A novel approach to brain connectivity reveals early structural changes in Alzheimer’s disease

Alzheimer’s disease (AD) is a leading cause of dementia, which causes serious health and socioeconomic problems. A progressive neurodegenerative disorder, Alzheimer’s causes the structural change in the brain, thereby affecting behavior, cognition, emotions, and memory. Numerous multivariate analysis algorithms have been used for classifying AD, distinguishing it from healthy controls (HC). Efficient early classification of AD and mild cognitive impairment (MCI) from HC is imperative as early preventive care could help to mitigate risk factors. Magnetic resonance imaging (MRI), a noninvasive biomarker, displays morphometric differences and cerebral structural changes. A novel approach for distinguishing AD from HC using dual-tree complex wavelet transforms (DTCWT), principal coefficients from the transaxial slices of MRI images, linear discriminant analysis, and twin support vector machine is proposed here. The prediction accuracy of the proposed method yielded up to 92.65 ± 1.18 over the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset, with a specificity of 92.19 ± 1.56 and sensitivity of 93.11 ± 1.29, and 96.68 ± 1.44 over the Open Access Series of Imaging Studies (OASIS) dataset, with a sensitivity of 97.72 ± 2.34 and specificity of 95.61 ± 1.67. The accuracy, sensitivity, and specificity achieved using the proposed method are comparable or superior to those obtained by various conventional AD prediction methods.

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Retinal structural changes in patients with Alzheimer's disease

Oftalmologicheskii Zhurnal ◽

10.31288/oftalmolzh201943337 ◽

2019 ◽

Vol 81 (4) ◽

pp. 33-37

Author(s):

R. Guliyeva ◽

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Structural Changes

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Commonalities between Copper Neurotoxicity and Alzheimer’s Disease

Toxics ◽

10.3390/toxics9010004 ◽

2021 ◽

Vol 9 (1) ◽

pp. 4

Author(s):

Roshni Patel ◽

Michael Aschner

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Structural Changes ◽

Copper Ion ◽

Plaque Formation ◽

Ion Concentration ◽

Medical Community ◽

Disease Etiology ◽

Parent Protein ◽

Lead Zinc

Alzheimer’s disease, a highly prevalent form of dementia, targets neuron function beginning from the hippocampal region and expanding outwards. Alzheimer’s disease is caused by elevated levels of heavy metals, such as lead, zinc, and copper. Copper is found in many areas of daily life, raising a concern as to how this metal and Alzheimer’s disease are related. Previous studies have not identified the common pathways between excess copper and Alzheimer’s disease etiology. Our review corroborates that both copper and Alzheimer’s disease target the hippocampus, cerebral cortex, cerebellum, and brainstem, affecting motor skills and critical thinking. Additionally, Aβ plaque formation was analyzed beginning from synthesis at the APP parent protein site until Aβ plaque formation was completed. Structural changes were also noted. Further analysis revealed a relationship between amyloid-beta plaques and copper ion concentration. As copper ion levels increased, it bound to the Aβ monomer, expediting the plaque formation process, and furthering neurodegeneration. These conclusions can be utilized in the medical community to further research on the etiology of Alzheimer’s disease and its relationships to copper and other metal-induced neurotoxicity.

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

Statistical Applications in Genetics and Molecular Biology ◽

10.1515/sagmb-2019-0058 ◽

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.

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Changes in retinal microvasculature and retinal layer thickness in association with apolipoprotein E genotype in Alzheimer’s disease

Scientific Reports ◽

10.1038/s41598-020-80892-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Joo Youn Shin ◽

Eun Young Choi ◽

Min Kim ◽

Hyung Keun Lee ◽

Suk Ho Byeon

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Layer Thickness ◽

Structural Changes ◽

Foveal Avascular Zone ◽

Retinal Layer ◽

Inner Plexiform Layer ◽

Apoe Ε4 ◽

Retinal Microvasculature ◽

Capillary Plexus

AbstractBiomarker tests of Alzheimer’s disease (AD) are invasive and expensive. Recent developments in optical coherence tomography (OCT) and OCT angiography (OCTA) have enabled noninvasive, cost-effective characterization of retinal layer vasculature and thickness. Using OCTA and OCT, we characterized retinal microvascular changes in the mild cognitive impairment (MCI) stage of AD and assessed their correlation with structural changes in each retinal neuronal layer. We also evaluated the effect of the APOE-ε4 genotype on retinal microvasculature and layer thickness. Retinal layer thickness did not differ between MCI patients (40 eyes) and controls (37 eyes, all p > 0.05). MCI patients had lower vessel density (VD) (p = 0.003) of the superficial capillary plexus (SCP) and larger foveal avascular zone area (p = 0.01) of the deep capillary plexus (DCP) than those of controls. VD of the SCP correlated with the ganglion cell layer (r = 0.358, p = 0.03) and inner plexiform layer thickness (r = 0.437, p = 0.007) in MCI patients. APOE-ε4-carrying MCI patients had a lower VD of the DCP than non-carriers (p = 0.03). In conclusion, retinal microvasculature was reduced in patients with AD-associated MCI, but retinal thickness was not changed; these changes might be affected by the APOE genotype. OCTA of the retinal microvasculature may be useful to detect vascular changes in AD.

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Structural Changes in Thalamic Nuclei Across Prodromal and Clinical Alzheimer’s Disease

Journal of Alzheimer s Disease ◽

10.3233/jad-201583 ◽

2021 ◽

pp. 1-11

Author(s):

Adam S. Bernstein ◽

Steven Z. Rapcsak ◽

Michael Hornberger ◽

Manojkumar Saranathan ◽

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Large Scale ◽

Structural Changes ◽

Thalamic Nuclei ◽

Medial Temporal Lobes ◽

Cognitive Changes ◽

Temporal Lobes ◽

Medial Geniculate ◽

Healthy Control

Background: Increasing evidence suggests that thalamic nuclei may atrophy in Alzheimer’s disease (AD). We hypothesized that there will be significant atrophy of limbic thalamic nuclei associated with declining memory and cognition across the AD continuum. Objective: The objective of this work was to characterize volume differences in thalamic nuclei in subjects with early and late mild cognitive impairment (MCI) as well as AD when compared to healthy control (HC) subjects using a novel MRI-based thalamic segmentation technique (THOMAS). Methods: MPRAGE data from the ADNI database were used in this study (n = 540). Healthy control (n = 125), early MCI (n = 212), late MCI (n = 114), and AD subjects (n = 89) were selected, and their MRI data were parcellated to determine the volumes of 11 thalamic nuclei for each subject. Volumes across the different clinical subgroups were compared using ANCOVA. Results: There were significant differences in thalamic nuclei volumes between HC, late MCI, and AD subjects. The anteroventral, mediodorsal, pulvinar, medial geniculate, and centromedian nuclei were significantly smaller in subjects with late MCI and AD when compared to HC subjects. Furthermore, the mediodorsal, pulvinar, and medial geniculate nuclei were significantly smaller in early MCI when compared to HC subjects. Conclusion: This work highlights nucleus specific atrophy within the thalamus in subjects with early and late MCI and AD. This is consistent with the hypothesis that memory and cognitive changes in AD are mediated by damage to a large-scale integrated neural network that extends beyond the medial temporal lobes.

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

International Psychogeriatrics ◽

10.1017/s1041610220003944 ◽

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.

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