560 research outputs found
NEUROPSYCHIATRIC SYMPTOMS OF DEMENTIA AND BIOMARKERS OF NEURODEGENERATION: CSF TAU AND MRI
Background: Behavioral and psychological symptoms of dementia (BPSD) are a distressful condition. We aimed to investigate the BPSD distribution in subjects with cognitive impairment, and the potential correlations between BPSD and neurodegeneration in terms of cerebrospinal fluid (CSF) tau and brain atrophy. Materials and Methods: One-hundred patients with mild cognitive impairment (MCI) or dementia (Alzheimer’s disease; Dementia with Lewy-body disease, DLB; frontotemporal dementia; vascular dementia) underwent a complete diagnostic workup, including 3T-MRI and/or CT and CSF. Cortical atrophy was assessed i) first with visual rating scales (medial temporal atrophy MTA, posterior atrophy PA and global cortical atrophy-frontal lobe GCA-F scales), ii) secondly with quantitative measures (such as cortical thickness CT and volume V). BPSD were rated using Neuropsychiatric Inventory (NPI), and BPSD clusters were defined according to the European Alzheimer Disease Consortium. Results: Delusions, hallucinations and psychosis cluster were differently distributed among the diagnostic groups (p<0.05, p<0.001, and p<0.05), with DLB patients showing higher scores for hallucinations (vs MCI, p<0.001, and AD, p<0.05) and psychosis cluster (vs MCI, p<0.05). In primary dementias, we found a negative correlation between NPI total score and tau levels (p=0.08), confirmed by beta regression (p<0.01), while a positive non-significant relationship was observed in MCI. Higher GCA-F scores were associated with delusions and apathy (p<0.05, on both hemispheres) and to hallucinations (left: p<0.01, right: p<0.05). GCA-F scores were positively correlated with psychosis cluster (right: p<0.05), and agitation/aggression (left: p<0.05). With regard to the quantitative measures od atrophy, significant correlations were observed for 4 main neuropsychiatric symptoms: delusions, hallucinations, agitation, and apathy. Delusions showed negative correlations with CT and V of frontal areas (dorsolateral and orbital, with a prevalent involvement on the right side) and of areas of the limbic system (anterior and posterior cingulate, isthmus and entorhinal cortex). As well, hallucinations showed an involvement of the frontal lobe (dorsolateral) and the limbic system (anterior and posterior cingulate, isthmus, fusiform gyrus and hippocampus). A decrease in CT and V of the opercular region (insula and temporal pole) and the limbic system (entorhinal, parahippocampal and fusiform cortex and amygdala) was instead correlated with agitation/aggression. Finally, apathy showed a negative correlation with regions of the frontal lobe (dorsolateral, orbital, opercular, precentral and paracentral) insula and the limbic system (anterior cingulate and isthmus). Conclusion: This study provides a real-world overview of the most clinically relevant BPSD occurring in patients attending a memory clinic due to dementing conditions. The gathered evidence suggests that, in a future perspective, CSF biomarkers and visual rating scales for cortical atrophy could be hopefully included in a multidimensional evaluation of demented patients, aimed to predict prognosis and occurrence of BPSD. Moreover, quantitative measures of atrophy suggest that the limbic system cover a paramount role in the their pathophysiology through the dysfunction of the mesolimbic circuitry.Background: Behavioral and psychological symptoms of dementia (BPSD) are a distressful condition. We aimed to investigate the BPSD distribution in subjects with cognitive impairment, and the potential correlations between BPSD and neurodegeneration in terms of cerebrospinal fluid (CSF) tau and brain atrophy. Materials and Methods: One-hundred patients with mild cognitive impairment (MCI) or dementia (Alzheimer’s disease; Dementia with Lewy-body disease, DLB; frontotemporal dementia; vascular dementia) underwent a complete diagnostic workup, including 3T-MRI and/or CT and CSF. Cortical atrophy was assessed i) first with visual rating scales (medial temporal atrophy MTA, posterior atrophy PA and global cortical atrophy-frontal lobe GCA-F scales), ii) secondly with quantitative measures (such as cortical thickness CT and volume V). BPSD were rated using Neuropsychiatric Inventory (NPI), and BPSD clusters were defined according to the European Alzheimer Disease Consortium. Results: Delusions, hallucinations and psychosis cluster were differently distributed among the diagnostic groups (p<0.05, p<0.001, and p<0.05), with DLB patients showing higher scores for hallucinations (vs MCI, p<0.001, and AD, p<0.05) and psychosis cluster (vs MCI, p<0.05). In primary dementias, we found a negative correlation between NPI total score and tau levels (p=0.08), confirmed by beta regression (p<0.01), while a positive non-significant relationship was observed in MCI. Higher GCA-F scores were associated with delusions and apathy (p<0.05, on both hemispheres) and to hallucinations (left: p<0.01, right: p<0.05). GCA-F scores were positively correlated with psychosis cluster (right: p<0.05), and agitation/aggression (left: p<0.05). With regard to the quantitative measures od atrophy, significant correlations were observed for 4 main neuropsychiatric symptoms: delusions, hallucinations, agitation, and apathy. Delusions showed negative correlations with CT and V of frontal areas (dorsolateral and orbital, with a prevalent involvement on the right side) and of areas of the limbic system (anterior and posterior cingulate, isthmus and entorhinal cortex). As well, hallucinations showed an involvement of the frontal lobe (dorsolateral) and the limbic system (anterior and posterior cingulate, isthmus, fusiform gyrus and hippocampus). A decrease in CT and V of the opercular region (insula and temporal pole) and the limbic system (entorhinal, parahippocampal and fusiform cortex and amygdala) was instead correlated with agitation/aggression. Finally, apathy showed a negative correlation with regions of the frontal lobe (dorsolateral, orbital, opercular, precentral and paracentral) insula and the limbic system (anterior cingulate and isthmus). Conclusion: This study provides a real-world overview of the most clinically relevant BPSD occurring in patients attending a memory clinic due to dementing conditions. The gathered evidence suggests that, in a future perspective, CSF biomarkers and visual rating scales for cortical atrophy could be hopefully included in a multidimensional evaluation of demented patients, aimed to predict prognosis and occurrence of BPSD. Moreover, quantitative measures of atrophy suggest that the limbic system cover a paramount role in the their pathophysiology through the dysfunction of the mesolimbic circuitry
Advances in functional neuroimaging in dementias and potential pitfalls
Neuroimaging is continuously advancing at a rapid rate and has progressed from excluding relatively uncommon secondary causes (stroke, tumor) to assisting with early diagnosis and subtype of dementia. Structural imaging has given way to functional, metabolic and receptor imaging
Structural and diffusion MRI in dementia with Lewy bodies : a comparison with Alzheimer's disease and normal ageing
Purpose: Dementia with Lewy bodies (DLB) is a common form of dementia, yet its clinical features remain poorly understood. We investigated in vivo structural and micro-structural changes in DLB compared to Alzheimer’s disease (AD) and normal ageing using magnetic resonance imaging (MRI) techniques and their relationship to clinical features. Methods: Study subjects (35 DLB, 36 AD, 35 Controls) completed clinical and cognitive assessments and structural and diffusion tensor MRI scans. Voxel based morphometry (VBM) techniques were used to investigate patterns of regional grey matter atrophy. To investigate white matter tract change, diffusion tensor imaging (DTI) indices, fractional anisotropy (FA) and mean diffusivity (MD) were measured across the entire white matter skeleton using the tract based spatial statistics (TBSS) analysis. Results: Groups were well matched for demographic and clinical factors, although, as expected, the DLB group also had more neuropsychiatric features, greater parkinsonism and more functional impairment than the AD group. VBM analysis indicated a less diffuse pattern of grey matter atrophy in DLB than observed in AD, with areas of loss including the posterior and subcortical regions without significant frontal atrophy. DLB had greater preservation of the medial temporal lobe structures when compared to AD, which was associated with less impaired memory function. The pattern of FA change in DLB compared to controls involved the parieto-occipital white matter tracts; in AD, the FA change was more diffuse. In DLB, an association was found between reduced FA and the phonemic fluency tasks in the white-matter tracts of the precentral gyrus, anterior cingulate and precuneus in DLB. Abstract ii Conclusions: Despite a similar level of dementia severity, the patterns of structural and diffusion tensor MRI changes in AD and DLB differ significantly. DLB was associated with less grey matter volume loss and less white matter tract change than AD along with differing regional patterns of change.EThOS - Electronic Theses Online ServiceGBUnited Kingdo
Radiological-pathological correlation in Alzheimer's disease : systematic review of antemortem MRI findings
Background: The standard method of ascertaining Alzheimer’s disease (AD) remains postmortem
assessment of amyloid plaques and neurofibrillary degeneration. Vascular pathology,
Lewy bodies, TDP-43, and hippocampal sclerosis are frequent comorbidities. There is therefore
a need for biomarkers that can assess these aetiologies and provide a diagnosis in vivo.
Objective: We conducted a systematic review of published radiological-pathological correlation
studies to determine the relationship between antemortem magnetic resonance imaging (MRI)
and neuropathological findings in AD.
Methods: We explored PubMed in June-July 2015 using “Alzheimer’s disease” and
combinations of radiological and pathological terms. After exclusion following screening and
full-text assessment of the 552 extracted manuscripts, three others were added from their
reference list. In fine, we report results based on 27 articles.
Results: Independently of normal age-related brain atrophy, AD pathology is associated with
whole-brain and hippocampal atrophy and ventricular expansion as observed on T1-weighted
images. Moreover, cerebral amyloid angiopathy and cortical microinfarcts are also related to
brain volume loss in AD. Hippocampal sclerosis and TDP-43 are respectively associated with
hippocampal and medial temporal lobe atrophy. Brain volume loss correlates more strongly with
tangles than with any other pathological finding. White matter hyperintensities observed on
proton density, T2-weighted and FLAIR images are strongly related to vascular pathologies, but
are also associated with other histological changes such as gliosis or demyelination.
Discussion: Cerebral atrophy and white matter changes in the living brain reflect underlying
neuropathology and may be detectable using antemortem MRI. In vivo MRI may therefore be an
avenue for AD pathological staging
Asociace morfometrickĂ˝ch a metabolickĂ˝ch biomarkerĹŻ s kognitivnĂm postiĹľenĂm u Lewy body a Alzheimerovy demence
Asociace morfometrickĂ˝ch a metabolickĂ˝ch biomarkerĹŻ s kognitivnĂm postiĹľenĂm u Lewy body a Alzheimerovy demence Abstrakt Syndrom demence pĹ™edstavuje vĂ˝znamnou zdravotnickou a socioekonomickou vĂ˝zvu. Alzheimerova choroba (AD) je nejÄŤastÄ›jšà pĹ™ĂÄŤinou demence. Demence s Lewyho tÄ›lĂsky (DLB) pĹ™edstavuje druhou nejÄŤastÄ›jšà neurodegenerativnĂ demenci. ObÄ› demence jsou však heterogennĂ mnoĹľiny vyvĂjejĂcĂ se v klinicko-patologickĂ©m kontinuu, pĹ™iÄŤemĹľ tato kontinua se mohou vzájemnÄ› pĹ™ekrĂ˝vat. Metody, kterĂ© by umoĹľnily vytipovánĂ ÄŤi pĹ™Ămou identifikaci osob s rizikem rozvoje AD demence ÄŤi DLB v ÄŤasnĂ˝ch klinickĂ˝ch nebo dokonce preklinickĂ˝ch stadiĂch jsou v centru zájmu. VÄŤasnĂ© nefarmakologickĂ© a symptomatickĂ© farmakologickĂ© intervence ÄŤi novÄ› vyvĂjenĂ© biologickĂ© formy terapie AD jsou účinnÄ›jšà v ÄŤasnÄ›jšĂch stadiĂch neĹľ u klinicky plnÄ› rozvinutĂ©ho syndromu demence. PĹ™edpokladem pro efektivnĂ intervenci je jejĂ zacĂlenĂ na nejvĂce vnĂmavou populaci, vÄŤasnĂ˝ záchyt, diferenciálnĂ diagnostika, pochopenĂ prĹŻbÄ›hu nemoci a lĂ©ÄŤba komorbidit. PrvnĂ, obecná, část disertace je formou pĹ™ehlednĂ©ho referátu o AD a DLB. Druhá, vĂ˝zkumná, část práce shrnuje vĂ˝sledky vĂ˝zkumu autorky disertace. HlavnĂ cĂle vĂ˝zkumnĂ© práce byly tyto tĹ™i: za prvĂ©, aplikace testĹŻ experimentálnĂ neuropsychologie jako potenciálnĂch markerĹŻ ÄŤasnĂ˝ch stadiĂ AD a...Associations of morphometric and metabolic biomarkers with cognitive impairment in Alzheimer's disease and Lewy body dementias Abstract Dementia has become one of the major health care and socio-economic challenges. Alzheimer's disease (AD) is the most common dementia whereas dementia with Lewy bodies (DLB) is the second most common neurodegenerative after AD. However, both dementias exist in a quite heterogeneous contiua that can overlap with each other. Approaches that allow for the identification of individuals at risk of developing AD in preclinical or prodromal stages are of major interest to apply the symptomatic and newly introduced biological therapies and non- pharmacological interventions that are more effective early on. Similar efforts are undertaken in the DLB field although no causal treatment for DLB is available yet. A prerequisite for an efficacious and targeted intervention is a selection of individuals who would benefit the most from this intervention. This process includes the timely and accurate diagnosis, differential diagnosis, prognostication, and management of treatable comorbidities. This dissertation has two parts. Part one is an overview of AD and DLB. The second part summarizes author's research work. The main research aims corroborated in this thesis are three-fold: First, to...Neurologická klinikaDepartment of Neurology2. lĂ©kaĹ™ská fakultaSecond Faculty of Medicin
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Correlation of microglial activation with white matter changes in dementia with Lewy bodies.
Dementia with Lewy bodies (DLB) is characterized by alpha-synuclein protein deposition with variable degree of concurrent Alzheimer's pathology. Neuroinflammation is also increasingly recognized as a significant contributor to degeneration. We aimed to examine the relationship between microglial activation as measured with [11C]-PK11195 brain PET, MR diffusion tensor imaging (DTI) and grey matter atrophy in DLB. Nineteen clinically probable DLB and 20 similarly aged controls underwent 3T structural MRI (T1-weighted) and diffusion-weighted imaging. Eighteen DLB subjects also underwent [11C]-PK11195 PET imaging and 15 had [11C]-Pittsburgh compound B amyloid PET, resulting in 9/15 being amyloid-positive. We used Computational Anatomy Toolbox (CAT12) for volume-based morphometry (VBM) and Tract-Based Spatial Statistics (TBSS) for DTI to assess group comparisons between DLB and controls and to identify associations of [11C]-PK11195 binding with grey/white matter changes and cognitive score in DLB patients. VBM analyses showed that DLB had extensive reduction of grey matter volume in superior frontal, temporal, parietal and occipital cortices (family-wise error (FWE)-corrected p < 0.05). TBSS showed widespread changes in DLB for all DTI parameters (reduced fractional anisotropy, increased diffusivity), involving the corpus callosum, corona radiata and superior longitudinal fasciculus (FWE-corrected p < 0.05). Higher [11C]-PK11195 binding in parietal cortices correlated with widespread lower mean and radial diffusivity in DLB patients (FWE-corrected p < 0.05). Furthermore, preserved cognition in DLB (higher Addenbrookes Cognitive Evaluation revised score) also correlated with higher [11C]-PK11195 binding in frontal, temporal, and occipital lobes. However, microglial activation was not significantly associated with grey matter changes. Our study suggests that increased microglial activation is associated with a relative preservation of white matter and cognition in DLB, positioning neuroinflammation as a potential early marker of DLB etio-pathogenesis
Dementia: Types, What They Are and How They Differ
Dementia: types, what they are and how they differ centers on the known and unknown complexities of dementia. Dementia is a very complex cognitive disease that consumes the brain, an organ of which we know very little about. Even so, this common disorder is actively being researched and is the topic of special interest of this thesis research. Described are Alzheimer’s disease, Creutzfeldt-Jakob disease, Frontotemporal dementia, Huntington’s disease, Korsakoff’s syndrome, Lewy body dementia, Parkinson’s dementia, and Vascular dementia, focusing on what they are, their specific risks, diagnosis, treatment, and their differing progressions. Guidance of this study provided by thesis director Ranelle Nissen, who studies dementia and is a professor at USD. The remaining two thesis committee members are Mary H. Schmitz, Director of the memory unit and former director of activities at Grand Living at Lake Lorraine in Sioux Falls, and Joy Backes, Director of health and wellness, also, at Grand Living at Lake Lorraine; all of whom have extensive dementia experience and are reliable resources and mentors during this dementia thesis process
Visual signs and symptoms of dementia with Lewy bodies
Dementia with Lewy bodies ('Lewy body dementia' or 'diffuse Lewy body disease') (DLB) is the second most common form of dementia to affect elderly people, after Alzheimer's disease. A combination of the clinical symptoms of Alzheimer's disease and Parkinson's disease is present in DLB and the disorder is classified as a 'parkinsonian syndrome', a group of diseases which also includes Parkinson's disease, progressive supranuclear palsy, corticobasal degeneration and multiple system atrophy. Characteristics of DLB are fluctuating cognitive ability with pronounced variations in attention and alertness, recurrent visual hallucinations and spontaneous motor features, including akinesia, rigidity and tremor. In addition, DLB patients may exhibit visual signs and symptoms, including defects in eye movement, pupillary function and complex visual functions. Visual symptoms may aid the differential diagnoses of parkinsonian syndromes. Hence, the presence of visual hallucinations supports a diagnosis of Parkinson's disease or DLB rather than progressive supranuclear palsy. DLB and Parkinson's disease may exhibit similar impairments on a variety of saccadic and visual perception tasks (visual discrimination, space-motion and object-form recognition). Nevertheless, deficits in orientation, trail-making and reading the names of colours are often significantly greater in DLB than in Parkinson's disease. As primary eye-care practitioners, optometrists should be able to work with patients with DLB and their carers to manage their visual welfare
Brain Dynamics as Confirmatory Biomarker of Dementia with Lewy Bodies Versus Alzheimer’s Disease - an Electrophysiological Study
PhD ThesisIntroduction
Dementia with Lewy bodies (DLB), Parkinson’s disease dementia (PDD) and Alzheimer’s
disease dementia (AD) are associated with different pathologies. Nevertheless, symptomatic overlap between these conditions may lead to misdiagnosis. Resting-state functional connectivity features in DLB as assessed with electroencephalography (EEG) are emerging as diagnostic biomarkers. However, their pathological significance is still questioned. This study aims to further investigate this aspect and to infer functional and structural sources of EEG abnormalities in DLB.
Methods
Graph theory analysis was first performed to assess EEG network differences between healthy controls (HC) and dementia groups. Source localisation and Network Based Statistics (NBS) were used to infer EEG cortical network and dominant frequency (DF) alterations in DLB compared with AD. Further analysis aimed to assess the subnetwork associated with visual hallucination (VH) symptom in DLB and PDD, i.e. LBD, compared with not-hallucinating (NVH) patients. Finally, probabilistic tractography was performed on diffusion tensor imaging (DTI) data between cortical regions, thalamus, and basal forebrain (NBM). Correlation between structural and functional connectivity was tested.
Results
EEG α-band (7-13.5 Hz) network features were affected in LBD compared with HC, whilst DLB β-band network (14-20.5 Hz) was weaker and more segregated when compared with AD. This scenario replicated in the source domain. DF was significantly lower in DLB compared with AD, and positively correlated with structural connectivity strength between NBM and the cortex. Functional visual ventral network connectivity and cholinergic projections towards the cortex were affected in VH compared with NVH, and significantly correlated in NVH.
Conclusions
Functional connectivity as assessed with EEG is more affected in DLB compared with AD. Moreover, the visual ventral network is functionally altered in VH compared with NVH. Results from structural analysis provide empirical evidence on the role of cholinergic dysfunctions in DLB and PDD pathology and corresponding functional correlates
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