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OBJECTIVE: To explore the accuracy of plasma neurofilament light chain (NfL) as a biomarker for diagnosis and staging of cognitive impairment, in a large cohort with of previously diagnosed patients in clinical practice. METHODS: Retrospective, cross-sectional, monocentric study, from a tertiary memory clinic. Patients underwent cerebrospinal fluid core Alzheimer's disease (AD) biomarker evaluation using ELISA or Elecsys methods, and plasma NfL analysis using the single molecule array technology. The patients' biomarker data were examined for associations with: i/cognitive status ii/presence of neurodegenerative disease and iii/diagnostic groups. Associations between core CSF biomarkers and plasma NfL were determined. RESULTS: Participants (N = 558, mean age = 69.2 ± 8.8, 56.5% women) were diagnosed with AD (n = 274, considering dementia and MCI stages), frontotemporal dementia (FTD, n = 55), Lewy body disease (LBD, n = 40, considering MCI and dementia stages), other neurodegenerative diseases, n = 57 (e.g Supranuclear Palsy, Corticobasal syndrome), non-neurodegenerative cognitive impairment (NND, n = 79, e.g. vascular lesions, epilepsy or psychiatric disorders) or subjective cognitive impairment (SCI, n = 53). Mean plasma NfL (log, pg/mL) levels were higher in neurodegenerative than non-neurodegenerative disorders (1.35 ± 0.2 vs 1.16 ± 0.23, p < 0.001), higher in all diagnostic groups than in SCI (1.06 ± 0.23) p < 0.001), and associated with the stage of cognitive impairment (p < 0.001). The addition of plasma NfL to a clinical model (age, MMSE and APOE ε4 carriership) marginally improved the discrimination of degenerative from non-degenerative disorders in ROC analysis (AUC clinical model: 0.81, 95% CI = [0.77;0.85] AUC clinical model + plasma NfL: AUC = 0.83 95% CI = [0.78;0.87], delta Akaike information criterion = -11.7). DISCUSSION: Plasma NfL could help discrimination between degenerative and non-degenerative cognitive disorders, albeit not better than comprehensive clinical evaluation.
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Doença de Alzheimer , Disfunção Cognitiva , Demência Frontotemporal , Doença por Corpos de Lewy , Doenças Neurodegenerativas , Feminino , Humanos , Masculino , Doença de Alzheimer/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores , Disfunção Cognitiva/líquido cefalorraquidiano , Estudos Transversais , Filamentos Intermediários , Proteínas de Neurofilamentos , Estudos Retrospectivos , Proteínas tau/líquido cefalorraquidiano , Pessoa de Meia-Idade , IdosoRESUMO
OBJECTIVE: Behavioral and psychological symptoms of dementia (BPSD) profiles vary depending on etiology in patients with mild-to-moderate BPSD. It is not known if similar differences exist in patients with severe BPSD. METHODS: We analyzed data collected at baseline in 398 patients with severe BPSD (NPI ≥ 32) and defined diagnosis of dementia (Alzheimer's disease [AD] 297; frontotemporal dementia [FTD] 39; Lewy body disease/Parkinsonian dementia [LBD/PD] 31; and vascular dementia [VD] 31) included in the European multicenter cohort RECAGE. RESULTS: Mean total NPI was 52.11 (18.55). LBD/PD patients demonstrated more hallucinations, more anxiety and more delusions than patients with other dementia. FTD patients had less delusions and more disinhibition than patients with other neurodegenerative disorders. These profiles overlapped partially with those reported in the literature in patients with less severe symptoms. CONCLUSION: Patients with severe BPSD display different and specific profiles of neuropsychiatric symptoms depending on dementia etiology.
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Doença de Alzheimer , Demência Vascular , Demência Frontotemporal , Doença por Corpos de Lewy , Humanos , Demência Frontotemporal/complicações , Demência Frontotemporal/diagnóstico , Escalas de Graduação Psiquiátrica , Doença de Alzheimer/psicologia , Doença por Corpos de Lewy/psicologia , Demência Vascular/complicaçõesRESUMO
BACKGROUND: Parkinson's disease (PD) is associated with a 3-fold mortality risk, which is closely related to advancing age. Evidence is lacking regarding the factors associated with the risks of mortality or nursing-home (NH) admission, in elderly patients with PD. We aimed at identifying the clinical characteristics associated with these outcomes, in older community-dwelling patients with late-onset PD. METHODS: Retrospective, observational analysis of data from geriatric day hospital patients. Motor assessment included Unified Parkinson Disease Rating Scale (UPDRS) part III score, Tinetti Performance Oriented Mobility Assessment (POMA) balance and gait tests, and gait speed. Levodopa equivalent dose, comorbidity, cognitive performance, Activities of Daily Living performance were examined. Cox proportional hazards models were performed to identify the factors associated with mortality and NH admission rate (maximum follow-up time = 5 years). RESULTS: We included 98 patients, mean age 79.4 (SD = 5.3) of whom 18 (18.3%) died and 19 (19.4%) were admitted into NH, over a median follow-up of 4 years. In multivariate Cox models, poor balance on the Tinetti POMA scale (HR = 0.82 95%CI (0.66-0.96), p = .023) and older age (HR = 1.12 95%CI (1.01-1.25), p = .044) were the only variables significantly associated with increased mortality risk. A Tinetti balance score below 11/16 was associated with a 6.7 hazard for mortality (p = .006). No specific factor was associated with NH admissions. CONCLUSIONS: Age and the Tinetti POMA score were the only factors independently associated with mortality. The Tinetti POMA scale should be considered for balance assessment and as a screening tool for the most at-risk individuals, in this population.
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Doença de Parkinson , Idoso , Humanos , Atividades Cotidianas , Marcha , Estudos Longitudinais , Doença de Parkinson/diagnóstico , Equilíbrio Postural , Estudos RetrospectivosRESUMO
OBJECTIVE: Objective structured clinical examinations (OSCE) are one of the main modalities of skills' assessment of medical students. We aimed to evaluate the educational value of the participation of third-year medical students in OSCE as standardized patients. METHODS: We conducted a pilot OSCE session where third-year students participated in sixth-year students' OSCE as standardized patients (cases). Their scores in their own subsequent OSCE exams were compared with third-year students who had not participated (controls). Students' perceptions (stress, preparedness, ease) regarding their OSCE were compared with self-administered questionnaires. RESULTS: A total of 42 students were included (9 cases and 33 controls). Median [IQR] overall score (out of 20 points) obtained by the cases was 17 [16.3-18] versus 14.5 [12.7-16.3] for controls (p < 0.001). Students' perception of their evaluation (difficulty, stress, communication) was not significantly different between cases and controls. Most cases agreed that their participation was beneficial in reducing their stress (67%), increasing their preparedness (78%) and improving their communication skills (100%). All cases agreed that this participation should be offered more widely. CONCLUSION: Students' participation in OSCE as standardized patients led to better performance on their own OSCE and were considered beneficial. This approach could be more broadly generalized to improve student performance.
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Avaliação Educacional , Estudantes de Medicina , Humanos , Faculdades de Medicina , Paris , Competência ClínicaRESUMO
Cognitive functions enable us to receive, select, store, transform, process and retrieve the information we receive from the outside world. These functions are controlled by different brain structures that interact with each other, enabling us to interact with and understand the world around us. In the course of aging or the onset of neurocognitive diseases, these functions may be impaired to a greater or lesser extent, giving rise to a considerable variety of neurocognitive impairment profiles. When a patient appears to be suffering from neurocognitive disorders, a thorough neuropsychological evaluation can help to characterize this impairment precisely, before guiding therapeutic management. It also contributes significantly to the etiological diagnosis of the disorder.
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Cognição , Transtornos Neurocognitivos , Humanos , Testes NeuropsicológicosRESUMO
Background: Alpha-synuclein, abnormally aggregated in Dementia with Lewy Bodies (DLB), could represent a potential biomarker to improve the differentiation between DLB and Alzheimer's disease (AD). Our main objective was to compare Cerebrospinal Fluid (CSF) alpha-synuclein levels between patients with DLB, AD and Neurological Control (NC) individuals. Methods: In a monocentric retrospective study, we assessed CSF alpha-synuclein concentration with a validated ELISA kit (ADx EUROIMMUN) in patients with DLB, AD and NC from a tertiary memory clinic. Between-group comparisons were performed, and Receiver Operating Characteristic analysis was used to identify the best CSF alpha-synuclein threshold. We examined the associations between CSF alpha-synuclein, other core AD CSF biomarkers and brain MRI characteristics. Results: We included 127 participants (mean age: 69.3 ± 8.1, Men: 41.7%). CSF alpha-synuclein levels were significantly lower in DLB than in AD (1.28 ± 0.52 ng/mL vs. 2.26 ± 0.91 ng/mL, respectively, p < 0.001) without differences due to the stage of cognitive impairment. The best alpha-synuclein threshold was characterized by an Area Under the Curve = 0.85, Sensitivity = 82.0% and Specificity = 76.0%. CSF alpha-synuclein was associated with CSF AT(N) biomarkers positivity (p < 0.01) but not with hippocampal atrophy or white matter lesions. Conclusion: CSF Alpha-synuclein evaluation could help to early differentiate patients with DLB and AD in association with existing biomarkers.
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Doença de Alzheimer , Doença por Corpos de Lewy , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , alfa-Sinucleína/líquido cefalorraquidiano , Doença de Alzheimer/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Doença por Corpos de Lewy/diagnóstico , Doença por Corpos de Lewy/líquido cefalorraquidiano , Estudos Retrospectivos , Proteínas tau/líquido cefalorraquidiano , FemininoRESUMO
PURPOSE OF REVIEW: Ketogenic diets (KD) are validated treatments of pharmacoresistant epilepsy. Their interest in neurodegenerative diseases such as Alzheimer's disease (AD) has been suggested, because ketone bodies may reduce neuroinflammation, improve neurotransmitters transport pathway, synaptic maintenance, and reduce brain ß-amyloid deposition. In this updated review, we aimed at critically examining the evidence of the past 2 years regarding KD or ketogenic supplements (KS) on cognitive and biological/neuropathological outcomes. We conducted our search in preclinical studies (animal models of AD) or in humans with or without cognitive impairment. RECENT FINDINGS: Overall, 12 studies were included: four in animal models of AD and eight in humans. In preclinical studies, we found additional evidence for a decrease in cerebral inflammation as well as in specific features of AD: ß-amyloid, aggregates of tau protein under KD/KS. Several AD mouse models experienced clinical improvements. Human studies reported significant cognitive benefits, improved brain metabolism and biomarkers change under KD/KS, despite rather short-term interventions. Adherence to KD or KS was acceptable with frequent, but minor gastrointestinal adverse effects. SUMMARY: The present review gathered additional evidence for both pathophysiological and clinical benefits of KS/KD in AD. Further studies are warranted with a biomarker-based selection of AD participants and long-term follow-up.
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Doença de Alzheimer , Disfunção Cognitiva , Dieta Cetogênica , Peptídeos beta-Amiloides , Animais , Humanos , Corpos Cetônicos , CamundongosRESUMO
Post-lumbar puncture headache is the main adverse event from lumbar puncture and occurs in 3.5% to 33% of patients, causing functional and socio-professional disability. We searched the post-lumbar puncture headache literature and, based on this review and personal expertise, identified and addressed 19 frequently asked questions regarding post-lumbar puncture headache risk factors and prevention. Among the nonmodifiable factors, older age is associated with a lower incidence of post-lumbar puncture headache, while female sex, lower body mass index, and history of headache might be associated with increased risk. The use of atraumatic, noncutting needles is the most effective intervention for post-lumbar puncture headache prevention. These needles are not more difficult to use than cutting needles. Other commonly recommended measures (eg, fluid supplementation, caffeine) appear unhelpful, and some (eg, bed rest) may worsen post-lumbar puncture headache.
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Agulhas/classificação , Cefaleia Pós-Punção Dural/prevenção & controle , Punção Espinal/métodos , Fatores Etários , Índice de Massa Corporal , Feminino , Humanos , Masculino , Agulhas/efeitos adversos , Cefaleia Pós-Punção Dural/etiologia , Fatores de Risco , Fatores Sexuais , Punção Espinal/efeitos adversosRESUMO
BACKGROUND: The ε4 allele of apolipoprotein E (APOE) gene and increasing age are two of the most important known risk factors for developing Alzheimer disease (AD). The diagnosis of AD based on clinical symptoms alone is known to have poor specificity; recently developed diagnostic criteria based on biomarkers that reflect underlying AD neuropathology allow better assessment of the strength of the associations of risk factors with AD. Accordingly, we examined the global and age-specific association between APOE genotype and AD by using the A/T/N classification, relying on the cerebrospinal fluid (CSF) levels of ß-amyloid peptide (A, ß-amyloid deposition), phosphorylated tau (T, pathologic tau), and total tau (N, neurodegeneration) to identify patients with AD. METHODS AND FINDINGS: This case-control study included 1,593 white AD cases (55.4% women; mean age 72.8 [range = 44-96] years) with abnormal values of CSF biomarkers from nine European memory clinics and the American Alzheimer's Disease Neuroimaging Initiative (ADNI) study. A total of 11,723 dementia-free controls (47.1% women; mean age 65.6 [range = 44-94] years) were drawn from two longitudinal cohort studies (Whitehall II and Three-City), in which incident cases of dementia over the follow-up were excluded from the control population. Odds ratio (OR) and population attributable fraction (PAF) for AD associated with APOE genotypes were determined, overall and by 5-year age categories. In total, 63.4% of patients with AD and 22.6% of population controls carried at least one APOE ε4 allele. Compared with non-ε4 carriers, heterozygous ε4 carriers had a 4.6 (95% confidence interval 4.1-5.2; p < 0.001) and ε4/ε4 homozygotes a 25.4 (20.4-31.2; p < 0.001) higher OR of AD in unadjusted analysis. This association was modified by age (p for interaction < 0.001). The PAF associated with carrying at least one ε4 allele was greatest in the 65-70 age group (69.7%) and weaker before 55 years (14.2%) and after 85 years (22.6%). The protective effect of APOE ε2 allele for AD was unaffected by age. Main study limitations are that analyses were based on white individuals and AD cases were drawn from memory centers, which may not be representative of the general population of patients with AD. CONCLUSIONS: In this study, we found that AD diagnosis based on biomarkers was associated with APOE ε4 carrier status, with a higher OR than previously reported from studies based on only clinical AD criteria. This association differs according to age, with the strongest effect at 65-70 years. These findings highlight the need for early interventions for dementia prevention to mitigate the effect of APOE ε4 at the population level.
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Envelhecimento/líquido cefalorraquidiano , Envelhecimento/genética , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/genética , Apolipoproteína E4/líquido cefalorraquidiano , Apolipoproteína E4/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Biomarcadores/líquido cefalorraquidiano , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
A 70-year-old patient was admitted with rapidly progressive cognitive decline associated with limitations in activities of daily living, weight loss and cerebellar ataxia. The diagnosis of giant cell arteritis (GCA) with vascular involvement was made, based on the presence of a metabolically active vasculitis of the brachiocephalic trunk on 18FDG-PET imaging. Temporal artery biopsy also revealed pan-arteritis. A progressive regression of cognitive disorders occurred under corticosteroid treatment and immunosuppressive therapy. Previously published case reports concerning this atypical presentation of GCA are scarce. They suggest that numerous cognitive symptoms, such as impairment of short-term memory, disorientation, delirium, impaired attention or visual hallucinations might be related to GCA. Thus, this diagnosis should be considered as a curable cause of unexplained cognitive impairment associated with weight loss and systemic inflammation.
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Demência , Arterite de Células Gigantes , Atividades Cotidianas , Corticosteroides , Idoso , Biópsia , Arterite de Células Gigantes/complicações , Arterite de Células Gigantes/diagnóstico , Arterite de Células Gigantes/tratamento farmacológico , Humanos , Artérias TemporaisRESUMO
p-glycoprotein (P-gp) is an efflux transporter of xenobiotic and endogenous compounds across the blood-brain barrier (BBB). P-gp plays an essential role by limiting passage of these compounds into the brain tissue. It is susceptible to drug-drug interactions when interactors drugs are co-administrated. The efficiency of P-gp may be affected by the aging process and the development of neurodegenerative diseases. Studying this protein in older adults is therefore highly relevant for all these reasons. Understanding P-gp activity in vivo is essential when considering the physiological, pathophysiological, and pharmacokinetic perspectives, as these aspects seem to be interconnected to some extent. In vivo exploration in humans is based on neuroimaging techniques, which have been improving over the last years. The advancement of exploration and diagnostic tools is opening up new prospects for understanding P-gp activity at the BBB.
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Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Barreira Hematoencefálica , Barreira Hematoencefálica/metabolismo , Humanos , Idoso , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Envelhecimento/metabolismo , Envelhecimento/fisiologia , Idoso de 80 Anos ou mais , Encéfalo/metabolismo , FarmacocinéticaRESUMO
p-glycoprotein (P-gp) is an efflux transporter of xenobiotic and endogenous compounds across the blood-brain barrier (BBB). P-gp plays an essential role by limiting passage of these compounds into the brain tissue. It is susceptible to drug-drug interactions when interactors drugs are co-administrated. The efficiency of P-gp may be affected by the aging process and the development of neurodegenerative diseases. Studying this protein in older adults is therefore highly relevant for all these reasons. Understanding P-gp activity in vivo is essential when considering the physiological, pathophysiological, and pharmacokinetic perspectives, as these aspects seem to be interconnected to some extent. In vivo exploration in humans is based on neuroimaging techniques, which have been improving over the last years. The advancement of exploration and diagnostic tools is opening up new prospects for understanding P-gp activity at the BBB.
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Plasma neurofilament light chain (NfL) is a promising biomarker of axonal damage for the diagnosis of neurodegenerative diseases. Phosphorylated neurofilament heavy chain (pNfH) has demonstrated its value in motor neuron diseases diagnosis, but has less been explored for dementia diagnosis. In a cross-sectional study, we compared cerebrospinal fluid (CSF) and plasma NfL and pNfH levels in n = 188 patients from Lariboisière Hospital, Paris, France, including AD patients at mild cognitive impairment stage (AD-MCI, n = 36) and dementia stage (n = 64), non-AD MCI (n = 38), non-AD dementia (n = 28) patients and control subjects (n = 22). Plasma NfL, plasma and CSF pNfH levels were measured using Simoa and CSF NfL using ELISA. The correlation between CSF and plasma levels was stronger for NfL than pNfH (rho = 0.77 and rho = 0.52, respectively). All neurofilament markers were increased in AD-MCI, AD dementia and non-AD dementia groups compared with controls. CSF NfL, CSF pNfH and plasma NfL showed high performance to discriminate AD at both MCI and dementia stages from control subjects [AUC (area under the curve) = 0.82-0.91]. Plasma pNfH displayed overall lower AUCs for discrimination between groups compared with CSF pNfH. Neurofilament markers showed similar moderate association with cognition. NfL levels displayed significant association with mediotemporal lobe atrophy and white matter lesions in the AD group. Our results suggest that CSF NfL and pNfH as well as plasma NfL levels display equivalent performance in both positive and differential AD diagnosis in memory clinic settings. In contrast to motoneuron disorders, plasma pNfH did not demonstrate added value as compared with plasma NfL.
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Doença de Alzheimer , Disfunção Cognitiva , Doença dos Neurônios Motores , Doenças do Sistema Nervoso , Humanos , Doença de Alzheimer/líquido cefalorraquidiano , Biomarcadores , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/líquido cefalorraquidiano , Estudos Transversais , Proteínas de Neurofilamentos , Proteínas tau/líquido cefalorraquidianoRESUMO
Adiponectin is an adipokine playing a central role in the regulation of energy homeostasis, carbohydrate and lipid metabolism, as well as immunomodulation. The relationship between Alzheimer's disease (AD) and body composition has highlighted the bidirectional crosstalk between AD's pathophysiology and metabolic disorders. This review aimed to report the current state of knowledge about cellular and molecular mechanisms linking adiponectin and AD, in preclinical studies. Then, we reviewed human studies to assess the relationship between adiponectin levels and AD diagnosis. We also examined the risk of incident AD regarding the participants' baseline adiponectin level, as well as the relationship of adiponectin and cognitive decline in patients with AD. We conducted a systematic review, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline, of studies published over the last decade on MEDLINE and Cochrane databases. Overall, we reviewed 34 original works about adiponectin in AD, including 11 preclinical studies, two both preclinical and human studies and 21 human studies. Preclinical studies brought convincing evidence for the neuroprotective role of adiponectin on several key mechanisms of AD. Human studies showed conflicting results regarding the relationship between AD and adiponectin levels, as well as regarding the cross-sectional association between cognitive function and adiponectin levels. Adiponectin did not appear as a predictor of incident AD, nor as a predictor of cognitive decline in patients with AD. Despite solid preclinical evidence suggesting the protective role of adiponectin in AD, inconsistent results in humans supports the need for further research.
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Adiponectina , Doença de Alzheimer , Animais , Humanos , Adipocinas , Adiponectina/metabolismo , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico , Cognição , Estudos TransversaisRESUMO
Background: Psychosis, characterized by delusions and/or hallucinations, is frequently observed during the progression of Alzheimer's disease (AD) and other neurodegenerative dementias (ND) (i.e., dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD)) and cause diagnostic and management difficulties. Objective: This review aims at presenting a concise and up-to-date overview of psychotic symptoms that occur in patients with ND with a comparative approach. Methods: A systematic review was conducted following the PRISMA guidelines. 98 original studies investigating psychosis phenotypes in neurodegenerative dementias were identified (40 cohort studies, 57 case reports). Results: Psychosis is a frequently observed phenomenon during the course of ND, with reported prevalence ranging from 22.5% to 54.1% in AD, 55.9% to 73.9% in DLB, and 18% to 42% in FTD. Throughout all stages of these diseases, noticeable patterns emerge depending on their underlying causes. Misidentification delusions (16.6-78.3%) and visual hallucinations (50-69.6%) are frequently observed in DLB, while paranoid ideas and somatic preoccupations seem to be particularly common in AD and FTD, (respectively 9.1-60.3% and 3.10-41.5%). Limited data were found regarding psychosis in the early stages of these disorders. Conclusions: Literature data suggest that different ND are associated with noticeable variations in psychotic phenotypes, reflecting disease-specific tendencies. Further studies focusing on the early stages of these disorders are necessary to enhance our understanding of early psychotic manifestations associated with ND and help in differential diagnosis issues.
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Transtornos Psicóticos , Humanos , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/epidemiologia , Doenças Neurodegenerativas/epidemiologia , Doenças Neurodegenerativas/complicações , Doenças Neurodegenerativas/psicologia , Doenças Neurodegenerativas/diagnóstico , Doença por Corpos de Lewy/diagnóstico , Doença por Corpos de Lewy/complicações , Doença por Corpos de Lewy/psicologia , Doença por Corpos de Lewy/epidemiologia , Demência Frontotemporal/diagnóstico , Demência Frontotemporal/epidemiologia , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/psicologia , Doença de Alzheimer/complicações , Delusões/diagnóstico , Delusões/epidemiologia , Delusões/etiologia , Demência/epidemiologia , Demência/diagnósticoRESUMO
BACKGROUND: Increasing evidence supports the use of plasma biomarkers of amyloid, tau, neurodegeneration, and neuroinflammation for diagnosis of dementia. However, their performance for positive and differential diagnosis of dementia with Lewy bodies (DLB) in clinical settings is still uncertain. METHODS: We conducted a retrospective biomarker study in two tertiary memory centers, Paris Lariboisière and CM2RR Strasbourg, France, enrolling patients with DLB (n = 104), Alzheimer's disease (AD, n = 76), and neurological controls (NC, n = 27). Measured biomarkers included plasma Aß40/Aß42 ratio, p-tau181, NfL, and GFAP using SIMOA and plasma YKL-40 and sTREM2 using ELISA. DLB patients with available CSF analysis (n = 90) were stratified according to their CSF Aß profile. RESULTS: DLB patients displayed modified plasma Aß ratio, p-tau181, and GFAP levels compared with NC and modified plasma Aß ratio, p-tau181, GFAP, NfL, and sTREM2 levels compared with AD patients. Plasma p-tau181 best differentiated DLB from AD patients (ROC analysis, area under the curve [AUC] = 0.80) and NC (AUC = 0.78), and combining biomarkers did not improve diagnosis performance. Plasma p-tau181 was the best standalone biomarker to differentiate amyloid-positive from amyloid-negative DLB cases (AUC = 0.75) and was associated with cognitive status in the DLB group. Combining plasma Aß ratio, p-tau181 and NfL increased performance to identify amyloid copathology (AUC = 0.79). Principal component analysis identified different segregation patterns of biomarkers in the DLB and AD groups. CONCLUSIONS: Amyloid, tau, neurodegeneration and neuroinflammation plasma biomarkers are modified in DLB, albeit with moderate diagnosis performance. Plasma p-tau181 can contribute to identify Aß copathology in DLB.
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Peptídeos beta-Amiloides , Biomarcadores , Doença por Corpos de Lewy , Proteínas tau , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Alzheimer/sangue , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/sangue , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Axônios/patologia , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Proteína 1 Semelhante à Quitinase-3/sangue , Proteína 1 Semelhante à Quitinase-3/líquido cefalorraquidiano , Diagnóstico Diferencial , Proteína Glial Fibrilar Ácida/sangue , Proteína Glial Fibrilar Ácida/líquido cefalorraquidiano , Doença por Corpos de Lewy/sangue , Doença por Corpos de Lewy/líquido cefalorraquidiano , Doença por Corpos de Lewy/diagnóstico , Doença por Corpos de Lewy/patologia , Glicoproteínas de Membrana , Proteínas de Neurofilamentos/sangue , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Doenças Neuroinflamatórias/sangue , Doenças Neuroinflamatórias/diagnóstico , Doenças Neuroinflamatórias/líquido cefalorraquidiano , Fragmentos de Peptídeos/sangue , Fragmentos de Peptídeos/líquido cefalorraquidiano , Receptores Imunológicos/sangue , Estudos Retrospectivos , Proteínas tau/sangue , Proteínas tau/líquido cefalorraquidianoRESUMO
PURPOSE: To assess the skill level and self-confidence of medical residents in geriatrics with regard to conducting the lumbar puncture (LP) procedure and to study the potential benefits of training with simulation and virtual reality. METHODS: First, a questionnaire survey was conducted among all French residents in geriatrics in the Paris area to assess their knowledge and self-confidence regarding the practice of LP in older adults. Second, we set up a simulation LP training session combined with virtual reality (3D video) training for selected respondents of the first survey. Third, we performed post-simulation survey for the attendees of the simulation training. Finally, a follow-up survey was conducted to examine the change in self-confidence and the success rate in clinical practice. RESULTS: Fifty-five residents responded to the survey (response rate = 36.4%). The importance of mastering LP was fully recognized by the residents in geriatrics (95.3%), so most of them (94.5%) advocated for the need for additional practical training. Fourteen residents took part in the training (average rating = 4.7 on a 5-point scale). Simulation was regarded by 83% of the respondents as the most useful tool for their practice. We observed a significant pre/post-training mean improvement in self-estimated success of 20.6% (Wilcoxon matched-pairs signed-rank W = - 36, p = 0.008). The post-training success rate of the residents in real-life clinical practice was good (85.8%). CONCLUSION: Residents were aware of the importance of mastering LP and requested additional training. Simulation may represent a major driver to improve their self-confidence and practical skills.
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Geriatria , Internato e Residência , Treinamento por Simulação , Punção Espinal/métodos , Educação de Pós-Graduação em Medicina/métodosRESUMO
INTRODUCTION: Lumbar puncture (LP) is an essential diagnostic procedure, which raises major concerns in older adults. Some patients may be denied LP because of the fear of complications in healthcare teams which are not familiar with the procedure. The objectives of our work were to analyze the perspectives and the experiences regarding scheduled LP in cognitively impaired older adults, as well as in their relatives, and the healthcare teams from geriatric day hospitals. METHODS: We conducted a qualitative, observational and multicentric study, based on semi-directive interviews of patients aged over 70 years with cognitive complaints undergoing a scheduled LP in a day hospital. Patients were interviewed before and after LP. Their relatives and the involved healthcare teams were also interviewed to analyze their expectations and perspectives regarding the procedure. The full interviews were transcribed and analyzed using interpretative phenomenological analysis. RESULTS: Ten patients (mean age 80.2 ± 7.2), five relatives and four healthcare teams were included. The goals and operating procedure of LP were poorly understood by several patients. Some individuals feared irreversible neurological consequences or LP-related pain, which was often overestimated with regards to the post-LP interviews. The patients' major expectation was to establish an accurate and early diagnosis of their cognitive disorder to provide optimal care plan. Relatives reported similar fears of major adverse events. They also expected an accurate diagnosis with biomarkers. The perspectives and experiences of the healthcare teams were heterogeneous, according to their level of practice of LP, but seemed in line with current scientific guidelines. CONCLUSION: This study highlighted the existence of false beliefs and poor knowledge regarding the LP procedure and its associated risks. The post-LP patients' feedbacks were better than their expectations, especially in day hospitals with solid experience in LP. Better patient information may be a key to improve our practice.
Assuntos
Transtornos Cognitivos , Disfunção Cognitiva , Idoso , Idoso de 80 Anos ou mais , Humanos , Transtornos Cognitivos/etiologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Medo , Dor , Punção Espinal/efeitos adversos , Punção Espinal/métodos , Punção Espinal/psicologiaRESUMO
BACKGROUND: Metabolic dysfunction and dysregulation of leptin signaling have been linked to Alzheimer's disease (AD)'s pathophysiology. The objectives of this study were to examine the associations between plasma leptin, cerebrospinal fluid (CSF), beta-amyloid (Aß), and tau biomarkers (AT[N] status) and with the stage of cognitive impairment. METHODS: Cross-sectional analysis of data from cognitively impaired patients from a tertiary memory clinic. Plasma leptin levels were compared according to the stage of cognitive impairment and biomarker profiles, using the AT(N) classification. Linear regression models were performed to examine the relationship between leptin and CSF biomarkers. Results were adjusted for age, gender, body mass index (BMI), and APOE ε4. In a subgroup of A+T+ individuals, we compared the 2-year evolution of Mini-Mental State Examination scores, according to the participants' tertile of plasma leptin levels. RESULTS: We included 1 036 participants (age 68.7 ± 9.1, females = 54.1%). A+T+ and A+T- patients had significantly lower plasma leptin levels than amyloid negative participants (p < .01). CSF Aß concentration was significantly associated with lower plasma leptin ß = -4.3 (1.5), p = .005 unadjusted; and ß = -3.4 (1.6), p = .03 after adjustment for age, female gender, BMI, and APOE ε4. Patients with major neurocognitive disorder due to AD had a difference of leptin of -7.3 ng/mL 95% confidence interval (CI; -11.8; -2.8), p = .0002, compared to individuals with other causes of cognitive impairment. Leptin was not associated with the slope of cognitive decline. CONCLUSION: Plasma leptin levels were associated with CSF Aß and with the diagnosis of AD confirmed by CSF biomarkers, suggesting a molecular interplay between leptin metabolism and brain amyloid deposition.