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1.
Lancet Neurol ; 19(11): 951-962, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33098804

RESUMO

Various biomarkers are available to support the diagnosis of neurodegenerative diseases in clinical and research settings. Among the molecular imaging biomarkers, amyloid-PET, which assesses brain amyloid deposition, and 18F-fluorodeoxyglucose (18F-FDG) PET, which assesses glucose metabolism, provide valuable and complementary information. However, uncertainty remains regarding the optimal timepoint, combination, and an order in which these PET biomarkers should be used in diagnostic evaluations because conclusive evidence is missing. Following an expert panel discussion, we reached an agreement on the specific use of the individual biomarkers, based on available evidence and clinical expertise. We propose a diagnostic algorithm with optimal timepoints for these PET biomarkers, also taking into account evidence from other biomarkers, for early and differential diagnosis of neurodegenerative diseases that can lead to dementia. We propose three main diagnostic pathways with distinct biomarker sequences, in which amyloid-PET and 18F-FDG-PET are placed at different positions in the order of diagnostic evaluations, depending on clinical presentation. We hope that this algorithm can support diagnostic decision making in specialist clinical settings with access to these biomarkers and might stimulate further research towards optimal diagnostic strategies.


Assuntos
Doença de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Demência Vascular/metabolismo , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons/métodos , Idoso , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/psicologia , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Demência Vascular/diagnóstico por imagem , Demência Vascular/psicologia , Diagnóstico Diferencial , Humanos , Masculino
3.
J Prev Alzheimers Dis ; 7(4): 294-298, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32920634

RESUMO

Individuals experiencing brain aging, cognitive decline, and dementia are currently confronted with several more complex challenges due to the current Sars-Cov-2 pandemic as compared to younger and cognitively healthy people. During the first six months of the pandemic, we are experiencing critical issues related to the management of mild cognitive impairment (MCI) and dementia. The evolving, highly contagious global viral spread has created a pressure test of unprecedented proportions for the existing brain health care infrastructure and related services for management, diagnosis, treatment, and prevention. Social distancing and lock-down measures are catalyzing and accelerating a technological paradigm shift, away from a traditional model of brain healthcare focused on late symptomatic disease stages and towards optimized preventive strategies to slow brain aging and increase resilience at preclinical asymptomatic stages. Digital technologies transform global healthcare for accessible equality of opportunities in order to generate better outcomes for brain aging aligned with the paradigm of preventive medicine.


Assuntos
Doença de Alzheimer/prevenção & controle , Disfunção Cognitiva/prevenção & controle , Infecções por Coronavirus , Relações Interpessoais , Pandemias , Pneumonia Viral , Isolamento Social/psicologia , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Doença de Alzheimer/psicologia , Betacoronavirus , Disfunção Cognitiva/psicologia , Progressão da Doença , Humanos , Masculino , Quarentena/psicologia , Fatores de Risco , Tecnologia
4.
J Alzheimers Dis ; 77(2): 539-541, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32925073

RESUMO

The ongoing coronavirus disease 2019 (COVID-19) pandemic has substantially affected patients with dementia and their caregivers. However, we found not all Alzheimer's disease (AD) patients were afraid of COVID-19 infection. Therefore, we investigated the association between rate of awareness of COVID-19 and depressive tendency in AD. 126 consecutive outpatients with AD were enrolled in this study from May 25, on the day when the declaration of emergency was lifted in Japan, through June 30, 2020. In addition to routine psychological tests, the participants were asked the following two questions: "Do you know COVID-19?" and "Why are you wearing a face mask?". Moderate to severe AD patients were found to have a low COVID-19 recognition rate and did not fully understand why they were wearing face masks. In addition, because they did not understand the seriousness of the COVID-19 outbreak, their Geriatric Depression Scale scores were also substantially lower. These results may appear to simply indicate that people with severe dementia are unaware of current events. However, these results provide insights into how to care for patients with dementia and how to allocate the time and support of our limited staff during the COVID-19 outbreak.


Assuntos
Doença de Alzheimer , Conscientização , Infecções por Coronavirus , Competência Mental , Pandemias , Assistência ao Paciente , Pneumonia Viral , Idoso , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/psicologia , Doença de Alzheimer/virologia , Betacoronavirus , Cuidadores/psicologia , Controle de Doenças Transmissíveis/organização & administração , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/psicologia , Feminino , Humanos , Japão/epidemiologia , Masculino , Pandemias/prevenção & controle , Assistência ao Paciente/métodos , Assistência ao Paciente/tendências , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Pneumonia Viral/psicologia , Sistemas de Apoio Psicossocial , Índice de Gravidade de Doença
6.
Psychiatry Res ; 291: 113294, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32763552

RESUMO

To cope with Covid-19 and limits its spread among residents, retirement homes have prohibited physical contact between residents and families and friend and, in some cases, even between residents or between residents and caregivers. We investigated the effects of measures against Covid-19 on the mental health of participants with Alzheimer's disease (AD) who live in retirement homes in France. We instructed on-site caregivers to assess depression and anxiety in participants with mild AD who live in retirement homes. Fifty-eight participants consented to participate in the study. The participants rated their depression and anxiety during and before the Covid-19 crisis. Participants reported higher depression (p = .005) and anxiety (p = .004) during than before the Covid-19 crisis. These increases can be attributed to the isolation of the residents and/or to the drastic changes in their daily life and care they receive. While, in their effort to prevent infections, retirement homes are forced to physically separate residents from the outside world and to drastically reduce residents' activities, these decisions are likely to come at a cost to residents with AD and their mental health.


Assuntos
Doença de Alzheimer/complicações , Ansiedade/diagnóstico , Infecções por Coronavirus , Depressão/diagnóstico , Instituição de Longa Permanência para Idosos , Pandemias , Pneumonia Viral , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/psicologia , Ansiedade/complicações , Ansiedade/psicologia , Betacoronavirus , Cuidadores , Depressão/complicações , Depressão/psicologia , Feminino , França , Humanos , Masculino , Casas de Saúde , Índice de Gravidade de Doença
7.
Psychogeriatrics ; 20(5): 726-736, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32767414

RESUMO

AIM: Many researchers argue that Alzheimer's disease is at least partly caused by deposition of amyloid beta (Aß) in the brain. Ferulic acid (FA) and Angelica archangelica (AA) are candidate agents for reducing Aß and improving cognitive function. Feru-guard 100M is a supplement containing FA and AA extract. Using this supplement, we planned to assess the effect of FA and AA on Aß deposition in the human brain. METHODS: This was an open-label, interventional multi-institutional joint study of Kobe University and the Institute of Biomedical Research and Innovation (Kobe, Japan). Seventeen subjects diagnosed with mild cognitive impairment were divided into two groups: the intervention group (n = 10) and the control group (n = 7). The subjects in the intervention group used Feru-guard 100M every day for 48 weeks, whereas the subjects in the control group did not use the supplement. We assessed the differences between the two groups by examining Aß deposition and brain atrophy at 48 weeks and cognitive function every 24 weeks. We used carbon-11-labelled Pittsburgh compound B (PiB) positron emission tomography to evaluate Aß deposition. RESULTS: There were no significant differences in Aß deposition, brain atrophy, and cognitive function between the two groups. Specifically, differences in Aß deposition change in seven regions of interest examined with PiB positron emission tomography, brain atrophy change in four indicators of voxel-based morphometry, and cognitive impairment measured by five psychological tests were not significantly between the two groups. CONCLUSION: Treatment with Feru-guard 100M, a supplement containing FA and AA extract, for 48 weeks did not reduce cortical PiB retention, which reflects Aß deposition. It also did not suppress the aggravation of brain atrophy or decline in cognitive function.


Assuntos
Peptídeos beta-Amiloides/efeitos dos fármacos , Angelica archangelica/química , Encéfalo/patologia , Disfunção Cognitiva/diagnóstico , Ácidos Cumáricos/uso terapêutico , Idoso , Doença de Alzheimer/etiologia , Doença de Alzheimer/psicologia , Peptídeos beta-Amiloides/metabolismo , Compostos de Anilina , Atrofia , Encéfalo/diagnóstico por imagem , Radioisótopos de Carbono , Disfunção Cognitiva/diagnóstico por imagem , Progressão da Doença , Feminino , Humanos , Japão , Masculino , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Tiazóis
8.
J Alzheimers Dis ; 77(1): 67-73, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32804094

RESUMO

BACKGROUND: Facing the novel coronavirus disease 2019 (COVID-19), most vulnerable individuals are seniors, especially those with comorbidities. More attention needs to been paid to the COVID-19 patients with Alzheimer's disease (AD), which is the top age-related neurodegenerative disease. OBJECTIVE: Since it is unclear whether AD patients are prone to COVID-19 infection and progression to severe stages, we report for the first time a retrospective analysis of the clinical characteristics of AD patients with COVID-19 pneumonia. METHODS: We conducted a retrospective cohort study of the clinical data of 19 AD patients with COVID-19 pneumonia, compared with 23 non-AD COVID-19 patients admitted at the same time to our hospital. Demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. RESULTS: Between AD patients and non-AD patients with COVID-19 pneumonia, the pneumonia severity was not significantly different. AD patients had a higher clustering onset than non-AD patients. The median duration from symptom onset to hospitalization were shorter in AD patients than non-AD patients, indicating the former were sent to the hospital by their family or from nursing home earlier than the later. The median duration from hospitalization to discharge seemed shorter in AD patients than non-AD patients. Dementia patients seemed less likely to report fatigue. It is noticed that more AD patients might have pericardial effusion than the non-AD patients. CONCLUSION: AD patients with COVID-19 were in milder conditions with a better prognosis than non-AD patients. AD patients who had adequate access to healthcare showed resilience to COVID-19 with shorter hospital stays.


Assuntos
Doença de Alzheimer/complicações , Doença de Alzheimer/psicologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/psicologia , Pneumonia Viral/complicações , Pneumonia Viral/psicologia , Resiliência Psicológica , Idoso , Idoso de 80 Anos ou mais , Análise por Conglomerados , Estudos de Coortes , Progressão da Doença , Fadiga/etiologia , Fadiga/psicologia , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pandemias , Alta do Paciente/estatística & dados numéricos , Derrame Pleural/epidemiologia , Derrame Pleural/etiologia , Pneumonia/complicações , Pneumonia/terapia , Prognóstico
9.
ACS Chem Neurosci ; 11(15): 2145-2148, 2020 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-32662982

RESUMO

Studies have shown that the calcium ion (Ca2+) plays important roles both in Alzheimer's dementia and SARS-CoV S-mediated fusion to host cell entry. An elevated level of intracellular calcium causes neuronal dysfunction, cell death, and apoptosis. Dysregulation of calcium has also been shown to increase the production of amyloid beta (Aß) protein, the hallmark of Alzheimer's dementia. Reversely, deposition of Aß is also responsible for calcium dysregulation. On the other hand, it has been well investigated that viruses can disturb host cell Ca2+ homeostasis as well as modulate signal transduction mechanisms. Viruses can also hijack the host cell calcium channels and pumps to release more intracellular Ca2+ to utilize for their life cycle. Even though evidence has not been reported on SARS-CoV-2 concerning Ca2+ regulation, however, it has been well established that Ca2+ is essential for viral entry, viral gene replication, and virion maturation and release. Recent reports suggest that SARS-CoV needs two Ca2+ ions to fuse with the host cell at the entry step. Furthermore, some calcium channel blockers (CCBs), such as nimodipine, memantine, etc., have been reported to be effective in the treatment of dementia in Alzheimer's disease (AD) as well as have shown inhibition in various virus infections.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Betacoronavirus , Bloqueadores dos Canais de Cálcio/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/psicologia , Cálcio/metabolismo , Bloqueadores dos Canais de Cálcio/química , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio/metabolismo , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/psicologia , Humanos , Pandemias , Pneumonia Viral/metabolismo , Pneumonia Viral/psicologia , Resultado do Tratamento
10.
Value Health ; 23(6): 760-767, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32540234

RESUMO

OBJECTIVES: To assess the acceptability and validity of the 3 levels of the EQ-5D (EQ-5D-3L) compared with the Quality of Life in Alzheimer's Diseases (QoL-AD) in patients living with dementia. METHODS: The analysis was based on 560 dyads of persons with dementia and their caregivers of the multicenter observational study of dementia care networks in Germany (DemNet-D). Health-related quality of life was assessed by face-to-face interviews using the EQ-5D-3L (self-rating) and the QoL-AD (self- and proxy-rating). The number of missing values, the score ranges (observed vs possible range) and the floor and ceiling effects were used to assess the acceptability. We used one-way analyses of variance and multivariate linear regression models to evaluate the discriminative ability. The convergent validity was assessed using Spearman's correlation coefficient (rs) and multivariate regression models. RESULTS: The EQ-5D index had a higher response rate (89% vs 84%) and a comparable floor (>1%) but a higher ceiling effect (18% vs >1%) compared with the QoL-AD. Both measures can significantly differentiate between different stages of general health, instrumental activities of daily living, and depression. The EQ-5D index and the visual analog scale self-rating scores strongly correlated with the QoL-AD self-rating (rs = 0.644 and 0.553, respectively) but not with the proxy-rating score (rs = 0.314 and rs = 0.170, respectively), which was confirmed by multivariate regression analyses. CONCLUSION: The results satisfy acceptability, discriminative ability, and convergent validity for moderately cognitively and functionally impaired patients living with dementia. The EQ-5D-3L performed comparably with the QoL-AD, and could, therefore, be used in economic evaluations in dementia. The differences between self- and proxy-ratings should be evaluated and considered in the interpretation of health-related quality of life scores.


Assuntos
Doença de Alzheimer/psicologia , Cuidadores/psicologia , Demência/psicologia , Qualidade de Vida , Inquéritos e Questionários , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Depressão/epidemiologia , Feminino , Alemanha , Humanos , Masculino , Medidas de Resultados Relatados pelo Paciente , Reprodutibilidade dos Testes
11.
Neurology ; 95(2): e166-e178, 2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32580974

RESUMO

OBJECTIVE: To investigate sex differences in late-onset Alzheimer disease (AD) risks by means of multimodality brain biomarkers (ß-amyloid load via 11C-Pittsburgh compound B [PiB] PET, neurodegeneration via 18F-fluorodeoxyglucose [FDG] PET and structural MRI). METHODS: We examined 121 cognitively normal participants (85 women and 36 men) 40 to 65 years of age with clinical, laboratory, neuropsychological, lifestyle, MRI, FDG- and PiB-PET examinations. Several clinical (e.g., age, education, APOE status, family history), medical (e.g., depression, diabetes mellitus, hyperlipidemia), hormonal (e.g., thyroid disease, menopause), and lifestyle AD risk factors (e.g., smoking, diet, exercise, intellectual activity) were assessed. Statistical parametric mapping and least absolute shrinkage and selection operator regressions were used to compare AD biomarkers between men and women and to identify the risk factors associated with sex-related differences. RESULTS: Groups were comparable on clinical and cognitive measures. After adjustment for each modality-specific confounders, the female group showed higher PiB ß-amyloid deposition, lower FDG glucose metabolism, and lower MRI gray and white matter volumes compared to the male group (p < 0.05, family-wise error corrected for multiple comparisons). The male group did not show biomarker abnormalities compared to the female group. Results were independent of age and remained significant with the use of age-matched groups. Second to female sex, menopausal status was the predictor most consistently and strongly associated with the observed brain biomarker differences, followed by hormone therapy, hysterectomy status, and thyroid disease. CONCLUSION: Hormonal risk factors, in particular menopause, predict AD endophenotype in middle-aged women. These findings suggest that the window of opportunity for AD preventive interventions in women is early in the endocrine aging process.


Assuntos
Doença de Alzheimer/epidemiologia , Imagem Multimodal , Neuroimagem , Adulto , Idoso , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/psicologia , Compostos de Anilina , Apolipoproteínas E/genética , Feminino , Fluordesoxiglucose F18 , Hormônios/sangue , Humanos , Estilo de Vida , Imagem por Ressonância Magnética , Masculino , Menopausa/psicologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Fatores de Risco , Fatores Sexuais , Tiazóis
12.
Gerokomos (Madr., Ed. impr.) ; 31(2): 68-70, jun. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-193885

RESUMO

OBJETIVO: Valorar daños en salud mental de cuidadores familiares de personas con demencia de institución psiquiátrica para proponer acciones y mitigar sus efectos. MÉTODO: estudio descriptivo-correlacional de corte transversal en 28 sujetos con cuestionarios de salud SF-36, escala de sobrecarga de Zarit, cuestionario del paciente PHQ-9, análisis de porcentaje y pruebas de correlación t-Student y Pearson. RESULTADOS: Género predominante, mujeres (85,2%); edad media, 59,3 años; presentaron depresión menor un 44,4% y mayor un 14,8%, sobrecarga ligera un 22,2% y sobrecarga intensa un 37,0%, correlación negativa significativa (p = 0,02) entre depresión y vitalidad. La calidad de vida a nivel físico en un cuidador de 55 años o más se encuentra disminuida (media = 23,3). CONCLUSIONES: De acuerdo con los resultados, indican para este estudio que factores como tener más de 55 años, percibir una peor función física y sentirse menos vital son algunas variables asociadas a la aparición de depresión y sobrecarga


OBJECTIVE: to evaluate mental health damages of family caregivers of people with dementia of a psychiatric institution to propose actions and mitigate their effects. METHOD: descriptive-correlational cross-sectional study in 28 subjects with SF-36 health questionnaires, Zarit overload scale, PHQ-9 patient questionnaire, percentage analysis and t-Student and Pearson correlation tests. RESULTS: predominant gender women (85.2%); mean age of 59.3 years, had a minor depression of 44.4% and greater by 14.8%, slight overload in 22.2% and intense overload in 37.0%, significant negative correlation (p = 0.02) between depression and vitality. The quality of life at a physical level in a caregiver of 55 years or more is diminished (mean = 23.3). CONCLUSIONS: According to the results indicate for this study that factors such as being over 55 years of age, perceiving a worse physical function, and feeling less vital are some variables associated with the appearance of depression and overload


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Cuidadores/psicologia , Depressão/psicologia , Esgotamento Profissional/epidemiologia , Qualidade de Vida/psicologia , Esgotamento Profissional/psicologia , Inquéritos e Questionários , Saúde Mental , Estudos Transversais , Doença de Alzheimer/psicologia
13.
Medicine (Baltimore) ; 99(22): e20240, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32481389

RESUMO

Studies suggest that the use of alpha-blockers increases the risk of dementia in patients with benign prostate hyperplasia (BPH). Due to study limitations, the relationship between the use of alpha-blockers, such as tamsulosin, and the risk of dementia is still unclear. However, alpha1-adrenoreceptors are also present in the brain, so there is potential for adverse effects on cognitive function. Therefore, we investigated possible associations between the use of alpha-blockers and aggravation of cognitive decline in dementia patients using a clinical data analytic solution called the Smart Clinical Data Warehouse (CDW).We retrospectively investigated clinical data using the Smart CDW of Hallym University Medical Center from 2009 to 2019. We enrolled patients with probable Alzheimer disease (AD) who had completed the Mini-Mental State Examination (MMSE) at least twice during follow-up, and who had BPH. We compared the difference in MMSE scores between patients who took tamsulosin for >1000 days and those who did not take any alpha-blocker. We tested the effect of tamsulosin on cognitive decline in patients with AD, using propensity score-matched logistic regression analysis.Eligible cases were included in the tamsulosin (n = 68) or no-medication (n = 153) groups. After propensity score matching, clinical characteristics such as educational attainment and vascular risk factors were similar in the tamsulosin and no-medication groups. The MMSE scores did not differ significantly between the tamsulosin and no-medication groups (P = .470).The results suggest that tamsulosin for BPH is not associated with worsening of the cognitive decline in patients with AD.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/efeitos adversos , Doença de Alzheimer/psicologia , Cognição/efeitos dos fármacos , Hiperplasia Prostática/tratamento farmacológico , Tansulosina/efeitos adversos , Agentes Urológicos/efeitos adversos , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Idoso , Doença de Alzheimer/complicações , Data Warehousing , Humanos , Masculino , Pontuação de Propensão , Hiperplasia Prostática/complicações , Análise de Regressão , Estudos Retrospectivos , Tansulosina/uso terapêutico , Agentes Urológicos/uso terapêutico
14.
J Alzheimers Dis ; 76(1): 41-47, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32568211

RESUMO

BACKGROUND: Neuropsychiatric symptoms, such as depression, anxiety, apathy, agitation, and hallucinations, are frequent in Alzheimer's disease (AD) and their prevalence tends to increase with external stressors. OBJECTIVE: We offer the first investigation of the effects of confinement during the COVID-19 crisis on neuropsychiatric symptoms in patients with AD. METHODS: We contacted caregivers of 38 patients with AD who were confined to their homes for nearly two months and asked them to report whether patients experienced any change in neuropsychiatric symptoms during, compared to before, the confinement and rate its severity and impact on themselves using the Neuropsychiatric Inventory-Questionnaire. RESULTS: Among the 38 patients, only 10 demonstrated neuropsychiatric changes during the confinement. Cognitive function of these 10 patients, assessed with the Mini-Mental State Examination, was worse than that of patients who did not demonstrate neuropsychiatric changes. Interestingly, among the 10 patients with neuropsychiatric changes, the duration of confinement significantly correlated with the severity of symptoms as well as with their caregivers' distress. DISCUSSION: The confinement seems to impact neuropsychiatric symptomatology in AD patients with low baseline cognitive function.


Assuntos
Doença de Alzheimer/psicologia , Betacoronavirus , Infecções por Coronavirus/psicologia , Transtornos Mentais/psicologia , Pneumonia Viral/psicologia , Quarentena/psicologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/epidemiologia , Estudos de Coortes , Infecções por Coronavirus/epidemiologia , Feminino , Humanos , Masculino , Transtornos Mentais/epidemiologia , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Quarentena/tendências
15.
Neurobiol Aging ; 92: 98-113, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32417750

RESUMO

During aging, lifestyle-related factors shape the brain's response to insults and modulate the progression of neurodegenerative pathologies such as Alzheimer's disease (AD). This is the case for chronic hyperglycemia associated with type 2 diabetes, which reduces the brain's ability to handle the neurodegenerative burden associated with AD. However, the mechanisms behind the effects of chronic hyperglycemia in the context of AD are not fully understood. Here, we show that newly generated neurons in the hippocampal dentate gyrus of triple transgenic AD (3xTg-AD) mice present increased dendritic arborization and a number of synaptic puncta, which may constitute a compensatory mechanism allowing the animals to cope with a lower neurogenesis rate. Contrariwise, chronic hyperglycemia decreases the complexity and differentiation of 3xTg-AD newborn neurons and reduces the levels of ß-catenin, a key intrinsic modulator of neuronal maturation. Moreover, synaptic facilitation is depressed in hyperglycemic 3xTg-AD mice, accompanying the defective hippocampal-dependent memory. Our data suggest that hyperglycemia evokes cellular and functional alterations that accelerate the onset of AD-related symptoms, namely memory impairment.


Assuntos
Doença de Alzheimer/patologia , Doença de Alzheimer/psicologia , Hipocampo/patologia , Hiperglicemia/patologia , Memória , Neurogênese , Doença de Alzheimer/complicações , Animais , Doença Crônica , Modelos Animais de Doenças , Hiperglicemia/complicações , Masculino , Camundongos Transgênicos
16.
PLoS One ; 15(5): e0233468, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32469975

RESUMO

Transcription disequilibria are characteristic of many neurodegenerative diseases. The activity-evoked transcription of immediate early genes (IEGs), important for neuronal plasticity, memory and behavior, is altered in CNS diseases and governed by epigenetic modulation. KDM1A, a histone 3 lysine 4 demethylase that forms part of transcription regulation complexes, has been implicated in the control of IEG transcription. Here we report the development of vafidemstat (ORY-2001), a brain penetrant inhibitor of KDM1A and MAOB. ORY-2001 efficiently inhibits brain KDM1A at doses suitable for long term treatment, and corrects memory deficit as assessed in the novel object recognition testing in the Senescence Accelerated Mouse Prone 8 (SAMP8) model for accelerated aging and Alzheimer's disease. Comparison with a selective KDM1A or MAOB inhibitor reveals that KDM1A inhibition is key for efficacy. ORY-2001 further corrects behavior alterations including aggression and social interaction deficits in SAMP8 mice and social avoidance in the rat rearing isolation model. ORY-2001 increases the responsiveness of IEGs, induces genes required for cognitive function and reduces a neuroinflammatory signature in SAMP8 mice. Multiple genes modulated by ORY-2001 are differentially expressed in Late Onset Alzheimer's Disease. Most strikingly, the amplifier of inflammation S100A9 is highly expressed in LOAD and in the hippocampus of SAMP8 mice, and down-regulated by ORY-2001. ORY-2001 is currently in multiple Phase IIa studies.


Assuntos
Inibidores Enzimáticos/farmacologia , Histona Desmetilases/antagonistas & inibidores , Transtornos da Memória/tratamento farmacológico , Inibidores da Monoaminoxidase/farmacologia , Oxidiazóis/farmacologia , Envelhecimento/efeitos dos fármacos , Envelhecimento/psicologia , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/psicologia , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Modelos Animais de Doenças , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacocinética , Epigênese Genética/efeitos dos fármacos , Feminino , Expressão Gênica/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Inibidores da Monoaminoxidase/química , Inibidores da Monoaminoxidase/farmacocinética , Oxidiazóis/química , Oxidiazóis/farmacocinética , Ratos , Ratos Sprague-Dawley
17.
J Clin Neurosci ; 78: 291-295, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32402618

RESUMO

BACKGROUND: Theory of Mind (ToM) is defined as the ability to understand mental and emotional state. This ability is assessed also in neurodegenerative disease. Few studies have investigated the impact that social cognition of patients could have on caregiver burden. The aim of this study was to investigate a possible correlation in level of social cognition impairment between patients with different neurodegenerative disorders and their caregivers with possible impact on caregivers burden. METHODS: we enrolled 48 patients with dementia divided in different groups: Fronto-Temporal Dementia (FTD), Alzheimer Disease (AD), and Mild Cognitive Impairment (MCI) and also the three groups of their respective caregivers. All subjects were submitted to ToM tests, and the caregiver groups also to Caregiver Burden Inventory (CBI) to evaluate level of burden. RESULTS: Our results showed that ToM was more impaired in FTD patients and in their caregivers In addition, FTD group showed more impaired performances in tasks related to emotional skills. CONCLUSIONS: We suggested that ToM impairment of patients are related to ToM impairment of caregivers with differences of scores in caregiver groups. The caregiver difficulties to understand, attribute and describe emotional and mental states of their relatives develop distress and inability in burden management and disorders relative to neurodegenerative disease.


Assuntos
Atividades Cotidianas/psicologia , Doença de Alzheimer/psicologia , Cuidadores/psicologia , Disfunção Cognitiva/psicologia , Demência Frontotemporal/psicologia , Teoria da Mente , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Disfunção Cognitiva/diagnóstico , Emoções/fisiologia , Feminino , Demência Frontotemporal/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Neurodegenerativas/diagnóstico , Doenças Neurodegenerativas/psicologia , Doenças Neurodegenerativas/terapia , Teoria da Mente/fisiologia
18.
JAMA Netw Open ; 3(5): e206027, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32463470

RESUMO

Importance: Apathy is a frequent neuropsychiatric symptom in dementia of Alzheimer type and negatively affects the disease course and patients' and caregivers' quality of life. Effective treatment options are needed. Objective: To examine the efficacy and safety of the dopamine and noradrenaline reuptake inhibitor bupropion in the treatment of apathy in patients with dementia of Alzheimer type. Design, Setting, and Participants: This 12-week, multicenter, double-blind, placebo-controlled, randomized clinical trial was conducted in a psychiatric and neurological outpatient setting between July 2010 and July 2014 in Germany. Patients with mild-to-moderate dementia of Alzheimer type and clinically relevant apathy were included. Patients with additional clinically relevant depressed mood were excluded. Data analyses were performed between August 2018 and August 2019. Interventions: Patients received either bupropion or placebo (150 mg for 4 weeks plus 300 mg for 8 weeks). In case of intolerability of 300 mg, patients continued to receive 150 mg throughout the study. Main Outcomes and Measures: Change on the Apathy Evaluation Scale-Clinician Version (AES-C) (score range, 18-72 points) between baseline and week 12 was the primary outcome parameter. Secondary outcome parameters included measures of neuropsychiatric symptoms, cognition, activities of daily living, and quality of life. Outcome measures were assessed at baseline and at 4, 8, and 12 weeks. Results: A total of 108 patients (mean [SD] age, 74.8 [5.9] years; 67 men [62%]) were included in the intention-to-treat analysis, with 54 randomized to receive bupropion and 54 randomized to receive placebo. The baseline AES-C score was comparable between the bupropion group and the placebo group (mean [SD], 52.2 [8.7] vs 50.4 [8.2]). After controlling for the baseline AES-C score, site, and comedication with donepezil or galantamine, the mean change in the AES-C score between the bupropion and placebo groups was not statistically significant (mean change, 2.22; 95% CI, -0.47 to 4.91; P = .11). Results on secondary outcomes showed statistically significant differences between bupropion and placebo in terms of total neuropsychiatric symptoms (mean change, 5.52; 95% CI, 2.00 to 9.04; P = .003) and health-related quality of life (uncorrected for multiple comparisons; mean change, -1.66; 95% CI, -3.01 to -0.31; P = .02) with greater improvement in the placebo group. No statistically significant changes between groups were found for activities of daily living (mean change, -2.92; 95% CI, -5.89 to 0.06; P = .05) and cognition (mean change, -0.27; 95% CI, -3.26 to 2.73; P = .86). The numbers of adverse events (bupropion group, 39 patients [72.2%]; placebo group, 33 patients [61.1%]) and serious adverse events (bupropion group, 5 patients [9.3%]; placebo group, 2 patients [3.7%]) were comparable between groups. Conclusions and Relevance: Although it is safe, bupropion was not superior to placebo for the treatment of apathy in patients with dementia of Alzheimer type in the absence of clinically relevant depressed mood. Trial Registration: EU Clinical Trials Register Identifier: 2007-005352-17.


Assuntos
Doença de Alzheimer/psicologia , Antidepressivos de Segunda Geração/uso terapêutico , Apatia/efeitos dos fármacos , Bupropiona/uso terapêutico , Idoso , Doença de Alzheimer/tratamento farmacológico , Antidepressivos de Segunda Geração/efeitos adversos , Bupropiona/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Masculino , Testes de Estado Mental e Demência
19.
Neurobiol Aging ; 92: 92-97, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32408057

RESUMO

Association between the transactive response DNA-binding protein of 43 kDa (TDP-43), its newly described types (type α/type ß), and resilience to Alzheimer's disease neuropathological change (ADNC) defined as preservation of normal cognitive functioning despite advanced ADNC has been evaluated in this case-control study of 63 older adults. Twenty-one resilient to ADNC individuals were matched 1:2 to nonresilient (Alzheimer's dementia) using propensity scores, accounting for age at death, neuritic plaque density, and neurofibrillary tangle stage. Resilient and matched nonresilient participants were similar in terms of gender, apolipoprotein E ε4 carriership, education, occupation, AD, and other pathologies. Resilient participants had lower frequency of TDP-43 co-pathology compared to nonresilient (19% vs. 62%, p = 0.002). Among TDP-43-positive cases, TDP-43 type α inclusions were absent in resilient to ADNC participants and were dominant in matched nonresilient cases (65%, p = 0.03). TDP-43 and TDP-43 types appear to be one of the key pathological determinants of loss of cognitive resilience to ADNC and hence are important in the understanding of the clinical expression of ADNC.


Assuntos
Doença de Alzheimer/genética , Doença de Alzheimer/psicologia , Cognição , Proteínas de Ligação a DNA , Estudos de Associação Genética , Idoso de 80 Anos ou mais , Doença de Alzheimer/patologia , Apolipoproteína E4 , Encéfalo/metabolismo , Estudos de Casos e Controles , Proteínas de Ligação a DNA/metabolismo , Feminino , Humanos , Masculino
20.
Clin Interv Aging ; 15: 519-536, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32368019

RESUMO

Introduction: This study replicated and extended the findings from the author's previous pilot study to further explore how a spaced retrieval (SR) memory training program might be effectively applied to help persons with Alzheimer's disease (AD)  improve both short- and long-term recall of recent episodic events. Methods: A quasi-experimental within-subject group study was conducted with 15 participants with a diagnosis of AD. Results: Compared to a control condition, all participants were able to spontaneously recall significantly more specific details about trained events, and their recall was significantly enhanced when they were provided with cues. Although the findings indicated that people with AD were able to encode information during training, recall gains diminished by the end of the maintenance period. Discussion: This study provides evidence that individuals with mild to moderate AD can learn and recall new episodic information through SR training. These findings support the use of SR as an intervention tool to help individuals maintain their functioning in episodic recent memory. However, more research into maintaining the long-term recall of recent episodic events is warranted.


Assuntos
Doença de Alzheimer/reabilitação , Transtornos da Memória/reabilitação , Memória Episódica , Rememoração Mental , Idoso , Doença de Alzheimer/psicologia , Feminino , Humanos , Masculino , Transtornos da Memória/etiologia , Testes Neuropsicológicos , Projetos Piloto
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