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1.
J Clin Med ; 10(21)2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34768454

RESUMO

BACKGROUND: 18F-fluorodeoxyglucose (18F-FDG) positron-emission-tomography (PET) allows detection of cerebral metabolic alterations in neurological diseases vs. normal aging. We assess age- and sex-related brain metabolic changes in healthy subjects, exploring impact of activity normalization methods. METHODS: brain scans of Italian Association of Nuclear Medicine normative database (151 subjects, 67 Males, 84 Females, aged 20-84) were selected. Global mean, white matter, and pons activity were explored as normalization reference. We performed voxel-based and ROI analyses using SPM12 and IBM-SPSS software. RESULTS: SPM proved a negative correlation between age and brain glucose metabolism involving frontal lobes, anterior-cingulate and insular cortices bilaterally. Narrower clusters were detected in lateral parietal lobes, precuneus, temporal pole and medial areas bilaterally. Normalizing on pons activity, we found a more significant negative correlation and no positive one. ROIs analysis confirmed SPM results. Moreover, a significant age × sex interaction effect was revealed, with worse metabolic reduction in posterior-cingulate cortices in females than males, especially in post-menopausal age. CONCLUSIONS: this study demonstrated an age-related metabolic reduction in frontal lobes and in some parieto-temporal areas more evident in females. Results suggested pons as the most appropriate normalization reference. Knowledge of age- and sex-related cerebral metabolic changes is critical to correctly interpreting brain 18F-FDG PET imaging.

2.
Cereb Cortex ; 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34613369

RESUMO

In the present retrospective and exploratory study, we tested the hypothesis that sex may affect cortical sources of resting state eyes-closed electroencephalographic (rsEEG) rhythms recorded in normal elderly (Nold) seniors and patients with Alzheimer's disease and mild cognitive impairment (ADMCI). Datasets in 69 ADMCI and 57 Nold individuals were taken from an international archive. The rsEEG rhythms were investigated at individual delta, theta, and alpha frequency bands and fixed beta (14-30 Hz) and gamma (30-40 Hz) bands. Each group was stratified into matched females and males. The sex factor affected the magnitude of rsEEG source activities in the Nold seniors. Compared with the males, the females were characterized by greater alpha source activities in all cortical regions. Similarly, the parietal, temporal, and occipital alpha source activities were greater in the ADMCI-females than the males. Notably, the present sex effects did not depend on core genetic (APOE4), neuropathological (Aß42/phospho-tau ratio in the cerebrospinal fluid), structural neurodegenerative and cerebrovascular (MRI) variables characterizing sporadic AD-related processes in ADMCI seniors. These results suggest the sex factor may significantly affect neurophysiological brain neural oscillatory synchronization mechanisms underpinning the generation of dominant rsEEG alpha rhythms to regulate cortical arousal during quiet vigilance.

3.
Curr Alzheimer Res ; 2021 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-34711165

RESUMO

BACKGROUND: Early differentiation between Alzheimer's disease (AD) and Dementia with Lewy Bodies (DLB) is important for accurate prognosis, as DLB patients typically show faster disease progression. Cortical neural networks, necessary for human cognitive function, may be disrupted differently in DLB and AD patients, allowing diagnostic differentiation between AD and DLB. OBJECTIVE: This proof-of-concept study assessed whether the application of machine learning techniques to data derived from resting-state electroencephalographic (rsEEG) rhythms (discriminant sensor power, 19 electrodes) and source connectivity (between five cortical regions of interest) allowed differentiation between DLB and AD. METHODS: Clinical, demographic, and rsEEG datasets from DLB patients (N=30), AD patients (N=30), and control seniors (NOld, N=30), matched for age, sex, and education, were taken from our international database. Individual (delta, theta, alpha) and fixed (beta) rsEEG frequency bands were included. The rsEEG features for the classification task were computed at both sensor and source levels. The source level was based on eLORETA freeware toolboxes for estimating cortical source activity and linear lagged connectivity. Fluctuations of rsEEG recordings (band-pass waveform envelopes of each EEG rhythm) were also computed at both sensor and source levels. After blind feature reduction, rsEEG features served as input to support vector machine (SVM) classifiers. Discrimination of individuals from the three groups was measured with standard performance metrics (accuracy, sensitivity, and specificity). RESULTS: The trained SVM two-class classifiers showed classification accuracies of 97.6% for NOld vs. AD, 99.7% for NOld vs. DLB, and 97.8% for AD vs. DLB. Three-class classifiers (AD vs. DLB vs. NOld) showed classification accuracy of 94.79%. CONCLUSION: These promising preliminary results should encourage future prospective and longitudinal cross-validation studies using higher resolution EEG techniques and harmonized clinical procedures to enable the clinical application of these machine learning techniques.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34651219

RESUMO

PURPOSE: FDG-PET is an established supportive biomarker in dementia with Lewy bodies (DLB), but its diagnostic accuracy is unknown at the mild cognitive impairment (MCI-LB) stage when the typical metabolic pattern may be difficultly recognized at the individual level. Semiquantitative analysis of scans could enhance accuracy especially in less skilled readers, but its added role with respect to visual assessment in MCI-LB is still unknown. METHODS: We assessed the diagnostic accuracy of visual assessment of FDG-PET by six expert readers, blind to diagnosis, in discriminating two matched groups of patients (40 with prodromal AD (MCI-AD) and 39 with MCI-LB), both confirmed by in vivo biomarkers. Readers were provided in a stepwise fashion with (i) maps obtained by the univariate single-subject voxel-based analysis (VBA) with respect to a control group of 40 age- and sex-matched healthy subjects, and (ii) individual odds ratio (OR) plots obtained by the volumetric regions of interest (VROI) semiquantitative analysis of the two main hypometabolic clusters deriving from the comparison of MCI-AD and MCI-LB groups in the two directions, respectively. RESULTS: Mean diagnostic accuracy of visual assessment was 76.8 ± 5.0% and did not significantly benefit from adding the univariate VBA map reading (77.4 ± 8.3%) whereas VROI-derived OR plot reading significantly increased both accuracy (89.7 ± 2.3%) and inter-rater reliability (ICC 0.97 [0.96-0.98]), regardless of the readers' expertise. CONCLUSION: Conventional visual reading of FDG-PET is moderately accurate in distinguishing between MCI-LB and MCI-AD, and is not significantly improved by univariate single-subject VBA but by a VROI analysis built on macro-regions, allowing for high accuracy independent of reader skills.

5.
Neurol Sci ; 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34586541

RESUMO

BACKGROUND: Sleep disturbances are common non-motor symptoms of Parkinson's Disease (PD). METHODS: The aim of this study was to investigate the polysomnographic correlates of sleep changes, as investigated by the Parkinson's Disease Sleep Scale-2 (PDSS-2), in a cohort of sixty-two consecutive de novo, drug naïve PD patients (71.40 ± 7.84 y/o). RESULTS: PDSS-2 total score showed a direct correlation with stage shifts (p = 0.008). Fragmented sleep showed an inverse correlation with sleep efficiency (p = 0.012). Insomnia symptoms showed an inverse correlation with wake after sleep onset (p = 0.005) and direct correlation with periodic leg movements (p = 0.006) and stage shift indices (p = 0.003). Motor Symptoms showed a direct correlation with Apnoea-Hypopnoea (AHI; p = 0.02) and awakenings indices (p = 0.003). Dream distressing showed a direct correlation with REM without atonia (RWA, p = 0.042) and an inverse correlation with AHI (p = 0.012). Sleep quality showed an inverse correlation with RWA (p = 0.008). CONCLUSION: PDSS-2 features are significantly correlated with polysomnography objective findings, thus further supporting its reliability to investigate sleep disturbances in PD patients.

6.
Mov Disord ; 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34533239

RESUMO

BACKGROUND: Dopamine transporter single photon-emission computed tomography (DAT-SPECT) is the strongest risk factor for phenoconversion in patients with idiopathic rapid eye movement (REM)-sleep behavior disorder (iRBD). However, it might be used as a second-line stratification tool in clinical trials, because it is expensive and mini-invasive. OBJECTIVE: Aim of the study is to investigate whether other cost-effective and non-invasive biomarkers may be proposed as first-line stratification tools. METHODS: Forty-seven consecutive iRBD patients (68.53 ± 7.16 years, 40 males) underwent baseline clinical and neuropsychological assessment, olfaction test, resting electroencephalogram (EEG), and DAT-SPECT. All patients underwent 6 month-based clinical follow-up to investigate the emergence of parkinsonism and/or dementia. Survival analysis and Cox regression were used to estimate conversion risk. RESULTS: Seventeen patients developed an overt synucleinopathy (eight Parkinsonism and nine dementia) 32.8 ± 22 months after diagnosis. The strongest risk factors were putamen specific to non-displaceable binding ratio (SBR) (hazard ratio [HR], 7.3), attention/working memory cognitive function (NPS-AT/WM) (HR, 5.9), EEG occipital mean frequency (HR, 2.7) and clinical motor assessment (HR, 2.3). On multivariate Cox-regression analysis, only putamen SBR and NPS-AT/WM significantly contributed to the model (HR, 6.2, 95% confidence interval [CI], 1.9-19.8). At post-hoc analysis, the trail-making test B (TMT-B) was the single most efficient first-line stratification tool that allowed to reduce the number of eligible subjects to 76.6% (sensitivity 1, specificity 0.37). Combining TMT-B and DAT-SPECT further reduced the sample to 66% (sensitivity 0.88, specificity 0.47). CONCLUSION: The TMT-B seems to be a cost-effective and efficient first-line screening tool, to be used to select patients that deserve DAT-SPECT as second-line screening tool for disease-modifying clinical trials. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34328531

RESUMO

PURPOSE: The purpose of this study is to develop and validate a 3D deep learning model that predicts the final clinical diagnosis of Alzheimer's disease (AD), dementia with Lewy bodies (DLB), mild cognitive impairment due to Alzheimer's disease (MCI-AD), and cognitively normal (CN) using fluorine 18 fluorodeoxyglucose PET (18F-FDG PET) and compare model's performance to that of multiple expert nuclear medicine physicians' readers. MATERIALS AND METHODS: Retrospective 18F-FDG PET scans for AD, MCI-AD, and CN were collected from Alzheimer's disease neuroimaging initiative (556 patients from 2005 to 2020), and CN and DLB cases were from European DLB Consortium (201 patients from 2005 to 2018). The introduced 3D convolutional neural network was trained using 90% of the data and externally tested using 10% as well as comparison to human readers on the same independent test set. The model's performance was analyzed with sensitivity, specificity, precision, F1 score, receiver operating characteristic (ROC). The regional metabolic changes driving classification were visualized using uniform manifold approximation and projection (UMAP) and network attention. RESULTS: The proposed model achieved area under the ROC curve of 96.2% (95% confidence interval: 90.6-100) on predicting the final diagnosis of DLB in the independent test set, 96.4% (92.7-100) in AD, 71.4% (51.6-91.2) in MCI-AD, and 94.7% (90-99.5) in CN, which in ROC space outperformed human readers performance. The network attention depicted the posterior cingulate cortex is important for each neurodegenerative disease, and the UMAP visualization of the extracted features by the proposed model demonstrates the reality of development of the given disorders. CONCLUSION: Using only 18F-FDG PET of the brain, a 3D deep learning model could predict the final diagnosis of the most common neurodegenerative disorders which achieved a competitive performance compared to the human readers as well as their consensus.

8.
J Alzheimers Dis ; 82(3): 883-898, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34092646

RESUMO

Cognitive impairment following SARS-CoV-2 infection is being increasingly recognized as an acute and possibly also long-term sequela of the disease. Direct viral entry as well as systemic mechanisms such as cytokine storm are thought to contribute to neuroinflammation in these patients. Biomarkers of COVID-19-induced cognitive impairment are currently lacking, but there is some limited evidence that SARS-CoV-2 could preferentially target the frontal lobes, as suggested by behavioral and dysexecutive symptoms, fronto-temporal hypoperfusion on MRI, EEG slowing in frontal regions, and frontal hypometabolism on 18F-FDG-PET. Possible confounders include cognitive impairment due to hypoxia and mechanical ventilation and post-traumatic stress disorder. Conversely, patients already suffering from dementia, as well as their caregivers, have been greatly impacted by the disruption of their care caused by COVID-19. Patients with dementia have experienced worsening of cognitive, behavioral, and psychological symptoms, and the rate of COVID-19-related deaths is disproportionately high among cognitively impaired people. Multiple factors, such as difficulties in remembering and executing safeguarding procedures, age, comorbidities, residing in care homes, and poorer access to hospital standard of care play a role in the increased morbidity and mortality. Non-pharmacological interventions and new technologies have shown a potential for the management of patients with dementia, and for the support of their caregivers.


Assuntos
Doença de Alzheimer , Encéfalo , COVID-19/complicações , Disfunção Cognitiva , Doença de Alzheimer/fisiopatologia , Doença de Alzheimer/psicologia , Biomarcadores/análise , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Encéfalo/virologia , COVID-19/imunologia , COVID-19/psicologia , COVID-19/terapia , Disfunção Cognitiva/imunologia , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/virologia , Comorbidade , Humanos , Neuroimagem/métodos , Neuroimunomodulação/imunologia , Assistência ao Paciente , SARS-CoV-2
9.
J Alzheimers Dis ; 82(3): 1085-1114, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34151788

RESUMO

BACKGROUND: In relaxed adults, staying in quiet wakefulness at eyes closed is related to the so-called resting state electroencephalographic (rsEEG) rhythms, showing the highest amplitude in posterior areas at alpha frequencies (8-13 Hz). OBJECTIVE: Here we tested the hypothesis that age may affect rsEEG alpha (8-12 Hz) rhythms recorded in normal elderly (Nold) seniors and patients with mild cognitive impairment due to Alzheimer's disease (ADMCI). METHODS: Clinical and rsEEG datasets in 63 ADMCI and 60 Nold individuals (matched for demography, education, and gender) were taken from an international archive. The rsEEG rhythms were investigated at individual delta, theta, and alpha frequency bands, as well as fixed beta (14-30 Hz) and gamma (30-40 Hz) bands. Each group was stratified into three subgroups based on age ranges (i.e., tertiles). RESULTS: As compared to the younger Nold subgroups, the older one showed greater reductions in the rsEEG alpha rhythms with major topographical effects in posterior regions. On the contrary, in relation to the younger ADMCI subgroups, the older one displayed a lesser reduction in those rhythms. Notably, the ADMCI subgroups pointed to similar cerebrospinal fluid AD diagnostic biomarkers, gray and white matter brain lesions revealed by neuroimaging, and clinical and neuropsychological scores. CONCLUSION: The present results suggest that age may represent a deranging factor for dominant rsEEG alpha rhythms in Nold seniors, while rsEEG alpha rhythms in ADMCI patients may be more affected by the disease variants related to earlier versus later onset of the AD.


Assuntos
Envelhecimento/fisiologia , Ritmo alfa/fisiologia , Doença de Alzheimer/diagnóstico por imagem , Amnésia/diagnóstico por imagem , Cognição/fisiologia , Disfunção Cognitiva/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/psicologia , Doença de Alzheimer/fisiopatologia , Doença de Alzheimer/psicologia , Amnésia/fisiopatologia , Amnésia/psicologia , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/psicologia , Eletroencefalografia/métodos , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Descanso/fisiologia , Descanso/psicologia
11.
Mov Disord ; 36(10): 2293-2302, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34021923

RESUMO

BACKGROUND: Degeneration of the nigrostriatal dopaminergic (DA) and the raphe-thalamic serotonergic (SE) systems is among the earliest changes observed in Parkinson's disease (PD). The consequences of those changes on brain metabolism, especially regarding their impact on the cortex, are poorly understood. OBJECTIVES: Using multi-tracer molecular imaging, we assessed in a cohort of drug-naive PD patients the association between cortical metabolism and DA and SE system deafferentation of either striatum or thalamus, and we explored whether this association was mediated by either striatum or thalamus metabolism. METHODS: We recruited 96 drug-naive PD patients (aged 71.9 ± 7.5 years) who underwent [123 I]ioflupane single-photon emission computed tomography ([123 I]FP-CIT-SPECT) and brain [18 F]fluorodeoxyglucose positron emission tomography ([18 F]FDG-PET). We used a voxel-wise analysis of [18 F]FDG-PET images to correlate regional metabolism with striatal DA and thalamic SE innervation as assessed using [123 I]FP-CIT-SPECT. RESULTS: We found that [123 I]FP-CIT specific to nondisplaceable binding ratio (SBR) and glucose metabolism positively correlated with one another in the deep gray matter (thalamus: P = 0.001, r = 0.541; caudate P = 0.001, r = 0.331; putamen P = 0.001, r = 0.423). We then observed a direct correlation between temporoparietal metabolism and caudate DA innervation, as well as a direct correlation between prefrontal metabolism and thalamus SE innervation. The effect of caudate [123 I]FP-CIT SBR values on temporoparietal metabolism was mediated by caudate metabolic values (percentage mediated: 89%, P-value = 0.008), and the effect of thalamus [123 I]FP-CIT SBR values on prefrontal metabolism was fully mediated by thalamus metabolic values (P < 0.001). CONCLUSIONS: These data suggest that the impact of deep gray matter monoaminergic deafferentation on cortical function is mediated by striatal and thalamic metabolism in drug-naive PD. © 2021 International Parkinson and Movement Disorder Society.


Assuntos
Doença de Parkinson , Dopamina , Proteínas da Membrana Plasmática de Transporte de Dopamina , Humanos , Doença de Parkinson/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada de Emissão de Fóton Único
12.
Alzheimers Dement ; 2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-33984176

RESUMO

INTRODUCTION: Harmonized neuropsychological assessment for neurocognitive disorders, an international priority for valid and reliable diagnostic procedures, has been achieved only in specific countries or research contexts. METHODS: To harmonize the assessment of mild cognitive impairment in Europe, a workshop (Geneva, May 2018) convened stakeholders, methodologists, academic, and non-academic clinicians and experts from European, US, and Australian harmonization initiatives. RESULTS: With formal presentations and thematic working-groups we defined a standard battery consistent with the U.S. Uniform DataSet, version 3, and homogeneous methodology to obtain consistent normative data across tests and languages. Adaptations consist of including two tests specific to typical Alzheimer's disease and behavioral variant frontotemporal dementia. The methodology for harmonized normative data includes consensus definition of cognitively normal controls, classification of confounding factors (age, sex, and education), and calculation of minimum sample sizes. DISCUSSION: This expert consensus allows harmonizing the diagnosis of neurocognitive disorders across European countries and possibly beyond.

13.
Alzheimers Dement ; 17(9): 1528-1553, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33860614

RESUMO

The Electrophysiology Professional Interest Area (EPIA) and Global Brain Consortium endorsed recommendations on candidate electroencephalography (EEG) measures for Alzheimer's disease (AD) clinical trials. The Panel reviewed the field literature. As most consistent findings, AD patients with mild cognitive impairment and dementia showed abnormalities in peak frequency, power, and "interrelatedness" at posterior alpha (8-12 Hz) and widespread delta (< 4 Hz) and theta (4-8 Hz) rhythms in relation to disease progression and interventions. The following consensus statements were subscribed: (1) Standardization of instructions to patients, resting state EEG (rsEEG) recording methods, and selection of artifact-free rsEEG periods are needed; (2) power density and "interrelatedness" rsEEG measures (e.g., directed transfer function, phase lag index, linear lagged connectivity, etc.) at delta, theta, and alpha frequency bands may be use for stratification of AD patients and monitoring of disease progression and intervention; and (3) international multisectoral initiatives are mandatory for regulatory purposes.

14.
Biomedicines ; 9(3)2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33808956

RESUMO

We aimed to evaluate the brain hypometabolic signature of persistent isolated olfactory dysfunction after SARS-CoV-2 infection. Twenty-two patients underwent whole-body [18F]-FDG PET, including a dedicated brain acquisition at our institution between May and December 2020 following their recovery after SARS-Cov2 infection. Fourteen of these patients presented isolated persistent hyposmia (smell diskettes olfaction test was used). A voxel-wise analysis (using Statistical Parametric Mapping software version 8 (SPM8)) was performed to identify brain regions of relative hypometabolism in patients with hyposmia with respect to controls. Structural connectivity of these regions was assessed (BCB toolkit). Relative hypometabolism was demonstrated in bilateral parahippocampal and fusiform gyri and in left insula in patients with respect to controls. Structural connectivity maps highlighted the involvement of bilateral longitudinal fasciculi. This study provides evidence of cortical hypometabolism in patients with isolated persistent hyposmia after SARS-Cov2 infection. [18F]-FDG PET may play a role in the identification of long-term brain functional sequelae of COVID-19.

15.
Neurobiol Aging ; 103: 78-97, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33845399

RESUMO

Vascular contribution to cognitive impairment (VCI) and dementia is related to etiologies that may affect the neurophysiological mechanisms regulating brain arousal and generating electroencephalographic (EEG) activity. A multidisciplinary expert panel reviewed the clinical literature and reached consensus about the EEG measures consistently found as abnormal in VCI patients with dementia. As compared to cognitively unimpaired individuals, those VCI patients showed (1) smaller amplitude of resting state alpha (8-12 Hz) rhythms dominant in posterior regions; (2) widespread increases in amplitude of delta (< 4 Hz) and theta (4-8 Hz) rhythms; and (3) delayed N200/P300 peak latencies in averaged event-related potentials, especially during the detection of auditory rare target stimuli requiring participants' responses in "oddball" paradigms. The expert panel formulated the following recommendations: (1) the above EEG measures are not specific for VCI and should not be used for its diagnosis; (2) they may be considered as "neural synchronization" biomarkers to enlighten the relationships between features of the VCI-related cerebrovascular lesions and abnormalities in neurophysiological brain mechanisms; and (3) they may be tested in future clinical trials as prognostic biomarkers and endpoints of interventions aimed at normalizing background brain excitability and vigilance in wakefulness.

16.
Brain Commun ; 3(2): fcab045, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33870192

RESUMO

In patients with suspected dementia with Lewy bodies, the detection of the disease-associated α-synuclein in easily accessible tissues amenable to be collected using minimally invasive procedures remains a major diagnostic challenge. This approach has the potential to take advantage of modern molecular assays for the diagnosis of α-synucleinopathy and, in turn, to optimize the recruitment and selection of patients in clinical trials, using drugs directed at counteracting α-synuclein aggregation. In this study, we explored the diagnostic accuracy of α-synuclein real-time quaking-induced conversion assay by testing olfactory mucosa and CSF in patients with a clinical diagnosis of probable (n = 32) or prodromal (n = 5) dementia with Lewy bodies or mixed degenerative dementia (dementia with Lewy bodies/Alzheimer's disease) (n = 6). Thirty-eight patients with non-α-synuclein-related neurodegenerative and non-neurodegenerative disorders, including Alzheimer's disease (n = 10), sporadic Creutzfeldt-Jakob disease (n = 10), progressive supranuclear palsy (n = 8), corticobasal syndrome (n = 1), fronto-temporal dementia (n = 3) and other neurological conditions (n = 6) were also included, as controls. All 81 patients underwent olfactory swabbing while CSF was obtained in 48 participants. At the initial blinded screening of olfactory mucosa samples, 38 out of 81 resulted positive while CSF was positive in 19 samples out of 48 analysed. After unblinding of the results, 27 positive olfactory mucosa were assigned to patients with probable dementia with Lewy bodies, five with prodromal dementia with Lewy bodies and three to patients with mixed dementia, as opposed to three out 38 controls. Corresponding results of CSF testing disclosed 10 out 10 positive samples in patients with probable dementia with Lewy bodies and six out of six with mixed dementia, in addition to three out of 32 for controls. The accuracy among results of real-time quaking-induced conversion assays and clinical diagnoses was 86.4% in the case of olfactory mucosa and 93.8% for CSF. For the first time, we showed that α-synuclein real-time quaking-induced conversion assay detects α-synuclein aggregates in olfactory mucosa of patients with dementia with Lewy bodies and with mixed dementia. Additionally, we provided preliminary evidence that the combined testing of olfactory mucosa and CSF raised the concordance with clinical diagnosis potentially to 100%. Our results suggest that nasal swabbing might be considered as a first-line screening procedure in patients with a diagnosis of suspected dementia with Lewy bodies followed by CSF analysis, as a confirmatory test, when the result in the olfactory mucosa is incongruent with the initial clinical diagnosis.

17.
Brain Sci ; 11(2)2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33672401

RESUMO

Bipolar disorder (BD) is a chronic and disabling psychiatric condition that is linked to significant disability and psychosocial impairment. Although current neuropsychological, molecular, and neuroimaging evidence support the existence of neuroprogression and its effects on the course and outcome of this condition, whether and to what extent neuroprogressive changes may impact the illness trajectory is still poorly understood. Thus, this selective review was aimed toward comprehensively and critically investigating the link between BD and neurodegeneration based on the currently available evidence. According to the most relevant findings of the present review, most of the existing neuropsychological, neuroimaging, and molecular evidence demonstrates the existence of neuroprogression, at least in a subgroup of BD patients. These studies mainly focused on the most relevant effects of neuroprogression on the course and outcome of BD. The main implications of this assumption are discussed in light of specific shortcomings/limitations, such as the inability to carry out a meta-analysis, the inclusion of studies with small sample sizes, retrospective study designs, and different longitudinal investigations at various time points.

18.
J Alzheimers Dis ; 81(1): 75-81, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33720900

RESUMO

Acute delirium and other neuropsychiatric symptoms have frequently been reported in COVID-19 patients and are variably referred to as acute encephalopathy, COVID-19 encephalopathy, SARS-CoV-2 encephalitis, or steroid-responsive encephalitis. COVID-19 specific biomarkers of cognitive impairment are currently lacking, but there is some evidence that SARS-CoV-2 could preferentially and directly target the frontal lobes, as suggested by behavioral and dysexecutive symptoms, fronto-temporal hypoperfusion on MRI, EEG slowing in frontal regions, and frontal hypometabolism on 18F-FDG-PET imaging. We suggest that an inflammatory parainfectious process targeting preferentially the frontal lobes (and/or frontal networks) could be the underlying cause of these shared clinical, neurophysiological, and imaging findings in COVID-19 patients. We explore the biological mechanisms and the clinical biomarkers that might underlie such disruption of frontal circuits and highlight the need of standardized diagnostic procedures to be applied when investigating patients with these clinical findings. We also suggest the use of a unique label, to increase comparability across studies.


Assuntos
Encefalopatia Aguda Febril/fisiopatologia , COVID-19/fisiopatologia , Lobo Frontal/fisiopatologia , Lobo Frontal/virologia , SARS-CoV-2/patogenicidade , Encefalopatia Aguda Febril/diagnóstico , Encefalopatia Aguda Febril/virologia , Biomarcadores/análise , COVID-19/diagnóstico , COVID-19/virologia , Delírio/diagnóstico , Delírio/fisiopatologia , Delírio/virologia , Eletroencefalografia , Humanos , Imageamento por Ressonância Magnética , Rede Nervosa/fisiopatologia , Virulência
19.
Alzheimers Dement ; 17(8): 1277-1286, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33528089

RESUMO

INTRODUCTION: We assessed the influence of education as a proxy of cognitive reserve and age on the dementia with Lewy bodies (DLB) metabolic pattern. METHODS: Brain 18F-fluorodeoxyglucose positron emission tomography and clinical/demographic information were available in 169 probable DLB patients included in the European DLB-consortium database. Principal component analysis identified brain regions relevant to local data variance. A linear regression model was applied to generate age- and education-sensitive maps corrected for Mini-Mental State Examination score, sex (and either education or age). RESULTS: Age negatively covaried with metabolism in bilateral middle and superior frontal cortex, anterior and posterior cingulate, reducing the expression of the DLB-typical cingulate island sign (CIS). Education negatively covaried with metabolism in the left inferior parietal cortex and precuneus (making the CIS more prominent). DISCUSSION: These findings point out the importance of tailoring interpretation of DLB biomarkers considering the concomitant effect of individual, non-disease-related variables such as age and cognitive reserve.


Assuntos
Doença de Alzheimer , Escolaridade , Lobo Frontal/metabolismo , Giro do Cíngulo/metabolismo , Doença por Corpos de Lewy/metabolismo , Fatores Etários , Idoso , Encéfalo/metabolismo , Europa (Continente) , Fluordesoxiglucose F18/metabolismo , Humanos , Processamento de Imagem Assistida por Computador/estatística & dados numéricos , Tomografia por Emissão de Pósitrons
20.
J Alzheimers Dis ; 80(1): 383-396, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33554908

RESUMO

BACKGROUND: In clinical practice, the amy-PET is globally inspected to provide a binary outcome, but the role of a regional assessment has not been fully investigated yet. OBJECTIVE: To deepen the role of regional amyloid burden and its implication on clinical-neuropsychological features. MATERIALS: Amy-PET and a complete neuropsychological assessment (Trail Making Test, Rey Auditory Verbal Learning Test, semantic verbal fluency, Symbol Digit, Stroop, visuoconstruction) were available in 109 patients with clinical suspicion of Alzheimer's disease. By averaging the standardized uptake value ratio and ELBA, a regional quantification was calculated for each scan. Patients were grouped according to their overall amyloid load: correlation maps, based on regional quantification, were calculated and compared. A regression analysis between neuropsychological assessment and the regional amyloid-ß (Aß) load was carried out. RESULTS: Significant differences were observed between the correlation maps of patients at increasing levels of Aß and the overall dataset. The Aß uptake of the subcortical gray matter resulted not related to other brain regions independently of the global Aß level. A significant association of semantic verbal fluency was observed with ratios of cortical and subcortical distribution of Aß which represent a coarse measure of differences in regional distribution of Aß. CONCLUSION: Our observations confirmed the different susceptibility to Aß accumulation among brain regions. The association between cognition and Aß distribution deserves further investigations: it is possibly due to a direct local effect or it represents a proxy marker of a more aggressive disease subtype. Regional Aß assessment represents an available resource on amy-PET scan with possibly clinical and prognostic implications.


Assuntos
Amiloide/metabolismo , Amiloidose/diagnóstico por imagem , Amiloidose/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/psicologia , Amiloidose/psicologia , Mapeamento Encefálico , Feminino , Substância Cinzenta/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Teste de Stroop , Teste de Sequência Alfanumérica , Comportamento Verbal , Aprendizagem Verbal
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