Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 53
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Proc Natl Acad Sci U S A ; 120(36): e2302720120, 2023 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-37643212

RESUMO

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson's disease (PD) and Alzheimer's disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aß42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues.


Assuntos
Doença de Alzheimer , Cadeias HLA-DRB1 , Doença de Parkinson , Humanos , Doença de Alzheimer/genética , Antígenos de Histocompatibilidade , Antígenos HLA , Cadeias HLA-DRB1/genética , Doença de Parkinson/genética
2.
Alzheimers Dement ; 19(7): 2853-2864, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36588502

RESUMO

BACKGROUND: Apathy is the most frequent neuropsychiatric symptom in patients with dementia of the Alzheimer's type (DAT). We analyzed the influence of apathy on the resource use of DAT patients and their caregivers. METHODS: Included were baseline data of 107 DAT patients from a randomized clinical trial on apathy treatment. The Resource Utilization in Dementia (RUD) instrument assessed costs over a 1-month period prior to baseline. Cost predictors were determined via a least absolute shrinkage and selection operator (LASSO). RESULTS: On average, total monthly costs were €3070, of which €2711 accounted for caregivers' and €359 for patients' costs. An increase of one point in the Apathy Evaluation Scale resulted in a 4.1% increase in total costs. DISCUSSION: Apathy is a significant cost driving factor for total costs in mild to moderate DAT. Effective treatment of apathy might be associated with reduced overall costs in DAT.


Assuntos
Doença de Alzheimer , Apatia , Humanos , Doença de Alzheimer/diagnóstico , Cuidadores/psicologia , Resultado do Tratamento
3.
J Neural Transm (Vienna) ; 129(5-6): 477-486, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35061102

RESUMO

ApoE4, the strongest genetic risk factor for Alzheimer's disease (AD), has been shown to be associated with both beta-amyloid (Aß) and tau pathology, with the strongest evidence for effects on Aß, while the association between ApoE4 and tau pathology remains inconsistent. This study aimed to investigate the associations between ApoE4 with CSF Aß42, total tau (t-tau), phospho-tau181 (p-tau), and with the progression of decline in a large cohort of MCI subjects, both progressors to AD and other dementias, as well as non-progressors. We analyzed associations of CSF Aß42, p-tau and t-tau with ApoE4 allele frequency cross-sectionally and longitudinally over 3 years of follow-up in 195 individuals with a diagnosis of MCI-stable, MCI-AD converters and MCI progressing to other dementias from the German Dementia Competence Network. In the total sample, ApoE4 carriers had lower concentrations of CSF Aß42, and increased concentrations of t-tau and p-tau compared to non-carriers in a gene dose-dependent manner. Comparisons of these associations stratified by MCI-progression groups showed a significant influence of ApoE4 carriership and diagnostic group on all CSF biomarker levels. The effect of ApoE4 was present in MCI-stable individuals but not in the other groups, with ApoE4 + carriers having decreased CSF Aß 42 levels, and increased concentration of t-tau and p-tau. Longitudinally, individuals with abnormal t-tau and Aß42 had a more rapid progression of cognitive and clinical decline, independently of ApoE4 genotype. Overall, our results contribute to an emerging framework in which ApoE4 involves mechanisms associated with both CSF amyloid-ß burden and tau aggregation at specific time points in AD pathogenesis.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Apolipoproteína E4/genética , Biomarcadores/líquido cefalorraquidiano , Disfunção Cognitiva/diagnóstico , Genótipo , Humanos , Fragmentos de Peptídeos/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano
4.
BMC Geriatr ; 22(1): 755, 2022 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-36109693

RESUMO

BACKGROUND: Frailty has been associated with a decline in sensory and motor function. However, given that different frailty measures were shown to overlap but also differ in their diagnostic properties, sensory and motor correlates of frailty might be different depending on the operationalization of frailty. Our objective was to identify sensory and motor determinants of frailty and compare the results between frailty phenotype (FP) and frailty index (FI). METHODS: Data from 44 pre-frail and frail subjects aged 65 and above were used. Frailty was measured using the FP and the FI. Sensory function in the visual, auditory, and tactile domain was assessed using visual acuity, absolute hearing threshold and mechanical detection threshold. Upper extremity motor performance was evaluated by the Purdue Pegboard Test and the Short Physical Performance Battery was used to assess lower extremity motor function. Multiple logistic regression models were employed to determine associations of sensory and motor function with frailty vs. pre-frailty for both frailty measures. RESULTS: The frailty measures were moderately correlated (0.497, p ≤ 0.01) and had a Kappa agreement of 0.467 (p = 0.002). Using the FP, frailty was significantly associated with reduced upper extremity motor function only (OR = 0.50, 95% CI 0.29-0.87, p = 0.014). Frailty as assessed by the FI was significantly related to higher hearing thresholds (OR = 1.21, 95% CI 1.02-1.43, p = 0.027) and reduced lower extremity performance (OR = 0.32, 95% CI 0.13-0.77, p = 0.012). CONCLUSION: Frailty is related to reduced performance in measures of sensory and motor function. However, traditional measures of frailty might be differentially sensitive to capture sensory and motor decline, possibly contributing to the much-observed discordance between the diagnostic instruments. This should be taken into account by researchers and clinicians when planning and evaluating therapeutic interventions for frailty. TRIAL REGISTRATION: ClinicalTrials.gov NCT03666039 . Registered 11 September 2018 - Retrospectively registered.


Assuntos
Fragilidade , Idoso , Idoso Fragilizado , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Humanos , Fenótipo
5.
Fortschr Neurol Psychiatr ; 90(7-08): 361-367, 2022 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-35858613

RESUMO

Dementias are expensive diseases: the net annual cost in European healthcare is about € 28.000 per case with a strong stage dependency, of which medical care accounts for about 19%. Diagnostic costs, on the other hand, account for only a small proportion of the total costs. With changes in the guidelines, biomarker tests are becoming increasingly important. At present, the concrete economic impact of biomarker-based diagnosis is largely unknown. To determine the actual costs of diagnostic procedures based on guidelines, we conducted a survey among the members of the German Memory Clinic Network (DNG). From 15 expert centres, the staff engagement time for all procedures was collected. Based on the individual engagement times of the different professions, the total of personnel costs for diagnostics was calculated using current gross personnel costs. The total sum of diagnostic costs (personnel plus procedures) was calculated for three different scenarios e. g. € 633,97 for diagnostics without biomarkers, € 1.214,90 for diagnostics with CSF biomarkers and € 4.740,58 € for diagnostics with FDG- plus Amyloid-PET. In addition, the actual diagnostic costs of the current practice in expert memory clinics were estimated, taking into account personnel costs, costs for the different procedures and the frequency of their use across all patients. This results in total average costs of € 1.394,43 per case as the mean across all centres (personnel costs € 351,72, costs for diagnostic procedures € 1.042,71). The results show that state-of-the-art diagnosis of dementia and pre-dementia states, such as mild cognitive impairment (MCI) requires financial resources, which are currently not fully reimbursed in Germany. The need for a biomarker-based etiological diagnosis of dementia and pre-dementia states will increase, due to availability of disease-modifying treatments. Therefore, the current gap of reimbursement must be filled by new models of compensation.


Assuntos
Disfunção Cognitiva , Demência , Disfunção Cognitiva/diagnóstico , Demência/diagnóstico , Diagnóstico Precoce , Alemanha , Custos de Cuidados de Saúde , Humanos
6.
J Neurol Neurosurg Psychiatry ; 92(4): 349-356, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33380492

RESUMO

OBJECTIVE: Synaptic loss plays a major role in Alzheimer's disease (AD). However so far no neurochemical marker for synaptic loss has been introduced into clinical routine. By mass spectrometry beta-synuclein was established as a candidate marker. We now aimed to set up a novel ELISA for beta-synuclein for evaluation of its potential as a diagnostic and predictive marker for AD. METHODS: We analysed in total 393 patients from four specialised centres. The diagnostic groups comprised: AD (n=151), behavioural variant frontotemporal dementia (bvFTD, n=18), Parkinson syndrome (n=46), Creutzfeldt-Jakob disease (CJD, n=23), amyotrophic lateral sclerosis (ALS, n=29), disease control (n=66) and 60 non-neurodegenerative control patients. Results were compared with core AD biomarkers (total tau, phospho-tau and amyloid-ß peptide 1-42). Additionally, coexistence of beta-synuclein with vesicular glutamate transporter 1 (VGLUT1) was determined and beta-synuclein levels were quantified in brain homogenates. RESULTS: Beta-synuclein levels quantified with the newly established ELISA correlated strongly with antibody-free quantitative mass spectrometry data (r=0.92 (95% CI: 0.89 to 0.94), p<0.0001). Cerebrospinal fluid (CSF) beta-synuclein levels were increased in AD-mild cognitive impairment (p<0.0001), AD dementia (p<0.0001) and CJD (p<0.0001), but not in bvFTD, Parkinson syndrome or ALS. Furthermore, beta-synuclein was localised in VGLUT1-positive glutamatergic synapses, and its expression was significantly reduced in brain tissue from patients with AD (p<0.01). CONCLUSION: We successfully established a sensitive and robust ELISA for the measurement of brain-enriched beta-synuclein, which we could show is localised in glutamatergic synapses. We confirmed previous, mass spectrometry-based observations of increased beta-synuclein levels in CSF of patients with AD and CJD supporting its potential use as a marker of synaptic degeneration.


Assuntos
Doença de Alzheimer , Esclerose Lateral Amiotrófica , Doença de Parkinson , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Humanos , Doença de Parkinson/líquido cefalorraquidiano , Doença de Parkinson/diagnóstico , Fragmentos de Peptídeos/líquido cefalorraquidiano , beta-Sinucleína , Proteínas tau/líquido cefalorraquidiano
7.
Int J Geriatr Psychiatry ; 36(2): 324-333, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32896040

RESUMO

OBJECTIVES: Mild cognitive impairment (MCI) is associated with an increased risk of further cognitive decline, partly depending on demographics and biomarker status. The aim of the present study was to survey the clinical practices of physicians in terms of biomarker counseling, management, and follow-up in European expert centers diagnosing patients with MCI. METHODS: An online email survey was distributed to physicians affiliated with European Alzheimer's disease Consortium centers (Northern Europe: 10 centers; Eastern and Central Europe: 9 centers; and Southern Europe: 15 centers) with questions on attitudes toward biomarkers and biomarker counseling in MCI and dementia. This included postbiomarker counseling and the process of diagnostic disclosure of MCI, as well as treatment and follow-up in MCI. RESULTS: The response rate for the survey was 80.9% (34 of 42 centers) across 20 countries. A large majority of physicians had access to biomarkers and found them useful. Pre- and postbiomarker counseling varied across centers, as did practices for referral to support groups and advice on preventive strategies. Less than half reported discussing driving and advance care planning with patients with MCI. CONCLUSIONS: The variability in clinical practices across centers calls for better biomarker counseling and better training to improve communication skills. Future initiatives should address the importance of communicating preventive strategies and advance planning.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doença de Alzheimer/diagnóstico , Biomarcadores , Disfunção Cognitiva/diagnóstico , Aconselhamento , Revelação , Progressão da Doença , Europa (Continente) , Seguimentos , Humanos , Sensibilidade e Especificidade
8.
BMC Geriatr ; 21(1): 343, 2021 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-34082710

RESUMO

BACKGROUND: Frailty is characterized by an age-related decline in multiple physiological systems, leading to a high vulnerability to stressors, adverse health outcomes, and low quality of life. Neuroscientific models of pathological aging emphasize the loss of sensorimotor stimulation and reduced neuromodulatory capacities as core processes in age-related cognitive and bodily decline, which may be associated with maladaptive plastic changes in the brain. We plan to increase sensorimotor stimulation in frail persons through a newly developed app-based training program and link the training trials to biological and psychological correlates of age-associated vulnerability and health indices. METHODS: We will conduct a randomized trial, applying an app-based sensorimotor home training (N = 30) in people suffering from frailty. An app-based relaxation training will serve as an active control condition (N = 30). Both interventions will last for 90 days each. The sensorimotor training includes unimodal and multimodal sensory discrimination tasks in the visual, auditory, and tactile domain, as well as sensorimotor precision tasks. The tasks will be implemented using an adaptive training algorithm and enriched with motivational components embedded in a virtual training environment. We expect a pre-post reduction of frailty status and associated functional decline related to refinement of representational maps within the sensorimotor system and improved sensorimotor function such as extremity function. Secondary analyses will study the influence of BDNF genotype as moderating variable. Additional outcomes will include measures of perceptual and cognitive functioning, quality of life as well as BDNF serum levels. Measurements will take place before training (baseline), after 60 days (assessment 1), and at the end of the training after 90 days (assessment 2). DISCUSSION: In our randomized trial, we aim to characterize a multidimensional concept of frailty and to target maladaptive behaviors and neuroplasticity using an app-based sensorimotor training. This type of intervention might provide further knowledge and new possibilities for preventing decline and preserving function in older adults. TRIAL REGISTRATION: ClinicalTrials.gov NCT03666039 . Registered 11 September 2018 - Retrospectively registered. Protocol version: Version 4 revised (issue date: 19 May 2021).


Assuntos
Fragilidade , Aplicativos Móveis , Idoso , Envelhecimento , Fragilidade/diagnóstico , Fragilidade/terapia , Humanos , Plasticidade Neuronal , Qualidade de Vida
9.
Nervenarzt ; 92(12): 1239-1248, 2021 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-34735586

RESUMO

Alzheimer's disease is one the major common diseases but so far only with symptomatic treatment options. New insights define the disease as a slowly progressive continuum with very long preclinical and early symptomatic phases. Innovative molecular treatment strategies are based on an improved understanding of the molecular neurobiology of the disease, opening up a variety of therapeutic targets. For the first time, an anti-amyloid antibody has been approved in the USA in 2021 as a disease-modifying treatment for Alzheimer's disease, representing a first highly controversial step towards a molecular, cause-oriented treatment. This review presents the most advanced molecular treatment strategies and discusses the implications of the approved antibody treatment for the clinical practice. The special features of this long-term treatment with i.v. infusions in a particularly vulnerable population and a special side effect profile will impose significant challenges for implementation in the practice and will require a high degree of cooperation within the healthcare system. The future of Alzheimer's treatment with a multimodal therapeutic approach with different classes of drugs will probably reinforce these trends.


Assuntos
Doença de Alzheimer , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides , Humanos , Proteínas tau
10.
Nervenarzt ; 92(7): 708-715, 2021 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-33025072

RESUMO

BACKGROUND: Memory clinics (MC) are institutions specialized in the (differential) diagnostics, treatment, education, management and counseling of diseases related to dementia and their risk stages. In Germany, they have a variety of different organizational forms. Due to the growing diagnostic options in neurodegenerative diseases, the increasing demand for early detection and prediction as well as foreseeable new diagnostic procedures and disease-modifying treatment, it is important to standardize the structural prerequisites and areas of responsibility of MC. OBJECTIVE: The article proposes structural and organizational requirements and procedures and a harmonized mode of operation for MC in Germany. METHOD: Expert consensus of psychiatrists, neurologists and geriatricians from academic and nonacademic institutions. RESULTS: The MC should provide the specialist standards of psychiatry and/or neurology. They need to implement the recommendations of the national guidelines on dementia (S3LL) with respect to the (differential) diagnostics and treatment of dementia. With respect to the early detection and prediction of neurodegenerative disorders, they extend beyond the current German guideline standards. In MC, mild cognitive impairment (MCI) is understood as an at-risk or prodromal stage of diseases related to dementia and biomarkers are consistently applied for etiological (early and differential) diagnostics. There is a requirement for close interaction with specialized diagnostic disciplines. Furthermore, MC should also offer comprehensive advice on social and legal issues and provide caregiver support. They should integrate current knowledge from research into care and serve as regional expert centers. CONCLUSION: The MC should implement evidence-based standards in diagnostics and treatment and introduce innovations in the care of patients with cognitive disorders and at-risk and prodromal stages. Their role in the German healthcare system must be strengthened. Sufficient and sustained funding needs to be established, since current reimbursement does not cover costs.


Assuntos
Transtornos Cognitivos , Disfunção Cognitiva , Demência , Doenças Neurodegenerativas , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/terapia , Demência/diagnóstico , Demência/terapia , Alemanha , Humanos
11.
J Proteome Res ; 19(3): 1310-1318, 2020 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-32101007

RESUMO

Synaptic degeneration is a major hallmark of Alzheimer's disease (AD) and the best pathological correlate of cognitive dysfunction. Synaptic markers are therefore a highly desired read-out for patient diagnosis and possible follow-up in clinical trials. Several synaptic markers for AD are described in cerebrospinal fluid (CSF), but studies in blood have failed so far. Using quantitative mass spectrometry (IP-MS, MRM) we observed increased concentrations of the presynaptic protein beta-synuclein (ßSyn) in CSF and blood of AD patients (n = 64, p < 0.01) and confirmed this finding in two validation cohorts (AD: n = 40 and n = 49, controls: n = 44 and n = 25). ßSyn was already increased in patients with mild cognitive impairment (p < 0.01) and was also markedly increased in Creutzfeldt-Jakob disease (CJD; n = 25, p < 0.001) but not behavioral variant frontotemporal dementia (n = 16), dementia with Lewy bodies/Parkinson's disease dementia (n = 13), Parkinson's disease (n = 25), or amyotrophic lateral sclerosis (n = 30). The diagnostic sensitivity and specificity for CJD versus other neurodegenerative diseases was ≥96%. These findings suggest ßSyn as a candidate blood marker for synaptic degeneration that might be used in clinical AD trials and patient follow-up as part of the recently suggested ATN biomarker panel. It can also serve in the differential diagnosis of CJD.


Assuntos
Doença de Alzheimer , Doença de Alzheimer/diagnóstico , Biomarcadores , Diagnóstico Diferencial , Humanos , Espectrometria de Massas , beta-Sinucleína , Proteínas tau
12.
BMC Psychiatry ; 19(1): 274, 2019 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488095

RESUMO

BACKGROUND: Intracranial arachnoid cysts are usually benign congenital findings of neuroimaging modalities, sometimes however, leading to focal neurological and psychiatric comorbidities. Whether primarily clinically silent cysts may become causally involved in cognitive decline in old age is neither well examined nor understood. CASE PRESENTATION: A 66-year old caucasian man presenting with a giant left-hemispheric frontotemporal cyst without progression of size, presented with slowly progressive cognitive decline. Neuropsychological assessment revealed an amnestic mild cognitive impairment (MCI) without further neurological or psychiatric symptoms. The patient showed mild medio-temporal lobe atrophy on structural MRI. Diffusion tensor and functional magnetic resonance imaging depicted a rather sustained function of the strongly suppressed left hemisphere. Amyloid-PET imaging was positive for increased amyloid burden and he was homozygous for the APOEε3-gene. A diagnosis of MCI due to Alzheimer's disease was given and a co-morbidity with a silent arachnoid cyst was assumed. To investigate, if a potentially reduced CSF flow due to the giant arachnoid cyst contributed to the early manifestation of AD, we reviewed 15 case series of subjects with frontotemporal arachnoid cysts and cognitive decline. However, no increased manifestation of neurodegenerative disorders was reported. CONCLUSIONS: With this case report, we illustrate the necessity of a systematic work-up for neurodegenerative disorders in patients with arachnoid cysts and emerging cognitive decline. We finally propose a modus operandi for the stratification and management of patients with arachnoid cysts potentially susceptive for cognitive dysfunction.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Cistos Aracnóideos/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Idoso , Doença de Alzheimer/etiologia , Cistos Aracnóideos/psicologia , Disfunção Cognitiva/etiologia , Humanos , Masculino , Testes Neuropsicológicos , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/patologia
13.
Cereb Cortex ; 27(3): 1841-1848, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-26879092

RESUMO

The basal forebrain cholinergic system (BFCS) is the major source of acetylcholine for the cerebral cortex in humans. The aim was to analyze the pattern of BFCS and cortical atrophy in MCI patients to find evidence for a parallel atrophy along corticotopic organization of BFCS projections. BFCS volume and cortical thickness were analyzed using high-definition 3D structural magnetic resonance imaging data from 1.5-T and 3.0-T scanners of 64 MCI individuals and 62 cognitively healthy elderly controls from the European DTI study in dementia. BFCS volume reduction was correlated with thinning of cortical areas with known BFCS projections, such as Ch2 and parahippocampal gyrus in the MCI group, but not in the control group. Additionally, we found correlations between BFCS and cortex atrophy beyond the known corticotopic projections, such as between Ch4p and the cingulate gyrus. BFCS volume reduction was associated with regional thinning of cortical areas that included, but was not restricted to, the pattern of corticotopic projections of the BFCS as derived from animal studies. Our in vivo results may indicate the existence of more extended projections from the BFCS to the cerebral cortex in humans than that known from prior studies with animals.


Assuntos
Disfunção Cognitiva/diagnóstico por imagem , Prosencéfalo/diagnóstico por imagem , Acetilcolina/metabolismo , Idoso , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Atrofia , Biomarcadores/líquido cefalorraquidiano , Disfunção Cognitiva/metabolismo , Feminino , Humanos , Imageamento Tridimensional , Imageamento por Ressonância Magnética , Masculino , Entrevista Psiquiátrica Padronizada , Vias Neurais/diagnóstico por imagem , Vias Neurais/metabolismo , Tamanho do Órgão , Prosencéfalo/metabolismo
14.
Neuroimage ; 144(Pt B): 305-308, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27046114

RESUMO

The European DTI Study on Dementia (EDSD) is a multicenter framework created to study the diagnostic accuracy and inter-site variability of DTI-derived markers in patients with manifest and prodromal Alzheimer's disease (AD). The dynamically growing database presently includes 493 DTI, 512 T1-weighted MRI, and 300 FLAIR scans from patients with AD dementia, patients with Mild Cognitive Impairment (MCI) and matched Healthy Controls, acquired on 13 different scanner platforms. The imaging data is publicly available, along with the subjects' demographic and clinical characterization. Detailed neuropsychological information, cerebrospinal fluid information on biomarkers and clinical follow-up diagnoses are included for a subset of subjects. This paper describes the rationale and structure of the EDSD, summarizes the available data, and explains how to gain access to the database. The EDSD is a useful database for researchers seeking to investigate the contribution of DTI to dementia diagnostics.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Bases de Dados Factuais , Imagem de Tensor de Difusão , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Disseminação de Informação , Masculino , Pessoa de Meia-Idade
15.
Int J Geriatr Psychiatry ; 32(4): 446-454, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27113993

RESUMO

OBJECTIVE: Age-related white matter lesions (ARWMLs) have been identified in various clinical conditions such as reduced gait speed, cognitive impairment, urogenital dysfunction, and mood disturbances. Previous studies indicated an association between ARWML and late-onset major depression. However, most of these focused on the extent of supratentorial ARWML and neglected presence and degree of infratentorial lesions. METHODS: In 45 patients (mean age 73.7 ± 6.3 years, 17 (37.8%) men, 28 (62.2%) women) with late-onset major depression, MRI findings (3.0-T MR system, Magnetom Trio, Siemens Medical Systems, Erlangen, Germany) were analyzed with emphasis on the extent of supratentorial and infratentorial, as well as brainstem ARWMLs, and compared with control subjects. ARWMLs were determined by semiquantitative rating scales (modified Fazekas rating scale, Scheltens' rating scale), as well as a semiautomatic volumetric assessment, using a specific software (MRIcron). Supratentorial and infratentorial, as well as brainstem ARWMLs, were assessed both on fluid attenuated inversion recovery and T2-weighted images. RESULTS: Patients with late-onset major depression had significantly higher infratentorial ARWML rating scores (5 (5-7) vs 4.5 (3-6), p = 0.003) on T2-weighted images and volumes (1.58 ± 1.35 mL vs 1.05 ± 0.81 mL, p = 0.03) on T2-weighted images, as well as fluid attenuated inversion recovery images (2.07 ± 1.35 mL vs 1.52 ± 1.10 mL, p = 0.04), than normal controls. In more detail, in particular, the pontine ARWML rating subscore was significantly higher in patients with late-onset major depression (1 (1-2) vs 1 (1-1), p = 0.004). CONCLUSIONS: The extent and localization of brainstem ARWML might be of importance for the pathophysiology of late-onset major depression. In particular, this may hold true for pontine ARWML. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Tronco Encefálico/patologia , Transtorno Depressivo Maior/patologia , Substância Branca/patologia , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Alemanha , Humanos , Modelos Logísticos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade
17.
Alzheimers Dement ; 12(2): 154-163, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26368321

RESUMO

INTRODUCTION: Lumbar puncture (LP) is increasingly performed in memory clinics. We investigated patient-acceptance of LP, incidence of and risk factors for post-LP complications in memory clinic populations. METHODS: We prospectively enrolled 3868 patients (50% women, age 66 ± 11 years, mini mental state examination 25 ± 5) at 23 memory clinics. We used logistic regression analysis using generalized estimated equations to investigate risk factors for post-LP complications, such as typical postlumbar puncture headache (PLPH) and back pain. RESULTS: A total of 1065 patients (31%) reported post-LP complaints; 589 patients (17%) reported back pain, 649 (19%) headache, of which 296 (9%) reported typical PLPH. Only few patients needed medical intervention: 11 (0.3%) received a blood patch, 23 (0.7%) were hospitalized. The most important risk factor for PLPH was medical history of headache. An atraumatic needle and age >65 years were preventive. Gender, rest after LP, or volume of cerebrospinal fluid had no effect. DISCUSSIONS: The overall risk of complications is relatively low. If risk factors shown in this study are taken into account, LPs can be safely performed in memory clinics.


Assuntos
Instituições de Assistência Ambulatorial , Memória/fisiologia , Punção Espinal/efeitos adversos , Idoso , Transtornos Cognitivos/líquido cefalorraquidiano , Demência/líquido cefalorraquidiano , Estudos de Viabilidade , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Cefaleia Pós-Punção Dural/epidemiologia , Cefaleia Pós-Punção Dural/etiologia , Estudos Prospectivos , Fatores de Risco , Punção Espinal/métodos
18.
JAMA ; 313(19): 1924-38, 2015 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-25988462

RESUMO

IMPORTANCE: Cerebral amyloid-ß aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies. OBJECTIVE: To use individual participant data meta-analysis to estimate the prevalence of amyloid pathology as measured with biomarkers in participants with normal cognition, subjective cognitive impairment (SCI), or mild cognitive impairment (MCI). DATA SOURCES: Relevant biomarker studies identified by searching studies published before April 2015 using the MEDLINE and Web of Science databases and through personal communication with investigators. STUDY SELECTION: Studies were included if they provided individual participant data for participants without dementia and used an a priori defined cutoff for amyloid positivity. DATA EXTRACTION AND SYNTHESIS: Individual records were provided for 2914 participants with normal cognition, 697 with SCI, and 3972 with MCI aged 18 to 100 years from 55 studies. MAIN OUTCOMES AND MEASURES: Prevalence of amyloid pathology on positron emission tomography or in cerebrospinal fluid according to AD risk factors (age, apolipoprotein E [APOE] genotype, sex, and education) estimated by generalized estimating equations. RESULTS: The prevalence of amyloid pathology increased from age 50 to 90 years from 10% (95% CI, 8%-13%) to 44% (95% CI, 37%-51%) among participants with normal cognition; from 12% (95% CI, 8%-18%) to 43% (95% CI, 32%-55%) among patients with SCI; and from 27% (95% CI, 23%-32%) to 71% (95% CI, 66%-76%) among patients with MCI. APOE-ε4 carriers had 2 to 3 times higher prevalence estimates than noncarriers. The age at which 15% of the participants with normal cognition were amyloid positive was approximately 40 years for APOE ε4ε4 carriers, 50 years for ε2ε4 carriers, 55 years for ε3ε4 carriers, 65 years for ε3ε3 carriers, and 95 years for ε2ε3 carriers. Amyloid positivity was more common in highly educated participants but not associated with sex or biomarker modality. CONCLUSIONS AND RELEVANCE: Among persons without dementia, the prevalence of cerebral amyloid pathology as determined by positron emission tomography or cerebrospinal fluid findings was associated with age, APOE genotype, and presence of cognitive impairment. These findings suggest a 20- to 30-year interval between first development of amyloid positivity and onset of dementia.


Assuntos
Peptídeos beta-Amiloides/análise , Apolipoproteína E4/genética , Encéfalo/patologia , Disfunção Cognitiva/patologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Líquido Cefalorraquidiano/química , Demência/patologia , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Prevalência , Fatores de Risco
19.
Alzheimers Dement ; 11(2): 195-206.e1, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25150733

RESUMO

We investigated the use of Alzheimer's disease (AD) biomarkers in European Alzheimer's Disease Consortium centers and assessed their perceived usefulness for the etiologic diagnosis of mild cognitive impairment (MCI). We surveyed availability, frequency of use, and confidence in diagnostic usefulness of markers of brain amyloidosis (amyloid positron emission tomography [PET], cerebrospinal fluid [CSF] Aß42) and neurodegeneration (medial temporal atrophy [MTA] on MR, fluorodeoxyglucose positron emission tomography [FDG-PET], CSF tau). The most frequently used biomarker is visually rated MTA (75% of the 37 responders reported using it "always/frequently") followed by CSF markers (22%), FDG-PET (16%), and amyloid-PET (3%). Only 45% of responders perceive MTA as contributing to diagnostic confidence, where the contribution was rated as "moderate". Seventy-nine percent of responders felt "very/extremely" comfortable delivering a diagnosis of MCI due to AD when both amyloid and neuronal injury biomarkers were abnormal (P < .02 versus any individual biomarker). Responders largely agreed that a combination of amyloidosis and neuronal injury biomarkers was a strongly indicative AD signature.


Assuntos
Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Padrões de Prática Médica , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Atrofia , Biomarcadores/líquido cefalorraquidiano , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Disfunção Cognitiva/líquido cefalorraquidiano , Disfunção Cognitiva/patologia , Europa (Continente) , Fluordesoxiglucose F18 , Internet , Imageamento por Ressonância Magnética , Fragmentos de Peptídeos/líquido cefalorraquidiano , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Inquéritos e Questionários , Proteínas tau/líquido cefalorraquidiano
20.
Alzheimers Dement ; 10(2): e27-39, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23850332

RESUMO

BACKGROUND: Early-onset familial Alzheimer disease (AD) is an autosomal dominant disorder caused by mutations in the amyloid precursor protein, presenilin 1 (PSEN1), or presenilin 2 gene. The objective of this study was to characterize the phenotype in a large family with a PSEN1 F177S mutation by performing detailed clinical assessments, neuroimaging, and neuropathological analysis. METHODS: In two subjects, clinical and neuropsychological assessments, structural magnetic resonance imaging, F-18-2-fluoro-2-deoxy-D-glucose positron emission tomographic imaging, AD biomarkers in cerebrospinal fluid and genetic analysis were available. In three deceased affected subjects, medical records were reviewed. In one subject, a complete neuropathological examination was available. RESULTS: Cognitive impairment and neurological symptoms developed homogeneously around 30 years of age and worsened rapidly. All subjects died about 7 years (range, 6-8 years) after disease onset before 40 years of age. All technical diagnostic information (neuroimaging, cerebrospinal fluid) were typically for AD. Neuropathology showed abundant neuritic plaques and neurofibrillary tangles, typical of severe AD. Antidementia treatment in one subject did not alter the length of survival. CONCLUSIONS: The PSEN1 F177S mutation leads to typical AD starting at age 30 and a homogeneous phenotype with rapid cognitive decline and prominent neurological symptoms. Excessive amyloid beta 42 production in the brain cortex corresponds well with other PSEN1 mutations.


Assuntos
Doença de Alzheimer/genética , Saúde da Família , Predisposição Genética para Doença/genética , Mutação/genética , Presenilina-1/genética , Adulto , Idade de Início , Idoso , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Ondas Encefálicas/genética , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/genética , Eletroencefalografia , Feminino , Humanos , Masculino , Entrevista Psiquiátrica Padronizada , Pessoa de Meia-Idade , Fragmentos de Peptídeos/líquido cefalorraquidiano , Fenilalanina/genética , Tomografia por Emissão de Pósitrons , Radiografia , Serina/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA