RESUMO
BACKGROUND AND OBJECTIVE: Alzheimer's disease is a progressive neurodegenerative disorder characterized by cognitive decline, behavioral changes, and functional impairments. Apathy, a common symptom in Alzheimer's disease, refers to a lack of motivation, interest, and emotional responsiveness. It can significantly impact patients' quality of life and increase caregiver burden. This study aimed to determine the effects of a diversified rehabilitation program combined with donepezil on apathy, cognitive function, and family caregiver burden of Alzheimer's disease patients. METHODS: A total of 105 Alzheimer's disease patients treated at our hospital between January 2020 and January 2023 were selected and analyzed retrospectively. They were assigned to the control group (n = 50) or the observation group (n = 55). The two groups did not differ in terms of general data such as age and sex. All patients were treated with donepezil orally. The control group was given routine nursing, whereas the observation group was given a diversified rehabilitation program intervention, including cognitive training and emotional support. The Hasegawa's dementia scale, mini-mental state examination, and Montreal cognitive assessment scale were adopted to evaluate the cognitive function of the two groups before and after treatment. A caregiver burden scale, the Zarit Burden Interview (ZBI) and the Apathy Evaluation Scale Informant version (AES-I) were used to evaluate the caregiver burden and apathy of the two groups. RESULTS: A significantly higher overall response rate to treatment was found in the observation group (94.55%) than in the control group (80.00%) (p = 0.024). After treatment, scores on the Hasegawa's dementia scale, mini-mental state examination, and Montreal cognitive assessment scale of the two groups increased to varying degrees, with greater increases in the observation group than in the control group (p < 0.05). The ZBI and AES-I scores of the two groups decreased to different degrees after treatment, with greater decreases in the observation group than in the control group (p < 0.05). CONCLUSION: A diversified rehabilitation program combined with donepezil can substantially alleviate the apathy of Alzheimer's disease patients, improve their cognitive function, and reduce the burden on their families.
Assuntos
Doença de Alzheimer , Apatia , Sobrecarga do Cuidador , Cognição , Donepezila , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/reabilitação , Donepezila/administração & dosagem , Apatia/efeitos dos fármacos , Cognição/efeitos dos fármacos , Sobrecarga do Cuidador/prevenção & controle , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Cuidadores/educação , Resultado do Tratamento , Estudos de Casos e ControlesRESUMO
BACKGROUND AND OBJECTIVE: Cerebral small vessel disease (CSVD) often coexists with cognitive dysfunction in patients, leading to significant challenges in treatment and management. This study aimed to examine the efficacy of combined application of donepezil and nimodipine on patients with comorbid CSVD and cognitive dysfunction and the effects on patients' albumin and prealbumin levels. METHODS: The records of 112 patients with comorbid CSVD and cognitive dysfunction treated at the People's Hospital of Suzhou New District from January 2019 to December 2022 were analysed retrospectively. A total of 50 patients receiving donepezil were allocated to the control group, and 62 patients receiving both nimodipine and donepezil to the study group. Outcomes compared between the two groups included serum homocysteine (Hcy), high sensitivity C-reactive protein (hs-CRP), albumin, and prealbumin before and after therapy, efficacy, and adverse reactions. Additionally, logistic regression was performed to analyze the risk factors impacting patient prognosis. RESULTS: Prior to therapy, the two groups did not differ significantly in Hcy and hs-CRP levels (p > 0.05), whereas after therapy, the levels in both groups dropped significantly (p < 0.01), with more obvious lower levels in the study group (p < 0.05). After treatment, the study group presented significantly higher albumin and prealbumin levels than the control group (p < 0.001). An obvious higher overall response rate was observed in the study group compared to the control group (p = 0.012). No significant inter-group discrepancy was found regarding the total incidence of adverse reactions (p = 0.752). Univariate analysis identified age, course of disease, heart rate (HR), Montreal Cognitive Assessment (MoCA) score, diastolic blood pressure (DBP), systolic blood pressure (SBP), drinking history, as well as medication regimen as risk factors impacting patient prognosis. Multivariate logistic regression analysis identified SBP, DBP, and medication regimen as the independent risk factors. CONCLUSION: Combined application of donepezil and nimodipine can effectively treat patients with comorbid CSVD and cognitive dysfunction. It can significantly lower the Hcy and hs-CRP levels and improve the nutritional status without increasing the frequency of adverse reactions. In addition, for CSVD patients with cognitive dysfunction, age, course of disease, MoCA score, HR, SBP, DBP, drinking history, and medication regimen are risk factors impacting patient prognosis, while SBP, DBP, and medication regimen are independent risk factors.
Assuntos
Doenças de Pequenos Vasos Cerebrais , Disfunção Cognitiva , Donepezila , Quimioterapia Combinada , Nimodipina , Estado Nutricional , Humanos , Feminino , Masculino , Donepezila/administração & dosagem , Donepezila/uso terapêutico , Doenças de Pequenos Vasos Cerebrais/tratamento farmacológico , Doenças de Pequenos Vasos Cerebrais/complicações , Disfunção Cognitiva/tratamento farmacológico , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Nimodipina/administração & dosagem , Nimodipina/uso terapêutico , Resultado do Tratamento , Nootrópicos/administração & dosagem , Nootrópicos/uso terapêutico , Nootrópicos/efeitos adversos , Homocisteína/sangueRESUMO
BACKGROUND: Choline alfoscerate (alpha-glycerylphosphorylcholine) is a phospholipid that includes choline, which increases the release of acetylcholine. The ASCOMALVA trial, a combination of donepezil and choline alfoscerate, slowed cognitive decline in Alzheimer disease. This study aims to replicate the effect by combining donepezil with other nootropics currently used in South Korea. METHODS: The 119 patients with cognitive decline who were eligible to use donepezil, with an mini-mental state examination (MMSE) score of 26 or less, were assigned to: donepezil alone (DO); donepezil and choline alfoscerate (DN); donepezil and acetyl-l-carnitine (DA); or donepezil and ginkgo biloba extract (DG). Cognitive evaluations such as MMSE, clinical dementia rating, Alzheimer disease assessment scale-cognitive subscale (ADAS-Cog), and Alzheimer disease assessment scale-noncognitive subscale were performed at the 12th and 24th weeks from the baseline time point. RESULTS: At the 12th week, the MMSE score increased 3.52% in the DN group, whereas it increased by 1.36% in the DO group. In the DAâ +â DG group, it decreased by 2.17%. At the 24th week, the MMSE score showed an increase of 1.07% in the DO group and 1.61% in the DN group, but decreased by 5.71% in the DAâ +â DG group. ADAS-Cog decreased by 0.9% in the DO group, while it improved by 13.9% in the DN group at the 12th week. At the 24th week, ADAS-Cog showed improvement in the DN group by 18.5%, whereas it improved by 9.4% in the DO group. Alzheimer disease assessment scale-noncognitive subscale also revealed better performance in the DN group than in the DO group at the 12th and 24th weeks. CONCLUSION: Choline alfoscerate exhibits additional cognitive improvement in both cognitive and noncognitive domains, supporting the findings of the ASCOMALVA trial.
Assuntos
Donepezila , Quimioterapia Combinada , Ginkgo biloba , Glicerilfosforilcolina , Indanos , Nootrópicos , Humanos , Donepezila/uso terapêutico , Donepezila/administração & dosagem , Masculino , Feminino , Idoso , Método Duplo-Cego , Glicerilfosforilcolina/uso terapêutico , Glicerilfosforilcolina/administração & dosagem , Nootrópicos/administração & dosagem , Nootrópicos/uso terapêutico , Indanos/uso terapêutico , Indanos/administração & dosagem , Doença de Alzheimer/tratamento farmacológico , Piperidinas/uso terapêutico , Piperidinas/administração & dosagem , Extratos Vegetais/uso terapêutico , Extratos Vegetais/administração & dosagem , República da Coreia , Acetilcarnitina/uso terapêutico , Acetilcarnitina/administração & dosagem , Disfunção Cognitiva/tratamento farmacológico , Testes de Estado Mental e Demência , Resultado do Tratamento , Idoso de 80 Anos ou mais , Cognição/efeitos dos fármacos , Extrato de GinkgoRESUMO
PURPOSE: To test efficacy of donepezil, a cognitive enhancer, to improve memory in breast cancer survivors who report cancer-related cognitive impairment 1-5 years postchemotherapy. PATIENTS AND METHODS: Adult female BCS exposed to ≥4 cycles of adjuvant chemotherapy 1-5 years before enrollment who reported cancer-related cognitive impairment were eligible. Participants, enrolled at sites affiliated with the Wake Forest NCI Community Oncology Research Program (NCORP) Research Base, were randomly assigned to receive 5 mg of donepezil once daily for 6 weeks titrated to 10 mg once daily for 18 weeks or placebo. Cognition and self-report cognitive functioning was assessed at baseline, 12, 24 (end of intervention), and 36 (washout) weeks postrandomization. Mixed-effects repeated measures analysis of covariance models were used to assess treatment differences in immediate recall (primary outcome) on the Hopkins Verbal Learning Test-Revised (HVLT-R) and other cognitive domains (secondary outcomes) with covariates of treatment, time, time by treatment interaction, baseline outcome level, age stratification, and an unstructured covariance matrix to account for within participant correlation over time. RESULTS: Two hundred seventy-six BCS from 87 NCORP practices (mean age, 57.1, standard deviation [SD], 10.5) who were at a mean of 29.6 months (SD, 14.2) postchemotherapy were randomly assigned to donepezil (n = 140) or placebo (n = 136). At 24 weeks, treatment groups did not differ on HVLT-R scores (donepezil mean = 25.98, placebo = 26.50, P = .32). There were no statistically significant differences between treatments at 12, 24, or 36 weeks for attention, executive function, verbal fluency, processing speed, or self-reported cognitive functioning. Endocrine therapy and menopausal status did not affect results. CONCLUSION: BCS 1-5 years after completing chemotherapy with documented memory problems, randomly assigned to 24 weeks of 5-10 mg of donepezil once daily, did not perform differently at the end of treatment on tests of memory, other cognitive functions, or subjective functioning than those randomly assigned to placebo.
Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Disfunção Cognitiva , Donepezila , Humanos , Donepezila/uso terapêutico , Donepezila/efeitos adversos , Donepezila/administração & dosagem , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/complicações , Neoplasias da Mama/psicologia , Pessoa de Meia-Idade , Quimioterapia Adjuvante/efeitos adversos , Sobreviventes de Câncer/psicologia , Idoso , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/tratamento farmacológico , Piperidinas/uso terapêutico , Piperidinas/efeitos adversos , Piperidinas/administração & dosagem , Método Duplo-Cego , Adulto , Nootrópicos/uso terapêutico , Nootrópicos/efeitos adversos , Nootrópicos/administração & dosagem , Indanos/uso terapêutico , Indanos/efeitos adversos , Indanos/administração & dosagem , Cognição/efeitos dos fármacosRESUMO
INTRODUCTION: Cholinesterase inhibitors, along with memantine, are the mainstay of symptomatic treatment for AD (Alzheimer's disease); however, these medications are typically administered orally, which can be difficult for people with AD and their caregivers. AREAS COVERED: In this drug profile and narrative review, the authors trace the development of the new FDA-approved transdermal donepezil. The authors discuss the studies showing its bioequivalence with the oral formulation, including two double-blinded placebo controlled non-inferiority trials. The authors also compare the patch to the only other transdermal cholinesterase inhibitor on the market, rivastigmine, and highlight the potential advantages and disadvantages between these two treatments. EXPERT OPINION: While the patch is bio-equivalent, it is rather large and may not be affordable for some patients. In addition, there is no high dose (e.g. 23 mg) equivalent. Nevertheless, transdermal donepezil will be useful for people with AD and their caregivers, given its effectiveness and potential convenience.
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Administração Cutânea , Doença de Alzheimer , Inibidores da Colinesterase , Donepezila , Humanos , Donepezila/administração & dosagem , Donepezila/uso terapêutico , Doença de Alzheimer/tratamento farmacológico , Inibidores da Colinesterase/administração & dosagem , Inibidores da Colinesterase/uso terapêutico , Adesivo Transdérmico , Rivastigmina/administração & dosagem , Rivastigmina/uso terapêutico , Índice de Gravidade de DoençaRESUMO
Alzheimer's disease is the most serious neurodegenerative disorder characterized by cognitive and memorial defects alongside deterioration in behavioral, thinking and social skills. Donepezil hydrochloride (DPZ) is one of the current two FDA-approved cholinesterase inhibitors used for the management of Alzheimer's disease. The current study aimed to formulate hyaluronic acid-coated transfersomes containing DPZ (DPZ-HA-TFS) for brain delivery through the intranasal pathway to surpass its oral-correlated GIT side effects. DPZ-HA-TFS were produced using a thin film hydration method and optimized with a 24 factorial design. The influence of formulation parameters on vesicle diameter, entrapment, cumulative release after 8 h, and ex vivo nasal diffusion after 24 h was studied. The optimal formulation was then evaluated for morphology, stability, histopathology and in vivo biodistribution studies. The optimized DPZ-HA-TFS formulation elicited an acceptable vesicle size (227.5 nm) with 75.83% entrapment efficiency, 37.94% cumulative release after 8 h, 547.49 µg/cm2 permeated through nasal mucosa after 24 h and adequate stability. Histopathological analysis revealed that the formulated DPZ-HA-TFS was nontoxic and tolerable for intranasal delivery. Intranasally administered DPZ-HA-TFS manifested significantly superior values for drug targeting index (5.08), drug targeting efficiency (508.25%) and direct nose-to-brain transport percentage (80.32%). DPZ-HA-TFS might be deemed as a promising intranasal nano-cargo for DPZ cerebral delivery to tackle Alzheimer's disease safely, steadily and in a non-invasive long-term pattern.
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Administração Intranasal , Doença de Alzheimer , Encéfalo , Inibidores da Colinesterase , Donepezila , Ácido Hialurônico , Mucosa Nasal , Donepezila/administração & dosagem , Donepezila/farmacocinética , Donepezila/farmacologia , Doença de Alzheimer/tratamento farmacológico , Ácido Hialurônico/química , Ácido Hialurônico/administração & dosagem , Animais , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Inibidores da Colinesterase/administração & dosagem , Inibidores da Colinesterase/farmacocinética , Mucosa Nasal/metabolismo , Mucosa Nasal/efeitos dos fármacos , Liberação Controlada de Fármacos , Distribuição Tecidual , Ratos , Masculino , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Portadores de Fármacos/química , Ratos Wistar , Tamanho da PartículaRESUMO
La enfermedad con cuerpos de Lewy incluye 2 entidades que podrían ser consideradas variantes clínicas de una misma patología: la demencia con cuerpos de Lewy y la demencia en enfermedad de Parkinson. Con la finalidad de describir correctamente lo que sucede en la evolución de la enfermedad se divide el cuadro en etapa prodrómica y de demencia propiamente dicha. La primera está clínicamente representada por aquel período en el cual, si bien el paciente exhibe algunos signos y síntomas propios de la enfermedad, no reúne criterios de demencia. A pesar de ser difícil de definir y por carecerse todavía de contundentes datos clínicos y biomarcadores, se caracteriza principalmente por deterioro leve selectivo en función atencional visuoespacial, trastorno del sueño REM y disautonomíaâ. La segunda etapa está claramente caracterizada en los criterios de consenso del año 2005. Recientemente hemos publicado la validación de un instrumento llamado ALBA Screening Instrument, que permite diagnosticar con alta sensibilidad y especificidad la enfermedad aun en etapas tempranas y diferenciarla de otras patologías semejantes. La tomografía por emisión de positrones (PET) para transportador de dopamina es el procedimiento de referencia (gold standard) del diagnóstico. El tratamiento sintomático con anticolinesterásicos y neurolépticos atípicos favorece una buena evolución de la enfermedad y es fundamental tener en cuenta evitar medicamentos que pueden dañar gravemente a los pacientes como los anticolinérgicos y antipsicóticos típicos. Los avances en el diagnóstico y la difusión del impacto de esta enfermedad en la población contribuirán a generar mayores esfuerzos de investigación para hallar un tratamiento eficaz, preventivo o curativo o de ambas características. (AU)
Lewy body disease includes 2 entities that could be considered clinical variants of the same pathology: Dementia with Lewy bodies and Parkinson's disease Dementia. Two stages of the disease are described in this review, a prodromal stage and one of explicit dementia. The first one is clinically represented by that period in which, the patient exhibits some typical features of the disease, but not dementia criteria. Despite being difficult to define the prodromal stage and that strong clinical data and biomarkers are still lacking, there is evidence to characterize it mainly by mild selective impairment in attention and visuo-spatial function, REM sleep disorder and dysautonomia. The second stage is clearly characterized in the known consensus criteria of 2005. We have recently published the validation of an instrument called ALBA Screening Instrument which showed a high sensitivity and specificity for diagnosis of the disease even in the early stages. It´s useful to differentiate the disease from other similar pathologies. Positron Emission Tomography for dopamine transporter is the gold standard of diagnosis in life. Symptomatic treatment with anticholinesterases and atypical neuroleptics help patients in their evolution of the disease. Anticholinergics and typical antipsychotics are agents to avoid in the treatmen of the disease because can severely damage patients. Future advances in the diagnosis and dissemination of the knowledge of the disease will contribute to generate greater research efforts to find an effective preventive and / or curative treatment. (AU)