Bridging the gap between Morphometric Similarity Mapping and gene transcription in Alzheimer's disease

2021 ◽  
Author(s):  
Yang Zhang ◽  
Min Ma ◽  
Zhonghua Xie ◽  
Heng Wu ◽  
Nan Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Connectivity ◽  
Memory Function ◽  
Structural Connectivity ◽  
Occipital Cortex ◽  
Significant Term ◽  
Changing Patterns ◽  
Cortical Regions ◽  
With Memory

Abstract Disruptions of brain connectivity have been widely reported in Alzheimer's disease (AD). Morphometric similarity (MS) mapping provides a new way of estimating structural connectivity by inter-regional correlation of T1WI and DTI derived parameters within individual brains. Here, we aimed to identify AD-related MS changing patterns and genes related to the changes and further explore the molecular and cellular mechanism underlying MS changes in AD. Both 3D-T1WI and DTI data of 106 AD patients and well-matched 106 healthy elders from the ADNI database were included in our study. Cortical regions with significantly decreased MS were found in the temporal and parietal cortex, increased MS in the frontal cortex and variant changes in the occipital cortex in AD patients. Mean MS in regions with significantly changed MS was positively or negatively associated with memory function. The negative MS-related genes were significantly down-regulated in AD, specifically enriched in neurons, and participated in biological process with the most significant term in synaptic transmission. This study revealed AD-related cortical MS changes associated with memory function. Linking gene expression to cortical MS changes may provide a possible molecular and cellular substrate for MS abnormality and cognition decline in AD.

scholarly journals Bridging the Gap Between Morphometric Similarity Mapping and Gene Transcription in Alzheimer’s Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Yang Zhang ◽  
Min Ma ◽  
Zhonghua Xie ◽  
Heng Wu ◽  
Nan Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Connectivity ◽  
Memory Function ◽  
Structural Connectivity ◽  
Occipital Cortex ◽  
Healthy Elderly ◽  
Significant Term ◽  
Cortical Regions ◽  
With Memory

Disruptions in brain connectivity have been widely reported in Alzheimer’s disease (AD). Morphometric similarity (MS) mapping provides a new way of estimating structural connectivity by interregional correlation of T1WI- and DTI-derived parameters within individual brains. Here, we aimed to identify AD-related MS changing patterns and genes related to the changes and further explored the molecular and cellular mechanism underlying MS changes in AD. Both 3D-T1WI and DTI data of 106 AD patients and 106 well-matched healthy elderly individuals from the ADNI database were included in our study. Cortical regions with significantly decreased MS were found in the temporal and parietal cortex, increased MS was found in the frontal cortex and variant changes were found in the occipital cortex in AD patients. Mean MS in regions with significantly changed MS was positively or negatively associated with memory function. Negative MS-related genes were significantly downregulated in AD, specifically enriched in neurons, and participated in biological processes, with the most significant term being synaptic transmission. This study revealed AD-related cortical MS changes associated with memory function. Linking gene expression to cortical MS changes may provide a possible molecular and cellular substrate for MS abnormality and cognitive decline in AD.

scholarly journals Relating Global and Local Connectome Changes to Dementia and Targeted Gene Expression in Alzheimer's Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Samar S. M. Elsheikh ◽  
Emile R. Chimusa ◽  
Nicola J. Mulder ◽  
Alessandro Crimi ◽  
Keyword(s):  
Gene Expression ◽  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Genetic Risk ◽  
Betweenness Centrality ◽  
Brain Connectivity ◽  
Structural Connectivity ◽  
Genetic Risk Factors ◽  
Functional Connections

Networks are present in many aspects of our lives, and networks in neuroscience have recently gained much attention leading to novel representations of brain connectivity. The integration of neuroimaging characteristics and genetics data allows a better understanding of the effects of the gene expression on brain structural and functional connections. The current work uses whole-brain tractography in a longitudinal setting, and by measuring the brain structural connectivity changes studies the neurodegeneration of Alzheimer's disease. This is accomplished by examining the effect of targeted genetic risk factors on the most common local and global brain connectivity measures. Furthermore, we examined the extent to which Clinical Dementia Rating relates to brain connections longitudinally, as well as to gene expression. For instance, here we show that the expression of PLAU gene increases the change over time in betweenness centrality related to the fusiform gyrus. We also show that the betweenness centrality metric impact dementia-related changes in distinct brain regions. Our findings provide insights into the complex longitudinal interplay between genetics and brain characteristics and highlight the role of Alzheimer's genetic risk factors in the estimation of regional brain connectivity alterations.

Impact of Comorbid Depression on Serial Position Effects in Alzheimer’s Disease

GeroPsych ◽  
2014 ◽  
Vol 27 (4) ◽  
pp. 161-169 ◽  
Author(s):  
Nienke A. Hofrichter ◽  
Sandra Dick ◽  
Thomas G. Riemer ◽  
Carsten Schleussner ◽  
Monique Goerke ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Serial Position ◽  
Episodic Memory ◽  
Memory Performance ◽  
Memory Function ◽  
Word List ◽  
Position Effects ◽  
Serial Position Effects ◽  
List Memory

Hippocampal dysfunction and deficits in episodic memory have been reported for both Alzheimer’s disease (AD) and major depressive disorder (MDD). Primacy performance has been associated with hippocampus-dependent episodic memory, while recency may reflect working memory performance. In this study, serial position profiles were examined in a total of 73 patients with MDD, AD, both AD and MDD, and healthy controls (HC) by means of CERAD-NP word list memory. Primacy performance was most impaired in AD with comorbid MDD, followed by AD, MDD, and HC. Recency performance, on the other hand, was comparable across groups. These findings indicate that primacy in AD is impaired in the presence of comorbid MDD, suggesting additive performance decrements in this specific episodic memory function.

Many caregivers of persons with memory loss or Alzheimer's disease are unaware of the abilities of their persons with AD to recall their drugs and medical histories

Dementia ◽  
2018 ◽  
pp. 147130121882096
Author(s):  
Thomas A Ala ◽  
GaToya Simpson ◽  
Marshall T Holland ◽  
Vajeeha Tabassum ◽  
Maithili Deshpande ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Memory Loss ◽  
Medical Histories ◽  
With Memory

scholarly journals Structural connectivity networks in Alzheimer’s disease and Lewy body disease

2021 ◽  
Author(s):  
Kyoungwon Baik ◽  
Jin‐Ju Yang ◽  
Jin Ho Jung ◽  
Yang Hyun Lee ◽  
Seok Jong Chung ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lewy Body ◽  
Structural Connectivity ◽  
Lewy Body Disease

Spectral dynamic causal modelling of resting-state fMRI: an exploratory study relating effective brain connectivity in the default mode network to genetics

2020 ◽  
Vol 19 (3) ◽  
Author(s):  
Yunlong Nie ◽  
Eugene Opoku ◽  
Laila Yasmin ◽  
Yin Song ◽  
Jie Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Default Mode Network ◽  
Resting State ◽  
Brain Connectivity ◽  
Parametric Bootstrap ◽  
Imaging Genetics ◽  
Nucleotide Polymorphisms ◽  
Mixed Effect ◽  
Default Mode

AbstractWe conduct an imaging genetics study to explore how effective brain connectivity in the default mode network (DMN) may be related to genetics within the context of Alzheimer’s disease and mild cognitive impairment. We develop an analysis of longitudinal resting-state functional magnetic resonance imaging (rs-fMRI) and genetic data obtained from a sample of 111 subjects with a total of 319 rs-fMRI scans from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. A Dynamic Causal Model (DCM) is fit to the rs-fMRI scans to estimate effective brain connectivity within the DMN and related to a set of single nucleotide polymorphisms (SNPs) contained in an empirical disease-constrained set which is obtained out-of-sample from 663 ADNI subjects having only genome-wide data. We relate longitudinal effective brain connectivity estimated using spectral DCM to SNPs using both linear mixed effect (LME) models as well as function-on-scalar regression (FSR). In both cases we implement a parametric bootstrap for testing SNP coefficients and make comparisons with p-values obtained from asymptotic null distributions. In both networks at an initial q-value threshold of 0.1 no effects are found. We report on exploratory patterns of associations with relatively high ranks that exhibit stability to the differing assumptions made by both FSR and LME.

scholarly journals Functional connectivity of the nucleus basalis of Meynert in Lewy body dementia and Alzheimer’s disease

2021 ◽  
pp. 1-6
Author(s):  
Julia Schumacher ◽  
Alan J. Thomas ◽  
Luis R. Peraza ◽  
Michael Firbank ◽  
John T. O’Brien ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Functional Connectivity ◽  
Lewy Body ◽  
Cholinergic System ◽  
Structural Changes ◽  
Lewy Body Dementia ◽  
Occipital Cortex ◽  
Nucleus Basalis ◽  
Nucleus Basalis Of Meynert

ABSTRACT Cholinergic deficits are a hallmark of Alzheimer’s disease (AD) and Lewy body dementia (LBD). The nucleus basalis of Meynert (NBM) provides the major source of cortical cholinergic input; studying its functional connectivity might, therefore, provide a tool for probing the cholinergic system and its degeneration in neurodegenerative diseases. Forty-six LBD patients, 29 AD patients, and 31 healthy age-matched controls underwent resting-state functional magnetic resonance imaging (fMRI). A seed-based analysis was applied with seeds in the left and right NBM to assess functional connectivity between the NBM and the rest of the brain. We found a shift from anticorrelation in controls to positive correlations in LBD between the right/left NBM and clusters in right/left occipital cortex. Our results indicate that there is an imbalance in functional connectivity between the NBM and primary visual areas in LBD, which provides new insights into alterations within a part of the corticopetal cholinergic system that go beyond structural changes.

scholarly journals Bayesian model reveals latent atrophy factors with dissociable cognitive trajectories in Alzheimer’s disease

2016 ◽  
Vol 113 (42) ◽  
pp. E6535-E6544 ◽  
Author(s):  
Xiuming Zhang ◽  
Elizabeth C. Mormino ◽  
Nanbo Sun ◽  
Reisa A. Sperling ◽  
Mert R. Sabuncu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Executive Function ◽  
Bayesian Model ◽  
Late Onset ◽  
Temporal Cortex ◽  
Cortical Atrophy ◽  
Future Research ◽  
Dementia Patients ◽  
With Memory

We used a data-driven Bayesian model to automatically identify distinct latent factors of overlapping atrophy patterns from voxelwise structural MRIs of late-onset Alzheimer’s disease (AD) dementia patients. Our approach estimated the extent to which multiple distinct atrophy patterns were expressed within each participant rather than assuming that each participant expressed a single atrophy factor. The model revealed a temporal atrophy factor (medial temporal cortex, hippocampus, and amygdala), a subcortical atrophy factor (striatum, thalamus, and cerebellum), and a cortical atrophy factor (frontal, parietal, lateral temporal, and lateral occipital cortices). To explore the influence of each factor in early AD, atrophy factor compositions were inferred in beta-amyloid–positive (Aβ+) mild cognitively impaired (MCI) and cognitively normal (CN) participants. All three factors were associated with memory decline across the entire clinical spectrum, whereas the cortical factor was associated with executive function decline in Aβ+ MCI participants and AD dementia patients. Direct comparison between factors revealed that the temporal factor showed the strongest association with memory, whereas the cortical factor showed the strongest association with executive function. The subcortical factor was associated with the slowest decline for both memory and executive function compared with temporal and cortical factors. These results suggest that distinct patterns of atrophy influence decline across different cognitive domains. Quantification of this heterogeneity may enable the computation of individual-level predictions relevant for disease monitoring and customized therapies. Factor compositions of participants and code used in this article are publicly available for future research.

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