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1.
Nutr Neurosci ; 27(4): 361-381, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37039128

RESUMO

OBJECTIVE: To review the evidence on the association between maternal exposure to ultra-processed food (UPF) categories, UPF diet items, and overall diet quality, as assessed by recognized dietary indices, and neurodevelopmental outcomes in offspring. METHODS: PubMed, MEDLINE, EMBASE, Scopus, Ovid, and Scholar databases were searched for original articles on female gestational exposure to UPF categories, individual elements of the UPF diet, or indices of diet quality, in relation to outcomes regarding their offspring's neurocognitive development, according to neuropsychometric and behavioral scales, anthropometric/psychomotor indices, and symptoms/diagnosis of neurodevelopmental disorders (NDDs). RESULTS: Fourteen articles were selected and underwent the quantitative analysis. Six of these examined diet quality, and eight exposure to UPF categories or specific UPF foods. The maternal population was adult (18+). Child cognitive development was negatively impacted by a diet featuring many processed foods, saturated fats, and sugars. Conversely, a Med-diet led to better neurodevelopment, particularly verbal intelligence and executive functions, in middle childhood. DISCUSSION: A maternal diet with many UPFs, saturated fats, and total sugars (especially those added or hidden in packaged carbonated beverages) can adversely affect a child's cognitive development. Knowledge needs to be further extended and managed from a prevention perspective in light of the well-known negative effects of UPFs on human health in all age groups.


Assuntos
Ingestão de Energia , Alimento Processado , Adulto , Humanos , Criança , Feminino , Gravidez , Fast Foods , Manipulação de Alimentos , Dieta , Açúcares
2.
Eur J Nutr ; 62(3): 1217-1229, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36484807

RESUMO

PURPOSE: Growing awareness of the biological and clinical value of nutrition in frailty settings calls for further efforts to investigate dietary gaps to act sooner to achieve focused management of aging populations. We cross-sectionally examined the eating habits of an older Mediterranean population to profile dietary features most associated with physical frailty. METHODS: Clinical and physical examination, routine biomarkers, medical history, and anthropometry were analyzed in 1502 older adults (65 +). CHS criteria were applied to classify physical frailty, and a validated Food Frequency Questionnaire to assess diet. The population was subdivided by physical frailty status (frail or non-frail). Raw and adjusted logistic regression models were applied to three clusters of dietary variables (food groups, macronutrients, and micronutrients), previously selected by a LASSO approach to better predict diet-related frailty determinants. RESULTS: A lower consumption of wine (OR 0.998, 95% CI 0.997-0.999) and coffee (OR 0.994, 95% CI 0.989-0.999), as well as a cluster of macro and micronutrients led by PUFAs (OR 0.939, 95% CI 0.896-0.991), zinc (OR 0.977, 95% CI 0.952-0.998), and coumarins (OR 0.631, 95% CI 0.431-0.971), was predictive of non-frailty, but higher legumes intake (OR 1.005, 95%CI 1.000-1.009) of physical frailty, regardless of age, gender, and education level. CONCLUSIONS: Higher consumption of coffee and wine, as well as PUFAs, zinc, and coumarins, as opposed to legumes, may work well in protecting against a physical frailty profile of aging in a Mediterranean setting. Longitudinal investigations are needed to better understand the causal potential of diet as a modifiable contributor to frailty during aging.


Assuntos
Idoso Fragilizado , Fragilidade , Humanos , Idoso , Café , Dieta , Fragilidade/epidemiologia , Fenótipo , Exame Físico
3.
Nutr Metab Cardiovasc Dis ; 33(11): 2233-2241, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37541928

RESUMO

BACKGROUND AND AIMS: Non-alcoholic hepatic steatosis affects 25% of adults worldwide and its prevalence increases with age. There is currently no definitive treatment for NAFLD but international guidelines recommend a lifestyle-based approach, including a healthy diet. The aim of this study was to investigate the interactions between eating habits and the risk of steatosis and/or hepatic fibrosis, using a machine learning approach, in a non-institutionalized elderly population. METHODS AND RESULTS: We recruited 1929 subjects, mean age 74 years, from the population-based Salus in Apulia Study. Dietary habits and the risk of steatosis and hepatic fibrosis were evaluated with a validated food frequency questionnaire, the Fatty Liver Index (FLI) and the FIB-4 score, respectively. Two dietary patterns associated with the risk of steatosis and hepatic fibrosis have been identified. They are both similar to a "western" diet, defined by a greater consumption of refined foods, with a rich content of sugars and saturated fats, and alcoholic and non-alcoholic calorie drinks. CONCLUSION: This study further supports the concept of diet as a factor that significantly influences the development of the most widespread liver diseases. However, longitudinal studies are needed to better understand the causal effect of the consumption of particular foods on fat accumulation in the liver.

4.
Aging Clin Exp Res ; 35(6): 1145-1160, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37160649

RESUMO

This paper reports the proceedings of a virtual meeting convened by the European Interdisciplinary Council on Ageing (EICA), to discuss the involvement of infectious disorders in the pathogenesis of dementia and neurological disorders leading to dementia. We recap how our view of the infectious etiology of dementia has changed over the last 30 years in light of emerging evidence, and we present evidence in support of the implication of infection in dementia, notably Alzheimer's disease (AD). The bacteria and viruses thought to be responsible for neuroinflammation and neurological damage are reviewed. We then review the genetic basis for neuroinflammation and dementia, highlighting the genes that are currently the focus of investigation as potential targets for therapy. Next, we describe the antimicrobial hypothesis of dementia, notably the intriguing possibility that amyloid beta may itself possess antimicrobial properties. We further describe the clinical relevance of the gut-brain axis in dementia, the mechanisms by which infection can move from the intestine to the brain, and recent findings regarding dysbiosis patterns in patients with AD. We review the involvement of specific pathogens in neurological disorders, i.e. SARS-CoV-2, human immunodeficiency virus (HIV), herpes simplex virus type 1 (HSV1), and influenza. Finally, we look at the role of vaccination to prevent dementia. In conclusion, there is a large body of evidence supporting the involvement of various infectious pathogens in the pathogenesis of dementia, but large-scale studies with long-term follow-up are needed to elucidate the role that infection may play, especially before subclinical or clinical disease is present.


Assuntos
Doença de Alzheimer , COVID-19 , Vacinas , Humanos , Peptídeos beta-Amiloides , Doenças Neuroinflamatórias , COVID-19/complicações , SARS-CoV-2 , Doença de Alzheimer/prevenção & controle , Vacinas/uso terapêutico
5.
J Integr Neurosci ; 22(5): 109, 2023 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-37735130

RESUMO

Research on the causal relationship between age-related hearing loss (ARHL) and/or tinnitus and dementia is an important and fast-moving field. In this opinion paper, the up-to-date evidence and potential mechanisms for the bidirectional relationship are reviewed. We also present several critical factors that increase the challenges of understanding the causal relationship. These factors include common causes (such as aging, frailty, vascular impairment, and chronic inflammation), auditory and cognitive reserves, and the difficulty in distinguishing central auditory processing disorder (CAPD) from cognitive impairment. Finally, based on cumulative evidence, we propose an integrated mechanism in which the central auditory system might be the common target of both peripheral auditory impairment and dementia or its precursor. There is a bidirectional interaction between the peripheral and central auditory systems and between the central auditory systems and the cognitive brain. CAPD causes the depletion of auditory and cognitive reserves, and indirectly affects the peripheral auditory system via the auditory efferent system. According to the proposal, multimodal intervention might be beneficial for patients with ARHL and/or tinnitus and cognitive impairment, apart from hearing restoration by hearing aids or cochlear implants.


Assuntos
Disfunção Cognitiva , Demência , Perda Auditiva , Zumbido , Humanos , Envelhecimento , Disfunção Cognitiva/complicações , Perda Auditiva/complicações , Zumbido/complicações
6.
Alzheimers Dement ; 19(8): 3306-3315, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36757048

RESUMO

INTRODUCTION: Frailty is a critical intermediate status of the aging process including physical, cognitive, and psychosocial phenotypes. We operationalized a biopsychosocial frailty construct, estimating its association with mild cognitive impairment (MCI) and its subtypes. METHODS: In 1980, older individuals from the population-based Italian PRoject on the Epidemiology of Alzheimer's disease (IPREA), we investigated cross-sectional associations among biopsychosocial frailty, MCI, and its subtypes. RESULTS: Participants with biopsychosocial frailty showed an increased odds ratio (OR) of MCI [OR: 4.36; 95% confidence interval (CI): 2.60-7.29; Fisher's exact p < 0.01], particularly for nonamnestic MCI single domain (naMCI-SD, OR:3.28; 95% CI: 1.35-7.97; Fisher's exact p = 0.02) and for nonamnestic MCI multiple domain (naMCI-MD, OR:6.92; 95% CI: 3.37-14.21; Fisher's exact p < 0.01). No statistically significant associations between amnestic MCI single or multiple domain and biopsychosocial frailty were observed. DISCUSSION: In a large, older Italian cohort, a biopsychosocial frailty phenotype was associated with MCI, in particular, could be associated with some of its subtypes, that is, naMCI-SD, and naMCI-MD.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Fragilidade , Humanos , Doença de Alzheimer/complicações , Fragilidade/complicações , Estudos Transversais , Disfunção Cognitiva/psicologia , Itália/epidemiologia
7.
Alzheimers Dement ; 19(1): 353-368, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35900209

RESUMO

Human apolipoprotein E (apoE) is a 299-amino acid secreted glycoprotein binding cholesterol and phospholipids, and with three common isoforms (APOE ε2, APOE ε3, and APOE ε4). The exact mechanism by which APOE gene variants increase/decrease Alzheimer's disease (AD) risk is not fully understood, but APOE isoforms differently affect brain homeostasis and neuroinflammation, blood-brain barrier (BBB) permeability, glial function, synaptogenesis, oral/gut microbiota, neural networks, amyloid beta (Aß) deposition, and tau-mediated neurodegeneration. In this perspective, we propose a comprehensive interpretation of APOE-mediated effects within AD pathophysiology, describing some specific cellular, biochemical, and epigenetic mechanisms and updating the different APOE-targeting approaches being developed as potential AD therapies. Intracisternal adeno-associated viral-mediated delivery of APOE ε2 is being tested in AD APOE ε4/ε4 carriers, while APOE mimetics are being used in subjects with perioperative neurocognitive disorders. Other approaches including APOE ε4 antisense oligonucleotides, anti-APOE ε4 monoclonal antibodies, APOE ε4 structure correctors, and APOE-Aß interaction inhibitors produced positive results in transgenic AD mouse models.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Camundongos , Animais , Humanos , Apolipoproteína E2/genética , Peptídeos beta-Amiloides/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Apolipoproteína E4/genética , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Apolipoproteína E3/genética , Camundongos Transgênicos , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo
8.
Age Ageing ; 51(2)2022 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-35134842

RESUMO

BACKGROUND: the possible relationship between dietary habits and the incidence of late-onset depression (LOD), defined as first depression onset at later age, is unclear. OBJECTIVE: to investigate the relationship between consumption of different food groups and incident LOD. DESIGN: longitudinal population-based study with a 12-year follow-up. SETTING: Castellana Grotte, Bari, Italy. SUBJECTS: five hundred and forty-six older subjects from the Salus in Apulia Study. METHODS: baseline data were recorded in 2003-06, and diagnostic data were recorded in 2013-18 at follow-up. Dietary intake was assessed with a food frequency questionnaire. Depressive disorders were assessed with the Structured Clinical Interview for DSM-IV Axis I Disorders. Subjects who already suffered from depression or other psychiatric disorders at baseline were excluded from the analysis. The association between LOD and single dietary determinants was examined by Cox regression analysis and then applying the hazard ratio (HR). RESULTS: subjects with incident LOD (n = 34) had lower global cognition and total cholesterol levels and a higher body mass index (BMI) at baseline. Only processed meat significantly increased the risk of incident LOD of about 10% by 5 g/day intake (HR adjusted for age, sex, education, multimorbidity and BMI: 1.13, 95% confidence intervals: 1.04-1.22). A similar relationship was found for single foods in the processed meat food group such as sausages, salami and mortadella and baked ham, but not for raw ham. CONCLUSIONS: in midlife, a higher intake of processed meat was not only associated with an increased risk of cardiovascular- and metabolic-related chronic diseases in older age but also with an increased risk of developing LOD.


Assuntos
Depressão , Carne , Depressão/diagnóstico , Depressão/epidemiologia , Depressão/etiologia , Dieta/efeitos adversos , Comportamento Alimentar , Seguimentos , Humanos , Carne/efeitos adversos , Pessoa de Meia-Idade , Fatores de Risco
9.
Nutr Neurosci ; 25(6): 1300-1309, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33448914

RESUMO

OBJECTIVES: Consistency among population-based studies investigating the relationship between diet and cognition in older inhabitants in the Mediterranean area is poor. The present study investigated whether diet changes over 12 years were associated with cognitive function in older people in Southern-Italy. METHODS: From the 'Salus in Apulia Study', that includes the MICOL and GreatAGE Studies, 584 participants were selected, firstly enrolled in MICOL3 (M3) and later in the GreatAGE Study (MICOL4, M4). Foods and micronutrients intake were recorded in both studies, and global cognitive function in M4, assessed with the Mini Mental State Examination. RESULTS: Plant-based foods, particularly coffee and vegetables, as well as vitamin A sources, were inversely associated to age-related cognitive impairment. Alcohol consumption showed a detrimental role on cognition, while red meat appeared to be beneficial in the present study, although its role is traditionally considered harmful for cognitive function. DISCUSSION: Our study confirmed that a traditional Mediterranean dietary pattern based on agricultural products and low alcohol consumption may help to prevent/delay age-related cognitive impairment.


Assuntos
Disfunção Cognitiva , Dieta Mediterrânea , Idoso , Cognição , Dieta , Dieta Vegetariana , Ingestão de Alimentos , Humanos
10.
BMC Health Serv Res ; 22(1): 1283, 2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36284319

RESUMO

BACKGROUND: The most impacting direct costs associated to COPD for the National Health Systems (NHS) are those related to accesses to the emergency room and hospital admissions, due to the onset of one or more COPD exacerbations. At the same time, severe COPD treatment, that often require a combination of medicaments, represents a substantial economic burden for the National Health Systems (NHS). This study aimed to evaluate the potential saving deriving from the implementation in the prescription of the two currently available single-inhaler triple therapies (SITTs) versus the currently used multiple-inhaler triple therapies (MITTs) in an eligible COPD population residing in the Apulia Region. METHODS: A budget impact model was developed hypothesizing the progressive replacement of the different MITTs on the reference market (Scenario A) with the pre-established SITTs, assuming a degree of penetration of 30%, 50% and 100% (Scenario B). Drug costs were based on prices published on the Official Gazette and therapy durations were based on prescribing information over the year 2019 (IQVIA™ prescription dataset). RESULTS: Our analysis showed that the extemporaneous MITT with the highest prevalence on the reference market was the inhaled corticosteroids/long-acting ß2-agonists (ICS/LABA) combination plus a long-acting muscarinic antagonists (LAMA). This association of medicaments was paradoxically also the one associated to the highest expense value. The expanded use of a pre-established ICS/LAMA/LABA SITT was associated to a significant economic saving, ranging from a minimum of -€ 1,108,814 (SITT use: 30%) to a maximum of -€ 3,658,950 (SITT use: 100%). The cheapest pre-established SITT contained the fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) combination. CONCLUSION: A pre-fixed ICS/LAMA/LABA SITT is cost-saving, compared to the different currently used extemporaneous MITTs. Clinicians should consider the potential benefits of finding less expensive regimens while maintaining adequate efficacy in the prescriptive decision making process of COPD patients.


Assuntos
Antagonistas Muscarínicos , Doença Pulmonar Obstrutiva Crônica , Humanos , Antagonistas Muscarínicos/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Administração por Inalação , Nebulizadores e Vaporizadores , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Corticosteroides/uso terapêutico , Prescrições , Broncodilatadores/uso terapêutico , Combinação de Medicamentos
11.
Sensors (Basel) ; 22(6)2022 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-35336365

RESUMO

Dietary behaviour is a core element in diabetes self-management. There are no remarkable differences between nutritional guidelines for people with type 2 diabetes and healthy eating recommendations for the general public. This study aimed to evaluate dietary differences between subjects with and without diabetes and to describe any emerging dietary patterns characterizing diabetic subjects. In this cross-sectional study conducted on older adults from Southern Italy, eating habits in the "Diabetic" and "Not Diabetic" groups were assessed with FFQ, and dietary patterns were derived using an unsupervised learning algorithm: principal component analysis. Diabetic subjects (n = 187) were more likely to be male, slightly older, and with a slightly lower level of education than subjects without diabetes. The diet of diabetic subjects reflected a high-frequency intake of dairy products, eggs, vegetables and greens, fresh fruit and nuts, and olive oil. On the other hand, the consumption of sweets and sugary foods was reduced compared to non-diabetics (23.74 ± 35.81 vs. 16.52 ± 22.87; 11.08 ± 21.85 vs. 7.22 ± 15.96). The subjects without diabetes had a higher consumption of red meat, processed meat, ready-to-eat dishes, alcoholic drinks, and lower vegetable consumption. The present study demonstrated that, in areas around the Mediterranean Sea, older subjects with diabetes had a healthier diet than their non-diabetic counterparts.


Assuntos
Diabetes Mellitus Tipo 2 , Idoso , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Comportamento Alimentar , Feminino , Humanos , Itália/epidemiologia , Masculino , Aprendizado de Máquina não Supervisionado
12.
J Intern Med ; 290(5): 1071-1082, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34437740

RESUMO

INTRODUCTION: Preventive nutritional management of frailty, a multidimensional intermediate status in the ageing process, may reduce the risk of adverse health-related outcomes. We investigated the ability of a measure combining physical frailty with nutritional imbalance, defined as nutritional frailty, to predict all-cause mortality over a period of up to 8 years. METHODS: We analysed data on 1,943 older adults from the population-based 'Salus in Apulia Study'. Physical frailty was operationalized using Cardiovascular Health Study criteria and cognitive frailty by combining physical frailty with cognitive impairment. A novel five-item construct was built to assess the extent of nutritional imbalance identified with a machine learning algorithm. Cox models and Kaplan-Meier survival probability analyses of physical frailty, nutritional imbalance (two or more of the following: low body mass index, low skeletal muscle index, ≥2.3 g/day sodium intake, <3.35 g/day potassium intake and <9.9 g/day iron intake), cognitive frailty and the novel nutritional frailty phenotype (physical frailty plus nutritional imbalance) were applied to assess all-cause mortality risk, adjusted for age, sex, education and multimorbidity. RESULTS: The overall prevalence of nutritional frailty was 4.52% (95% confidence interval, CI:3.55-5.44), being more frequent in males. Subjects with nutritional frailty were at higher risk for all-cause mortality [hazard ratio (HR):2.31; 95%CI:1.41-3.79] than those with physical frailty (HR:1.45,95% CI:1.0-2.02), nutritional imbalance (HR:1.39; 95%CI:1.05-1.83) and cognitive frailty (HR:1.06; 95%CI:0.56-2.01). CONCLUSIONS: Efforts to identify, manage and prevent frailty should include the nutritional domain. The nutritional frailty phenotype may highlight major nutritional determinants that could drive survival and health trajectories in older adults.


Assuntos
Fragilidade , Mortalidade , Estado Nutricional , Idoso , Humanos , Masculino , Multimorbidade , Prevalência
13.
Respir Res ; 22(1): 16, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33451327

RESUMO

BACKGROUND: Some studies investigated epidemiological and clinical features of laboratory-confirmed patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) the virus causing coronavirus disease 2019 (COVID-19), but limited attention has been paid to the follow-up of hospitalized patients on the basis of clinical setting and the expertise of clinical management. METHODS: In the present single-centered, retrospective, observational study, we reported findings from 87 consecutive laboratory-confirmed COVID-19 patients with moderate-to-severe acute respiratory syndrome hospitalized in an intermediate Respiratory Intensive Care Unit (RICU), subdividing the patients in two groups according to the admission date (before and after March 29, 2020). RESULTS: With improved skills in the clinical management of COVID-19, we observed a significant lower mortality in the T2 group compared with the T1 group and a significantly difference in terms of mortality among the patients transferred in Intensive Care Unit (ICU) from our intermediate RICU (100% in T1 group vs. 33.3% in T2 group). The average length of stay in intermediate RICU of ICU-transferred patients who survived in T1 and T2 was significantly longer than those who died (who died 3.3 ± 2.8 days vs. who survived 6.4 ± 3.3 days). T CONCLUSIONS: The present findings suggested that an intermediate level of hospital care may have the potential to modify survival in COVID-19 patients, particularly in the present phase of a more skilled clinical management of the pandemic.


Assuntos
COVID-19/terapia , Competência Clínica , Cuidados Críticos , Unidades de Terapia Intensiva , Idoso , Idoso de 80 Anos ou mais , COVID-19/diagnóstico , COVID-19/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Itália , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
14.
Eur J Neurol ; 28(8): 2565-2573, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33899997

RESUMO

BACKGROUND AND PURPOSE: In older age, physical and cognitive declines have been shown to occur simultaneously or consequent to one another, and several operational definitions have been proposed to consider the co-presence of the two declines; for example, "Motoric cognitive risk syndrome" (MCR) has been proposed as a definition for the coexistence of slow gait plus subjective cognitive complaints. Given the increasing interest in MCR and its potential role as both biomarker and therapeutic target, we aimed to estimate its prevalence in a large cohort of non-demented older subjects, and to examine the associations between physical status, global cognitive dysfunction, and impairment in various cognitive domains in MCR. METHODS: A population-based sample of 1041 older people in Southern Italy (mean age 75.15 years) was enrolled. We defined MCR using slowness and a single question for subjective cognitive complaints. We also administered a comprehensive neuropsychological test battery, together with tests assessing physical function. RESULTS: The prevalence of MCR was 9.9% (95% confidence interval 8.2-11.9). MCR was associated with decreased processing speed and executive function after adjusting for all relevant confounders. However, we found no significant association of MCR with decreased global cognition and immediate/delayed free recall of verbal memory. MCR was also associated with increased exhaustion, low muscle strength, and low physical activity, and increased levels of C-reactive protein and interleukin-6. CONCLUSIONS: The present findings on MCR prevalence and associated cognitive and physical domains and inflammatory biomarkers may help to uncover altered pathways and therapeutic targets for intervention during the long preclinical phase of neurodegenerative dementia.


Assuntos
Disfunção Cognitiva , Marcha , Idoso , Cognição , Disfunção Cognitiva/epidemiologia , Humanos , Testes Neuropsicológicos , Fatores de Risco
15.
Ann Neurol ; 85(3): 303-315, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30635926

RESUMO

The amyloid-ß (Aß) cascade hypothesis of Alzheimer disease (AD) holds that brain accumulation of Aß initiates the disease process. Accordingly, drug research has targeted Aß production, clearance, and deposition as therapeutic strategies. Unfortunately, candidate drugs have failed to show clinical benefit in established, early, or prodromal disease, or in those with high AD risk. Currently, monoclonal antibodies specifically directed against the most neurotoxic Aß forms are undergoing large-scale trials to confirm initially encouraging results. However, recent findings on the normal physiology of Aß suggest that accumulation may be compensatory rather than the pathological initiator. If this is true, alternative strategies will be needed to defeat this devastating disease. ANN NEUROL 2019;85:303-315.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Anticorpos Monoclonais/uso terapêutico , Encéfalo/metabolismo , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Encéfalo/patologia , Desenvolvimento de Medicamentos , Humanos , Imunoterapia , Terapia de Alvo Molecular
16.
Expert Opin Emerg Drugs ; 25(3): 319-335, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32772738

RESUMO

INTRODUCTION: Currently available Alzheimer's disease (AD) therapeutics are only symptomatic, targeting cholinergic and glutamatergic neurotransmissions. Several putative disease-modifying drugs in late-stage clinical development target amyloid-ß (Aß) peptide and tau protein, the principal neurophatological hallmarks of the disease. AREAS COVERED: Phase III randomized clinical trials of anti-Aß drugs for AD treatment were searched in US and EU clinical trial registries and principal biomedical databases until May 2020. EXPERT OPINION: At present, compounds in Phase III clinical development for AD include four  anti-Ab monoclonal antibodies (solanezumab, gantenerumab, aducanumab, BAN2401), the combination of cromolyn sodium and ibuprofen (ALZT-OP1), and two small molecules (levetiracetam, GV-971). These drugs are mainly being tested in subjects during early AD phases or at preclinical stage of familial AD or even in asymptomatic subjects at high risk of developing AD. The actual results support the hypothesis that elevated Aß represents an early stage in the AD continuum and demonstrate the feasibility of enrolling these high-risk participants in secondary prevention trials to slow cognitive decline during the AD preclinical stages. However, a series of clinical failures may question further development of Aß-targeting drugs and the findings from current ongoing Phase III trials will hopefully give light to this critical issue.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Desenvolvimento de Medicamentos , Doença de Alzheimer/fisiopatologia , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/farmacologia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Proteínas tau/metabolismo
17.
Brain ; 142(10): 2905-2929, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31532495

RESUMO

Alzheimer's disease is associated with cerebral accumulation of amyloid-ß peptide and hyperphosphorylated tau. In the past 28 years, huge efforts have been made in attempting to treat the disease by reducing brain accumulation of amyloid-ß in patients with Alzheimer's disease, with no success. While anti-amyloid-ß therapies continue to be tested in prodromal patients with Alzheimer's disease and in subjects at risk of developing Alzheimer's disease, there is an urgent need to provide therapeutic support to patients with established Alzheimer's disease for whom current symptomatic treatment (acetylcholinesterase inhibitors and N-methyl d-aspartate antagonist) provide limited help. The possibility of an infectious aetiology for Alzheimer's disease has been repeatedly postulated over the past three decades. Infiltration of the brain by pathogens may act as a trigger or co-factor for Alzheimer's disease, with Herpes simplex virus type 1, Chlamydia pneumoniae, and Porphyromonas gingivalis being most frequently implicated. These pathogens may directly cross a weakened blood-brain barrier, reach the CNS and cause neurological damage by eliciting neuroinflammation. Alternatively, pathogens may cross a weakened intestinal barrier, reach vascular circulation and then cross blood-brain barrier or cause low grade chronic inflammation and subsequent neuroinflammation from the periphery. The gut microbiota comprises a complex community of microorganisms. Increased permeability of the gut and blood-brain barrier induced by microbiota dysbiosis may impact Alzheimer's disease pathogenesis. Inflammatory microorganisms in gut microbiota are associated with peripheral inflammation and brain amyloid-ß deposition in subjects with cognitive impairment. Oral microbiota may also influence Alzheimer's disease risk through circulatory or neural access to the brain. At least two possibilities can be envisaged to explain the association of suspected pathogens and Alzheimer's disease. One is that patients with Alzheimer's disease are particularly prone to microbial infections. The other is that microbial infection is a contributing cause of Alzheimer's disease. Therapeutic trials with antivirals and/or antibacterials could resolve this dilemma. Indeed, antiviral agents are being tested in patients with Alzheimer's disease in double-blind placebo-controlled studies. Although combined antibiotic therapy was found to be effective in animal models of Alzheimer's disease, antibacterial drugs are not being widely investigated in patients with Alzheimer's disease. This is because it is not clear which bacterial populations in the gut of patients with Alzheimer's disease are overexpressed and if safe, selective antibacterials are available for them. On the other hand, a bacterial protease inhibitor targeting P. gingivalis toxins is now being tested in patients with Alzheimer's disease. Clinical studies are needed to test if countering bacterial infection may be beneficial in patients with established Alzheimer's disease.


Assuntos
Doença de Alzheimer/microbiologia , Doença de Alzheimer/terapia , Antibacterianos/uso terapêutico , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Animais , Encéfalo/patologia , Disfunção Cognitiva , Modelos Animais de Doenças , Método Duplo-Cego , Microbioma Gastrointestinal , Humanos , Inflamação/patologia , Microbiota , Neuroimunomodulação/fisiologia , Placebos
18.
Adv Exp Med Biol ; 1260: 267-281, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32304037

RESUMO

The link between depression and Alzheimer's disease (AD) is controversial, because it is not clear if depression is an independent risk factor for the disease or a prodromal symptom in the older population. Cerebral amyloid-ß (Aß) peptide deposition is associated with both cognitive symptoms and neuropsychiatric symptoms (NPS), which may be a biological mechanism of compensation. Despite the widespread use of antidepressant therapeutics (30-50% of patients with AD/dementia are on antidepressants), there is mixed evidence regarding the benefits from their use in AD depression. Monoaminergic antidepressant drugs have shown only modest or no clinical benefits. Therefore, it is important to understand the reason of this drug-resistance and the relationship between antidepressant drugs and the Aß peptide. The goal of the present review is to highlight the etiology of depression in patients affected by AD in comparison to depressive disorders without AD, and to speculate on more appropriate and alternative therapeutics.


Assuntos
Doença de Alzheimer/complicações , Doença de Alzheimer/psicologia , Antidepressivos/uso terapêutico , Depressão/complicações , Depressão/tratamento farmacológico , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Depressão/metabolismo , Depressão/psicologia , Humanos
19.
Sensors (Basel) ; 20(16)2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32824206

RESUMO

Self-report questionnaires are a valuable method of physical activity measurement in public health research; however, accuracy is often lacking. Resolving the differences between self-reported and objectively measured physical activity is an important surveillance challenge currently facing population health experts. The present work aims at providing the relationship between activity energy expenditure estimated from wrist-worn accelerometers and intensity of self-reported physical activity (InCHIANTI structured interview questionnaire) in a sub-cohort of a population-based study on aging in Southern Italy. Linear regression was used to test the association between measured and reported physical activity. We found that activity energy expenditure predicted clinical average levels of PA assessed through InCHIANTI classification.


Assuntos
Metabolismo Energético , Exercício Físico , Idoso , Humanos , Itália , Autorrelato , Punho
20.
Adv Exp Med Biol ; 1118: 135-162, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30747421

RESUMO

Psychiatric illnesses are cognitive and behavioral disorders of the brain. At present, psychiatric diagnosis is based on DSM-5 criteria. Even if endophenotype specificity for psychiatric disorders is discussed, it is difficult to study and identify psychiatric biomarkers to support diagnosis, prognosis, or clinical response to treatment. This chapter investigates the innovative biomarkers of psychiatric diseases for diagnosis and personalized treatment, in particular post-genomic data and proteomic analyses.


Assuntos
Biomarcadores , Transtornos Mentais/diagnóstico , Psiquiatria , Encéfalo , Humanos , Proteômica
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