RESUMO
BACKGROUND: Dementia in Parkinson's disease (PD) is defined as cognitive decline severe enough to affect activities of daily living function (ADL). The aim of our exploratory study was to compare two groups of PD patients. Both groups had cognitive deficits severe enough to justify diagnosis of dementia, but they differed according to caregivers' rating on ADL dysfunction. Parameters which differed between the two groups were interpreted to affect the caregivers' perception of ADL dysfunction in PD patients with cognitive impairment indicative of Parkinson's disease dementia. METHODOLOGY/PRINCIPAL FINDINGS: Thirty of 131 Parkinson's disease patients fulfilled the Movement Disorders Society Task Force - recommended, cognitive Level-I-criteria for dementia. According to standardized caregiver ratings, volunteers were grouped into 18 patients with (ADL-) and 12 without instrumental activities of daily living dysfunction (ADL+). Caregiver activities of daily living function ratings closely correlated with self-estimates of patients and those of physician (p<0.001). ADL- patients performed worse on tests assessing visual-construction (p<0.05) and attention (p=0.03) than ADL+ patients. Moreover, the postural instability and gait disorder subtype was more frequent in ADL- patients (p=0.009). ADL- patients tended to have more communication problems (p=0.05), more anxiety (p=0.05) and showed a tendency to be treated more often with neuroleptics (p=0.049) than ADL+. CONCLUSIONS/SIGNIFICANCE: Results indicate that worse attention, visual-construction abilities, the postural instability and gait disorder subtype, communication problems, medication and presence of anxiety are related to activities of daily living dysfunctions in Parkinson's disease patients with cognitive decline indicative of dementia. Our data suggests that not only cognitive factors but also non-cognitive factors seem to be linked to the diagnosis of Parkinson's disease dementia associated with significant impact on instrumental activities of daily living function. Further studies with larger sample sizes are needed to verify our results.
Assuntos
Atividades Cotidianas , Transtornos da Comunicação , Demência , Doença de Parkinson , Comitês Consultivos , Idoso , Idoso de 80 Anos ou mais , Transtornos da Comunicação/etiologia , Transtornos da Comunicação/fisiopatologia , Demência/etiologia , Demência/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Doença de Parkinson/fisiopatologia , Índice de Gravidade de DoençaRESUMO
BACKGROUND: The clinical diagnosis of Parkinson's disease (PD) is proposed to be too late for the application of beneficial neuroprotective treatment. Thus, it is important to identify and follow individuals at risk for PD in order to gain knowledge about the prodromal course of the disease. Substantia nigra hyperechogenicity (SN+) has been confirmed as a risk factor for PD and appears promising as a predictor of PD, particularly in combination with other putative PD markers. We present the design and initial data of a 2-year longitudinal investigation of subjects proposed to be at high risk of developing PD (HRPD), compared to early PD patients and control subjects. The aim of the presented study is to monitor progression of the neurodegenerative process to motor PD. METHODS: In total, 40 HRPD, 16 PD and 41 control individuals were recruited. The HRPD subjects had SN+ and additionally either 1 cardinal PD motor sign or 2 further risk (e.g. positive family history) or prodromal markers (e.g. hyposmia). In this cohort, motor function, olfaction, mood and blood markers will be evaluated every 6 months, complemented by a comprehensive clinical, imaging and electrophysiological assessment. RESULTS: PD, HRPD and control subjects did not differ significantly regarding age, but the HRPD group consisted mainly of males (72.5% of HRPD subjects vs. 43.9% of controls; p = 0.013). Mean disease duration in PD patients was 31 months (range 15-56). HRPD subjects were predominantly recruited according to the occurrence of slight motor signs (HRPD 77.5%, PD 100%, p = 0.05; controls 0%, HRPD vs. controls, p < 0.017). The Unified Parkinson's Disease Rating Scale motor score (mean, range) indicated that the HRPD group (4, 0-12) had values between those of controls (0, 0-2; p < 0.017) and PD subjects (26, 9-55; p < 0.017). Among nonmotor symptoms, hyposmia was more common in both HRPD (47.5%) and PD subjects (75%) than in controls (5.1%; p < 0.017 for both comparisons). CONCLUSIONS: Here, we describe the recruitment of a highly enriched-risk cohort and a promising study design to assess progression to motor PD. Whether the HRPD group indeed suffers from early, PD-specific neurodegeneration remains to be verified in the ongoing follow-up examinations.
Assuntos
Progressão da Doença , Doença de Parkinson/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estudos Longitudinais/métodos , Masculino , Pessoa de Meia-Idade , Sintomas Prodrômicos , Estudos Prospectivos , Fatores de RiscoRESUMO
BACKGROUND: Beside the presence of cognitive deficits, impaired activities of daily living (ADL) are crucial for the diagnosis of dementia in Parkinson's disease (PD). Several scales can be used to evaluate PD patients' ADL (dys)function. However, only a few of them sufficiently discriminate between demented and non-demented PD patients. It is well-known that the diagnostic accuracy of ADL scales for Parkinson's disease dementia (PDD) is influenced by confounding variables such as motor worsening. OBJECTIVE: To evaluate the diagnostic accuracy of ADL scales for PDD. METHODS: In a cohort of 106 patients (21 with dementia), we evaluated observer-based activities of daily living rating scales (e.g. Pill Questionnaire, Schwab & England Scale), caregiver assessments, and patient questionnaires (e.g. Lawton Instrumental Activities of Daily Living Scale). RESULTS: Each inventory showed moderate or even high specificity for dementia (>75.3%). Sensitivity was highest for the Pill Questionnaire (90.5%). Interestingly, the ratings of caregivers and trained clinical observers overestimated the presence of dementia. CONCLUSIONS: Standardized activities of daily living assessments like the Pill Questionnaire accompanied by neuropsychological testing can be a helpful tool for the diagnosis of PDD. Further studies are needed to verify these first results in larger cohorts.
Assuntos
Atividades Cotidianas/psicologia , Demência/diagnóstico , Doença de Parkinson/complicações , Idoso , Demência/etiologia , Demência/psicologia , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Projetos Piloto , Inquéritos e QuestionáriosRESUMO
Parkinson's disease is characterized by a substantial cognitive heterogeneity, which is apparent in different profiles and levels of severity. To date, a distinct clinical profile for patients with a potential risk of developing dementia still has to be identified. We introduce a data-driven approach to detect different cognitive profiles and stages. Comprehensive neuropsychological data sets from a cohort of 121 Parkinson's disease patients with and without dementia were explored by a factor analysis to characterize different cognitive domains. Based on the factor scores that represent individual performance in each domain, hierarchical cluster analyses determined whether subgroups of Parkinson's disease patients show varying cognitive profiles. A six-factor solution accounting for 65.2% of total variance fitted best to our data and revealed high internal consistencies (Cronbach's alpha coefficients >0.6). The cluster analyses suggested two independent patient clusters with different cognitive profiles. They differed only in severity of cognitive impairment and self-reported limitation of activities of daily living function but not in motor performance, disease duration, or dopaminergic medication. Based on a data-driven approach, divers cognitive profiles were identified, which separated early and more advanced stages of cognitive impairment in Parkinson's disease without dementia. Importantly, these profiles were independent of motor progression.
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Recent studies have suggested a tightly connected perisylvian neural network associated with spatial neglect. Here we investigated whether structural damage in one part of the network typically is accompanied with functional damage in other, structurally intact areas of this network. By combining normalized fluid-attenuated inversion-recovery (FLAIR) imaging, diffusion-weighted imaging (DWI), and perfusion-weighted imaging (PWI) we asked whether or not lesions centering on fronto-temporal regions co-occur with abnormal perfusion in structurally intact parietal cortex. With thresholds applied to delineate behaviourally relevant malperfusion of brain tissue, the analysis of normalized time-to-peak (TTP) and maximal signal reduction (MSR) perfusion maps did not reveal significant changes outside the area of structural damage. In particular, we found no abnormal perfusion in the structurally intact inferior parietal lobule (IPL) and/or the temporo-parietal junction (TPJ). The present results obtained in three consecutively admitted neglect patients with fronto-temporal lesions indicate that structural damage in one part of the right perisylvian network associated with spatial neglect does not necessarily require dysfunction by malperfusion in other, structurally intact parts of the network to provoke spatial neglect. The neural tissue in the fronto-temporal cortex appears to have an original role in processes of spatial orienting and exploration.
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Compared to cortical lesions, spatial neglect following subcortical stroke is most frequently seen as a mild and transient phenomenon. Since this assumption is based on only few observations, we reexamined the prognosis and severity of spatial neglect in patients with circumscribed right-sided basal ganglia or thalamic lesions in the acute and in the chronic phase of the stroke. On average, 1.15 years after stroke, spatial neglect had persisted in about 40% of the patients with subcortical lesions. The severity was reduced to about one third. The results argue against the view that spatial neglect following subcortical lesions typically has a favorable prognosis.
Assuntos
Córtex Cerebral/fisiopatologia , Transtornos da Percepção/patologia , Transtornos da Percepção/fisiopatologia , Recuperação de Função Fisiológica/fisiologia , Idoso , Idoso de 80 Anos ou mais , Córtex Cerebral/patologia , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Transtornos da Percepção/etiologia , Índice de Gravidade de Doença , Acidente Vascular Cerebral/complicaçõesRESUMO
Spatial neglect is characterized by a deviation of the eyes and the head during active search, as well as at rest. Here the authors investigate the hitherto unknown relationship between these striking behaviors in the course of recovery. Gaze, eye-in-head, and head-on-trunk positions were recorded separately under two experimental conditions: (i) at rest (i.e., without any specific requirements, doing nothing) and (ii) during active exploratory search in a large visual array of 240 degrees x 80 degrees over a 10-month period. The authors observed a parallel decrease of eye and head (= gaze) deviation in both conditions, accompanied by a comparable decline in neglect severity. The results strengthen the view that the marked gaze deviation toward the ipsilesional side in patients with spatial neglect is due to a very elementary disturbance of human spatial information processing.
Assuntos
Dano Encefálico Crônico/fisiopatologia , Movimentos Oculares/fisiologia , Movimentos da Cabeça/fisiologia , Transtornos da Percepção/fisiopatologia , Desempenho Psicomotor/fisiologia , Acidente Vascular Cerebral/fisiopatologia , Idoso , Comportamento Exploratório/fisiologia , Feminino , Lateralidade Funcional/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos da Percepção/diagnóstico , Transtornos da Percepção/etiologia , Testes Psicológicos/estatística & dados numéricos , Percepção Espacial/fisiologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/patologia , Fatores de Tempo , Percepção Visual/fisiologiaRESUMO
Intraoperative electrical stimulation in awake patients is a seminal technique during brain surgery allowing one to infer the function of brain areas by temporary inactivation. Using this technique, we found that inactivation of the middle portion of the superior temporal gyrus (STG) leads to disturbed serial exploratory visual search. The data supplement recent findings by Ellison et al. [Ellison, A., Schindler, I., Pattison, L. L., & Milner, A. D. (2004). An exploration of the role of the superior temporal gyrus in visual search and spatial perception using TMS. Brain, 127, 2307-2315] using repetitive transcranial magnetic stimulation over the STG in healthy subjects. Our data demonstrate that the STG is integral to human exploration behaviour and challenge the traditional view that only the right posterior parietal cortex is involved in the mediation of visual search processes.
Assuntos
Estimulação Elétrica/métodos , Período Intraoperatório , Lobo Temporal/fisiopatologia , Percepção Visual/fisiologia , Idoso , Mapeamento Encefálico , Humanos , Transtornos da Linguagem/patologia , Transtornos da Linguagem/cirurgia , Imageamento por Ressonância Magnética/métodos , Masculino , Lobo Temporal/efeitos da radiação , Estimulação Magnética TranscranianaRESUMO
One major function of parietal cortex is to direct our attention towards salient stimuli. The present data suggest that it also plays an important role in visual gestalt perception. Patients with simultanagnosia following lesions in this area are not able to extract the meaning of a visual scene whereas being perfectly able to recognise individual objects of this scene. We tested two patients with simultanagnosia with hierarchical Navon figures combined with eye movements recordings. The patients' performance allowed us to compare directly the scan paths in trials in which the global letter shape was recognised with trials in which the global letter shape was not recognised. We did not find any obvious differences in the eye movement pattern related to the two perceptual situations. The two patients did not show a significant problem in shifting their eyes (and thus possibly also their attentional focus) to all aspects of the complex visual stimulus when attempting to bind together the different elements of spatially distributed information. The results demonstrate that restricted ocular exploration cannot be the reason for the patients' inability to recognise the global shape of stimuli. Our data rather suggest a role of parietal cortex in visual gestalt perception that is beyond its role of directing attention towards relevant objects.
Assuntos
Agnosia/fisiopatologia , Atenção/fisiologia , Movimentos Oculares/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Mapeamento Encefálico , Córtex Cerebral/patologia , Eletromiografia/métodos , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos/estatística & dados numéricos , Estimulação Luminosa/métodos , Tomografia por Emissão de Pósitrons/métodos , Fatores de TempoRESUMO
Neglect patients classically fail to orient and respond to stimuli appearing on their contralesional side. Traditionally, the neglect syndrome has been associated with damage to the right inferior parietal lobule (IPL) and the right temporo-parietal junction (TPJ). Neglect is popularly assessed by two different tasks: line bisection and cancellation. In a previous study (S. Ferber, H.-O. Karnath, How to assess spatial neglect-line bisection or cancellation tasks. J. Clin. Exp. Neuropsychol. 23 (2001) 599-607), we observed that performance on the cancellation task correlates well with the characteristic behavioral disorders used to clinically diagnose spatial neglect, while line bisection was a poor predictor. This might indicate that the disability to correctly bisect lines is a distinct disorder separable from spatial neglect. Here, we assess the anatomy of the patients investigated in that study, and reveal that damage to the temporo-occipital junction correlates with poor performance in the line bisection task. This work extends previous work by Binder et al. (J. Binder, R. Marshall, R. Lazar, J. Benjamin, J.P. Mohr, Distinct syndromes of hemineglect. Arch. Neurol. 49 (1992) 1187-1194) suggesting that line bisection and cancellation identify distinct syndromes. The data suggest that these two tasks dissociate both in terms of behavior and anatomy. This anatomical distinction may help reconcile our recent finding that spatial neglect is associated with damage to the superior temporal cortex and insula, while others have identified the IPL and TPJ. Specifically, we note that our previous anatomical studies did not use the line bisection task to select neglect patients, while many others used this task. We suggest that anatomical studies that combine patients from both of these two distinct groups may result in misleading findings.
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Percepção de Forma , Lobo Occipital/patologia , Transtornos da Percepção/patologia , Desempenho Psicomotor , Lobo Temporal/patologia , Adulto , Idoso , Atenção , Dano Encefálico Crônico/etiologia , Dano Encefálico Crônico/fisiopatologia , Feminino , Lateralidade Funcional , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Transtornos da Percepção/classificação , Transtornos da Percepção/etiologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/fisiopatologiaRESUMO
Perfusion-weighted imaging (PWI) is used to identify brain regions that are receiving enough blood supply to remain structurally intact, but not enough to function normally. Previous observations suggest that spatial neglect due to subcortical stroke can be explained by dysfunction of cortical areas rather than through the neuronal loss in the subcortical structures itself. The present study aimed to identify the dysfunctional cortical regions induced by basal ganglia stroke in patients with spatial neglect. In a patient group with stroke lesions centring on the basal ganglia, we examined the common area(s) of structurally intact but dysfunctional cortical tissue by using spatial normalization of PWI maps as well as symmetric voxel-wise inter-hemispheric comparisons. These new techniques allow comparison of the structurally intact but abnormally perfused areas of different individuals in the same stereotaxic space, and at the same time avoid problems due to regional perfusion differences and to possible observer-dependent biases. We found that strokes centring on the right basal ganglia which provoke spatial neglect induce abnormal perfusion in a circumscribed area of intact cortex that typically involves those three regions that have previously been described to provoke spatial neglect when damaged directly by cortical infarction: the superior temporal gyrus, the inferior parietal lobule and the inferior frontal gyrus. The data suggest that spatial neglect following a right basal ganglia lesion typically is caused by the dysfunction of (part of) these specific cortical areas.
Assuntos
Doença Cerebrovascular dos Gânglios da Base/patologia , Transtornos da Percepção/patologia , Acidente Vascular Cerebral/patologia , Atenção , Gânglios da Base/patologia , Doença Cerebrovascular dos Gânglios da Base/complicações , Doença Cerebrovascular dos Gânglios da Base/fisiopatologia , Angiografia Cerebral/métodos , Circulação Cerebrovascular/fisiologia , Feminino , Lobo Frontal/patologia , Lobo Frontal/fisiopatologia , Humanos , Angiografia por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Lobo Parietal/patologia , Lobo Parietal/fisiopatologia , Transtornos da Percepção/etiologia , Transtornos da Percepção/fisiopatologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/fisiopatologia , Lobo Temporal/patologia , Lobo Temporal/fisiopatologia , Percepção Visual/fisiologiaRESUMO
The most prominent deficit in patients with spatial neglect is a bias of their active behaviour, i. e. a deviation of exploratory movements towards the right. When searching for targets, copying, or reading, the patients direct their eye and hand movements towards the ipsilesional side, leading to neglect of the contralesional side. The present study investigated whether spatial neglect is predominantly linked with such active behaviour or if it is obvious also without any explicit requirements, namely in the patients' spontaneous eye and head position. To address this issue we investigated the patients' spontaneous resting position while "doing nothing", i. e. just sitting and waiting for an experiment to start. Using magnetic search coil technique, we recorded spontaneous eye-in-head and head-on-trunk orientation in that waiting period in 24 patients with and without spatial neglect. In contrast to controls, neglect patients showed a marked deviation of spontaneous eye and head orientation of about 30 degrees (= gaze position) towards the right. The findings strengthen the view that one component of the behaviour in neglect patients is due to a very elementary disturbance of spatial information processing. The deviation of eye and head may be understood as a pathological adjustment of the subject's normal resting position to a more rightward position. While the position in healthy subjects is in line with trunk orientation, this "default position" is shifted to a new origin in patients with spatial neglect.
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Dano Encefálico Crônico/fisiopatologia , Movimentos Oculares/fisiologia , Percepção Espacial/fisiologia , Acidente Vascular Cerebral/fisiopatologia , Percepção Visual/fisiologia , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Lateralidade Funcional/fisiologia , Cabeça/fisiologia , Humanos , Magnetoencefalografia , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/patologiaRESUMO
A major challenge for any anatomical study of spatial neglect in neurological patients is that human lesions vary tremendously in extent and location between individuals. Approaches to this problem used in previous studies were to focus on subgroups of patients that are more homogeneous either with respect to the branch territory affected by the stroke or with respect to existing additional neurological symptoms (e.g. additional visual field defects). It could be argued that such strategies might bias the conclusions on the critical substrate associated with spatial neglect. The present study thus addressed the high variability inherent in naturally occurring lesions by using an unselected, but very large sample size and by comparing a neglect group with a non-neglect group using voxelwise statistical testing. We investigated an unselected 7 year sample of 140 consecutively admitted patients with right hemisphere strokes. Seventy-eight had spatial neglect, 62 did not show the disorder. The incidence of visual field defects was comparable in both groups. For assessing lesion location, in a first step, we used conventional lesion density plots together with subtraction analysis. Moreover, due to the large size of the sample voxelwise statistical testing was possible to objectively estimate which brain regions are more frequently compromised in neglect patients relative to patients without neglect. The results demonstrate that the right superior temporal cortex, the insula and subcortically putamen and caudate nucleus are the neural structures damaged significantly more often in patients with spatial neglect.