiras e Enfermeiros , Pesquisa Qualitativa , COVID-19/epidemiologia , Papel Profissional , Pessoa de Meia-Idade , Adulto
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