scholarly journals Cognitive Domain Decline in Healthy Apolipoprotein E ε4 Homozygotes Before the Diagnosis of Mild Cognitive Impairment

2007 ◽  
Vol 64 (9) ◽  
pp. 1306 ◽  
Author(s):  
Richard J. Caselli ◽  
Eric M. Reiman ◽  
Dona E. C. Locke ◽  
Michael L. Hutton ◽  
Joseph G. Hentz ◽  
...  
2021 ◽  
pp. 1-15
Author(s):  
Sung Hoon Kang ◽  
Bo Kyoung Cheon ◽  
Ji-Sun Kim ◽  
Hyemin Jang ◽  
Hee Jin Kim ◽  
...  

Background: Amyloid (Aβ) evaluation in amnestic mild cognitive impairment (aMCI) patients is important for predicting conversion to Alzheimer’s disease. However, Aβ evaluation through amyloid positron emission tomography (PET) is limited due to high cost and safety issues. Objective: We therefore aimed to develop and validate prediction models of Aβ positivity for aMCI using optimal interpretable machine learning (ML) approaches utilizing multimodal markers. Methods: We recruited 529 aMCI patients from multiple centers who underwent Aβ PET. We trained ML algorithms using a training cohort (324 aMCI from Samsung medical center) with two-phase modelling: model 1 included age, gender, education, diabetes, hypertension, apolipoprotein E genotype, and neuropsychological test scores; model 2 included the same variables as model 1 with additional MRI features. We used four-fold cross-validation during the modelling and evaluated the models on an external validation cohort (187 aMCI from the other centers). Results: Model 1 showed good accuracy (area under the receiver operating characteristic curve [AUROC] 0.837) in cross-validation, and fair accuracy (AUROC 0.765) in external validation. Model 2 led to improvement in the prediction performance with good accuracy (AUROC 0.892) in cross validation compared to model 1. Apolipoprotein E genotype, delayed recall task scores, and interaction between cortical thickness in the temporal region and hippocampal volume were the most important predictors of Aβ positivity. Conclusion: Our results suggest that ML models are effective in predicting Aβ positivity at the individual level and could help the biomarker-guided diagnosis of prodromal AD.


2014 ◽  
Vol 15 (4) ◽  
pp. 422-427 ◽  
Author(s):  
Takehiko Doi ◽  
Hiroyuki Shimada ◽  
Hyuma Makizako ◽  
Kota Tsutsumimoto ◽  
Kazuki Uemura ◽  
...  

2021 ◽  
Vol 84 (6) ◽  
pp. 472-480
Author(s):  
Yulin Luo ◽  
Li Tan ◽  
Joseph Therriault ◽  
Hua Zhang ◽  
Ying Gao ◽  
...  

<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.


2019 ◽  
Vol 32 (6) ◽  
pp. 344-353 ◽  
Author(s):  
Zhiyu Sun ◽  
Zhijiang Wang ◽  
Lujie Xu ◽  
Xiaozhen Lv ◽  
Quanzheng Li ◽  
...  

It is widely recognized that depression may precipitate the incidence of dementia in the elderly individuals and individuals with amnestic mild cognitive impairment (aMCI) in particular. However, the association between subthreshold depression (SD) and cognitive deficits in patients with aMCI remains unclear. To address this, we collected demographic information and conducted a battery of neuropsychological cognitive assessments in 33 aMCI participants with SD (aMCI/SD+), 33 nondepressed aMCI participants (aMCI/SD−), and 53 normal controls (NC). Both aMCI groups showed significantly poorer performance in most cognitive domains relative to the NC group (ie, memory, language, processing speed, and executive function). Notably, the aMCI/SD+ group showed significantly poorer attention/working memory compared with the aMCI/SD− group. Multiple linear regression analyses revealed a significant negative association between the severity of depressive symptoms and attention/working memory capacity (β = − .024, P = .024), accounting for 8.28% of the variations in this cognitive domain. All statistical analyses were adjusted by age, sex, and years of education. A logistic regression model had an accuracy of 72.4% in discriminating between the aMCI/SD+ and aMCI/SD− groups based on individual cognitive profiles over 6 domains. Our findings indicate that patients with aMCI with and without SD have distinct patterns of cognitive impairment. This finding may facilitate the diagnosis and treatment of SD in patients with aMCI.


2009 ◽  
Vol 15 (2) ◽  
pp. 231-238 ◽  
Author(s):  
HYEON-AE JEON ◽  
KYOUNG-MIN LEE

AbstractWhile it is well known that picture naming (PN) is impaired in Alzheimer’s disease (AD), sound naming (SN) has not been thoroughly investigated. We postulated that SN might be impaired more severely and earlier than PN, given the early involvement of the temporal cortex by AD-related pathology. SN and PN were assessed in 21 normal participants, 40 patients with mild cognitive impairment (MCI), and 27 patients in early stages of AD. Our results showed that SN accuracy and latency were more sensitive to advancing pathology in AD than PN accuracy and latency. SN was more useful and specific in distinguishing MCI patients from normal participants and therefore in potentially identifying the subset of MCI patients who already have impairment in more than one cognitive domain and may actually have incipient AD. These findings indicate a potential diagnostic utility of SN for early detection of the disease. Furthermore, even though most AD patients demonstrated more or less comparable impairment in both tasks, some were disproportionately impaired on SN and others were differentially impaired on PN. Future studies may be able to show that these discrepant groups correspond to patients with right and left hemisphere predominant AD, respectively. (JINS, 2009, 15, 231–238.)


2019 ◽  
Vol 20 (6) ◽  
pp. 1394 ◽  
Author(s):  
Oscar Mancera-Páez ◽  
Kelly Estrada-Orozco ◽  
María Mahecha ◽  
Francy Cruz ◽  
Kely Bonilla-Vargas ◽  
...  

Background: Biomarkers are essential for identification of individuals at high risk of mild cognitive impairment (MCI) for potential prevention of dementia. We investigated DNA methylation in the APOE gene and apolipoprotein E (ApoE) plasma levels as MCI biomarkers in Colombian subjects with MCI and controls. Methods: In total, 100 participants were included (71% women; average age, 70 years; range, 43–91 years). MCI was diagnosed by neuropsychological testing, medical and social history, activities of daily living, cognitive symptoms and neuroimaging. Using multivariate logistic regression models adjusted by age and gender, we examined the risk association of MCI with plasma ApoE and APOE methylation. Results: MCI was diagnosed in 41 subjects (average age, 66.5 ± 9.6 years) and compared with 59 controls. Elevated plasma ApoE and APOE methylation of CpGs 165, 190, and 198 were risk factors for MCI (p < 0.05). Higher CpG-227 methylation correlated with lower risk for MCI (p = 0.002). Only CpG-227 was significantly correlated with plasma ApoE levels (correlation coefficient = −0.665; p = 0.008). Conclusion: Differential APOE methylation and increased plasma ApoE levels were correlated with MCI. These epigenetic patterns require confirmation in larger samples but could potentially be used as biomarkers to identify early stages of MCI.


2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S946-S946
Author(s):  
George Mois ◽  
Bailley Collette ◽  
Lisa M Renzi-Hammond ◽  
Laura Boccanfuso ◽  
Aditi Ramachandran ◽  
...  

Abstract Cognitive training has been shown to improve neural plasticity, increase cognitive reserve and reduce the risk of dementia in older adults. Specifically, learning to play the piano has been shown to be an engaging, multimodal form of cognitive training. However, accessing this form of cognitive training can pose a challenge for older adults. Socially assistive robots present a unique opportunity to increase access to user-tailored piano learning cognitive training. The present study utilized a robot-led four-week piano lesson feasibility intervention for older adults with mild cognitive impairment (N = 11; M= 74.64 ± 6.02 years of age; 72.72% female; 90.1% White/Caucasian). Cognitive Status was assessed during screening via the Telephone Interview for Cognitive Status, and after screening via the Mini-Mental State Exam and the CNS Vital Signs computerized test suite to measure cognitive domain-specific functioning. Perceptions and acceptance of the robot were measured using the Robotic Social Attributes Scale (RoSAS) and Technology Acceptance Scale. Cognitive function improved after four weeks of training in the verbal memory, executive function, reaction time and cognitive flexibility domains, and in the computed neurocognitive index score (p&lt;0.05). Survey data and qualitative interviews show that participants perceived the robot instructor as socially engaging, competent, useful, and easy to use. These results provide insight into the potential of SARs to facilitate cognitive training in the form of piano lessons, as well as recommendations for creating a suitable robot instructor for this application.


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