Microglial activation in early Alzheimer trajectory is associated with higher gray matter volume

ObjectiveTo investigate the influence of microglial activation in the early stages of Alzheimer's disease trajectory, we assessed the relationship between microglial activation and gray matter volume and hippocampal volume in patients with mild cognitive impairment (MCI).MethodsIn this study, 55 participants (37 with early stages of MCI and 18 controls) underwent [11C]PBR28 PET, a marker of microglial activation; volumetric MRI to evaluate gray matter and hippocampal volumes as well as clinical and neuropsychometric evaluation. [11C]PBR28 VT(volume of distribution) was calculated using arterial input function and Logan graphical analysis. Gray matter volume and hippocampal volumes were calculated from MRI for each participant. Statistical parametric mapping software was used to perform voxel-wise correlations and biological parametric mapping analysis. Amyloid status was assessed using [18F]flutemetamol PET.ResultsHigher [11C]PBR28 VTin different cortical areas correlated with higher gray matter volume in both amyloid-positive and -negative MCI. In addition, higher hippocampal volume correlated with higher cortical [11C]PBR28 Logan VT.ConclusionsIn this in vivo study, we have demonstrated that microglial activation quantified using [11C]PBR28 PET was associated with higher gray matter volume and higher hippocampal volume in patients with MCI. This might suggest that microglial activation may not always be associated with neuronal damage, and indeed it may have a beneficial effect in the early stages of the Alzheimer trajectory. While further longitudinal studies are necessary, these findings have significant implications on therapeutic strategies targeting microglial activation.

Download Full-text

Effects of cumulative illness severity on hippocampal gray matter volume in major depression: a voxel-based morphometry study

Psychological Medicine ◽

10.1017/s0033291718000016 ◽

2018 ◽

Vol 48 (14) ◽

pp. 2391-2398 ◽

Cited By ~ 13

Author(s):

Dario Zaremba ◽

Verena Enneking ◽

Susanne Meinert ◽

Katharina Förster ◽

Christian Bürger ◽

...

Keyword(s):

Major Depression ◽

Gray Matter ◽

Gray Matter Volume ◽

Principal Component ◽

Hippocampal Volume ◽

Illness Severity ◽

Voxel Based Morphometry ◽

Matter Volume ◽

Duration Of Illness ◽

Component Scores

AbstractBackgroundPatients with major depression show reduced hippocampal volume compared to healthy controls. However, the contribution of patients’ cumulative illness severity to hippocampal volume has rarely been investigated. It was the aim of our study to find a composite score of cumulative illness severity that is associated with hippocampal volume in depression.MethodsWe estimated hippocampal gray matter volume using 3-tesla brain magnetic resonance imaging in 213 inpatients with acute major depression according to DSM-IV criteria (employing the SCID interview) and 213 healthy controls. Patients’ cumulative illness severity was ascertained by six clinical variables via structured clinical interviews. A principal component analysis was conducted to identify components reflecting cumulative illness severity. Regression analyses and a voxel-based morphometry approach were used to investigate the influence of patients’ individual component scores on hippocampal volume.ResultsPrincipal component analysis yielded two main components of cumulative illness severity: Hospitalization and Duration of Illness. While the component Hospitalization incorporated information from the intensity of inpatient treatment, the component Duration of Illness was based on the duration and frequency of illness episodes. We could demonstrate a significant inverse association of patients’ Hospitalization component scores with bilateral hippocampal gray matter volume. This relationship was not found for Duration of Illness component scores.ConclusionsVariables associated with patients’ history of psychiatric hospitalization seem to be accurate predictors of hippocampal volume in major depression and reliable estimators of patients’ cumulative illness severity. Future studies should pay attention to these measures when investigating hippocampal volume changes in major depression.

Download Full-text

Social Cognition and Emotional Assessment (SEA) is a Marker of Medial and Orbital Frontal Functions: A Voxel-Based Morphometry Study in Behavioral Variant of Frontotemporal Degeneration

Journal of the International Neuropsychological Society ◽

10.1017/s1355617712001300 ◽

2012 ◽

Vol 18 (6) ◽

pp. 972-985 ◽

Cited By ~ 44

Author(s):

Maxime Bertoux ◽

Emmanuelle Volle ◽

Aurélie Funkiewiez ◽

Leonardo Cruz de Souza ◽

Delphine Leclercq ◽

...

Keyword(s):

Social Cognition ◽

Theory Of Mind ◽

Reversal Learning ◽

Gray Matter ◽

Gray Matter Volume ◽

Structural Mri ◽

Voxel Based Morphometry ◽

Matter Volume ◽

Early Stages ◽

Emotional Assessment

AbstractThe aim of this study was to explore the cerebral correlates of functional deficits that occur in behavioral variant frontotemporal dementia (bvFTD). A specific neuropsychological battery, the Social cognition & Emotional Assessment (SEA; Funkiewiez et al., 2012), was used to assess impaired social and emotional functions in 20 bvFTD patients who also underwent structural MRI scanning. The SEA subscores of theory of mind, reversal-learning tests, facial emotion identification, and apathy evaluation were entered as covariates in a voxel-based morphometry analysis. The results revealed that the gray matter volume in the rostral part of the medial prefrontal cortex [mPFC, Brodmann area (BA) 10] was associated with scores on the theory of mind subtest, while gray matter volume within the orbitofrontal (OFC) and ventral mPFC (BA 11 and 47) was related to the scores observed in the reversal-learning subtest. Gray matter volume within BA 9 in the mPFC was correlated with scores on the emotion recognition subtest, and the severity of apathetic symptoms in the Apathy scale covaried with gray matter volume in the lateral PFC (BA 44/45). Among these regions, the mPFC and OFC cortices have been shown to be atrophied in the early stages of bvFTD. In addition, SEA and its abbreviated version (mini-SEA) have been demonstrated to be sensitive to early impairments in bvFTD (Bertoux et al., 2012). Taken together, these results suggest a differential involvement of orbital and medial prefrontal subregions in SEA subscores and support the use of the SEA to evaluate the integrity of these regions in the early stages of bvFTD. (JINS, 2012, 18, 972–985)

Download Full-text

Depressive symptoms in Parkinson’s disease are related to decreased left hippocampal volume: correlation with the 15-item shortened version of the Geriatric Depression Scale

Acta Radiologica ◽

10.1177/0284185117719100 ◽

2017 ◽

Vol 59 (3) ◽

pp. 341-345 ◽

Cited By ~ 4

Author(s):

Masami Goto ◽

Koji Kamagata ◽

Taku Hatano ◽

Nobutaka Hattori ◽

Osamu Abe ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Gray Matter ◽

Gray Matter Volume ◽

Geriatric Depression Scale ◽

Depression Scale ◽

Hippocampal Volume ◽

Geriatric Depression ◽

Matter Volume ◽

The Relationship

Background The relationship between hippocampal and amygdaloid volumes and depression in patients with Parkinson’s disease (PD) is a controversial issue. Purpose To investigate the correlation between the 15-item shortened version of the Geriatric Depression Scale (GDS-15) and gray matter volume in PD. Material and Methods In the present study, 46 participants with PD were scanned with 3 T magnetic resonance imaging (MRI) to obtain three-dimensional (3D) T1-weighted (T1W) images. Neurologists specializing in movement disorders performed clinical evaluations of the participants (e.g. GDS-15, Mini-Mental State Examination, PD duration, age, sex). Statistical Parametric Mapping 8 software was used for image gray matter segmentation and for a correlation analysis between gray matter volume and GDS-15 score. Results The results showed a significant negative correlation between GDS-15 score and left hippocampal volume, and between GDS-15 score and right parahippocampal gyrus volume. No significant positive correlations were found in the whole brain. Conclusion The current results provide new evidence regarding the relationship between depression in PD and hippocampal volume.

Download Full-text

Vascular Inflammation Is a Risk Factor Associated with Brain Atrophy and Disease Severity in Parkinson’s Disease: A Case-Control Study

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/2591248 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Chiun-Chieh Yu ◽

Hsiu-Ling Chen ◽

Meng-Hsiang Chen ◽

Cheng-Hsien Lu ◽

Nai-Wen Tsai ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Disease Severity ◽

Gray Matter ◽

Vascular Inflammation ◽

Gray Matter Volume ◽

Statistical Parametric Mapping ◽

Clinical Disease ◽

Matter Volume ◽

Gray Matter Atrophy

Introduction. Systemic inflammation with elevated oxidative stress causing neuroinflammation is considered a major factor in the pathogenesis of Parkinson’s disease (PD). The interface between systemic circulation and the brain parenchyma is the blood-brain barrier (BBB), which also plays a role in maintaining neurovascular homeostasis. Vascular cell adhesion molecule-1 (VCAM-1) and microRNAs (miRNAs) regulate brain vessel endothelial function, neoangiogenesis, and, in turn, neuronal homeostasis regulation, such that their dysregulation can result in neurodegeneration, such as gray matter atrophy, in PD. Objective. Our aim was to evaluate the associations among specific levels of gray matter atrophy, peripheral vascular adhesion molecules, miRNAs, and clinical disease severity in order to achieve a clearer understanding of PD pathogenesis. Methods. Blood samples were collected from 33 patients with PD and 27 healthy volunteers, and the levels of VCAM-1 and several miRNAs in those samples were measured. Voxel-based morphometry (VBM) analysis was performed using 3 T magnetic resonance imaging (MRI) and SPM (Statistical Parametric Mapping software program). The associations among the vascular parameter, miRNAs, gray matter volume, and clinical disease severity measurements were evaluated by partial correlation analysis. Results. The levels of VCAM-1, miRNA-22, and miRNA-29a expression were significantly elevated in the PD patients. The gray matter volume atrophy in the left parahippocampus, bilateral posterior cingulate gyrus, fusiform gyrus, left temporal gyrus, and cerebellum was significantly correlated with increased clinical disease severity, the upregulation of miRNA levels, and increased vascular inflammation. Conclusion. Patients with PD seem to have abnormal levels of vascular inflammatory markers and miRNAs in the peripheral circulation, and these levels are correlated with specific brain volume changes. This study reinforces the associations among peripheral inflammation, the BBB interface, and gray matter atrophy in PD and further demonstrates that BBB dysfunction with neurovascular impairment may play an important role in PD progression.

Download Full-text

Vascular inflammation is a risk factor associated with brain atrophy and disease severity in Parkinson’s disease: a case-control study

10.21203/rs.2.19756/v1 ◽

2019 ◽

Author(s):

Chiun-Chieh Yu ◽

Hsiu-Ling Chen ◽

Meng-Hsiang Chen ◽

Cheng-Hsien Lu ◽

Nai-Wen Tsai ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Disease Severity ◽

Gray Matter ◽

Vascular Inflammation ◽

Gray Matter Volume ◽

Statistical Parametric Mapping ◽

Clinical Disease ◽

Matter Volume ◽

Gray Matter Atrophy

Abstract Background: Systemic inflammation with elevated oxidative stress causing neuroinflammation is considered a major factor in the pathogenesis of Parkinson’s disease (PD).The interface between systemic circulation and the brain parenchyma is the blood - brain barrier (BBB), which also plays a role in maintaining neurovascular homeostasis. Relatedly, intermediate vascular inflammation causing BBB dysfunction is a key component of PD pathogenesis. Vascular cell adhesion molecule-1 (VCAM-1) and microRNAs (miRNAs) regulate brain endothelial function, neoangiogenesis, and, in turn, neuronal homeostasis regulation, such that their dysregulation can result in neurodegeneration, such as gray matter atrophy, in PD. In this study, our aim was to evaluate the associations among specific levels of gray matter atrophy, peripheral vascular adhesion molecules, miRNAs, and clinical disease severity in order to achieve a clearer understanding of PD pathogenesis.Methods: Blood samples were collected from 33 patients with PD and 27 healthy volunteers, and the levels of VCAM-1 and several miRNAs in those samples were measured. Voxel-based morphometry (VBM) analysis was performed using 3T magnetic resonance imaging (MRI) and SPM (Statistical Parametric Mapping software program). The associations among the vascular parameter, miRNAs, gray matter volume and clinical disease severity measurements were evaluated by partial correlation analysis.Results: The levels of VCAM-1, miRNA-22 and miRNA-29a expression were significantly elevated in the PD patients. The gray matter volume atrophy in the left parahippocampus, bilateral posterior cingulate gyrus, fusiform gyrus, left temporal gyrus, and cerebellum was significantly correlated with increased clinical disease severity, the upregulation of miRNA levels, and increased vascular inflammation.Conclusions: Patients with PD seem to have abnormal levels of vascular inflammatory markers and miRNAs in the peripheral circulation, and these levels are correlated with specific brain volume changes. This study reinforces the associations among peripheral inflammation, the BBB interface, and gray matter atrophy in PD, and further demonstrates that BBB dysfunction with neurovascular impairment may play an important role in PD progression.

Download Full-text