RESUMO
BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an established treatment for disabling motor symptoms of Parkinson's disease (PD) that persist despite optimal pharmacological treatment. Currently, DBS is not performed if there is concomitant significant cognitive impairment based on concerns of cognitive deterioration, higher complication rate and less functional improvement. However, this has not been investigated so far. METHODS: A single center, prospective, randomized, open-label, blinded end-point (PROBE design) pilot clinical trial is being performed. Patients are eligible for the trial if they have PD dementia (PDD), are able to provide informed consent, and experience disabling motor response fluctuations, bradykinesia, dyskinesia, or painful dystonia, despite optimal pharmacological treatment. In total 44 patients will be randomized to either STN-DBS accompanied by best medical treatment (DBS group) or to best medical treatment alone (BMT group). The primary outcome measure is the change from baseline to 30 weeks on the Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III score in a standardized off-drug phase. The main secondary outcome measures consist of scales assessing cognitive aspects of daily living, neuropsychiatric symptoms and impulsive compulsive disorders. Additional secondary outcome measures include motor signs during on-drug phase, dyskinesia, motor fluctuations, cognitive performance, (severe) adverse events, treatment satisfaction, and caregiver burden. Patients will be followed during 52 weeks after randomization. DISCUSSION: The Deep Brain Stimulation for MOtor symptoms in patients with Parkinson's disease DEmentia (DBS-MODE) trial directly compares the effectiveness and safety of DBS with BMT in patients with PDD. TRIAL REGISTRATION: The DBS-MODE trial has been registered in the International Clinical Trial Registry Platform (NL9361) on the 24th of March 2021 ( https://trialsearch.who.int/Trial2.aspx?TrialID=NL9361 ).
Assuntos
Doença de Alzheimer , Estimulação Encefálica Profunda , Demência , Discinesias , Doença de Parkinson , Humanos , Doença de Parkinson/terapia , Doença de Parkinson/tratamento farmacológico , Estimulação Encefálica Profunda/efeitos adversos , Estimulação Encefálica Profunda/métodos , Estudos Prospectivos , Resultado do Tratamento , Doença de Alzheimer/terapia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVE: To investigate whether concomitant Alzheimer's disease (AD) pathology, reflected by cerebrospinal fluid (CSF) biomarkers, has an impact on dementia with Lewy bodies (DLB) in terms of clinical presentation, cognitive decline, nursing home admittance and survival. PARTICIPANTS: We selected 111 patients with probable DLB and CSF available from the Amsterdam Dementia Cohort. On the basis of the AD biomarker profile (CSF tau/amyloid-ß 1-42 (Aß42) ratio >0.52), we divided patients into a DLB/AD+ and DLB/AD- group. Of the 111 patients, 42 (38%) had an AD CSF biomarker profile. We investigated differences between groups in memory, attention, executive functions, language and visuospatial functions. Difference in global cognitive decline (repeated Mini-Mental State Examination (MMSE)) was investigated using linear mixed models. Cox proportional hazard analyses were used to investigate the effects of the AD biomarker profile on time to nursing home admittance and time to death. RESULTS: Memory performance was worse in DLB/AD+ patients compared with DLB/AD- patients (p<0.01), also after correction for age and sex. Hallucinations were more frequent in DLB/AD+ (OR=3.34, 95% CI 1.22-9.18). There was no significant difference in the rate of cognitive decline. DLB/AD+ patients had a higher mortality risk (HR=3.13, 95% CI 1.57 to 6.24) and nursing home admittance risk (HR=11.70, 95% CI 3.74 to 36.55) compared with DLB/AD- patients. CONCLUSIONS: DLB-patients with a CSF AD profile have a more severe manifestation of the disease and a higher risk of institutionalisation and mortality. In clinical practice, CSF biomarkers may aid in predicting prognosis in DLB. In addition, DLB-patients with positive AD biomarkers could benefit from future treatment targeting AD pathology.
Assuntos
Doença de Alzheimer/patologia , Encéfalo/patologia , Transtornos Cognitivos/patologia , Doença por Corpos de Lewy/patologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/complicações , Doença de Alzheimer/mortalidade , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Transtornos Cognitivos/líquido cefalorraquidiano , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/mortalidade , Progressão da Doença , Feminino , Humanos , Doença por Corpos de Lewy/líquido cefalorraquidiano , Doença por Corpos de Lewy/complicações , Doença por Corpos de Lewy/mortalidade , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Fragmentos de Peptídeos/líquido cefalorraquidiano , Fosforilação , Estudos Retrospectivos , Taxa de Sobrevida , Proteínas tau/líquido cefalorraquidianoRESUMO
PURPOSE: Decreased striatal dopamine transporter (DAT) binding on SPECT imaging is a strong biomarker for the diagnosis of dementia with Lewy bodies (DLB). There is still a lot of uncertainty about patients meeting the clinical criteria for probable DLB who have a normal DAT SPECT scan (DLB/S-). The aim of this study was to describe the clinical and imaging follow-up in these patients, and compare them to DLB patients with abnormal baseline scans (DLB/S+). METHODS: DLB patients who underwent DAT imaging ([(123)I]FP-CIT SPECT) were selected from the Amsterdam Dementia Cohort. All [(123)I]FP-CIT SPECT scans were evaluated independently by two nuclear medicine physicians and in patients with normal scans follow-up imaging was obtained. We matched DLB/S-- patients for age and disease duration to DLB/S+ patients and compared their clinical characteristics. RESULTS: Of 67 [(123)I]FP-CIT SPECT scans, 7 (10.4 %) were rated as normal. In five DLB/S- patients, a second [(123)I]FP-CIT SPECT was performed (after on average 1.5 years) and these scans were all abnormal. No significant differences in clinical characteristics were found at baseline. DLB/S- patients could be expected to have a better MMSE score after 1 year. CONCLUSION: This study was the first to investigate DLB patients with the initial [(123)I]FP-CIT SPECT scan rated as normal and subsequent scans during disease progression rated as abnormal. We hypothesize that DLB/S- scans could represent a relatively rare DLB subtype with possibly a different severity or spread of alpha-synuclein pathology ("neocortical predominant subtype"). In clinical practice, if an alternative diagnosis is not imminent in a DLB/S- patient, repeating [(123)I]FP-CIT SPECT should be considered.
Assuntos
Doença por Corpos de Lewy/diagnóstico por imagem , Doença por Corpos de Lewy/metabolismo , Tomografia Computadorizada de Emissão de Fóton Único , Tropanos/metabolismo , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
BACKGROUND: To investigate trajectories of cognitive decline in patients with different types of dementia compared to controls in a longitudinal study. METHOD: In 199 patients with Alzheimer's disease (AD), 10 with vascular dementia (VaD), 26 with dementia with Lewy bodies (DLB), 20 with behavioural variant frontotemporal dementia (bvFTD), 15 with language variant frontotemporal dementia (lvFTD) and 112 controls we assessed five cognitive domains: memory, language, attention, executive and visuospatial functioning, and global cognition (Mini-Mental State Examination, MMSE). All subjects had at least two neuropsychological assessments (median 2, range 2-7). Neuropsychological data were standardized into z scores using baseline performance of controls as reference. Linear mixed models (LMMs) were used to estimate baseline cognitive functioning and cognitive decline over time for each group, adjusted for age, gender and education. RESULTS: At baseline, patients with dementia performed worse than controls in all cognitive domains (p < 0.05) except visuospatial functioning, which was only impaired in patients with AD and DLB (p < 0.001). During follow-up, patients with AD declined in all cognitive domains (p < 0.001). DLB showed decline in every cognitive domain except language and global cognition. bvFTD showed rapid decline in memory, language, attention and executive functioning (all p < 0.01) whereas visuospatial functioning remained fairly stable. lvFTD declined mostly in attention and executive functioning (p < 0.01). VaD showed decline in attention and executive functioning. CONCLUSIONS: We show cognitive trajectories of different types of dementia. These estimations of natural disease course have important value for the design of clinical trials as neuropsychological measures are increasingly being used as outcome measures.
Assuntos
Doença de Alzheimer/psicologia , Transtornos Cognitivos/psicologia , Demência Vascular/psicologia , Demência Frontotemporal/psicologia , Doença por Corpos de Lewy/psicologia , Idoso , Doença de Alzheimer/fisiopatologia , Estudos de Casos e Controles , Transtornos Cognitivos/fisiopatologia , Demência Vascular/fisiopatologia , Progressão da Doença , Função Executiva , Feminino , Demência Frontotemporal/fisiopatologia , Humanos , Idioma , Doença por Corpos de Lewy/fisiopatologia , Estudos Longitudinais , Masculino , Memória , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estudos ProspectivosRESUMO
BACKGROUND: The DEmEntia with LEwy bOdies Project (DEvELOP) aims to phenotype patients with dementia with Lewy bodies (DLB) and study the symptoms and biomarkers over time. Here, we describe the design and baseline results of DEvELOP. We investigated the associations between core and suggestive DLB symptoms and different aspects of disease burden, i.e., instrumental activities of daily living (IADL) functioning, quality of life (QoL), and caregiver burden. METHODS: We included 100 DLB patients (69 ± 6 years, 10%F, MMSE 25 ± 3) in the prospective DEvELOP cohort. Patients underwent extensive assessment including MRI, EEG/MEG, 123FP-CIT SPECT, and CSF and blood collection, with annual follow-up. Core (hallucinations, parkinsonism, fluctuations, RBD) and suggestive (autonomous dysfunction, neuropsychiatric symptoms) symptoms were assessed using standardized questionnaires. We used multivariate regression analyses, adjusted for age, sex, and MMSE, to evaluate how symptoms related to the Functional Activities Questionnaire, QoL-AD questionnaire, and Zarit Caregiver Burden Interview. RESULTS: In our cohort, RBD was the most frequently reported core feature (75%), while visual hallucinations were least frequently reported (39%) and caused minimal distress. Suggestive clinical features were commonly present, of which orthostatic hypotension was most frequently reported (64%). Ninety-five percent of patients showed EEG/MEG abnormalities, 88% of 123FP-CIT SPECT scans were abnormal, and 53% had a CSF Alzheimer's disease profile. Presence of fluctuations, lower MMSE, parkinsonism, and apathy were associated with higher IADL dependency. Depression, constipation, and lower IADL were associated with lower QoL-AD. Apathy and higher IADL dependency predisposed for higher caregiver burden. CONCLUSION: Baseline data of our prospective DLB cohort show clinically relevant associations between symptomatology and disease burden. Cognitive and motor symptoms are related to IADL functioning, while negative neuropsychiatric symptoms and functional dependency are important determinants of QoL and caregiver burden. Follow-up is currently ongoing to address specific gaps in DLB research.
Assuntos
Doença de Alzheimer , Doença por Corpos de Lewy , Atividades Cotidianas , Efeitos Psicossociais da Doença , Humanos , Doença por Corpos de Lewy/complicações , Doença por Corpos de Lewy/diagnóstico por imagem , Estudos Prospectivos , Qualidade de VidaRESUMO
PURPOSE: To study the influence of concomitant Alzheimer's disease (AD) pathology in dementia with Lewy bodies (DLB) on dopamine transporter (DAT) and serotonin transporter (SERT) availability, using 123I-N-ω-fluoropropyl-2ß-carbomethoxy-3ß-(4-iodophenyl) nortropane (123I-FP-CIT) single photon emission computed tomography (SPECT). METHODS: Based on their cerebrospinal fluid biomarker profile, fifty-two patients with probable DLB were divided in a group with (DLB/AD+, Nâ¯=â¯15) and without concomitant AD-pathology (DLB/AD-, Nâ¯=â¯37). We conducted atrophy-corrected region of interest (ROI) analyses comparing binding ratios (BRs) in the DAT-rich striatal and SERT-rich extrastriatal brain areas (amygdala, hippocampus, thalamus, midbrain and pons). RESULTS: DLB/AD+ patients had significantly lower 123I-FP-CIT BRs in the left amygdala, and a trend was seen in the right hippocampus. Groups did not differ significantly in striatal 123I-FP-CIT BRs, neuropsychiatric or motor symptoms. Motor symptoms correlated negatively with striatal DAT BRs. CONCLUSIONS: DLB/AD+ patients may have lower SERT binding in limbic brain regions than DLB/AD- patients, possibly indicating faster neurodegeneration in mixed pathology.
Assuntos
Doença de Alzheimer , Tonsila do Cerebelo/metabolismo , Corpo Estriado/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Hipocampo/metabolismo , Doença por Corpos de Lewy , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Tomografia Computadorizada de Emissão de Fóton Único , Tropanos/farmacocinética , Idoso , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Doença de Alzheimer/fisiopatologia , Tonsila do Cerebelo/diagnóstico por imagem , Comorbidade , Corpo Estriado/diagnóstico por imagem , Feminino , Hipocampo/diagnóstico por imagem , Humanos , Doença por Corpos de Lewy/diagnóstico por imagem , Doença por Corpos de Lewy/metabolismo , Doença por Corpos de Lewy/patologia , Doença por Corpos de Lewy/fisiopatologia , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Dementia with Lewy bodies (DLB) is more prevalent in men than in women. In addition, post-mortem studies found sex differences in underlying pathology. It remains unclear whether these differences are also present antemortem in in vivo biomarkers, and whether sex differences translate to variability in clinical manifestation. The objective of this study was to evaluate sex differences in cerebrospinal fluid (CSF) biomarker concentrations (i.e., alpha-synuclein (α-syn), amyloid ß1-42 (Aß42), total tau (Tau), phosphorylated tau at threonine 181 (pTau)) and clinical characteristics in DLB. METHODS: We included 223 DLB patients from the Amsterdam Dementia Cohort, of which 39 were women (17%, age 70 ± 6, MMSE 21 ± 6) and 184 men (83%, age 68 ± 7, MMSE 23 ± 4). Sex differences in CSF biomarker concentrations (i.e., α-syn, Aß42, Tau, and pTau) were evaluated using age-corrected general linear models (GLM). In addition, we analyzed sex differences in core clinical features (i.e., visual hallucinations, parkinsonism, cognitive fluctuations, and REM sleep behavior disorder (RBD) and cognitive test scores using age- and education-adjusted GLM. RESULTS: Women had lower CSF α-syn levels (F 1429 ± 164 vs M 1831 ± 60, p = 0.02) and CSF Aß42 levels (F 712 ± 39 vs M 821 ± 18, p = 0.01) compared to men. There were no sex differences for (p) Tau concentrations (p > 0.05). Clinically, women were older, had a shorter duration of complaints (F 2 ± 1 vs M 4 ± 3, p < 0.001), more frequent hallucinations (58% vs 38%, p = 0.02), and scored lower on MMSE and a fluency task (MMSE, p = 0.02; animal fluency, p = 0.006). Men and women did not differ on fluctuations, RBD, parkinsonism, or other cognitive tests. CONCLUSIONS: Women had lower Aß42 and α-syn levels than men, alongside a shorter duration of complaints. Moreover, at the time of diagnosis, women had lower cognitive test scores and more frequent hallucinations. Based on our findings, one could hypothesize that women have a more aggressive disease course in DLB compared to men. Future research should investigate whether women and men with DLB might benefit from sex-specific treatment strategies.
Assuntos
Doença de Alzheimer , Biomarcadores , Doença por Corpos de Lewy , Idoso , Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides , Feminino , Humanos , Doença por Corpos de Lewy/diagnóstico , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos , Fatores Sexuais , Proteínas tauRESUMO
PURPOSE: Alpha-synuclein often co-occurs with Alzheimer's disease (AD) pathology in Dementia with Lewy Bodies (DLB). From a dynamic [18F]flortaucipir PET scan we derived measures of both tau binding and relative cerebral blood flow (rCBF). We tested whether regional tau binding or rCBF differed between DLB patients and AD patients and controls and examined their association with clinical characteristics of DLB. METHODS: Eighteen patients with probable DLB, 65 AD patients and 50 controls underwent a dynamic 130-minute [18F]flortaucipir PET scan. DLB patients with positive biomarkers for AD based on cerebrospinal fluid or amyloid PET were considered as DLB with AD pathology (DLB-AD+). Receptor parametric mapping (cerebellar gray matter reference region) was used to extract regional binding potential (BPND) and R1, reflecting (AD-specific) tau pathology and rCBF, respectively. First, we performed regional comparisons of [18F]flortaucipir BPND and R1 between diagnostic groups. In DLB patients only, we performed regression analyses between regional [18F]flortaucipir BPND, R1 and performance on ten neuropsychological tests. RESULTS: Regional [18F]flortaucipir BPND in DLB was comparable with tau binding in controls (p > 0.05). Subtle higher tau binding was observed in DLB-AD+ compared to DLB-AD- in the medial temporal and parietal lobe (both p < 0.05). Occipital and lateral parietal R1 was lower in DLB compared to AD and controls (all p < 0.01). Lower frontal R1 was associated with impaired performance on digit span forward (standardized beta, stß = 0.72) and category fluency (stß = 0.69) tests. Lower parietal R1 was related to lower delayed (stß = 0.50) and immediate (stß = 0.48) recall, VOSP number location (stß = 0.70) and fragmented letters (stß = 0.59) scores. Lower occipital R1 was associated to worse performance on VOSP fragmented letters (stß = 0.61), all p < 0.05. CONCLUSION: The amount of tau binding in DLB was minimal and did not differ from controls. However, there were DLB-specific occipital and lateral parietal relative cerebral blood flow reductions compared to both controls and AD patients. Regional rCBF, but not tau binding, was related to cognitive impairment. This indicates that assessment of rCBF may give more insight into disease mechanisms in DLB than tau PET.
Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doença por Corpos de Lewy , Doença de Alzheimer/diagnóstico por imagem , Circulação Cerebrovascular , Humanos , Doença por Corpos de Lewy/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Proteínas tauRESUMO
INTRODUCTION: The disease course of dementia with Lewy bodies (DLB) can be rapidly progressive, clinically resembling Creutzfeldt-Jakob's disease (CJD). To better understand factors contributing to this rapidly progressive disease course, we describe load and distribution of neuropathology, and the presence of possible disease-associated genetic defects in a post-mortem series of DLB cases clinically suspected of CJD. METHODS: We included pathologically confirmed DLB cases with a disease duration of 3.5 years or less from the Dutch Surveillance Center for Prion Diseases, collected between 1998 and 2014. Lewy body disease (LBD) and Alzheimer's disease (AD)-related pathology were staged and semi-quantitatively scored in selected brain regions. Whole exome sequencing analysis of known disease-associated genes, copy number analysis, APOE ε genotyping and C9orf72 repeat expansion analysis were performed to identify defects in genes with a well-established involvement in Parkinson's disease or AD. RESULTS: Diffuse LBD was present in nine cases, transitional LBD in six cases and brainstem-predominant LBD in one case. Neocortical alpha-synuclein load was significantly higher in cases with intermediate-to-high than in cases with low-to-none AD-related pathology (pâ¯=â¯0.007). We found two GBA variants (p.D140H and p.E326K) in one patient and two heterozygous rare variants of unknown significance in SORL1 in two patients. CONCLUSION: A high load of neocortical alpha-synuclein pathology was present in most, but not all DLB cases. Additional burden from presence of concomitant pathologies, synergistic effects and specific genetic defects in the known disease-associated genes may have contributed to the rapid disease progression.
Assuntos
Síndrome de Creutzfeldt-Jakob/genética , Síndrome de Creutzfeldt-Jakob/patologia , Progressão da Doença , Doença por Corpos de Lewy/genética , Doença por Corpos de Lewy/patologia , Neocórtex/patologia , alfa-Sinucleína/metabolismo , Idoso , Idoso de 80 Anos ou mais , Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/metabolismo , Diagnóstico , Feminino , Glucosilceramidase/metabolismo , Humanos , Proteínas Relacionadas a Receptor de LDL/metabolismo , Doença por Corpos de Lewy/diagnóstico , Doença por Corpos de Lewy/metabolismo , Masculino , Proteínas de Membrana Transportadoras/metabolismo , Neocórtex/metabolismo , Sequenciamento do ExomaRESUMO
BACKGROUND: Growing evidence suggests a role of occupation in the emergence and manifestation of dementia. Occupations are often defined by complexity level, although working environments and activities differ in several other important ways. We aimed to capture the multi-faceted nature of occupation through its measurement as a qualitative (instead of a quantitative) variable and explored its relationship with different types of dementia. METHODS: We collected occupational information of 2121 dementia patients with various suspected etiologies from the Amsterdam Dementia Cohort (age 67 ± 8, 57% male; MMSE 21 ± 5). Our final sample included individuals with Alzheimer's disease (AD) dementia (n = 1467), frontotemporal dementia (n = 281), vascular dementia (n = 98), Lewy body disease (n = 174), and progressive supranuclear palsy/corticobasal degeneration (n = 101). Within the AD group, we used neuropsychological data to further characterize patients by clinical phenotypes. All participants were categorized into 1 of 11 occupational classes, across which we evaluated the distribution of dementia (sub)types with χ2 analyses. We gained further insight into occupation-dementia relationships through post hoc logistic regressions that included various demographic and health characteristics as explanatory variables. RESULTS: There were significant differences in the distribution of dementia types across occupation groups (χ2 = 85.87, p < .001). Vascular dementia was relatively common in the Transportation/Logistics sector, and higher vascular risk factors partly explained this relationship. AD occurred less in Transportation/Logistics and more in Health Care/Welfare occupations, which related to a higher/lower percentage of males. We found no relationships between occupational classes and clinical phenotypes of AD (χ2 = 53.65, n.s.). CONCLUSIONS: Relationships between occupation and dementia seem to exist beyond the complexity level, which offers new opportunities for disease prevention and improvement of occupational health policy.
Assuntos
Demência Vascular/diagnóstico , Ocupações , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Fatores de Risco , Fatores SexuaisRESUMO
Since Alzheimer's disease may affect driving performance, patients with Alzheimer's disease are assessed on fitness to drive. On-road driving assessments are widely used, and attempts have also been made to develop strategies to assess fitness to drive in a clinical setting. Preferably, a first indication of fitness to drive is obtained quickly after diagnosis using a single test such as the Mini-Mental State Examination (MMSE). The aim of this study is to investigate whether the MMSE can be used to predict whether patients with Alzheimer's disease will pass or fail an on-road driving assessment. Patients with Alzheimer's disease (n = 81) participated in a comprehensive fitness-to-drive assessment which included the MMSE as well as an on-road driving assessment [PLoS One 11(2):e0149566, 2016]. MMSE cutoffs were applied as suggested by Versijpt and colleagues [Acta Neurol Belg 117(4):811-819, 2017]. All patients with Alzheimer's disease who scored below the lower cutoff (MMSE ≤ 19) failed the on-road driving assessment. However, a third of the patients with Alzheimer's disease who scored above the upper cutoff (MMSE ≥ 25) failed the on-road driving assessment as well. We conclude that the MMSE alone has insufficient predictive value to correctly identify fitness to drive in patients with very mild-to-mild Alzheimer's disease implicating the need for comprehensive assessments to determine fitness to drive in a clinical setting.
Assuntos
Doença de Alzheimer/psicologia , Condução de Veículo/psicologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Feminino , Humanos , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Índice de Gravidade de DoençaAssuntos
Encéfalo/patologia , Insônia Familiar Fatal/genética , Insônia Familiar Fatal/patologia , Insônia Familiar Fatal/fisiopatologia , Príons/genética , População Negra , Western Blotting , Egito , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Países Baixos , Linhagem , Mutação Puntual , Proteínas PriônicasRESUMO
- The Dutch dementia guideline has been extended to include recommendations in the area of psychosocial interventions for patients, caregivers and professionals.- The diagnostic recommendations in the revised directive are based on a stepwise work-up with the aim of establishing the cause of the dementia. This is guided by the recent diagnostic criteria, evidence of the diagnostic value of additional investigations, and the patient's wishes.- Although there have been no major breakthroughs in the treatment of patients with Alzheimer's disease in recent years, the revised guideline also contains important new recommendations in this area. For example, it includes recommendations on administration routes (first-choice use of patches or preparations with slow release of cholinesterase inhibitors), the use of combination therapy (not prescribing memantine in combination with cholinesterase inhibitors) and regular monitoring of the effectiveness of antipsychotics and cholinesterase inhibitors.- The guideline (in Dutch) can be found at www.richtlijnendatabase.nl (search for 'dementie') and will be actively implemented.
Assuntos
Antipsicóticos/uso terapêutico , Demência/diagnóstico , Demência/tratamento farmacológico , Guias de Prática Clínica como Assunto , Padrões de Prática Médica , Idoso , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/tratamento farmacológico , Inibidores da Colinesterase/uso terapêutico , Terapia Combinada , Humanos , Países Baixos , Resultado do TratamentoRESUMO
OBJECTIVE: To study the sensitivity and specificity of 14-3-3 testing in a prospective series of patients suspected of having Creutzfeldt-Jakob disease (CJD). BACKGROUND: The 14-3-3 protein immunoassay on CSF has favorable test characteristics as a premortem diagnostic tool in CJD. However, the 14-3-3 protein is a normal cellular protein expressed in various tissues, and its presence in CSF reflects extensive destruction of brain tissue as in CJD, but also in ischemic stroke and meningoencephalitis. METHODS: 14-3-3 was tested in the CSF of a prospective series of 110 consecutive patients suspected of having CJD. RESULTS: The sensitivity was 97% and the specificity was 87% in this series. False-positive results were mainly caused by stroke and meningoencephalitis. CONCLUSION: The 14-3-3 protein is a highly sensitive and specific marker for CJD when used in the appropriate clinical context.
Assuntos
Astrocitoma/diagnóstico , Neoplasias Encefálicas/diagnóstico , Síndrome de Creutzfeldt-Jakob/diagnóstico , Linfoma/diagnóstico , Proteínas/análise , Tirosina 3-Mono-Oxigenase , Proteínas 14-3-3 , Adulto , Idoso , Astrocitoma/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Encefalopatias/líquido cefalorraquidiano , Encefalopatias/diagnóstico , Neoplasias Encefálicas/líquido cefalorraquidiano , Líquido Cefalorraquidiano/química , Síndrome de Creutzfeldt-Jakob/líquido cefalorraquidiano , Diagnóstico Diferencial , Reações Falso-Positivas , Feminino , Humanos , Linfoma/líquido cefalorraquidiano , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e EspecificidadeRESUMO
Creutzfeldt-Jakob disease (CJD) can be transmitted through human growth hormone or gonadotrophin administration, dura mater or cornea transplantation, depth EEG monitoring and the use of contaminated neurosurgical instruments. We describe the first two dura mater associated CJD cases in the Netherlands. Ten and fourteen years before the onset of symptoms both patients received a Lyodura implantation. Findings are discussed in light of the growing epidemic of CJD among dura mater recipients.
Assuntos
Síndrome de Creutzfeldt-Jakob/etiologia , Dura-Máter/transplante , Transplante Autólogo/efeitos adversos , Adulto , Encéfalo/patologia , Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Transplante HomólogoRESUMO
Neurons in the internal segment of the globus pallidus (GPi) oscillate at approximately the frequency of parkinsonian tremor. However, the correlation of that activity with tremor has not previously been studied. We now describe the relationship between single neuron activity in the arm sensorimotor portion of GPi and upper extremity tremor in patients with Parkinson's disease. There was a significant concentration of power in the tremor-frequency range (3-6 Hz) for 11/44 GPi neurons. However, pallidal tremor-frequency activity correlated significantly with electromyogram (EMG) activity during tremor for only a single GPi neuron. These data are most consistent with the hypothesis that the output of neurons in GPi is transformed in thalamus by a non-linear mechanism, before transmission via the cortex to the spinal motorneurons that drive movement.
Assuntos
Globo Pálido/fisiologia , Doença de Parkinson/fisiopatologia , Córtex Somatossensorial/fisiologia , Tremor/fisiopatologia , Mapeamento Encefálico , Eletromiografia , Humanos , Neurônios Motores/fisiologia , Neurônios Aferentes/fisiologia , Tálamo/fisiologiaRESUMO
Cholinesterase inhibitors are licensed for the treatment of dementia in Alzheimer's disease. In clinical practice, these drugs have little effect on the cognitive symptoms of dementia. Several studies report a beneficial effect of cholinesterase inhibitors on neuropsychiatric symptoms. We hypothesise that symptoms such as the impairment of attention and concentration, anxiety, restlessness and hallucinations, delineate a specific central cholinergic deficiency syndrome. It is postulated that this syndrome crosses boundaries of nosological entities and occurs in various neurodegenerative diseases. Symptoms resulting from cholinergic deficiency might be a much better target for treatment than cognitive deficits.
Assuntos
Acetilcolinesterase/deficiência , Inibidores da Colinesterase/uso terapêutico , Doenças Neurodegenerativas/etiologia , Doença de Alzheimer/tratamento farmacológico , Demência/tratamento farmacológico , Humanos , SíndromeRESUMO
OBJECTIVE: To study whether an algorithm that includes additional diagnostic information could increase the specificity of the 14-3-3 protein testing in patients suspected to suffer from Creutzfeldt-Jakob disease (CJD). DESIGN: The development of a diagnostic algorithm. METHOD: The 14-3-3 protein was tested in the cerebrospinal fluid from 69 consecutive patients suspected of having CJD. On the basis of a former study and literature research, a diagnostic algorithm was constructed, which restricted the indication for performing the 14-3-3 protein test. RESULTS: By taking into consideration the findings of neuroimaging and routine cerebrospinal fluid examination prior to 14-3-3 testing, the specificity increased to 97% (95%-CI: 85.5-99.9) thus changing the prior probability of having CJD of 35% to a posterior probability of 75-100%, in the case of a positive test result. CONCLUSION: Determining the presence of 14-3-3 protein is a highly sensitive and specific marker for sporadic CJD when used in combination with imaging and cerebrospinal fluid examination.
Assuntos
Síndrome de Creutzfeldt-Jakob/líquido cefalorraquidiano , Síndrome de Creutzfeldt-Jakob/diagnóstico , Tirosina 3-Mono-Oxigenase/líquido cefalorraquidiano , Proteínas 14-3-3 , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Biomarcadores/líquido cefalorraquidiano , Criança , Diagnóstico Diferencial , Feminino , Humanos , Immunoblotting , Masculino , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
Rivastigmine was recently licensed for treatment of Alzheimer's disease on the basis of large double-blind placebo-controlled clinical trials. However, it is difficult to determine the clinical relevance for individual patients from the results of this type of clinical trial. With the help of standardised measurements in individual patients the clinical relevance can be better established. In order to avoid extra burden on patients, caregivers and doctors, these measurements should be simple. A combination of three clinimetrical scales for cognition, ability to perform daily activities and behaviour, which takes about 15 min to complete, appears to be efficient. Comparison of these data with data from a group of untreated Alzheimer's patients can give an impression of the efficacy of the medication. With the use of goal-attainment scaling, measurements can be individualised even more. This approach allows the clinician, in consultation with the caregiver and the patient, to make an informed decision about whether or not to continue treatment.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Carbamatos/uso terapêutico , Nootrópicos/uso terapêutico , Fenilcarbamatos , Escalas de Graduação Psiquiátrica , Atividades Cotidianas/psicologia , Doença de Alzheimer/psicologia , Cognição/efeitos dos fármacos , Humanos , Países Baixos , Guias de Prática Clínica como Assunto , Rivastigmina , Índice de Gravidade de Doença , Comportamento Social , Resultado do TratamentoRESUMO
Many disorders, such as Alzheimer's disease and diabetes, are characterised by the misfolding and aggregation of proteins. Pepys et al. described a new approach of destabilizing these aggregates by removing an associated protein, serum amyloid P. This offers opportunities for treating amyloidosis and possibly other protein folding diseases. Understanding the mechanism of this unique disease process and the different elements involved is necessary for future drug development.