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1.
Medicine (Baltimore) ; 100(3): e23969, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33545981

RESUMO

ABSTRACT: This study aimed to evaluated the clinical impact of adding [11C] Pittsburgh compound-B (11C-PiB) PET for clinical diagnosis of mild cognitive impairment (MCI) to Alzheimer's disease (AD) dementia.Twenty six (mean age 78.5 ±â€Š5.18 years, 21 females) AD (n = 7), amnestic MCI (n = 12), non-amnestic MCI (n = 3), vascular dementia, progressive supranuclear palsy (PSP) with frontotemporal dementia (FTD), FTD (n = 1 each), and normal (n = 1) patients underwent 11C-PiB-PET, MRI, and SPECT scanning. 11C-PiB-PET was compared with MRI and SPECT for clinical impact.11C-PiB-PET showed positivity in 6, 9, and 0 of the AD, amnestic MCI, and non-amnestic MCI patients, respectively, and 0 of those with another disease. Parahippocampal atrophy at VSASD was observed in 5 AD patients, 6 amnestic and PiB-positive MCI patients, 1 amnestic and PiB-negative MCI patient, and 1 vascular dementia patient. Parietal lobe hypoperfusion in SPECT findings was observed in 6, 4, and 2 of those, respectively, as well as 1 each of non-amnestic MCI, vascular dementia, and normal cases. Sensitivity/specificity/accuracy for selecting PiB-positive patients among the 15 MCI patients for 11C-PiB-PET were 100% (9/9)/100% (6/6)/100% (15/15), for VSRAD were 66.7% (6/9)/83.3% (5/6)/73.3% (11/15), and for SPECT were 44.4% (4/9)/50.0% (3/6)/46.7% (7/15), while those were 88.9% (8/9)/33.3% (2/6)/66.7% (10/15)/for combined VSRAD and SPECT. 11C-PiB-PET accuracy was significantly higher than that of SPECT.11PiB-PET alone may be useful for selecting patients who will progress from MCI to AD in the future, although follow-up study is necessary to clarify the outcome of MCI patients.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/diagnóstico , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Compostos de Anilina/uso terapêutico , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Tomografia por Emissão de Pósitrons/métodos , Tiazóis/uso terapêutico , Tomografia Computadorizada de Emissão de Fóton Único/métodos
2.
Neurology ; 96(7): e975-e985, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33443136

RESUMO

OBJECTIVE: To assess the frequency of biologically defined Alzheimer disease (AD) in relation to age, sex, APOE ε4, and clinical diagnosis in a prospective cohort study evaluated with amyloid-PET and tau-PET. METHODS: We assessed cognitively unimpaired (CU) elderly (n = 166), patients with amnestic mild cognitive impairment (n = 77), and patients with probable AD dementia (n = 62) who underwent evaluation by dementia specialists and neuropsychologists in addition to amyloid-PET with [18F]AZD4694 and tau-PET with [18F]MK6240. Individuals were grouped according to their AD biomarker profile. Positive predictive value for biologically defined AD was assessed in relation to clinical diagnosis. Frequency of AD biomarker profiles was assessed using logistic regressions with odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The clinical diagnosis of probable AD dementia demonstrated good agreement with biologically defined AD (positive predictive value 85.2%). A total of 7.88% of CU were positive for both amyloid-PET and tau-PET. Frequency of biologically defined AD increased with age (OR 1.14; p < 0.0001) and frequency of APOE ε4 allele carriers (single ε4: OR 3.82; p < 0.0001; double ε4: OR 17.55, p < 0.0001). CONCLUSION: Whereas we observed strong, but not complete, agreement between clinically defined probable AD dementia and biomarker positivity for both ß-amyloid and tau, we also observed that biologically defined AD was not rare in CU elderly. Abnormal tau-PET was almost exclusively observed in individuals with abnormal amyloid-PET. Our results highlight that even in tertiary care memory clinics, detailed evaluation by dementia specialists systematically underestimates the frequency of biologically defined AD and related entities. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that biologically defined AD (abnormal amyloid PET and tau PET) was observed in 85.2% of people with clinically defined AD and 7.88% of CU elderly.


Assuntos
Doença de Alzheimer/diagnóstico , Apolipoproteína E4/genética , Encéfalo/diagnóstico por imagem , Cognição/fisiologia , Disfunção Cognitiva/diagnóstico , Fatores Etários , Idoso , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Doença de Alzheimer/psicologia , Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/genética , Disfunção Cognitiva/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons , Fatores Sexuais , Proteínas tau/metabolismo
3.
J Alzheimers Dis ; 79(3): 1015-1021, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33386809

RESUMO

We explored the impact of the Spanish COVID-19 strict home confinement on mental health and cognition in non-infected subjects (N = 16, 60-80 years) diagnosed with subjective cognitive decline and APOEɛ3/ɛ4 carriers. Mental health was monitored for 2 months on a daily, weekly, or monthly basis, and compared to pre-confinement values. Emotional distress, anxiety, and depression scores increased to pathological threshold values during and after confinement. Those with lower mood during confinement experienced a decline in their mood after confinement. Cognition did not change. These preliminary results suggest that mental health consequences of corona measures in preclinical stages of Alzheimer's disease should be further evaluated.


Assuntos
Doença de Alzheimer/psicologia , Transtornos Cognitivos/psicologia , Saúde Mental , Quarentena/psicologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/genética , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/genética , Transtornos de Ansiedade/psicologia , Apolipoproteína E3/genética , Apolipoproteína E4/genética , /terapia , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/genética , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/genética , Disfunção Cognitiva/psicologia , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/genética , Transtorno Depressivo/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Angústia Psicológica , Risco , Espanha
5.
J Alzheimers Dis ; 79(3): 931-948, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33459706

RESUMO

Proinflammatory cytokines such as tumor necrosis factor (TNF), with its now appreciated key roles in neurophysiology as well as neuropathophysiology, are sufficiently well-documented to be useful tools for enquiry into the natural history of neurodegenerative diseases. We review the broader literature on TNF to rationalize why abruptly-acquired neurodegenerative states do not exhibit the remorseless clinical progression seen in those states with gradual onsets. We propose that the three typically non-worsening neurodegenerative syndromes, post-stroke, post-traumatic brain injury (TBI), and post cardiac arrest, usually become and remain static because of excess cerebral TNF induced by the initial dramatic peak keeping microglia chronically activated through an autocrine loop of microglial activation through excess cerebral TNF. The existence of this autocrine loop rationalizes post-damage repair with perispinal etanercept and proposes a treatment for cerebral aspects of COVID-19 chronicity. Another insufficiently considered aspect of cerebral proinflammatory cytokines is the fitness of the endogenous cerebral anti-TNF system provided by norepinephrine (NE), generated and distributed throughout the brain from the locus coeruleus (LC). We propose that an intact LC, and therefore an intact NE-mediated endogenous anti-cerebral TNF system, plus the DAMP (damage or danger-associated molecular pattern) input having diminished, is what allows post-stroke, post-TBI, and post cardiac arrest patients a strong long-term survival advantage over Alzheimer's disease and Parkinson's disease sufferers. In contrast, Alzheimer's disease and Parkinson's disease patients remorselessly worsen, being handicapped by sustained, accumulating, DAMP and PAMP (pathogen-associated molecular patterns) input, as well as loss of the LC-origin, NE-mediated, endogenous anti-cerebral TNF system. Adrenergic receptor agonists may counter this.


Assuntos
Lesões Encefálicas/fisiopatologia , Doenças Neurodegenerativas/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Fator de Necrose Tumoral alfa/fisiologia , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/fisiopatologia , Doença de Alzheimer/terapia , Anti-Inflamatórios não Esteroides/uso terapêutico , Encéfalo/fisiopatologia , Lesões Encefálicas/diagnóstico , Lesões Encefálicas/terapia , /fisiopatologia , Progressão da Doença , Etanercepte/uso terapêutico , Parada Cardíaca/diagnóstico , Parada Cardíaca/fisiopatologia , Parada Cardíaca/terapia , Humanos , Locus Cerúleo/fisiopatologia , Doenças Neurodegenerativas/diagnóstico , Doenças Neurodegenerativas/terapia , Norepinefrina/fisiologia , Doença de Parkinson/diagnóstico , Doença de Parkinson/fisiopatologia , Doença de Parkinson/terapia , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapia , Sobreviventes , Fator de Necrose Tumoral alfa/antagonistas & inibidores
6.
Lakartidningen ; 1182021 01 21.
Artigo em Sueco | MEDLINE | ID: mdl-33491762

RESUMO

Posterior cortical atrophy (PCA) is a neurodegenerative disease which was described originally in 1988 by dr Frank Benson. PCA is characterized by progressive deficits in higher visual functions while episodic memory and speech are relatively preserved. Studies have shown that the neuropathologic findings in most cases are consistent with Alzheimer's disease (AD). However, patients with PCA show greater occipitoparietal atrophy on neuroimaging compared with the more prominent mesiotemporal atrophy in patients with amnestic AD. Until recently, diagnostics were based mainly on clinical experience due to the lack of validated diagnostic criteria. In 2017, new consensus criteria for the diagnosis and classification of PCA were published. In this article we make a brief review of the disease and describe a 58 year old man with complex visual deficits and apraxia who was ultimately diagnosed with PCA.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/diagnóstico por imagem , Atrofia/patologia , Córtex Cerebral/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Neurodegenerativas/diagnóstico , Doenças Neurodegenerativas/diagnóstico por imagem
7.
Rev Med Suisse ; 17(723): 225-229, 2021 Jan 27.
Artigo em Francês | MEDLINE | ID: mdl-33507666

RESUMO

Cognitive impairment can interfere with the fitness to drive. An increase in requests to assess this aspect is observed at Leenaards Memory Centre. Changes in the law could be an explanatory factor. The views formulated in 2019 are mainly unfavorable because all the patients present cognitive disorders, generally attributed to Alzheimer's disease or a related disorder, but never linked with aging only. Moreover, unfavorable views are frequently expressed before the age of 75. Therefore, each patient is unique, and each decision is based neither on the patient's age or his diagnosis, but rather on his cognitive profile. In this article we discuss the reasons for an unfavorable view and discuss them in the context of the tasks of our centre.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doença de Alzheimer/diagnóstico , Cognição , Disfunção Cognitiva/diagnóstico , Retroalimentação , Humanos , Testes Neuropsicológicos
8.
Harefuah ; 160(1): 30-37, 2021 01.
Artigo em Hebraico | MEDLINE | ID: mdl-33474876

RESUMO

INTRODUCTION: Brief medical certificates are central in legal proceedings for guardianship appointments. They have been increasingly criticized, especially for relying upon medical diagnoses, ignoring functioning, decision-making capacity, needs, and preferences of the individual. Changes in social and legal conceptions led in 2016 to the approval of the 18th amendment to the Legal Capacity and Guardianship Law, with less restrictive alternatives to guardianship, and the necessity to hear the person and his preferences. In parallel there have been changes in the understanding and definition of mental disorders. The American Psychiatric Association's DSM-5 of 2013 suggests in its diagnostic criteria and text, explicitly or implicitly, a diagnostic approach for Neurocognitive Disorders that includes: a. an auxiliary table containing six defined cognitive domains and twenty two subdomains, examples of symptoms or observations and assessments, b. a three-step evaluation process: step one, determining a neurocognitive disorder (major or mild) through careful questioning of one to three sources and person and situation appropriate cognitive tests chosen from three groups with various complexities and thresholds or a documented clinical evaluation, and in addition, assessment of independence in everyday activities is required. Step two examines etiology and step three, behavioral symptomatology, and current severity based on instrumental and basic activities of daily living. The approach offers a reliable and precise diagnosis and a multi-level evaluation. We report a case ruled at a Family Court, concerning an elderly person for whom a guardian was sought for an Alzheimer`s dementia diagnosis based on one brief cognitive score. The court, denying the request, preferred several descriptions of instrumental (mostly financial) and basic activities of daily living and hearing the person directly, his arguments and preferences over the mere diagnosis and test score. Implementation of the above approach would have prevented the unnecessary legal proceeding. The approach might serve as a solid, not complicated, platform for clinical assessment of a person on several levels - diagnosis, cognition, mental state and functioning. Coupled with needs and expressed preferences, this platform would help the court in legal proceedings for guardianship in a person with cognitive deterioration.


Assuntos
Doença de Alzheimer , Transtornos Cognitivos , Atividades Cotidianas , Idoso , Doença de Alzheimer/diagnóstico , Humanos , Tutores Legais , Testes Neuropsicológicos
10.
Eur J Epidemiol ; 36(1): 117-127, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33324997

RESUMO

Brain development and deterioration across the lifespan are integral to the etiology of late-life neurodegenerative disease. Factors that influence the health of the adult brain remain to be elucidated and include risk factors, protective factors, and factors related to cognitive and brain reserve. To address this knowledge gap we designed a life-course study on brain health, which received funding through the EU ERC Programme under the name Origins of Alzheimer's Disease Across the Life course (ORACLE) Study. The ORACLE Study is embedded within Generation R, a prospective population-based cohort study of children and their parents, and links this with the Rotterdam Study, a population-based study in middle-aged and elderly persons. The studies are based in Rotterdam, the Netherlands. Generation R focuses on child health from fetal life until adolescence with repeated in-person examinations, but has also included data collection on the children's parents. The ORACLE Study aims to extend the parental data collection in nearly 2000 parents with extensive measures on brain health, including neuroimaging, cognitive testing and motor testing. Additionally, questionnaires on migraine, depressive symptoms, sleep, and neurological family history were completed. These data allow for the investigation of longitudinal influences on adult brain health as well as intergenerational designs involving children and parents. As a secondary focus, the sampling is enriched by mothers (n = 356) that suffered from hypertensive disorders during pregnancy in order to study brain health in this high-risk population. This article provides an overview of the rationale and the design of the ORACLE Study.


Assuntos
Doença de Alzheimer/diagnóstico , Encéfalo/diagnóstico por imagem , Neuroimagem , Vigilância da População/métodos , Adolescente , Adulto , Idoso , Doença de Alzheimer/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Gravidez , Estudos Prospectivos , Projetos de Pesquisa , Fatores de Risco , Inquéritos e Questionários
11.
Psychiatr Danub ; 32(3-4): 389-394, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33370737

RESUMO

BACKGROUND: Cerebrospinal levels of isoprostanes (IsoPs) have been established as biomarkers of oxidative stress in Alzheimer's disease (AD) and vascular dementia (VD). The value of peripheral levels in the diagnostics of these diseases is less conclusive. The aim of this study was to determine serum 8-iso-prostaglandin-F2alpha (8-iso-PGF2α) levels in Bosnian AD and VD patients and to establish whether there is an association between 8-iso-PGF2α serum concentration and cognitive impairment (CI) in patients with dementia. SUBJECTS AND METHODS: Serum levels of 8-iso-PGF2α were measured by enzyme immunoassay method in AD (n=30) and VD patients (n=30) and control subjects (CG, n=30). The AD and VD group were further stratified according to the level of CI. RESULTS: The serum 8-iso-PGF2α levels were significantly higher in the AD (74.00 pg/mL) and VD groups (38.00 pg/mL) compared to the CG (17.50 pg/mL). A significant difference in serum 8-iso-PGF2α levels between patients with moderate and severe CI was not established in either AD or VD. CONCLUSION: Serum 8-iso-PGF2α proved to be a good biomarker in AD and VD, however it cannot be recommended for the differentiation of moderate and severe CI.


Assuntos
Doença de Alzheimer/diagnóstico , Demência Vascular/diagnóstico , Dinoprosta/análogos & derivados , Estresse Oxidativo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Bósnia e Herzegóvina , Dinoprosta/análise , Feminino , Humanos
12.
PLoS One ; 15(12): e0243041, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33362250

RESUMO

Alzheimer disease (AD) is a neurodegenerative disorder characterized by the aberrant production and accumulation of amyloid-ß (Aß) peptides in the brain. Accumulated Aß in soluble oligomer and insoluble plaque forms are considered to be a pathological culprit and biomarker of the disorder. Here, we report a fluorescent universal Aß-indicator YI-13, 5-(4-fluorobenzoyl)-7,8-dihydropyrrolo[1,2-b]isoquinolin-9(6H)-one, which detects Aß monomers, dimers, and plaques. We synthesized a library of 26 fluorescence chemicals with the indolizine core and screen them through a series of in vitro tests utilizing Aß as a target and YI-13 was selected as the final imaging candidate. YI-13 was found to stain and visualize insoluble Aß plaques in the brain tissue, of a transgenic mouse model with five familial AD mutations (5XFAD), by a histochemical approach and to label soluble Aß oligomers within brain lysates of the mouse model under a fluorescence plate reader. Among oligomers aggregated from monomers and synthetic dimers from chemically conjugated monomers, YI-13 preferred the dimeric Aß.


Assuntos
Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/química , Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Indolizinas/síntese química , Indolizinas/farmacologia , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Fluorescência , Humanos , Indolizinas/química , Camundongos , Camundongos Transgênicos , Estrutura Molecular , Mutação , Multimerização Proteica , Bibliotecas de Moléculas Pequenas/síntese química , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia
13.
Arq Neuropsiquiatr ; 78(11): 713-723, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33331465

RESUMO

Spatial disorientation has been observed in mild cognitive impairment (MCI) and is associated with a higher risk of progression to Alzheimer's disease (AD). However, there is no gold standard assessment for spatial orientation and paper-and-pencil tests lack ecological validity. Recently, there has been an increasing number of studies demonstrating the role of spatial disorientation as a cognitive marker of pathological decline, shedding new light on its importance for MCI. This systematic review aimed to investigate the accuracy of spatial orientation tasks for the diagnosis of MCI by comparison with cognitively healthy elderly. The search was conducted in the databases Medical Literature Analysis and Retrieval System Online (MEDLINE/PubMed), Web of Science, Scopus, Excerpta Medica Database (Embase), Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs) and Scientific Electronic Library Online (SciELO). Only original studies reporting spatial orientation assessment in MCI patients compared to a healthy control group were included. Studies were excluded if the MCI classification did not follow well described criteria and/or if accuracy results of spatial orientation assessment were not provided. Seven studies met the eligibility criteria, describing a variety of spatial orientation assessments including questionnaires, paper-and-pencil, office-based route learning, and computer-based and virtual reality tasks. Spatial orientation tasks demonstrated moderate to high accuracy in detecting elderly with MCI compared to cognitively healthy elderly, with areas under the curve (AUC) ranging from 0.77 to 0.99. However, important methodological issues were found in the selected studies which should be considered when interpreting results. Although the inclusion of spatial orientation assessments in MCI evaluations seems to have significant value, further studies are needed to clarify their true capacity to distinguish pathological from non-pathological aging.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Idoso , Doença de Alzheimer/diagnóstico , Disfunção Cognitiva/diagnóstico , Progressão da Doença , Humanos , Orientação Espacial , Sensibilidade e Especificidade
14.
PLoS One ; 15(12): e0243535, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33320870

RESUMO

High-frequency oscillations of the frontal cortex are involved in functions of the brain that fuse processed data from different sensory modules or bind them with elements stored in the memory. These oscillations also provide inhibitory connections to neural circuits that perform lower-level processes. Deficit in the performance of these oscillations has been examined as a marker for Alzheimer's disease (AD). Additionally, the neurodegenerative processes associated with AD, such as the deposition of amyloid-beta plaques, do not occur in a spatially homogeneous fashion and progress more prominently in the medial temporal lobe in the early stages of the disease. This region of the brain contains neural circuitry involved in olfactory perception. Several studies have suggested that olfactory deficit can be used as a marker for early diagnosis of AD. A quantitative assessment of the performance of the olfactory system can hence serve as a potential biomarker for Alzheimer's disease, offering a relatively convenient and inexpensive diagnosis method. This study examines the decline in the perception of olfactory stimuli and the deficit in the performance of high-frequency frontal oscillations in response to olfactory stimulation as markers for AD. Two measurement modalities are employed for assessing the olfactory performance: 1) An interactive smell identification test is used to sample the response to a sizable variety of odorants, and 2) Electroencephalography data are collected in an olfactory perception task with a pair of selected odorants in order to assess the connectivity of frontal cortex regions. Statistical analysis methods are used to assess the significance of selected features extracted from the recorded modalities as Alzheimer's biomarkers. Olfactory decline regressed to age in both healthy and mild AD groups are evaluated, and single- and multi-modal classifiers are also developed. The novel aspects of this study include: 1) Combining EEG response to olfactory stimulation with behavioral assessment of olfactory perception as a marker of AD, 2) Identification of odorants most significantly affected in mild AD patients, 3) Identification of odorants which are still adequately perceived by mild AD patients, 4) Analysis of the decline in the spatial coherence of different oscillatory bands in response to olfactory stimulation, and 5) Being the first study to quantitatively assess the performance of olfactory decline due to aging and AD in the Iranian population.


Assuntos
Doença de Alzheimer/diagnóstico , Lobo Frontal/patologia , Percepção Olfatória/fisiologia , Idoso , Doença de Alzheimer/fisiopatologia , Biomarcadores/metabolismo , Encéfalo/patologia , Córtex Cerebral/patologia , Diagnóstico Precoce , Eletroencefalografia/métodos , Feminino , Lobo Frontal/metabolismo , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Odorantes , Olfato/fisiologia , Lobo Temporal/patologia
15.
Artigo em Russo | MEDLINE | ID: mdl-33244960

RESUMO

BACKGROUND: Amnestic mild cognitive impairment (aMCI) is considered as a possible earliest pre-dementia clinical stage of Alzheimer's disease (AD). Taking into account the prominent role of neuroinflammation in the pathogenesis of AD, it is quite important to study possible immunological markers of the risk of aMCI progression and the changes in immune parameters in patients. OBJECTIVE: To study the immunological variants of aMCI and AD based on the parameters of humoral and cell immunity, levels of key cytokines and presence of systemic inflammation, and to explore the link between changes in the immune parameters and clinical prognosis. MATERIAL AND METHODS: One hundred patients with a diagnosis of aMCI, 45 patients with AD at the stage of mild to moderate dementia and 40 people without cognitive impairment (the control group) were enrolled into the study. Immunological assessment included determination of the concentration of key cytokines, C-reactive protein, circulating immune complexes and immunoglobulins (Ig A, M, G) in blood serum by ELISA, determination of the main subpopulations of lymphocytes by flow cytometry. RESULTS AND CONCLUSION: Four main immunological variants of aMCI syndrome associated with clinical prognosis were identified. The detected changes in immune parameters are important for further studies to assess an effect of viral and bacterial infections, intestinal microflora disorders on a clinical prognosis in patients with different immunological variants of aMCI syndrome.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Microbioma Gastrointestinal , Doença de Alzheimer/diagnóstico , Disfunção Cognitiva/diagnóstico , Progressão da Doença , Humanos , Testes Neuropsicológicos
18.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 3204-3207, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018686

RESUMO

Alzheimer's disease (AD) affects approximately 30 million people worldwide, and this number is predicted to triple by 2050 unless further discoveries facilitate the early detection and prevention of the disease. Computerized walkways for simultaneous assessment of motor-cognitive performance, known as a dual-task assessment, has been used to associate changes in gait characteristics to mild cognitive impairment (MCI) with early-stage disease. However, to our best knowledge, there is no validated method to detect MCI using the collective analysis of these gait characteristics. In this paper, we develop a machine learning approach to analyze the gait data from the dual-task assessment in order to detect subjects with cognitive impairment from healthy individuals. We collected dual-task gait data from a computerized walkway of a total of 92 subjects with 31 healthy control (HC) and 61 MCI. Using support vector machine (SVM) and gradient tree boosting, we developed a classifier to differentiate MCI from HC subjects and compared the results with a paper-based questionnaire assessment that has been commonly used in clinical practice. SVM provided the highest accuracy of 77.17% with 81.97% sensitivity and 67.74% specificity. Our results indicate the potential of machine learning + dual-task assessment to enable early diagnosis of cognitive decline before it advances to dementia and AD, so that early intervention or prevention strategies can be initiated.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doença de Alzheimer/diagnóstico , Disfunção Cognitiva/diagnóstico , Diagnóstico Precoce , Marcha , Humanos , Aprendizado de Máquina
19.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 4226-4228, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018929

RESUMO

The purpose of this paper is to develop an inexpensive, wearable, and portable monitoring system with wireless capabilities for signal acquisition of the user's surrounding soundscape and electroencephalography (EEG). The end-goal of this device is to monitor high-risk populations that are developing into earlier stages of Alzheimer's Disease (AD). Currently, the development of such device is still within preliminary phase and has only been tested in healthy individuals. Future applications of our monitoring system may be used as a non-invasive and inexpensive diagnostic tool for early detection of AD, potentially paving a new platform for therapeutic intervention. The system consists of low-weight bearing components, including an analog front-end and a single-board computer. The analog front-end contains three independent EEG, reference, bias, and auditory recording channels. The single-board computer timestamps and encrypts the incoming channels prior to local or "cloud" storage. Cloud storage provides ease-of-access and offline data analysis without the need to physically extract the data from the monitoring system. A portable/rechargeable battery provides power to the entire monitoring system for over 4 hours of operation. A graphical user-interface (GUI) was developed for secured remote access to data, parameter settings, and system configurations. The performance of the system was tested by measuring the frequency following response (FFR) in the captured EEG signals with respect to periodic auditory stimuli.


Assuntos
Doença de Alzheimer , Doença de Alzheimer/diagnóstico , Eletrocardiografia , Eletroencefalografia , Desenho de Equipamento , Humanos , Monitorização Fisiológica
20.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 5432-5435, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33019209

RESUMO

Early detection of Alzheimer's Disease (AD) is critical in creating better outcomes for patients. Performance in complex tasks such as vehicular driving may be a sensitive tool for early detection of AD and serve as a good indicator of functional status. In this study, we investigate the classification of AD patients and controls using driving simulator data. Our results show that machine learning algorithms, especially random forest classifier, can accurately discriminate AD patients and controls (AUC = 0.96, Sensitivity = 87%, and Specificity = 93%). The model-identified most important features include Pothole Avoidance, Road Signs Recalled, Inattention Measurements, Reaction Time, and Detection Times, among others, all of which closely align with previous studies about cognitive functions that are affected by AD.


Assuntos
Doença de Alzheimer , Condução de Veículo , Doença de Alzheimer/diagnóstico , Cognição , Humanos , Aprendizado de Máquina , Tempo de Reação
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