RESUMEN
OBJECTIVE: Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) prevalence is expected to increase in East Africa as treatment coverage increases, survival improves, and this population ages. This study aimed to better understand the current cognitive phenotype of this newly emergent population of older combination antiretroviral therapy (cART)-treated people living with HIV (PLWH), in which current screening measures lack accuracy. This will facilitate the refinement of HAND cognitive screening tools for this setting. METHOD: This is a secondary analysis of 253 PLWH aged ≥50 years receiving standard government HIV clinic follow-up in Kilimanjaro, Tanzania. They were evaluated with a detailed locally normed low-literacy neuropsychological battery annually on three occasions and a consensus panel diagnosis of HAND by Frascati criteria based on clinical evaluation and collateral history. RESULTS: Tests of verbal learning and memory, categorical verbal fluency, visual memory, and visuoconstruction had an area under the receiver operating characteristic curve >0.7 for symptomatic HAND (s-HAND) (0.70-0.72; p < 0.001 for all tests). Tests of visual memory, verbal learning with delayed recall and recognition memory, psychomotor speed, language comprehension, and categorical verbal fluency were independently associated with s-HAND in a logistic mixed effects model (p < 0.01 for all). Neuropsychological impairments varied by educational background. CONCLUSIONS: A broad range of cognitive domains are affected in older, well-controlled, East African PLWH, including those not captured in widely used screening measures. It is possible that educational background affects the observed cognitive impairments in this setting. Future screening measures for similar populations should consider assessment of visual memory, verbal learning, language comprehension, and executive and motor function.
RESUMEN
Free-water imaging can predict and monitor dopamine system degeneration in people with Parkinson's disease. It can also enhance the sensitivity of traditional diffusion tensor imaging (DTI) metrics for indexing neurodegeneration. However, these tools are yet to be applied to investigate cholinergic system degeneration in Parkinson's disease, which involves both the pedunculopontine nucleus and cholinergic basal forebrain. Free-water imaging, free-water-corrected DTI and volumetry were used to extract structural metrics from the cholinergic basal forebrain and pedunculopontine nucleus in 99 people with Parkinson's disease and 46 age-matched controls. Cognitive ability was tracked over 4.5 years. Pearson's partial correlations revealed that free-water-corrected DTI metrics in the pedunculopontine nucleus were associated with performance on cognitive tasks that required participants to make rapid choices (behavioural flexibility). Volumetric, free-water content and DTI metrics in the cholinergic basal forebrain were elevated in a sub-group of people with Parkinson's disease with evidence of cognitive impairment, and linear mixed modelling revealed that these metrics were differently associated with current and future changes to cognition. Free water and free-water-corrected DTI can index cholinergic degeneration that could enable stratification of patients in clinical trials of cholinergic interventions for cognitive decline. In addition, degeneration of the pedunculopontine nucleus impairs behavioural flexibility in Parkinson's disease, which may explain this region's role in increased risk of falls.
Asunto(s)
Prosencéfalo Basal , Enfermedad de Parkinson , Núcleo Tegmental Pedunculopontino , Humanos , Enfermedad de Parkinson/complicaciones , Imagen de Difusión Tensora , Prosencéfalo Basal/diagnóstico por imagen , Colinérgicos , Agua , Neuronas ColinérgicasRESUMEN
BACKGROUND: Inpatient prevalence of Parkinson's disease (PD) delirium varies widely across the literature. Delirium in general older populations is associated with adverse outcomes, such as increased mortality, dementia, and institutionalisation. However, to date there are no comprehensive prospective studies in PD delirium. This study aimed to determine delirium prevalence in hospitalised PD participants and the association with adverse outcomes, compared to a control group of older adults without PD. METHODS: Participants were hospitalised inpatients from the 'Defining Delirium and its Impact in Parkinson's Disease' and the 'Delirium and Cognitive Impact in Dementia' studies comprising 121 PD participants and 199 older adult controls. Delirium was diagnosed prospectively using the Diagnostic and Statistical Manual of Mental Disorders 5th Edition criteria. Outcomes were determined by medical note reviews and/or home visits 12 months post hospital discharge. RESULTS: Delirium was identified in 66.9% of PD participants compared to 38.7% of controls (p < 0.001). In PD participants only, delirium was associated with a significantly higher risk of mortality (HR = 3.3 (95% confidence interval [CI] = 1.3-8.6), p = 0.014) and institutionalisation (OR = 10.7 (95% CI = 2.1-54.6), p = 0.004) 12 months post-discharge, compared to older adult controls. However, delirium was associated with an increased risk of developing dementia 12 months post-discharge in both PD participants (OR = 6.1 (95% CI = 1.3-29.5), p = 0.024) and in controls (OR = 13.4 (95% CI = 2.5-72.6), p = 0.003). CONCLUSION: Delirium is common in hospitalised PD patients, affecting two thirds of patients, and is associated with increased mortality, institutionalisation, and dementia. Further research is essential to understand how to accurately identify, prevent and manage delirium in people with PD who are in hospital.
Asunto(s)
Delirio , Demencia , Enfermedad de Parkinson , Humanos , Anciano , Estudios Prospectivos , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/epidemiología , Delirio/diagnóstico , Delirio/epidemiología , Delirio/etiología , Estudios Longitudinales , Cuidados Posteriores , Alta del Paciente , Demencia/diagnóstico , Demencia/epidemiología , Demencia/complicacionesRESUMEN
BACKGROUND: Delirium is an acute onset and fluctuating impairment of cognition, attention and arousal, often precipitated by acute illness. Lewy body disease (LBD) is an umbrella term for a range of clinical conditions, including Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB). People living with LBD seem to be more susceptible to delirium than those with other subtypes of dementia. AIM: To describe the challenges in clinical diagnosis and management of LBD. METHODS: A systematic review of published literature on diagnosis and management of delirium in LBD. RESULTS: Delirium is particularly challenging to diagnose in LBD as many of the clinical characteristics which define delirium such as inattention, fluctuating arousal, complex visual hallucinations and delusions, are also common to LBD. Distinguishing delirium from LBD can be very difficult clinically especially in the prodromal stages. Both under and over diagnosis of delirium, and under and over treatment of the symptoms have the potential to compromise the care and safety of people with a diagnosed or undiagnosed LBD. Clinicians are currently working with an extremely limited set of evidence-based management options for those with delirium in the context of a LBD diagnosis. For patients with LBD and their families this is an area of clinical practice that needs focused research.
Asunto(s)
Enfermedad de Alzheimer , Delirio , Demencia , Enfermedad por Cuerpos de Lewy , Enfermedad de Parkinson , Humanos , Enfermedad por Cuerpos de Lewy/terapia , Enfermedad por Cuerpos de Lewy/tratamiento farmacológico , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico , Alucinaciones , Delirio/diagnóstico , Delirio/etiología , Delirio/terapiaRESUMEN
OBJECTIVE: To assess the accuracy of documentation of the symptoms and diagnosis of delirium in medical notes of inpatients with Parkinson's disease (PD). METHODS: The DETERMINE-PD pilot study assessed PD inpatients over 4-months. Delirium prevalence was classified prospectively using a standardized assessment at a single visit on the basis of Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-5) criteria. Incident delirium was diagnosed retrospectively using detailed clinical vignettes and validated consensus method. Inpatient medical notes and discharge summaries of those with delirium were reviewed for documentation of symptoms, diagnosis and follow-up. RESULTS: Forty-four PD patients consented to take part in the study, accounting for 53 admissions. We identified 30 cases (56.6%) of delirium during the participants' stay in hospital. Of those with delirium identified by the research team, delirium symptoms were documented in the clinical notes of 72.3%; 37.9% had a delirium diagnosis documented. Older patients were more likely to have delirium (p = 0.027) and have this diagnosis documented (p = 0.034). Time from documentation of symptoms to diagnosis ranged from <24 h to 7 days (mean 1.6 ± 4.4 days). Hypoactive delirium was significantly less likely to have been identified and formally diagnosed (63% of not documented were hypoactive vs. 37% hyperactive, mixed or unclear, p = 0.016). Only 11.5% of discharge summaries included diagnosis of delirium. CONCLUSION: Delirium in PD is common. Documentation of symptoms of delirium was common; however, fails to lead to a documentation of diagnosis in over half of admissions with delirium and was even less commonly communicated in the Primary Care discharge summaries. This highlights the need for increased education about delirium symptomatology and diagnosis in PD.
Asunto(s)
Delirio , Enfermedad de Parkinson , Humanos , Delirio/diagnóstico , Delirio/epidemiología , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico , Proyectos Piloto , Estudios Retrospectivos , Documentación/métodosRESUMEN
Low levels of physical activity (PA) and sleep disruption are commonly seen in older adult inpatients and are associated with poor health outcomes. Wearable sensors allow for objective continuous monitoring; however, there is no consensus as to how wearable sensors should be implemented. This review aimed to provide an overview of the use of wearable sensors in older adult inpatient populations, including models used, body placement and outcome measures. Five databases were searched; 89 articles met inclusion criteria. We found that studies used heterogenous methods, including a variety of sensor models, placement and outcome measures. Most studies reported the use of only one sensor, with either the wrist or thigh being the preferred location in PA studies and the wrist for sleep outcomes. The reported PA measures can be mostly characterised as the frequency and duration of PA (Volume) with fewer measures relating to intensity (rate of magnitude) and pattern of activity (distribution per day/week). Sleep and circadian rhythm measures were reported less frequently with a limited number of studies providing both physical activity and sleep/circadian rhythm outcomes concurrently. This review provides recommendations for future research in older adult inpatient populations. With protocols of best practice, wearable sensors could facilitate the monitoring of inpatient recovery and provide measures to inform participant stratification and establish common objective endpoints across clinical trials.
Asunto(s)
Pacientes Internos , Dispositivos Electrónicos Vestibles , Humanos , Anciano , Muñeca , Ejercicio Físico , SueñoRESUMEN
BACKGROUND: Gait impairments are characteristic motor manifestations and significant predictors of poor quality of life in Parkinson's disease (PD). Neuroimaging biomarkers for gait impairments in PD could facilitate effective interventions to improve these symptoms and are highly warranted. OBJECTIVE: The aim of this study was to identify neural networks of discrete gait impairments in PD. METHODS: Fifty-five participants with early-stage PD and 20 age-matched healthy volunteers underwent quantitative gait assessment deriving 12 discrete spatiotemporal gait characteristics and [18 F]-2-fluoro-2-deoxyglucose-positron emission tomography measuring resting cerebral glucose metabolism. A multivariate spatial covariance approach was used to identify metabolic brain networks that were related to discrete gait characteristics in PD. RESULTS: In PD, we identified two metabolic gait-related covariance networks. The first correlated with mean step velocity and mean step length (pace gait network), which involved relatively increased and decreased metabolism in frontal cortices, including the dorsolateral prefrontal and orbital frontal, insula, supplementary motor area, ventrolateral thalamus, cerebellum, and cuneus. The second correlated with swing time variability and step time variability (temporal variability gait network), which included relatively increased and decreased metabolism in sensorimotor, superior parietal cortex, basal ganglia, insula, hippocampus, red nucleus, and mediodorsal thalamus. Expression of both networks was significantly elevated in participants with PD relative to healthy volunteers and were not related to levodopa dosage or motor severity. CONCLUSIONS: We have identified two novel gait-related brain networks of altered glucose metabolism at rest. These gait networks could serve as a potential neuroimaging biomarker of gait impairments in PD and facilitate development of therapeutic strategies for these disabling symptoms. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Asunto(s)
Enfermedad de Parkinson , Marcha , Glucosa , Humanos , Levodopa/uso terapéutico , Imagen por Resonancia Magnética/métodos , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/tratamiento farmacológico , Calidad de VidaRESUMEN
BACKGROUND: Common genetic variance in apolipoprotein E (APOE), ß-glucocerebrosidase (GBA), microtubule-associated protein tau (MAPT), and α-synuclein (SNCA) has been linked to cognitive decline in Parkinson's disease (PD), although studies have yielded mixed results. OBJECTIVES: To evaluate the effect of genetic variants in APOE, GBA, MAPT, and SNCA on cognitive decline and risk of dementia in a pooled analysis of six longitudinal, non-selective, population-based cohorts of newly diagnosed PD patients. METHODS: 1002 PD patients, followed for up to 10 years (median 7.2 years), were genotyped for at least one of APOE-ε4, GBA mutations, MAPT H1/H2, or SNCA rs356219. We evaluated the effect of genotype on the rate of cognitive decline (Mini-Mental State Examanation, MMSE) using linear mixed models and the development of dementia (diagnosed using standardized criteria) using Cox regression; multiple comparisons were accounted for using Benjamini-Hochberg corrections. RESULTS: Carriers of APOE-ε4 (n = 281, 29.7%) and GBA mutations (n = 100, 10.3%) had faster cognitive decline and were at higher risk of progression to dementia (APOE-ε4, HR 3.57, P < 0.001; GBA mutations, HR 1.76, P = 0.001) than non-carriers. The risk of cognitive decline and dementia (HR 5.19, P < 0.001) was further increased in carriers of both risk genotypes (n = 23). No significant effects were observed for MAPT or SNCA rs356219. CONCLUSIONS: GBA and APOE genotyping could improve the prediction of cognitive decline in PD, which is important to inform the clinical trial selection and potentially to enable personalized treatment © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Asunto(s)
Disfunción Cognitiva , Demencia , Enfermedad de Parkinson , Apolipoproteína E4/genética , Apolipoproteínas E/genética , Disfunción Cognitiva/genética , Demencia/genética , Glucosilceramidasa/genética , Humanos , Mutación/genética , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/psicologíaRESUMEN
BACKGROUND AND PURPOSE: Recent application of the mild cognitive impairment concept to Parkinson disease (PD) has proven valuable in identifying patients at risk of dementia. However, it has sparked controversy regarding the existence of cognitive subtypes. The present review evaluates the current literature pertaining to data-driven subtypes of cognition in PD. METHODS: Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, systematic literature searches for peer-reviewed articles on the topic of cognitive subtyping in PD were performed. RESULTS: Twenty-two relevant articles were identified in the systematic search. Subtype structures showed either a spectrum of severity or specific domains of impairment. Domain-specific subtypes included amnestic/nonamnestic, memory/executive, and frontal/posterior dichotomies, as well as more complex structures with less definitive groupings. Preliminary longitudinal evidence showed some differences in cognitive progression among subtypes. Neuroimaging evidence provided insight into distinct patterns of brain alterations among subtypes. CONCLUSIONS: Recurring phenotypes in the literature suggest strong clinical relevance of certain cognitive subtypes in PD. Although the current literature is limited, it raises critical questions about the utility of data-driven methods in cognitive research. The results encourage further integration of neuroimaging research to define the latent neural mechanisms behind divergent subtypes. Although there is no consensus, there appears to be growing consistency and inherent value in identifying cognitive subtypes in PD.
Asunto(s)
Disfunción Cognitiva , Enfermedad de Parkinson , Encéfalo , Cognición , Disfunción Cognitiva/etiología , Disfunción Cognitiva/psicología , Humanos , Neuroimagen , Pruebas Neuropsicológicas , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/psicologíaRESUMEN
Participating in habitual physical activity (HPA) may slow onset of dependency and disability for people with Parkinson's disease (PwP). While cognitive and physical determinants of HPA are well understood, psychosocial influences are not. This pilot study aimed to identify psychosocial factors associated with HPA to guide future intervention development. Sixty-four PwP participated in this study; forty had carer informants. PwP participants wore a tri-axial accelerometer on the lower back continuously for seven days at two timepoints (18 months apart), measuring volume, pattern and variability of HPA. Linear mixed effects analysis identified relationships between demographic, clinical and psychosocial data and HPA from baseline to 18 months. Key results in PwP with carers indicated that carer anxiety and depression were associated with increased HPA volume (p < 0.01), while poorer carer self-care was associated with reduced volume of HPA over 18 months (p < 0.01). Greater carer strain was associated with taking longer walking bouts after 18 months (p < 0.01). Greater carer depression was associated with lower variability of HPA cross-sectionally (p = 0.009). This pilot study provides preliminary novel evidence that psychosocial outcomes from PwP's carers may impact HPA in Parkinson's disease. Interventions to improve HPA could target both PwP and carers and consider approaches that also support psychosocial wellbeing.
Asunto(s)
Cuidadores , Enfermedad de Parkinson , Ejercicio Físico , Humanos , Proyectos Piloto , Calidad de VidaRESUMEN
BACKGROUND: Parkinson's disease (PD) is associated with cholinergic dysfunction, although the role of M1 and M4 receptors remains unclear. OBJECTIVE: To investigate spatial covariance patterns of cholinergic muscarinic M1 /M4 receptors in PD and their relationship with cognition and motor symptoms. METHODS: Some 19 PD and 24 older adult controls underwent 123 I-iodo-quinuclidinyl-benzilate (QNB) (M1 /M4 receptor) and 99m Tc-exametazime (perfusion) single-photon emission computed tomography (SPECT) scanning. We implemented voxel principal components analysis, producing a series of images representing patterns of intercorrelated voxels across individuals. Linear regression analyses derived specific M1 /M4 spatial covariance patterns associated with PD. RESULTS: A cholinergic M1 /M4 pattern that converged onto key hubs of the default, auditory-visual, salience, and sensorimotor networks fully discriminated PD patients from controls (F1,41 = 135.4, P < 0.001). In PD, we derived M1 /M4 patterns that correlated with global cognition (r = -0.62, P = 0.008) and motor severity (r = 0.53, P = 0.02). Both patterns emerged with a shared topography implicating the basal forebrain as well as visual, frontal executive, and salience circuits. Further, we found a M1 /M4 pattern that predicted global cognitive decline (r = 0.46, P = 0.04) comprising relative decreased binding within default and frontal executive networks. CONCLUSIONS: Cholinergic muscarinic M1 /M4 modulation within key brain networks were apparent in PD. Cognition and motor severity were associated with a similar topography, inferring both phenotypes possibly rely on related cholinergic mechanisms. Relative decreased M1 /M4 binding within default and frontal executive networks could be an indicator of future cognitive decline. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Asunto(s)
Disfunción Cognitiva , Enfermedad de Parkinson , Anciano , Encéfalo , Colinérgicos , Humanos , Enfermedad de Parkinson/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
BACKGROUND: Gait disturbance is an early, disabling feature of Parkinson's disease (PD) that is typically refractory to dopaminergic medication. The cortical cholinergic system, originating in the nucleus basalis of Meynert of the basal forebrain, has been implicated. However, it is not known if degeneration in this region relates to a worsening of disease-specific gait impairment. OBJECTIVE: To evaluate associations between sub-regional cholinergic basal forebrain volumes and longitudinal progression of gait impairment in PD. METHODS: 99 PD participants and 47 control participants completed gait assessments via an instrumented walkway during 2 minutes of continuous walking, at baseline and for up to 3 years, from which 16 spatiotemporal characteristics were derived. Sub-regional cholinergic basal forebrain volumes were measured at baseline via MRI and a regional map derived from post-mortem histology. Univariate analyses evaluated cross-sectional associations between sub-regional volumes and gait. Linear mixed-effects models assessed whether volumes predicted longitudinal gait changes. RESULTS: There were no cross-sectional, age-independent relationships between sub-regional volumes and gait. However, nucleus basalis of Meynert volumes predicted longitudinal gait changes unique to PD. Specifically, smaller nucleus basalis of Meynert volume predicted increasing step time variability (P = 0.019) and shortening swing time (P = 0.015); smaller posterior nucleus portions predicted shortening step length (P = 0.007) and increasing step time variability (P = 0.041). CONCLUSIONS: This is the first study to demonstrate that degeneration of the cortical cholinergic system predicts longitudinal progression of gait impairments in PD. Measures of this degeneration may therefore provide a novel biomarker for identifying future mobility loss and falls. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Asunto(s)
Prosencéfalo Basal , Enfermedad de Parkinson , Prosencéfalo Basal/diagnóstico por imagen , Colinérgicos , Estudios Transversales , Marcha , Humanos , Enfermedad de Parkinson/complicacionesRESUMEN
BACKGROUND: Acute hospitalisation and delirium have individually been shown to adversely affect trajectories of cognitive decline but have not previously been considered together. This work aimed to explore the impact on cognition of hospital admission with and without delirium, compared to a control group with no hospital admissions. METHODS: The Delirium and Cognitive Impact in Dementia (DECIDE) study was nested within the Cognitive Function and Ageing Study II (CFAS II)-Newcastle cohort. CFAS II participants completed two baseline interviews, including the Mini-Mental State Examination (MMSE). During 2016, surviving participants from CFAS II-Newcastle were recruited to DECIDE on admission to hospital. Participants were reviewed daily to determine delirium status.During 2017, all DECIDE participants and age, sex and years of education matched controls without hospital admissions during 2016 were invited to repeat the CFAS II interview. Delirium was excluded in the control group using the Informant Assessment of Geriatric Delirium Scale (i-AGeD). Linear mixed effects modelling determined predictors of cognitive decline. RESULTS: During 2016, 82 of 205 (40%) DECIDE participants had at least one episode of delirium. At 1 year, 135 of 205 hospitalised participants completed an interview along with 100 controls. No controls experienced delirium (i-AGeD>4). Delirium was associated with a faster rate of cognitive decline compared to those without delirium (ß = -2.2, P < 0.001), but number of hospital admissions was not (P = 0.447). CONCLUSIONS: These results suggest that delirium during hospitalisation rather than hospitalisation per se is a risk factor for future cognitive decline, emphasising the need for dementia prevention studies that focus on delirium intervention.
Asunto(s)
Disfunción Cognitiva , Delirio , Anciano , Estudios de Cohortes , Delirio/diagnóstico , Delirio/epidemiología , Hospitalización , Humanos , Estudios LongitudinalesRESUMEN
The Dementias Platform UK Data Portal is a data repository facilitating access to data for 3 370 929 individuals in 42 cohorts. The Data Portal is an end-to-end data management solution providing a secure, fully auditable, remote access environment for the analysis of cohort data. All projects utilising the data are by default collaborations with the cohort research teams generating the data. The Data Portal uses UK Secure eResearch Platform infrastructure to provide three core utilities: data discovery, access, and analysis. These are delivered using a 7 layered architecture comprising: data ingestion, data curation, platform interoperability, data discovery, access brokerage, data analysis and knowledge preservation. Automated, streamlined, and standardised procedures reduce the administrative burden for all stakeholders, particularly for requests involving multiple independent datasets, where a single request may be forwarded to multiple data controllers. Researchers are provided with their own secure 'lab' using VMware which is accessed using two factor authentication. Over the last 2 years, 160 project proposals involving 579 individual cohort data access requests were received. These were received from 268 applicants spanning 72 institutions (56 academic, 13 commercial, 3 government) in 16 countries with 84 requests involving multiple cohorts. Projects are varied including multi-modal, machine learning, and Mendelian randomisation analyses. Data access is usually free at point of use although a small number of cohorts require a data access fee.
Asunto(s)
Manejo de Datos , Sistemas de Administración de Bases de Datos , Demencia , Investigación Biomédica , Estudios de Cohortes , Conjuntos de Datos como Asunto , Humanos , Reino UnidoRESUMEN
INTRODUCTION: People with Parkinson disease (PD) may be at increased risk of delirium and associated adverse outcomes. Delirium is an acute neuropsychiatric syndrome defined by confusion and inattention and is common in older adults. Previous studies may have underestimated the prevalence of delirium in PD because of overlapping symptoms, lack of awareness, and poorly defined criteria. We aimed to identify the prevalence and incidence of delirium in inpatients with PD. MEASUREMENTS: Participants were inpatients with PD admitted over a 4-month period. Delirium prevalence was classified using a standardised assessment at a single visit on the basis of the Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM-5) criteria. To capture remaining time in hospital, incident delirium was diagnosed using detailed clinical vignettes and a validated consensus method. RESULTS: Forty-four PD patients consented to take part in the study, accounting for 53 admissions. Delirium prevalence was 34.0% (n = 18); reviewing participants over the duration of their hospital stay identified 30 (56.6%) incident delirium cases. The admitting team screened 24.5% for delirium, and delirium was documented in eight (14.8%) patients' medical notes. Patients with delirium were significantly older, had higher frailty scores, and had a longer hospital stay (P < .05 for all). CONCLUSIONS: Delirium is common in PD inpatients at admission and incidence increases during hospital stay, but delirium is commonly missed. Our results highlight the importance of screening for delirium throughout patients' stay in hospital. Future studies should consider frequent evaluation over the duration of hospital stay to identify emergent delirium during the admission.
Asunto(s)
Cognición/fisiología , Delirio/epidemiología , Pacientes Internos/estadística & datos numéricos , Enfermedad de Parkinson/complicaciones , Anciano , Anciano de 80 o más Años , Delirio/diagnóstico , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Femenino , Humanos , Incidencia , Tiempo de Internación , Masculino , Tamizaje Masivo , Enfermedad de Parkinson/epidemiología , Proyectos Piloto , PrevalenciaRESUMEN
BACKGROUND: Cumulative dementia incidence in Parkinson's disease (PD) is significant, with major personal and socioeconomic impacts on individuals with PD and their carers. Early identification of dementia risk is vital to ensuring optimal intervention. Saccadic deficits often distinguish neurodegenerative disorders and cognitive impairment, but their ability to predict cognitive decline in PD has yet to be determined. The aims of this study were to (1) evaluate baseline (6.4 ± 6.1 months since PD diagnosis) differences in pro-saccadic metrics between those with early PD and healthy age-matched adults; and (2) assess the ability of baseline pro-saccades to predict subsequent cognitive decline over 4.5 years. METHODS: One hundred and forty-one PD and 90 age-matched participants recruited at diagnosis underwent saccadometric assessment of pro-saccades at baseline and had cognition assessed at baseline, 18, 36, and 54 months. Pro-saccadic characteristics included latency, duration, amplitude, peak, and average velocity. Cognitive assessment included executive function, attention, fluctuating attention, and memory. Linear mixed-effects models examined pro-saccadic metrics as predictors of cognitive decline over 54 months. RESULTS: Pro-saccades were significantly impaired at baseline in PD compared with controls. Pro-saccadic characteristics of latency, duration, peak, and average velocity predicted decline in global cognition, executive function, attention, and memory over 54 months in PD. In addition, only reduction in global cognition and attention were predicted by pro-saccadic metrics in age-matched adults, indicating that PD findings were not purely age related. CONCLUSIONS: Saccadic characteristics are impaired in early PD and are predictive of cognitive decline in several domains. Assessment of saccades may provide a useful non-invasive biomarker for long-term PD cognitive decline in early disease. © 2019 International Parkinson and Movement Disorder Society.
Asunto(s)
Cognición/fisiología , Disfunción Cognitiva/fisiopatología , Memoria/fisiología , Enfermedad de Parkinson/fisiopatología , Adulto , Anciano , Atención/fisiología , Disfunción Cognitiva/etiología , Demencia/complicaciones , Demencia/fisiopatología , Función Ejecutiva/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/complicacionesRESUMEN
BACKGROUND: Inflammation appears to play a role in the progression of neurodegenerative diseases. However, little is known about inflammation during early stages of cognitive decline or whether this differs in different disease groups. We sought to investigate this by assessing the inflammatory profile in patients with Parkinson disease with the early stages of cognitive impairment (PD-MCI), patients with prodromal Alzheimer disease (MCI-AD), prodromal Lewy body disease (MCI-LB), and controls. METHODS: We obtained venous blood samples from participants with PD-MCI (n = 44), PD-normal cognition (n = 112), MCI-LB (n = 38), MCI-AD (n = 21), and controls (n = 84). We measured 10 cytokines using Meso Scale Discovery V-Plex Plus including interferon gamma, interleukin (IL)-10, IL-12p70, IL-13, IL-1beta, IL-2, IL-4, IL-6, IL-8, and tumour necrosis factor alpha. High-sensitivity C-reactive protein was measured. RESULTS: There was a higher level of inflammation in patients with MCI-AD and MCI-LB compared with controls. PD noncognitively impaired had higher inflammatory markers than controls, but there was no difference between PD-MCI and controls. There was a decrease in inflammatory markers with increasing motor severity based on the Unified Parkinson's Disease Rating Scale. CONCLUSIONS: Inflammation may be involved in the onset of cognitive decline in patients with MCI-AD and MCI-LB but appears to be less prominent PD-MCI albeit in a small data set. This suggests that anti-inflammatory medications may have most benefit at the earliest stages of neurodegenerative diseases. For PD cases, this might be in advance of the development of MCI.
Asunto(s)
Enfermedad de Alzheimer/patología , Disfunción Cognitiva/patología , Inflamación/patología , Enfermedad por Cuerpos de Lewy/patología , Enfermedad de Parkinson/patología , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/psicología , Biomarcadores/análisis , Proteína C-Reactiva/análisis , Estudios de Casos y Controles , Disfunción Cognitiva/psicología , Citocinas/análisis , Progresión de la Enfermedad , Femenino , Humanos , Inflamación/sangre , Interleucina-1beta , Enfermedad por Cuerpos de Lewy/psicología , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Enfermedad de Parkinson/psicologíaRESUMEN
OBJECTIVES: To evaluate the impact of an antimicrobial stewardship (AMS) intervention, involving introduction of new guidelines on the treatment of febrile neutropenia (FN), on improving the use of gentamicin in paediatric oncology patients. DESIGN AND INTERVENTION: Updated guidelines for gentamicin usage in paediatrics with FN were implemented at a tertiary children's teaching hospital, in Brisbane, Australia. Data on gentamicin usage before and after the guideline change were collected retrospectively from children with cancer admitted to hospital with FN between January 2012 and December 2013. Gentamicin use, duration of gentamicin therapy and therapeutic monitoring practice were compared against bacterial culture status for admissions before and after the guideline change to assess the impact on practice. RESULTS: Data were collected from 227 children corresponding to 453 separate admissions, 195 preguideline and 257 post-guideline change. Following guideline change, the proportion of admissions in which gentamicin was administered reduced from 79.0 to 20.9% (P-value < 0.001) and administrations not associated with a cultured Gram-negative organism dropped from 87.2 to 58.2% (P-value < 0.001), indicating a change in practice according to the new guideline. Following guideline change, admissions in which gentamicin was used for >48 hr despite the absence of a confirmed Gram-negative infection decreased from 85.6 to 46.9% (P-value < 0.001). CONCLUSIONS: Guideline changes driven through an AMS initiative involving paediatric oncology patients significantly improved targeted- and nontargeted-antimicrobial use potentially reducing the risk of emergence of resistance against gentamicin in this cohort.
Asunto(s)
Neutropenia Febril/tratamiento farmacológico , Gentamicinas/administración & dosificación , Bacterias Gramnegativas , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Niño , Preescolar , Neutropenia Febril/microbiología , Neutropenia Febril/patología , Femenino , Infecciones por Bacterias Gramnegativas/microbiología , Infecciones por Bacterias Gramnegativas/patología , Adhesión a Directriz , Humanos , Masculino , Neoplasias/microbiología , Neoplasias/patología , Neoplasias/terapia , Guías de Práctica Clínica como Asunto , Estudios RetrospectivosRESUMEN
AIMS: Glomerular filtration rate (GFR) is estimated daily in paediatric oncology patients; however, few equations, particularly ones that do not include serum creatinine, have been evaluated in this population. We aimed to compare the predictive performance of different equations available to estimate GFR in paediatric oncology patients. METHODS: GFR was measured (mGFR) in paediatric oncology patients based on a chromium 51-labeled ethylene diamine tetraacetic acid excretion test. GFR was estimated (eGFR) in these same patients using equations identified from the literature. mGFR and eGFR values were compared, and the predictive performance of various eGFR equations was assessed in terms of their bias, precision and accuracy. RESULTS: In total, 124 mGFR values ranging from 7 to 146 mL/min were available for analysis from 73 children. Twenty-two equations were identified from the literature. The Flanders metadata equation displayed the lowest absolute bias (mean error of 0.9 mL/min) and the greatest precision (root mean square error of 13.1 mL/min). The univariate Schwartz equation predicted the highest percentage (81.5%) of eGFR values within 30% of mGFR values, and the Rhodin fat-free mass equation predicted the highest percentage (37.1%) of eGFR values within 10% of mGFR values. CONCLUSIONS: A number of equations were identified that could be used to estimate renal function in paediatric oncology patients; however, none was found to be highly accurate. The Flanders metadata equation and univariate Schwartz performed the best in this study, and we would suggest that these two equations may be used cautiously in paediatric oncology patients for clinical decision making, understanding their limitations.
Asunto(s)
Algoritmos , Pruebas Diagnósticas de Rutina/métodos , Tasa de Filtración Glomerular , Pediatría , Preescolar , Femenino , Humanos , Lactante , Masculino , Neoplasias , Valor Predictivo de las Pruebas , Insuficiencia Renal CrónicaRESUMEN
Mild cognitive impairment (MCI) is prevalent in 15%-40% of Parkinson's disease (PD) patients at diagnosis. In this investigation, we study brain intra- and inter-network alterations in resting state functional magnetic resonance imaging (rs-fMRI) in recently diagnosed PD patients and characterise them as either cognitive normal (PD-NC) or with MCI (PD-MCI). Patients were divided into two groups, PD-NC (N = 62) and PD-MCI (N = 37) and for comparison, healthy controls (HC, N = 30) were also included. Intra- and inter-network connectivity were investigated from participants' rs-fMRIs in 26 resting state networks (RSNs). Intra-network differences were found between both patient groups and HCs for networks associated with motor control (motor cortex), spatial attention and visual perception. When comparing both PD-NC and PD-MCI, intra-network alterations were found in RSNs related to attention, executive function and motor control (cerebellum). The inter-network analysis revealed a hyper-synchronisation between the basal ganglia network and the motor cortex in PD-NC compared with HCs. When both patient groups were compared, intra-network alterations in RSNs related to attention, motor control, visual perception and executive function were found. We also detected disease-driven negative synchronisations and synchronisation shifts from positive to negative and vice versa in both patient groups compared with HCs. The hyper-synchronisation between basal ganglia and motor cortical RSNs in PD and its synchronisation shift from negative to positive compared with HCs, suggest a compensatory response to basal dysfunction and altered basal-cortical motor control in the resting state brain of PD patients. Hum Brain Mapp 38:1702-1715, 2017. © 2016 Wiley Periodicals, Inc.