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1.
Lancet ; 395(10225): 735-748, 2020 02 29.
Artigo em Inglês | MEDLINE | ID: mdl-32113502

RESUMO

Globally, as populations age there will be challenges and opportunities to deliver optimal health care to senior citizens. Epilepsy, a condition characterised by spontaneous recurrent seizures, is common in older adults (aged >65 years) and yet has received comparatively little attention in this age group. In this Review, we evaluate the underlying causes of epilepsy in older people, explore difficulties in establishing a diagnosis of epilepsy in this population, discuss appropriate antiseizure medications, and evaluate potential surgical treatment options. We consider cognitive, psychological, and psychosocial comorbidities and the effect that epilepsy might have on an older person's broader social or care network in high-income versus middle-income and low-income countries. We emphasise the need for clinical trials to be more inclusive of older people with epilepsy to help inform therapeutic decision making and discuss whether measures to improve vascular risk factors might be an important strategy to reduce the probability of developing epilepsy.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/terapia , Procedimentos Neurocirúrgicos/métodos , Idoso , Doença de Alzheimer/complicações , Doenças Autoimunes do Sistema Nervoso/complicações , Neoplasias Encefálicas/complicações , Transtornos Cerebrovasculares/complicações , Tomada de Decisão Clínica , Ensaios Clínicos como Assunto , Disfunção Cognitiva/epidemiologia , Comorbidade , Países Desenvolvidos , Países em Desenvolvimento , Epilepsia/diagnóstico , Epilepsia/epidemiologia , Epilepsia/etiologia , Humanos , Incidência , Transtornos Mentais/epidemiologia , Prevalência , Estado Epiléptico/epidemiologia , /epidemiologia
3.
Nihon Yakurigaku Zasshi ; 154(6): 306-309, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31787681

RESUMO

Sleep abnormality such as frequent nocturnal arousal and decreased deep non-REM (rapid-eye-movement) sleep is a prevalent but under-recognized symptom that affects patients with various neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD). In contrast to the conventional understanding that the sleep abnormality in these patients is caused by AD or PD pathology in the brain regions regulating sleep-wake or circadian rhythm, various epidemiological studies have demonstrated the association of sleep abnormality with an increased risk of these diseases. Through various recent studies using relevant animal models to test the causal relationship between sleep abnormality and neurodegenerative diseases, the recent concept of a bidirectional relationship between sleep abnormality and neurodegenerative diseases was established. However, whether therapeutic interventions against sleep abnormality would modify the disease course of neurodegenerative diseases remains unknown. In this review, we will first provide an overview of previous studies that link neurodegenerative diseases and sleep abnormality, mainly focusing on the sleep abnormality in patients with AD. We will then introduce the studies that examined the causal relationship between sleep abnormality and neurodegenerative diseases. Finally, we will discuss possible mechanisms underlying the bidirectional relationship between sleep abnormality and neurodegenerative diseases. A better understanding of these mechanisms would lead to the development of novel pharmacological and/or non-pharmacological treatments that would modify the disease course of neurodegenerative diseases through targeting the processes related to sleep abnormality in the patients of neurodegenerative diseases.


Assuntos
Doenças Neurodegenerativas/complicações , Transtornos do Sono-Vigília/complicações , Doença de Alzheimer/complicações , Animais , Humanos , Sono
4.
Am J Case Rep ; 20: 1883-1887, 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31841453

RESUMO

BACKGROUND The diagnosis of early non-convulsant status epilepticus (NCSE) can be challenging and can overlap with other critical conditions. Two patients with Alzheimer's disease are reported with clinically suspected NCSE presenting in the emergency setting who were diagnosed using arterial spin-labeling magnetic resonance imaging (ASL-MRI) sequences. CASE REPORT In Case 1, a 69-year-old woman with mild Alzheimer's disease and diabetes presented with acute worsening of cognitive status and fluctuating level of consciousness. In Case 2, a 70-year-old man with mild cognitive impairment due to Alzheimer's disease and hypertension presented with acute loss of consciousness and left hemiparesis, without evidence of hypoglycemia or a hypertensive crisis. In both cases, ASL-MRI perfusion images showed focal cerebral hyperperfusion in the posterior cingulate and parietal associative cortex, which involved neurodegenerative areas associated with epilepsy in early Alzheimer's disease. In both cases, the patients developed generalized tonic-clonic epileptic seizures that lasted for 5 minutes or more, which indicated the emergence of status epilepticus that developed from the initial presentation of NCSE. In both cases, electroencephalogram (EEG) findings confirmed that the seizures were controlled by intravenous administration of antiepileptic drugs. Both patients discharged home from the hospital without recurrence of seizures, between 10-12 days after the onset of symptoms. CONCLUSIONS These two cases have demonstrated that ASL-MRI is feasible as an emergency diagnostic tool in clinically suspected NCSE in patients with Alzheimer's disease.


Assuntos
Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico por imagem , Estado Epiléptico/diagnóstico por imagem , Estado Epiléptico/etiologia , Idoso , Anticonvulsivantes/uso terapêutico , Diagnóstico Diferencial , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Marcadores de Spin , Estado Epiléptico/tratamento farmacológico
5.
Mol Biol (Mosk) ; 53(6): 1020-1028, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31876280

RESUMO

Advances in the research of molecular factors involved in the onset and progression of Alzheimer's disease, have led to the creation of several pathogenesis concepts of the most common neurodegenerative disease in the world, and amyloid, cholinergic, and neuroinflammatory hypotheses became leading. Over past twenty years, based on these hypotheses, hundreds of drug prototypes were developed, but none of them were able to stop the development of Alzheimer's disease. In this review, based on the latest experimental data on structure-function properties of chemically modified amyloid-beta isoforms, the concept of the origin and the mechanism of action of amyloid-beta with isomerized Asp7 residue, as a molecular agent of Alzheimer's disease pathogenesis, is presented. This concept makes it possible not only to combine the most important aspects of existing hypotheses but also indicates ways of creating agents for fighting Alzheimer's disease with a principally new mechanism of action, "disease-modifying drugs."


Assuntos
Doença de Alzheimer/etiologia , Doença de Alzheimer/patologia , Doença de Alzheimer/complicações , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Proteínas Amiloidogênicas/metabolismo , Humanos , Inflamação/complicações , Inflamação/tratamento farmacológico
6.
Neurology ; 93(24): e2237-e2246, 2019 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-31719134

RESUMO

OBJECTIVE: To determine the frequency of high-convexity tight sulci (HCTS) in a population-based sample and whether the presence of HCTS and related features influenced participants' cognitive status and classification within the new Alzheimer-biomarker framework. METHODS: We analyzed 684 participants ≥50 years of age who were enrolled in the prospective population-based Mayo Clinic Study of Aging and underwent structural MRI, amyloid PET imaging, and tau PET imaging. A fully automated machine-learning algorithm that had been developed previously in house was used to detect neuroimaging features of HCTS. On the basis of PET and MRI measures, participants were classified as having normal (A-) or abnormal (A+) amyloid, normal (T-) or abnormal (T+) tau, and normal (N-) or abnormal (N+) neurodegeneration. The neuropsychological battery assessed domain-specific and global cognitive scores. Gait speed also was assessed. Analyses were adjusted for age and sex. RESULTS: Of 684 participants, 45 (6.6%) were classified with HCTS according to the automated algorithm. Patients with HCTS were older than patients without HCTS (mean [SD] 78.0 [8.3] vs 71.9 [10.8] years; p < 0.001). More were cognitively impaired after age and sex adjustment (27% vs 9%; p = 0.005). Amyloid PET status was similar with and without HCTS, but tau PET standard uptake value ratio (SUVR) was lower for those with HCTS after age and sex adjustment (p < 0.001). Despite a lower tau SUVR, patients with HCTS had lower Alzheimer disease (AD) signature cortical thickness. With the amyloid-tau-neurodegeneration framework, HCTS was overrepresented in the T-(N)+ group, regardless of amyloid status. CONCLUSION: The HCTS pattern represents a definable subgroup of non-AD pathophysiology (i.e., T-[N]+) that is associated with cognitive impairment. HCTS may confound clinical and biomarker interpretation in AD clinical trials.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Hidrocefalia/diagnóstico por imagem , Neuroimagem/métodos , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/complicações , Doença de Alzheimer/patologia , Cognição/fisiologia , Feminino , Humanos , Hidrocefalia/complicações , Hidrocefalia/patologia , Interpretação de Imagem Assistida por Computador/métodos , Aprendizado de Máquina , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos , Espaço Subaracnóideo/patologia
8.
Medicine (Baltimore) ; 98(42): e17557, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31626119

RESUMO

BACKGROUND: Mild cognitive impairment (MCI) and Alzheimer's disease (AD) are neurodegenerative diseases associated with aging. The major clinical features of both are progressive memory loss and progressive cognitive loss. The objective of this systematic review protocol is to provide the methods for evaluating the effectiveness of acupuncture in the treatment on cognitive deficits in transgenic mouse. METHODS AND ANALYSIS: We will search the electronic databases of PubMed, Web of Science, Embase, PsycINFO, as well as the Chinese databases such as Chinese Biomedicine Literature (CBM), Chinese Medical Current Content (CMCC), Chinese Scientific Journal Database (VIP), WanFang Database and China National Knowledge Infrastructure (CNKI) from their inceptions to July 2019. RevMan 5.3 software will be used for the data synthesis and the quality of each study was assessed independently by use of the CAMARADES checklist. RESULTS: This review will provide a high-quality synthesis based on present evidence of acupuncture treatment for AD and MCI in transgenic mouse models. CONCLUSIONS: This systematic review will provide evidence for weather acupuncture is an effective intervention for AD and MCI in transgenic mouse models. ETHICS AND DISSEMINATION: Ethical approval is not necessary since this protocol is only for systematic review and does not involve privacy data or conduct an animal experiment. This protocol will be disseminated by a peer-review journal or conference presentation. TRIAL REGISTRATION NUMBER: PROSPERO CRD42019142985. STRENGTHS AND LIMITATIONS OF THIS STUDY: This systematic review will be the first to provide new knowledge underlying the effectiveness to improve cognitive function of acupuncture treatment for AD and MCI in transgenic mouse models. The result of this systematic review may provide experimental and theoretical basis for the future clinical application of acupuncture in the treatment of AD.The limitation of this systematic review may come from language barriers, because only English and Chinese can be included. Also, this study includes various kinds of acupuncture treatments which may result in essential heterogeneity.


Assuntos
Terapia por Acupuntura/métodos , Doença de Alzheimer/terapia , Cognição/fisiologia , Disfunção Cognitiva/terapia , Doença de Alzheimer/complicações , Doença de Alzheimer/fisiopatologia , Animais , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Modelos Animais de Doenças , Camundongos , Camundongos Transgênicos
9.
Artigo em Russo | MEDLINE | ID: mdl-31626214

RESUMO

AIM: To compare the frequency of age-related ophthalmic diseases in patients with Alzheimer's disease and vascular dementia. MATERIAL AND METHODS: The study included 60 patients with severe cognitive impairment divided into two equal groups matched for sex and age. The first group included patients diagnosed with Alzheimer's disease. The second group consisted of people with a diagnosis of vascular dementia. All patients underwent clinical and neuropsychological as well as standard (visometry, refraction, measurement of intraocular pressure, biomicroscopy, ophthalmoscopy, computed perimetry) and complex (optic coherent tomography) ophthalmologic examinations. RESULTS AND CONCLUSION: In patients with Alzheimer's disease, concomitant ophthalmologic pathology in the form of glaucoma was observed more often in 46,7% of cases, pseudoexfoliation syndrome in 20% of cases, age-related macular degeneration in 16,7% of cases, while in the vascular dementia group the majority (80%) of patients did not have concomitant ophthalmologic pathology. When analyzing the severity of cognitive impairment in patients with Alzheimer's disease and various concomitant ophthalmic pathology, it was shown that patients with Alzheimer's disease and glaucoma have more significant impairments compared to patients without concomitant ophthalmological pathology.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Demência Vascular , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico por imagem , Disfunção Cognitiva/complicações , Comorbidade , Demência Vascular/complicações , Demência Vascular/diagnóstico por imagem , Humanos , Tomografia Computadorizada por Raios X
10.
Arch Clin Neuropsychol ; 34(7): 1156-1164, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31504079

RESUMO

OBJECTIVE: The Neuropsychological Assessment Battery Bill Payment subtest has shown strong diagnostic accuracy in dementia due to Alzheimer's disease (AD) versus non-AD. Its relationship to mild cognitive impairment (MCI) or all-cause dementia has not been fully examined nor has its ecological validity as a proxy of financial independence. METHOD: We describe 270 women (63%) and men (age = 72 ± 8.39) who completed Bill Payment during outpatient neuropsychological evaluation. Seventy-one were cognitively normal (CN), 160 had MCI, and 39 had Dementia. Two hundred fourteen were independent in money management, 31 were assisted (had oversight/some help), and 25 were dependent (relied on others). Receiver operating characteristic (ROC) curves tested Bill Payment's utility as a dementia screen. Kruskal-Wallis tests examined whether Bill Payment differed by levels of financial independence. RESULTS: At a cutoff of 17, Bill Payment had strong sensitivity (0.87) and specificity (0.80) for dementia versus CN cases. A cutoff of 15 distinguished dementia from MCI (Sn = 0.64, Sp = 0.85), whereas a cutoff of 16 distinguished dementia from functionally unimpaired cases (MCI + CN) with greater sensitivity and similar specificity (Sn = 0.74, Sp = 0.81). Sensitivity attenuated in MCI versus CN cases (Sn = 0.46, Sp = 0.83). Those who were independent in money management had higher scores than assisted and dependent cases (p ≤ 0.046). Assisted and dependent cases were no different (p > 0.05). CONCLUSIONS: Bill Payment is a valid screen of all-cause dementia. Lower Bill Payment scores may mark subtle functional decline beyond cognitive impairment alone. Specifically, results provide preliminary evidence of Bill Payment's ecological validity as a measure related to financial independence. It may prove useful when impaired financial abilities are suspected but unreported.


Assuntos
Doença de Alzheimer/diagnóstico , Demência/diagnóstico , Administração Financeira , Testes Neuropsicológicos , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/complicações , Estudos de Casos e Controles , Cognição , Disfunção Cognitiva/diagnóstico , Demência/complicações , Feminino , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Psicometria , Curva ROC , Sensibilidade e Especificidade
13.
Clin Interv Aging ; 14: 1243-1254, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31371930

RESUMO

Objective: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of cognitive stimulation therapy (CST) of different durations for Alzheimer's disease (AD). Methods: A comprehensive search was carried out in three databases. The primary outcome was Mini-Mental State Examination (MMSE) score. We conducted a meta-analysis with Review Manager, version 5.3 and assessed the methodological quality of the included studies using the Cochrane Collaboration Recommendations assessment tool. Results: Treatment effects from the meta-analysis showed that CST plus acetylcholinesterase inhibitors (ChEIs) was better than the control assessed by MMSE. In addition, the meta-analysis indicated that long-term CST was better than short-term or maintenance CST. Conclusion: Our study confirmed that the combination of CST and drug treatment for AD is effective in AD, regardless of whether short-term CST, maintenance CST, or long-term CST is used. The long-term CST appears to be more effective.


Assuntos
Doença de Alzheimer/terapia , Transtornos Cognitivos/terapia , Terapia Cognitivo-Comportamental/métodos , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico , Inibidores da Colinesterase/uso terapêutico , Transtornos Cognitivos/etiologia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Comportamento Social
14.
J Clin Neurosci ; 70: 96-101, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31444048

RESUMO

Associations of sarcopenia and physical frailty in cognitive and affective (depression, apathy, and behavioral and psychological symptoms of dementia) functions of mild cognitive impairment (MCI) and Alzheimer's disease (AD) were not fully evaluated previously, especially not for gender differences. 165 AD, 84 MCI, and 48 control participants (175 female, 122 male) were evaluated for cognitive, affective, activities of daily living (ADL), and physical functions associated with sarcopenia and physical frailty. In both sexes, cognitive and affective functions, ADL, and physical functions worsened in MCI and AD compared to control subjects. Physical dysfunctions, especially slow gait speed (3 m up and go test), were significantly associated with cognitive, affective, and ADL declines in participants (control subjects, MCI, and AD) of each gender, which were especially noticeable in females. The present study may be the first to suggest significant associations of sarcopenia and physical frailty with cognitive and affective functions of MCI and AD, especially in females.


Assuntos
Doença de Alzheimer/complicações , Disfunção Cognitiva/complicações , Fragilidade/etiologia , Sarcopenia/etiologia , Atividades Cotidianas , Idoso , Apatia , Depressão/etiologia , Feminino , Fragilidade/epidemiologia , Humanos , Masculino , Sarcopenia/epidemiologia , Fatores Sexuais
15.
Nervenarzt ; 90(9): 914-920, 2019 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-31420690

RESUMO

BACKGROUND: Progressive cognitive deficits are the main clinical symptom of Alzheimer's disease; however, the precise recording of cognitive deficits and assessment of their progression pose major problems in patient care and early interventions. OBJECTIVE: Which problems for care and early intervention result from the current practice of cognitive assessment of patients with memory problems and which opportunities arise from the use of mobile apps? MATERIAL AND METHODS: Evaluation of current care structures, discussion of basic work, expert recommendations and current developments. RESULTS: The current practice of the pencil and paper-based diagnostics of cognitive deficits, which is temporally and spatially bound to a clinical environment, constrains the feasibility, validity and reliability of cognitive assessment and the quantification of progression. This limits the meaningful use of further diagnostic measures, such as magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) analyses. Recent progress in mobile app-based technologies, illustrated here with the example of the neotiv app, can help to overcome these problems. CONCLUSION: Mobile app-based technologies can help to improve the cognitive assessment of patients with the main symptom of memory complaints. They can reduce overuse and underuse of diagnostic and therapeutic pathways and enable a targeted and meaningful use of advanced diagnostics. In addition, they can structure risk-modifying preventive measures, identify iatrogenic impairment of cognition and in this respect also strengthen patient competence.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Aplicativos Móveis , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Progressão da Doença , Humanos , Aplicativos Móveis/normas , Aplicativos Móveis/tendências , Reprodutibilidade dos Testes
16.
Braz J Med Biol Res ; 52(8): e8443, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31365694

RESUMO

Brain-derived neurotrophic factor (BDNF) is widely expressed in the central nervous system and prolongs the survival of dopaminergic neurons in the substantia nigra. Several studies have recently investigated the association between BDNF G196A (Val66Met), a single nucleotide polymorphism influencing cognitive processes, and cognitive impairment in Parkinson's disease (PD), but with contradictory findings. Thus, this meta-analysis was performed to clarify the possible association. Relevant studies were identified by a systematic search of PubMed, Embase, and China National Knowledge Infrastructure (CNKI) databases. The strength of the association was evaluated using crude odds ratios and 95% confidence interval. Finally, six studies involving 532 cases and 802 controls were included. Our analyses suggested the G196A (Val66Met) polymorphism was significantly associated with cognitive impairment in PD, especially in Caucasian populations. In conclusion, BDNF G196A (Val66Met) is confirmed to be a risk factor for cognitive impairment in PD.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/genética , Disfunção Cognitiva/genética , Doença de Parkinson/genética , Doença de Alzheimer/complicações , Estudos de Casos e Controles , Disfunção Cognitiva/complicações , Grupo com Ancestrais do Continente Europeu , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Razão de Chances , Doença de Parkinson/complicações , Polimorfismo de Nucleotídeo Único , Fatores de Risco
17.
BMC Neurosci ; 20(1): 38, 2019 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-31366317

RESUMO

BACKGROUND: In this study, nonlinear based time-frequency (TF) and time domain investigations are employed for the analysis of electroencephalogram (EEG) signals of mild cognitive impairment-Alzheimer's disease (MCI-AD) patients and healthy controls. This study attempts to comprehend the cognitive decline of MCI-AD under both resting and cognitive task conditions. RESULTS: Wavelet-based synchrosqueezing transform (SST) alleviates the smearing of energy observed in the spectrogram around the central frequencies in short-time Fourier transform (STFT), and continuous wavelet transform (CWT). A precise TF representation is assured due to the reassignment of scale variable to the frequency variable. It is discerned from the studies of time domain measures encompassing fractal dimension (FD) and approximate entropy (ApEn), that the parietal lobe is the most affected in MCI-AD under both resting and cognitive states. Alterations in asymmetry in the brain hemispheres are analysed using the homologous areas inter-hemispheric symmetry (HArS). CONCLUSION: Time and time-frequency domain analysis of EEG signals have been used for distinguishing various brain states. Therefore, EEG analysis is highly useful for the screening of AD in its prodromal phase.


Assuntos
Doença de Alzheimer/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Lateralidade Funcional/fisiologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/complicações , Estudos de Casos e Controles , Disfunção Cognitiva/complicações , Eletroencefalografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Ondaletas
18.
Geriatr Psychol Neuropsychiatr Vieil ; 17(3): 307-316, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31449049

RESUMO

Visual perception is humans' preferred way for taking information on the surrounding world. Visual perception is frequently impaired in patients with Alzheimer's disease, lessening patients' quality of life, and making evaluation of other cognitive deficits more complicated. Our review covers the recent literature describing visual perception deficits in patients suffering from Alzheimer's disease by classifying them according to their neuroanatomical correspondence: retina, visual pathway, subcortical structures, occipital visual cortex, occipito-temporal "what" and occipito-parietal "where" pathways. Overall, both low-level and high-level visual perception disorders seem quite common in Alzheimer's disease, including, on a low-level, loss of visual field, decreased acuity and contrast sensitivity, and impaired color vision, and on a high-level, impaired color vision, motion perception, visuospatial deficits, object agnosia, prosopagnosia and impaired recognition of facial emotional expressions. Professionals working with Alzheimer's disease should be aware of visuoperceptual deficits, which could impair the quality of life of the patients, and distort the results of neuropsychological tests using visual material. Moreover, some tests assessing visual perception could be of interest for early diagnosis of the disease.


Assuntos
Doença de Alzheimer/psicologia , Transtornos da Percepção/psicologia , Transtornos da Visão/psicologia , Percepção Visual , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/complicações , Doença de Alzheimer/fisiopatologia , Humanos , Testes Neuropsicológicos , Transtornos da Percepção/etiologia , Transtornos da Percepção/fisiopatologia , Transtornos da Visão/etiologia , Transtornos da Visão/fisiopatologia , Vias Visuais/fisiopatologia
19.
Nutrients ; 11(8)2019 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-31426549

RESUMO

The biological effects of insulin signaling are regulated by the phosphorylation of insulin receptor substrate 1 (IRS1) at serine (Ser) residues. In the brain, phosphorylation of IRS1 at specific Ser sites increases in patients with Alzheimer's disease (AD) and its animal models. However, whether the activation of Ser sites on neural IRS1 is related to any type of memory decline remains unclear. Here, we show the modifications of IRS1 through its phosphorylation at etiology-specific Ser sites in various animal models of memory decline, such as diabetic, aged, and amyloid precursor protein (APP) knock-in NL-G-F (APPKINL-G-F) mice. Substantial phosphorylation of IRS1 at specific Ser sites occurs in type 2 diabetes- or age-related memory deficits independently of amyloid-ß (Aß). Furthermore, we present the first evidence that, in APPKINL-G-F mice showing Aß42 elevation, the increased phosphorylation of IRS1 at multiple Ser sites occurs without memory impairment. Our findings suggest that the phosphorylation of IRS1 at specific Ser sites is a potential marker of Aß-unrelated memory deficits caused by type 2 diabetes and aging; however, in Aß-related memory decline, the modifications of IRS1 may be a marker of early detection of Aß42 elevation prior to the onset of memory decline in AD.


Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Proteínas Substratos do Receptor de Insulina/metabolismo , Insulina/metabolismo , Transtornos da Memória/metabolismo , Memória , Envelhecimento , Doença de Alzheimer/complicações , Animais , Encéfalo/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Masculino , Transtornos da Memória/etiologia , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fosforilação , Serina/metabolismo , Transdução de Sinais
20.
Nat Commun ; 10(1): 3497, 2019 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-31375668

RESUMO

Human memory is thought to depend on a circuit of connected brain regions, but this hypothesis has not been directly tested. We derive a human memory circuit using 53 case reports of strokes causing amnesia and a map of the human connectome (n = 1000). This circuit is reproducible across discovery (n = 27) and replication (n = 26) cohorts and specific to lesions causing amnesia. Its hub is at the junction of the presubiculum and retrosplenial cortex. Connectivity with this single location defines a human brain circuit that incorporates > 95% of lesions causing amnesia. Lesion intersection with this circuit predicts memory scores in two independent datasets (N1 = 97, N2 = 176). This network aligns with neuroimaging correlates of episodic memory, abnormalities in Alzheimer's disease, and brain stimulation sites reported to enhance memory in humans.


Assuntos
Amnésia/patologia , Encéfalo/patologia , Conectoma , Memória/fisiologia , Rede Nervosa/patologia , Adulto , Idoso , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Amnésia/diagnóstico por imagem , Amnésia/etiologia , Encéfalo/diagnóstico por imagem , Conjuntos de Dados como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/patologia
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