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1.
BMJ ; 367: l6217, 2019 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-31810978

RESUMO

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the accumulation of amyloid ß in the form of extracellular plaques and by intracellular neurofibrillary tangles, with eventual neurodegeneration and dementia. There is currently no disease-modifying treatment though several symptomatic medications exist with modest benefit on cognition. Acetylcholinesterase inhibitors have a consistent benefit across all stages of dementia; their benefit in mild cognitive impairment and prodromal AD is unproven. Memantine has a smaller benefit on cognition overall which is limited to the moderate to severe stages, and the combination of a cholinesterase inhibitor and memantine may have additional efficacy. Evidence for the efficacy of vitamin E supplementation and medical foods is weak but might be considered in the context of cost, availability, and safety in individual patients. Apparently promising disease-modifying interventions, mostly addressing the amyloid cascade hypothesis of AD, have recently failed to demonstrate efficacy so novel approaches must be considered.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/psicologia , Peptídeos beta-Amiloides/farmacologia , Peptídeos beta-Amiloides/uso terapêutico , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/uso terapêutico , Doença de Alzheimer/fisiopatologia , Doença de Alzheimer/prevenção & controle , Preparações de Ação Retardada , Quimioterapia Combinada , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
2.
Psychol Aging ; 34(7): 954-977, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31682146

RESUMO

This meta-analysis examined how performance on various cognitive domains of neuropsychological functioning can contribute to predicting progression to dementia from mild cognitive impairment (MCI) or subjective memory complaints. Studies performed between the years of 1997 and 2018 were identified through a search of the electronic databases Medline and PsycINFO. Data from the articles identified were pooled to determine standardized mean differences, calculated as Hedges g, using a random-effects model. Twenty-four studies were included in the analysis. The majority of studies examined the progression of amnestic mild cognitive impairment (aMCI) to Alzheimer's disease (AD). Nonprogressors performed significantly better than did progressors in the domains of divided attention, executive function, expressive language, immediate recall, processing speed, delayed recall, visuospatial/constructional ability, working memory, and sustained attention. These findings indicate that individuals with MCI or subjective memory complaints who do not progress to dementia, perform better at baseline as compared with individuals that progress to dementia on a range of neuropsychological measures, and lends further support to the contention that neuropsychological assessment can make important contributions to predicting progression to dementia while individuals are still in the MCI or subjective memory complaint stage. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Doença de Alzheimer/psicologia , Disfunção Cognitiva/psicologia , Demência/etiologia , Testes Neuropsicológicos/normas , Idoso , Demência/patologia , Progressão da Doença , Feminino , Humanos , Masculino
3.
Clin Interv Aging ; 14: 1797-1815, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695349

RESUMO

Purpose: The main objective of this study was to investigate abuse of residents with either dementia or Alzheimer's disease in long-term care settings, to identify facilitators and barriers surrounding implementation of systems to prevent such occurrences, and to draw conclusions on combating the issue of abuse. Patients and methods: A systematic review was conducted using the Medline, CINAHL, and Academic Search Ultimate databases. With the use of key terms via Boolean search, 30 articles were obtained which were determined to be germane to research objectives. The review was conducted and structured based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: Residents with dementia or Alzheimer's disease are at greater risk of abuse. The growing population could increase this problem exponentially. The most common facilitators were the introduction of policies/programs in the facility, education, and working conditions. The most cited barriers were poor training, lack of research, and working conditions in the long-term care setting. Conclusion: The examples given would be useful in minimizing the potential for abuse in the long-term care setting. Leadership can take an active role in the prevention of abuse of the elderly through their actions, education of employees, and changes in the work environment.


Assuntos
Doença de Alzheimer , Maus-Tratos ao Idoso/prevenção & controle , Pessoal de Saúde/educação , Política Organizacional , Local de Trabalho/organização & administração , Idoso , Doença de Alzheimer/psicologia , Demência/psicologia , Instituição de Longa Permanência para Idosos/organização & administração , Humanos , Assistência de Longa Duração , Casas de Saúde/organização & administração , Fatores de Proteção , Fatores de Risco
4.
J Agric Food Chem ; 67(49): 13767-13774, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31722531

RESUMO

Recent studies indicated that neuroinflammation contributes to the exacerbation of Alzheimer's disease (AD) and plays an important role in AD. The NOD-like receptor protein 3 (NLRP3) inflammasome, which is an important component of innate immune system, is associated with a wide range of human central nervous system disorders, including AD. Most of the studies focus on the protective effects of docosahexaenoic acid (DHA) in AD, but eicosapentaenoic acid (EPA) has rarely been involved. Here, we investigate the effects of EPA in the forms of phosphatidylcholine (EPA-PC) and ethyl esters (EPA-EE) in improving Aß1-42-induced neurotoxicity. The spatial memory ability and the biochemical changes in the hippocampus were measured, including glial cell activation, tumor necrosis factor α production, NLRP3 inflammasome activation, and autophagic flux. The present results showed that the AD rats were significantly protected from spatial memory loss by the supplementation (EPA + DHA = 60 mg/kg, i.g., 20 days) of EPA-PC, while EPA-EE showed no significant benefit. Further mechanism studies suggested that EPA-PC could inhibit Aß-induced neurotoxicity by alleviating NLRP3 inflammasome activation and enhancing autophagy. These findings indicate that EPA could improve cognitive deficiency in Aß1-42-induced AD rats via autophagic inflammasomal pathway and the bioactivity differs in its molecular form.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/toxicidade , Autofagia/efeitos dos fármacos , Ácido Eicosapentaenoico/administração & dosagem , Inflamassomos/efeitos dos fármacos , Fosfatidilcolinas/administração & dosagem , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Doença de Alzheimer/psicologia , Peptídeos beta-Amiloides/metabolismo , Animais , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Humanos , Inflamassomos/genética , Inflamassomos/metabolismo , Masculino , Memória/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
5.
Clin Interv Aging ; 14: 1527-1553, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31692559

RESUMO

Purpose: There are few interventions on an individual basis to support community-dwelling people with dementia to continue to fulfill their potential in society and to support their informal caregivers via e-Health. This study explored the effectiveness of the individualized Meeting Centers Support Program (iMCSP) consisting of DemenTalent (people with dementia work as volunteers in a society based on their talents), Dementelcoach (telephone coaching), and STAR e-Learning for caregivers, compared to regular MCSP and No day care support. Method: An explorative randomized controlled trial with pre/post measurements (M0-M6) and two groups (iMCSP and regular MCSP). In addition, a comparison was made between iMCSP and a reference No day care control group. Standardized questionnaires were administered on self-esteem, neuropsychiatric symptoms, experienced autonomy and quality of life of the person with dementia, and on caregiver's sense of competence, quality of life, and happiness. Results: The iMCSP interventions resulted in a broader group of participants utilizing the Meeting Centers. Compared to regular MCSP, DemenTalent had a moderate positive effect on neuropsychiatric symptoms, which also proved less severe. Positive affect of participants improved within the DemenTalent and regular MCSP group after six months. Caregivers of DemenTalent participants experienced less emotional impact of neuropsychiatric symptoms. No differences were found in experienced burden, sense of competence, or quality of life in caregivers using iMCSP or regular MCSP. Compared to those receiving No day care support, caregivers of DemenTalent participants and caregivers using Dementelcoach or STAR e-Learning proved happier. Post-hoc analyses, accounting for potential between-group differences in outcome measures at baseline, generally showed results in the same direction. People with dementia and caregivers highly appreciated iMCSP and regular MCSP. Conclusion: iMCSP can be effectively applied as alternative or additional support via regular Meeting Centers for people with dementia and caregivers who prefer individualized activities/support. DemenTalent decreased the severity of neuropsychiatric symptoms of people with dementia and emotional burden of caregivers. All iMCSP interventions tended to result in caregivers being happier compared to those receiving no support. Larger-scale studies are needed to investigate the effect of iMCSP on other domains of quality of life of participants.


Assuntos
Doença de Alzheimer/reabilitação , Cuidadores/psicologia , Hospital Dia/organização & administração , Processos Grupais , Apoio Social , Idoso , Doença de Alzheimer/psicologia , Cuidadores/educação , Instrução por Computador , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Autonomia Pessoal , Qualidade de Vida/psicologia , Inquéritos e Questionários , Revisão da Utilização de Recursos de Saúde
6.
Nat Commun ; 10(1): 4900, 2019 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-31653847

RESUMO

The tau protein aggregates in aging and Alzheimer disease and may lead to memory loss through disruption of medial temporal lobe (MTL)-dependent memory systems. Here, we investigated tau-mediated mechanisms of hippocampal dysfunction that underlie the expression of episodic memory decline using fMRI measures of hippocampal local coherence (regional homogeneity; ReHo), distant functional connectivity and tau-PET. We show that age and tau pathology are related to higher hippocampal ReHo. Functional disconnection between the hippocampus and other components of the MTL memory system, particularly an anterior-temporal network specialized for object memory, is also associated with higher hippocampal ReHo and greater tau burden in anterior-temporal regions. These associations are not observed in the posteromedial network, specialized for context/spatial information. Higher hippocampal ReHo predicts worse memory performance. These findings suggest that tau pathology plays a role in disconnecting the hippocampus from specific MTL memory systems leading to increased local coherence and memory decline.


Assuntos
Envelhecimento/metabolismo , Córtex Entorrinal/diagnóstico por imagem , Hipocampo/diagnóstico por imagem , Emaranhados Neurofibrilares/metabolismo , Lobo Temporal/diagnóstico por imagem , Proteínas tau/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Envelhecimento/psicologia , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Doença de Alzheimer/psicologia , Peptídeos beta-Amiloides/metabolismo , Compostos de Anilina , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Carbolinas , Envelhecimento Cognitivo/fisiologia , Envelhecimento Cognitivo/psicologia , Meios de Contraste , Córtex Entorrinal/metabolismo , Córtex Entorrinal/fisiopatologia , Função Executiva , Feminino , Neuroimagem Funcional , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Humanos , Masculino , Memória Episódica , Memória de Curto Prazo , Pessoa de Meia-Idade , Vias Neurais/diagnóstico por imagem , Vias Neurais/metabolismo , Vias Neurais/fisiopatologia , Tomografia por Emissão de Pósitrons , Lobo Temporal/metabolismo , Lobo Temporal/fisiologia , Tiazóis , Adulto Jovem
7.
Artigo em Inglês | MEDLINE | ID: mdl-31591314

RESUMO

Caring for a person diagnosed with Alzheimer's disease has a negative impact on family caregivers' psychological health. This study examined the factors related to 'perceived health' and 'presence of new-onset mental health problems' in family caregivers of people diagnosed with mild and moderate Alzheimer's disease. A cross-sectional observational study carried out in Almeria's Healthcare District (Spain). A total of 255 family caregivers (42.4% cared for people with mild Alzheimer's disease and 57.6% cared for people with moderate Alzheimer's disease) participated in the study from January to December 2015. Mainly, caregivers were women (81.5% in the mild Alzheimer's disease group and 88.4% in the moderate Alzheimer's disease group), and their average age was 56.54 years (standard deviation (SD) = 13.13) and 54.47 years (SD = 11.71), respectively. Around 47% of the caregivers had been caring for the person with Alzheimer's between two and five years. The Goldberg General Health Questionnaire was used to measure perceived health and the presence of new-onset mental health problems. An exploratory descriptive analysis and a multivariate logistic regression analysis were conducted. For caregivers of people with mild Alzheimer's disease, 'perceived health' was related to 'perceived social support' (r = -0.21; p = 0.028), 'person's level of dependency' (r = -0.24, p = 0.05), 'severity of the person's neuropsychiatric symptoms' (r = 0.22; p = 0.05), and 'caregiver's emotional distress in response to the person's neuropsychiatric symptoms' (r = 0.22; p = 0.05). For caregivers of people with moderate Alzheimer's disease, 'perceived health' was related to 'perceived social support' (r = -0.31; p ˂ 0.01), 'presence of neuropsychiatric symptoms' (r = 0.27, p = 0.01), 'severity of the person's neuropsychiatric symptoms' (r = 0.32, p = 0.01) and 'caregiver's emotional distress in response to the person's neuropsychiatric symptoms' (r = 0.029; p = 0.01). The presence of new-onset mental health problems was detected in 46.3% (n = 50) of caregivers of people with mild Alzheimer's and 61.9% (n = 91) of caregivers of people with moderate Alzheimer's. When people are diagnosed with mild Alzheimer's disease, intervention programs for caregivers should aim to regulate emotions and promote positive coping strategies. When people are diagnosed with moderate Alzheimer's disease, intervention programs for caregivers must allow them to adapt to caregiving demands that arise with the progression of Alzheimer's disease.


Assuntos
Adaptação Psicológica , Doença de Alzheimer/terapia , Cuidadores/psicologia , Estresse Psicológico , Idoso , Doença de Alzheimer/psicologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida
8.
Neurology ; 93(19): e1807-e1819, 2019 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-31575706

RESUMO

OBJECTIVE: To determine if APOE ε4 influences the association between white matter hyperintensities (WMH) and cognitive impairment in Alzheimer disease (AD) and dementia with Lewy bodies (DLB). METHODS: A total of 289 patients (AD = 239; DLB = 50) underwent volumetric MRI, neuropsychological testing, and APOE ε4 genotyping. Total WMH volumes were quantified. Neuropsychological test scores were included in a confirmatory factor analysis to identify cognitive domains encompassing attention/executive functions, learning/memory, and language, and factor scores for each domain were calculated per participant. After testing interactions between WMH and APOE ε4 in the full sample, we tested associations of WMH with factor scores using linear regression models in APOE ε4 carriers (n = 167) and noncarriers (n = 122). We hypothesized that greater WMH volume would relate to worse cognition more strongly in APOE ε4 carriers. Findings were replicated in 198 patients with AD from the Alzheimer's Disease Neuroimaging Initiative (ADNI-I), and estimates from both samples were meta-analyzed. RESULTS: A significant interaction was observed between WMH and APOE ε4 for language, but not for memory or executive functions. Separate analyses in APOE ε4 carriers and noncarriers showed that greater WMH volume was associated with worse attention/executive functions, learning/memory, and language in APOE ε4 carriers only. In ADNI-I, greater WMH burden was associated with worse attention/executive functions and language in APOE ε4 carriers only. No significant associations were observed in noncarriers. Meta-analyses showed that greater WMH volume was associated with worse performance on all cognitive domains in APOE ε4 carriers only. CONCLUSION: APOE ε4 may influence the association between WMH and cognitive performance in AD and DLB.


Assuntos
Doença de Alzheimer/psicologia , Apolipoproteína E4/genética , Disfunção Cognitiva/psicologia , Doença por Corpos de Lewy/psicologia , Substância Branca/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Atenção , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/genética , Função Executiva , Análise Fatorial , Feminino , Humanos , Linguagem , Aprendizagem , Doença por Corpos de Lewy/diagnóstico por imagem , Doença por Corpos de Lewy/genética , Modelos Lineares , Imagem por Ressonância Magnética , Masculino , Memória , Pessoa de Meia-Idade , Testes Neuropsicológicos
9.
Eur J Med Chem ; 183: 111707, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31561043

RESUMO

The diverse nature of Alzheimer's disease (AD) has prompted researchers to develop multi-functional agents. Herein, we have designed and synthesized molecular hybrids of 2-pyridylpiperazine and 5-phenyl-1,3,4-oxadiazoles. Biological activities of synthesized compounds suggested significant and balanced inhibitory potential against target enzymes. In particular, compound 49 containing 2,4-difluoro substitution at terminal phenyl ring considered as most potential lead with inhibition of acetylcholinesterase (hAChE, IC50 = 0.054 µM), butyrylcholinesterase (hBChE, IC50 = 0.787 µM) and beta-secretase-1 (hBACE-1, IC50 = 0.098 µM). The enzyme kinetics study of 49 against hAChE suggested a mixed type of inhibition (Ki = 0.030 µM). Also, 48 and 49 showed significant displacement of propidium iodide from the peripheral anionic site (PAS) of hAChE, excellent blood-brain barrier (BBB) permeability in parallel artificial membrane permeation assay (PAMPA), and neuroprotective ability against SH-SY5Y neuroblastoma cell lines. Further, 49 also exhibited anti-Aß aggregation activity in self- and AChE-induced thioflavin T assay, which was ascertained by morphological characterization by atomic force microscopy (AFM). Moreover, in vivo behavioral studies signified learning and memory improvement by compound 49 in scopolamine- and Aß-induced cognitive dysfunctions performed on Y-maze and Morris water maze. The ex vivo studies suggested decreased AChE activity and antioxidant potential of compound 49, with good oral absorption characteristics ascertained by pharmacokinetic studies.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Fármacos Neuroprotetores/química , Oxidiazóis/química , Piperazinas/química , Piridinas/química , Acetilcolinesterase/metabolismo , Doença de Alzheimer/psicologia , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Secretases da Proteína Precursora do Amiloide/metabolismo , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Barreira Hematoencefálica/metabolismo , Butirilcolinesterase/metabolismo , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacocinética , Disfunção Cognitiva/tratamento farmacológico , Feminino , Humanos , Cinética , Simulação de Acoplamento Molecular , Fármacos Neuroprotetores/farmacocinética , Oxidiazóis/farmacocinética , Piperazinas/farmacocinética , Agregados Proteicos , Piridinas/farmacocinética , Ratos Wistar , Relação Estrutura-Atividade
10.
Arch Gerontol Geriatr ; 85: 103941, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31476630

RESUMO

Motor dysfunction increases in the moderate and severe stages of dementia. However, there is still no consensus on changes in mobility during its early stages. This meta-analysis aimed to measure the level of single-task functional mobility in older subjects with mild cognitive impairment (MCI) and/or Alzheimer's disease (AD). In a search of the PubMed, ISI Web of Knowledge, and Scopus databases, 2728 articles were identified. At the end of the selection, a total of 18 studies were included in the meta-analysis. Functional mobility was investigated using the timed up and go (TUG) test in all studies. When compared to healthy elderly (HE) adults, the following mean differences (MD) in seconds were found for the investigated subgroups: no amnestic MCI (MD = 0.26; CI95% = -0.77, 1.29), amnestic MCI (MD = 0.86; CI95% = -0.02, 1.73), very mild AD (MD = 1.32; CI95% = 0.63, 2.02), mild AD (MD = 2.43; CI95% = 1.84, 3.01), mild-moderate AD (MD = 3.01; CI95% = 2.47, 3.55), and mild-severe AD (MD = 4.51; CI95% = 1.14, 7.88); for the groups, the following MD were found: MCI (MD = 0.97; CI95% = 0.51, 1.44) and AD (MD = 2.66; CI95% = 2.16, 3.15). These results suggest a transition period in motor capacity between healthy aging and dementia, wherein functional mobility analysis in a single-task (TUG) can contribute to the diagnosis and staging of predementia states and AD.


Assuntos
Doença de Alzheimer/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Idoso , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/psicologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Feminino , Humanos , Masculino , Programas de Rastreamento , Equilíbrio Postural , Estudos de Tempo e Movimento
11.
EBioMedicine ; 47: 529-542, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31477562

RESUMO

BACKGROUND: Alzheimer's disease (AD) prevalence is increasing, but its etiology remains elusive. Gut microbes can contribute to AD pathology and may help identifying novel markers and therapies against AD. Herein, we examine how the gut microbiome differs in older adults with mild cognitive impairment compared to cognitively normal counterparts, and whether and how a modified Mediterranean-ketogenic diet (MMKD) alters the gut microbiome signature in association with cerebrospinal fluid (CSF) AD biomarkers. METHODS: A randomized, double-blind, cross-over, single-center pilot study of MMKD versus American Heart Association Diet (AHAD) intervention is performed on 17 subjects (age: 64.6 ±â€¯6.4 yr), of which 11 have mild cognitive impairment, while 6 are cognitively normal. Subjects undergo MMKD and AHAD intervention for 6-weeks separated by 6-weeks washout periods. Gut microbiome, fecal short-chain fatty acids (SCFAs), and markers of AD in CSF including amyloid ß (Aß)-40 and Aß-42, total tau, and phosphorylated tau-181 (tau-p181) are measured at before and after diet interventions. FINDINGS: At baseline, subjects with normal vs. impaired cognition show no notable difference in microbiome diversity but several unique microbial signatures are detected in subjects with mild cognitive impairment. Proteobacteria correlate positively with Aß-42: Aß-40 while fecal propionate and butyrate correlates negatively with Aß-42 in subjects with mild cognitive impairment. Several bacteria are differently affected by the two diets with distinct patterns between cognitively normal and impaired subjects. Notably, the abundance of Enterobacteriaceae, Akkermansia, Slackia, Christensenellaceae and Erysipelotriaceae increases while that of Bifidobacterium and Lachnobacterium reduces on MMKD, while AHAD increases Mollicutes. MMKD slightly reduces fecal lactate and acetate while increasing propionate and butyrate. Conversely, AHAD increases acetate and propionate while reducing butyrate. INTERPRETATION: The data suggest that specific gut microbial signatures may depict the mild cognitive impairment and that the MMKD can modulate the gut microbiome and metabolites in association with improved AD biomarkers in CSF.


Assuntos
Doença de Alzheimer/etiologia , Doença de Alzheimer/psicologia , Disfunção Cognitiva , Dieta Cetogênica , Dieta Mediterrânea , Ácidos Graxos Voláteis/metabolismo , Microbioma Gastrointestinal , Idoso , Doença de Alzheimer/metabolismo , Apolipoproteína E4/genética , Apolipoproteína E4/metabolismo , Biomarcadores , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
12.
Postgrad Med ; 131(7): 533-538, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31478419

RESUMO

Introduction: Depression in patients with mild cognitive impairment (MCI) and dementia of the Alzheimer's type (AD) is associated with worse prognosis. Indeed, depressed MCI patients have worse cognitive performance and greater loss of gray-matter volume in several brain areas. To date, knowledge of the factors that can mitigate this detrimental effect is still limited. The aim of the present study was to understand in what way cognitive reserve/brain reserve and depression interact and are linked to regional atrophy in early stage AD. Methods: Depression was evaluated with the Patient Health Questionnaire-9 in 90 patients with early AD, and a cutoff of ≥ 5 was used to separate depressed (n = 44) from non-depressed (n = 46) patients. Each group was further stratified into high/low cognitive reserve/brain reserve. Cognitive reserve was calculated using years of education as proxy, while normalized parenchymal volumes were used to estimate brain reserve. Voxel-based morphometry was carried out to extract and analyze gray-matter maps. 2 × 2 ANCOVAs were run to test the effect of the reserve-by-depression interaction on gray matter. Age and hippocampal ratio were used as covariates. Composite indices of major cognitive domains were also analyzed with comparable models. Results: No reserve-by-depression interaction was found in the analytical models of gray matter. Depression was associated with less gray matter volume in the cerebellum and parahippocampal gyrus. The brain reserve-by-depression interaction was a significant predictor of executive functioning. Among those with high brain reserve, depressed patients had poorer executive skills. No significant results were found in association with cognitive reserve. Conclusion: These findings suggest that brain reserve may modulate the association between neurodegeneration and depression in patients with MCI and dementia of the AD type, influencing in particular executive functioning.


Assuntos
Doença de Alzheimer/psicologia , Disfunção Cognitiva/psicologia , Reserva Cognitiva , Depressão/psicologia , Substância Cinzenta/diagnóstico por imagem , Idoso , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/fisiopatologia , Atrofia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Cerebelo/diagnóstico por imagem , Cerebelo/patologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/fisiopatologia , Depressão/diagnóstico por imagem , Depressão/fisiopatologia , Feminino , Substância Cinzenta/patologia , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Giro Para-Hipocampal/diagnóstico por imagem , Giro Para-Hipocampal/patologia , Questionário de Saúde do Paciente
13.
Nutrients ; 11(9)2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31514322

RESUMO

We examined the interactive associations of poor diet quality and Alzheimer's Disease (AD) genetic risk with cognitive performance among 304 African American adults (mean age~57 years) from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study. In this cross-sectional study, selected participants had complete predictors and covariate data with 13 cognitive test scores as outcomes. Healthy Eating Index-2010 (HEI-2010), Dietary Approaches to Stop Hypertension (DASH), and mean adequacy ratio (MAR) were measured. A genetic risk score for AD in HANDLS (hAlzScore) was computed from 12 selected single nucleotide polymorphisms (SNPs). Our key hypotheses were tested using linear regression models. The hAlzScore was directly associated with poor performance in verbal memory (-0.4 ± 0.2, 0.01) and immediate visual memory (0.4 ± 0.2, 0.03) measured in seconds, in women only. The hAlzScore interacted synergistically with poorer diet quality to determine lower cognitive performance on a test of verbal fluency. Among numerous SNP × diet quality interactions for models of cognitive performance as outcomes, only one passed correction for multiple testing, namely verbal fluency. Our results suggest that improved diet quality can potentially modify performance on cognitive tests of verbal fluency among individuals with higher AD genetic risk.


Assuntos
Afro-Americanos , Doença de Alzheimer/etnologia , Cognição , Dieta/etnologia , Valor Nutritivo/etnologia , Polimorfismo de Nucleotídeo Único , Saúde da População Urbana/etnologia , Adulto , Afro-Americanos/genética , Afro-Americanos/psicologia , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/genética , Doença de Alzheimer/psicologia , Baltimore/epidemiologia , Estudos Transversais , Feminino , Interação Gene-Ambiente , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Fatores de Risco
14.
Fisioter. Pesqui. (Online) ; 26(3): 311-321, jul.-set. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1039895

RESUMO

ABSTRACT The objective of this study is to evaluate the effects of physical therapy on the cognitive and functional capacity of patients with Alzheimer's Disease (AD). This is a systematic review of randomized or quasi-randomized clinical trials, using the descriptors: AD, dementia and physical therapy. Two studies were included with a total of 207 participants. In study 1, no statistically significant difference was found on the mini-mental state examination (MMSE) (MD 0.0, 95%CI −5.76 to 5.76), neuropsychiatric inventory (MD −4.50, 95%CI −21.24 to 12.24) and Pfeffer instrumental activities questionnaire (MD 0.0 95%CI −6.48 to 6.48). In study 2, there was no statistically significant difference on the MMSE (MD −1.60, 95% CI −3.57 to 0.37), clock-drawing test (MD −0.20, 95%CI −0.61 to 0.21) and Alzheimer's Disease Assessment Scale - cognitive subscale (MD 1.0, 95%CI −2.21 to 4.21) after 12 months. There was no consistent evidence on the effectiveness of physiotherapeutic intervention in improving cognitive function and functional capacity of patients with AD. More studies should be conducted for better evidence.


RESUMO O objetivo do estudo é avaliar os efeitos da fisioterapia na capacidade cognitiva e funcional de pacientes com doença de Alzheimer (DA). Trata-se de revisão sistemática de ensaios clínicos randomizados ou quasi-randomizados utilizando os descritores: DA, demência e fisioterapia. Dois estudos foram incluídos, com um total de 207 participantes. No Estudo 1, não houve diferença estatisticamente significativa no miniexame do estado mental (MEEM) (MD 0,0, IC 95% 5,76−5,76), inventário neuropsiquiátrico (MD −4,50, IC 95% 12,24−21,24) e questionário de atividades instrumentais Pfeffer (MD 0,0 IC 95% −6,48 a 6,48). No Estudo 2, não houve diferença estatisticamente significativa no MEEM (MD −1,60, IC 95% −3,57 a 0,37), teste do desenho do relógio (MD −0,20, IC95% −0,61 a 0,21) e escala de avaliação da doença de Alzheimer - subitem cognição (MD 1,0, IC95% −2,21 a 4,21) após 12 meses. Não houve evidência consistente da eficácia da intervenção fisioterapêutica na melhora da função cognitiva e capacidade funcional na DA. Recomenda-se a produção de mais estudos para encontrar possíveis evidências.


RESUMEN El presente estudio tiene como objetivo evaluar los efectos de la fisioterapia en la capacidad cognitiva y funcional de pacientes con enfermedad de Alzheimer (EA). Se trata de una revisión sistemática de ensayos clínicos aleatorizados o casi-aleatorizados, en que se utilizó los descriptores: EA, demencia y fisioterapia. Se incluyeron dos estudios, con un total de 207 participantes. En el Estudio 1, no hubo diferencias estadísticamente significativas en el Miniexamen del estado mental (MEEM) (MD 0,0, IC 95%: 5,6 -5,76), en el inventario neuropsiquiátrico (MD -4,50, IC 95%: 12,24 -21,24) y en el cuestionario de actividades instrumentales de Pfeffer (MD: 0,0 IC 95% IC: -6,48 a 6,48). En el Estudio 2, no hubo diferencias estadísticamente significativas en el MEEM (MD −1,60, IC 95% −3,57 a 0,37), el test de diseño del reloj (MD −0,20, IC 95% −0,61 a 0,21) y la escala de evaluación de la enfermedad de Alzheimer: subítem de cognición (MD 1,0, IC 95% −2,21 a 4,21) tras 12 meses. No hubo evidencia consistente de la eficacia de la intervención fisioterapéutica en la mejora de la función cognitiva y de la capacidad funcional en la EA. Se recomienda realizar estudios adicionales para encontrar posibles evidencias.


Assuntos
Humanos , Idoso , Idoso de 80 Anos ou mais , Modalidades de Fisioterapia , Doença de Alzheimer/psicologia , Doença de Alzheimer/terapia , Desempenho Psicomotor , Atividades Cotidianas , Resultado do Tratamento , Cognição
15.
Forensic Sci Int ; 302: 109880, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31390576

RESUMO

Forensic document examiners are often called upon to opine on the authenticity of handwritten signatures by individuals with diminished mental capacity. Legal arguments surrounding the decisional capacity of an individual with dementia can be found in many cases involving wills, deeds, trusts, and contracts. The purpose of this study was to provide estimates of feature variability derived from dynamic analyses of signatures written by individuals with dementia of the Alzheimer type (AD) compared with age-comparable healthy individuals. Dynamic features of digitally captured signatures were analyzed to test the hypothesis that AD signature features will show greater variability compared with signatures from age-comparable healthy subjects. The study enrolled 69 AD and 74 age comparable healthy subjects. Results revealed four main findings from AD signatures: (1) that the temporal, spatial and fluency characteristics of signature formation did not differ from signatures of healthy writers; (2) variability in dynamic features over a series of repetitive signatures fell within 10% of the natural variation of healthy subjects; (3) there was a significant association between increased dynamic signature feature variability and increased dementia severity for stylized and mixed signatures only; and (4) despite significant decline in cognitive status over a 1-year period, dynamic signature features remained stable. Overall, these results suggest that signature writing is preserved in AD. The association between dementia severity and dynamic feature variability among AD subjects with stylized or mixed signatures warrants further research.


Assuntos
Doença de Alzheimer/psicologia , Escrita Manual , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Índice de Gravidade de Doença
17.
Dement Geriatr Cogn Disord ; 47(4-6): 281-288, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31408867

RESUMO

BACKGROUND: Although simple reaction time (SRT) slowing is associated with dementia in Alzheimer's disease (AD), its presence in individuals with mild cognitive impairment (MCI) is subject to debate. OBJECTIVE: The aim of this study was to perform a systematic review and meta-analysis of the literature data on SRT slowing in MCI. METHODS: Publications with data on SRT, age, and educational level in participants with MCI were included. After calculating the log SRT and its variance for each study, we took interstudy heterogeneity into account by conducting a random effects (restricted maximum likelihood estimation) meta-analysis. RESULTS: The 7 selected studies featured a total of 327 participants with MCI and 468 healthy controls (HCs). The mean age was 68.2 years for participants with MCI and 72.3 years for HCs. The weighted mean Mini-Mental State Examination score was 26.4 in the MCI group, and 28.4 in the HC group. The mean SRT was significantly (p = 0.0217) longer in the MCI group (by 11%) than in the HC group. CONCLUSION: This meta-analysis showed that SRTs are longer in individuals with MCI. Further studies are needed to determine the mechanism of SRT slowing, its anatomical correlates, and a threshold value for diagnosing prodromal AD.


Assuntos
Doença de Alzheimer/psicologia , Tempo de Reação , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Disfunção Cognitiva/psicologia , Diagnóstico Precoce , Humanos , Pessoa de Meia-Idade
18.
Acupunct Med ; 37(6): 340-347, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31412703

RESUMO

OBJECTIVE: To study the effects of acupuncture on expression of heat shock protein (Hsp) 84 and 86, and brain ageing, in the senescence accelerated mouse prone 8 (SAMP8) model of Alzheimer's disease. METHODS: 7-month-old male senescence resistant mouse strain 1 (SAMR1) and SAMP8 mice were assigned to the following groups, with 15 animals in each group: SAMR1 control (Rc), SAMP8 control (Pc), SAMP8 acupuncture (Pa), SAMP8 sham-acupuncture (Psa). The Pa group was given acupuncture treatment once daily for 15 days. Neuromuscular coordination and cognitive function of the mice were evaluated by the tightrope test and Morris water maze test, respectively. The number of neurons in the CA1, CA3 and dentate gyrus (DG) regions of the hippocampus were measured. The levels of oxidative stress and protein carbonyl, mRNA and protein expression levels of Hsp84 and Hsp86 in the hippocampus were detected. RESULTS: Compared with the Rc group, in the Pc mice there was a lower success rate for the tightrope test, impaired cognitive abilities, a decline in neuron numbers, reduced levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), increased levels of superoxide anion and protein carbonyl, and decreased mRNA and protein levels of Hsp84 and Hsp86 (all P<0.05). After acupuncture treatment, the success rate for the tightrope test was elevated, cognitive function was improved, neuron numbers were enhanced, levels of SOD and GSH-Px were increased, levels of superoxide anion and protein carbonyl were decreased, and Hsp84 and Hsp86 mRNA and protein expression were increased in the Pa mice when compared with the Pc and Psa groups (all P<0.05). CONCLUSION: Acupuncture may delay brain ageing in SAMP8 mice by reducing oxidative protein damage and promoting Hsp84 and Hsp86 expression.


Assuntos
Terapia por Acupuntura , Doença de Alzheimer/psicologia , Doença de Alzheimer/terapia , Proteínas de Choque Térmico HSP90/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Animais , Cognição , Modelos Animais de Doenças , Proteínas de Choque Térmico HSP90/genética , Humanos , Masculino , Camundongos
19.
Food Funct ; 10(9): 5656-5668, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31433414

RESUMO

Schisandra chinensis (Turcz.) Baill (S. chinensis), a functional food, is used as a tonic and sedative agent in traditional Chinese medicine. Modern pharmacological research has proved that S. chinensis could prevent and treat age-related neurodegenerative diseases. The presence of bioactive lignans in S. chinensis is the main reason for its neuroprotective and cognitive enhancement effects. This study aimed to clarify the mechanism of lignans in S. chinensis in ameliorating learning and memory deficits in Alzheimer's disease (AD) animals. The step-down test and Morris water maze (MWM) test were used to verify the effects of lignans in S. chinensis on learning and memory in AD animals. Then, metabolomics approaches based on ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) were used to clarify the mechanism of lignans in S. chinensis in treating AD. Finally, quantitative analysis of AD-related neurotransmitters in the brain was conducted after treatment with lignans in S. chinensis. In the MWM and step-down tests, lignans in S. chinensis showed a clear ability to ameliorate the impaired learning and memory of AD animals. A total of 31 endogenous metabolites were identified after treatment with lignans in S. chinensis, which were associated with lignans ameliorating learning and memory. These biomarkers were mainly associated with polyunsaturated fatty acid metabolism and amino acid and vitamin metabolism. Moreover, lignans in S. chinensis upregulated the levels of γ-aminobutyric acid (GABA), 5-hydroxytryptamine (5-HT), acetylcholine (Ach), norepinephrine (NE) and glycine (Gly) and downregulate the level of aspartic acid (Asp). Lignans in S. chinensis might alleviate the neurotoxic effects of neurological inflammation and oxidative stress, Aß deposition, and tau phosphorylation via the regulation of multiple endogenous metabolic pathways during pathological AD. The research might provide useful support for the further study of pharmacology and new drug development of lignans in S. chinensis.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Lignanas/administração & dosagem , Schisandra/química , Doença de Alzheimer/sangue , Doença de Alzheimer/psicologia , Doença de Alzheimer/urina , Animais , Biomarcadores/sangue , Biomarcadores/urina , Cromatografia Líquida de Alta Pressão , Cognição/efeitos dos fármacos , Medicamentos de Ervas Chinesas/química , Humanos , Lignanas/química , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Metabolômica , Neurotransmissores/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Plasma/química , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem , Urina/química
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