scholarly journals The Effect of the APOE-ε4 Allele on the Cholinergic Circuitry for Subjects With Different Levels of Cognitive Impairment

2021 ◽  
Vol 12 ◽  
Author(s):  
Ying-Liang Larry Lai ◽  
Kuan Chen ◽  
Tzu-Wei Lee ◽  
Chao-Wei Tso ◽  
Hui-Hsien Lin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Cognitive Impairment ◽  
Cognitive Performance ◽  
Structural Changes ◽  
Group Differences ◽  
Disease Group ◽  
Structural Correlation ◽  
Cholinergic Pathway ◽  
Ε4 Allele ◽  
Different Levels

Background: Cholinergic deficiency has been suggested to associate with the abnormal accumulation of Aβ and tau for patients with Alzheimer's disease (AD). However, no studies have investigated the effect of APOE-ε4 and group differences in modulating the cholinergic basal forebrain–amygdala network for subjects with different levels of cognitive impairment. We evaluated the effect of APOE-ε4 on the cholinergic structural association and the neurocognitive performance for subjects with different levels of cognitive impairment.Methods: We used the structural brain magnetic resonance imaging scans from the Alzheimer's Disease Neuroimaging Initiative dataset. The study included cognitively normal (CN, n = 167) subjects and subjects with significant memory concern (SMC, n = 96), early mild cognitive impairment (EMCI, n = 146), late cognitive impairment (LMCI, n = 138), and AD (n = 121). Subjects were further categorized according to the APOE-ε4 allele carrier status. The main effects of APOE-ε4 and group difference on the brain volumetric measurements were assessed. Regression analyses were conducted to evaluate the associations among cholinergic structural changes, APOE-ε4 status, and cognitive performance.Results: We found that APOE-ε4 carriers in the disease group showed higher brain atrophy than non-carriers in the cholinergic pathway, while there is no difference between carriers and non-carriers in the CN group. APOE-ε4 allele carriers in the disease groups also exhibited a stronger cholinergic structural correlation than non-carriers did, while there is no difference between the carriers and non-carriers in the CN subjects. Disease subjects exhibited a stronger structural correlation in the cholinergic pathway than CN subjects did. Moreover, APOE-ε4 allele carriers in the disease group exhibited a stronger correlation between the volumetric changes and cognitive performance than non-carriers did, while there is no difference between carriers and non-carriers in CN subjects. Disease subjects exhibited a stronger correlation between the volumetric changes and cognitive performance than CN subjects did.Conclusion: Our results confirmed the effect of APOE-ε4 on and group differences in the associations with the cholinergic structural changes that may reflect impaired brain function underlying neurocognitive degeneration in AD.

The Role of Apolipoprotein E ε4 in Early and Late Mild Cognitive Impairment

2021 ◽  
Vol 84 (6) ◽  
pp. 472-480
Author(s):  
Yulin Luo ◽  
Li Tan ◽  
Joseph Therriault ◽  
Hua Zhang ◽  
Ying Gao ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Apolipoprotein E ◽  
Amyloid Β ◽  
Disease Assessment ◽  
Tau Pathology ◽  
Ε4 Allele ◽  
State Examination

<b><i>Background:</i></b> Apolipoprotein E (<i>APOE</i>) ε4 is highly associated with mild cognitive impairment (MCI). However, the specific influence of <i>APOE</i> ε4 status on tau pathology and cognitive decline in early MCI (EMCI) and late MCI (LMCI) is poorly understood. Our goal was to evaluate the association of <i>APOE</i> ε4 with cerebrospinal fluid (CSF) tau levels and cognition in EMCI and LMCI patients in the Alzheimer’s Disease Neuroimaging Initiative database, and whether this association was mediated by amyloid-β (Aβ). <b><i>Methods:</i></b> Participants were 269 cognitively normal (CN), 262 EMCI, and 344 LMCI patients. They underwent CSF Aβ42 and tau detection, <i>APOE</i> ε4 genotyping, Mini-Mental State Examination, (MMSE), and Alzheimer’s disease assessment scale (ADAS)-cog assessments. Linear regressions were used to examine the relation of <i>APOE</i> ε4 and CSF tau levels and cognitive scores in persons with and without Aβ deposition (Aβ+ and Aβ−). <b><i>Results:</i></b> The prevalence of <i>APOE</i> ε4 is higher in EMCI and LMCI than in CN (<i>p</i> &#x3c; 0.001 for both), and in LMCI than in EMCI (<i>p</i> = 0.001). <i>APOE</i> ε4 allele was significantly higher in Aβ+ subjects than in Aβ− subjects (<i>p</i> &#x3c; 0.001). Subjects who had a lower CSF Aβ42 level and were <i>APOE</i> ε4-positive experienced higher levels of CSF tau and cognitive scores in EMCI and/or LMCI. <b><i>Conclusions:</i></b> An <i>APOE</i> ε4 allele is associated with increased CSF tau and worse cognition in both EMCI and LMCI, and this association may be mediated by Aβ. We conclude that <i>APOE</i> ε4 may be an important mediator of tau pathology and cognition in the early stages of AD.

Neural Correlates of Cognitive Performance in Alzheimer’s Disease- and Lewy Bodies-Related Cognitive Impairment

2020 ◽  
Vol 73 (3) ◽  
pp. 873-885
Author(s):  
Seok Jong Chung ◽  
Seun Jeon ◽  
Han Soo Yoo ◽  
Yang Hyun Lee ◽  
Mijin Yun ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Cognitive Performance ◽  
Lewy Bodies ◽  
Neural Correlates

[P1-136]: BRAIN INTEGRITY ASSOCIATED WITH COGNITIVE PERFORMANCE BUT NOT POLYMORPHISMS IN GENES RELATED TO COGNITIVE IMPAIRMENT AND ALZHEIMER's DISEASE IN A HEALTHY, MIDDLE-AGED SAMPLE

2017 ◽  
Vol 13 (7S_Part_6) ◽  
pp. P294-P294
Author(s):  
Laura E. Korthauer ◽  
Jenna Blujus ◽  
Marijam Frahmand ◽  
Hannah Scherkenbach ◽  
Elizabeth Awe ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Cognitive Performance ◽  
Aged Sample ◽  
Middle Aged

scholarly journals Eigenvector alignment: assessing functional network changes in amnestic mild cognitive impairment and Alzheimer’s disease

2020 ◽  
Author(s):  
Ruaridh Clark ◽  
Niia Nikolova ◽  
William J. McGeown ◽  
Malcolm Macdonald
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Functional Connectivity ◽  
Structural Changes ◽  
Amnestic Mild Cognitive Impairment ◽  
Functional Networks ◽  
Limited Information ◽  
The Impact

AbstractEigenvector alignment, introduced herein to investigate human brain functional networks, is adapted from methods developed to detect influential nodes and communities in networked systems. It is used to identify differences in the brain networks of subjects with Alzheimer’s disease (AD), amnestic Mild Cognitive Impairment (aMCI) and healthy controls (HC). Well-established methods exist for analysing connectivity networks composed of brain regions, including the widespread use of centrality metrics such as eigenvector centrality. However, these metrics provide only limited information on the relationship between regions, with this understanding often sought by comparing the strength of pairwise functional connectivity. Our holistic approach, eigenvector alignment, considers the impact of all functional connectivity changes before assessing the strength of the functional relationship, i.e. alignment, between any two regions. This is achieved by comparing the placement of regions in a Euclidean space defined by the network’s dominant eigenvectors. Eigenvector alignment recognises the strength of bilateral connectivity in cortical areas of healthy control subjects, but also reveals degradation of this commissural system in those with AD. Surprisingly little structural change is detected for key regions in the Default Mode Network, despite significant declines in the functional connectivity of these regions. In contrast, regions in the auditory cortex display significant alignment changes that begin in aMCI and are the most prominent structural changes for those with AD. Alignment differences between aMCI and AD subjects are detected, including notable changes to the hippocampal regions. These findings suggest eigenvector alignment can play a complementary role, alongside established network analytic approaches, to capture how the brain’s functional networks develop and adapt when challenged by disease processes such as AD.

scholarly journals Changes in Cerebral Volume and White Matter Integrity in Adults on Hemodialysis and Relationship to Cognitive Function

Nephron ◽  
2020 ◽  
Vol 145 (1) ◽  
pp. 35-43
Author(s):  
Wesley T. Richerson ◽  
Laura G. Umfleet ◽  
Brian D. Schmit ◽  
Dawn F. Wolfgram
Keyword(s):  
Cognitive Impairment ◽  
White Matter ◽  
Cognitive Performance ◽  
Gray Matter ◽  
Structural Changes ◽  
Structural Integrity ◽  
Diffusion Tensor ◽  
White Matter Integrity ◽  
Healthy Controls ◽  
Matter Volume

<b><i>Introduction:</i></b> Patients on hemodialysis (HD) have a significant burden of cognitive impairment. Characterizing the cerebral structural changes in HD patients compared to healthy controls and evaluating the relationship of cerebral structural integrity with cognitive performance in HD patients can help clarify the pathophysiology of the cognitive impairment in HD patients. <b><i>Methods:</i></b> In this cross-sectional study, in-center HD patients ≥50 years of age underwent brain structural and diffusion MRIs and cognitive assessment using the NIH Toolbox cognition battery. The cerebral imaging measures of the HD participants were compared to imaging from age-matched controls. Gray matter volume, white matter volume, and white matter integrity determined by diffusion tensor imaging parameters (including fractional anisotropy [FA]) were measured in both cohorts to determine differences in the cerebral structure between HD participants and healthy controls. The association between cognitive performance on the NIH Toolbox cognition battery and cerebral structural integrity was evaluated using multiple linear regression models. <b><i>Results:</i></b> We compared imaging measures form 23 HD participants and 15 age-matched controls. The HD participants had decreased gray matter volumes (526.8 vs. 589.5 cm<sup>3</sup>, <i>p</i> &#x3c; 0.01) and worsened white matter integrity overall (FA values of 0.2864 vs. 0.3441, <i>p</i> &#x3c; 0.01) within major white matter tracts compared to healthy controls. Decreases in white matter integrity in the left superior longitudinal fasciculus was associated with lower executive function scores (<i>r</i><sup><i>2</i></sup> = 0.24, <i>p</i> = 0.02) and inferior longitudinal fasciculus with lower memory scores (<i>r</i> = 0.25 and <i>p</i> = 0.03 for left and <i>r</i><sup>2</sup> = 0.21 and <i>p</i> = 0.03 for right). <b><i>Conclusions:</i></b> HD patients have a pattern of decreased white matter integrity and gray matter atrophy compared to controls. Decreases in white matter integrity were associated with decreased cognitive performance in the HD population.

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