Risk Factors Predicting Amyloid PET Positivity in Patients with Mild Cognitive Impairment and Apolipoprotein E ɛ3/ɛ3 Genotypes

2020 ◽  
Vol 77 (3) ◽  
pp. 1017-1024
Author(s):  
Seong Hee Ho ◽  
Dong-Won Yang
Keyword(s):  
Risk Factors ◽  
Logistic Regression ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Apolipoprotein E ◽  
Brain Mri ◽  
Multivariate Logistic Regression Model ◽  
Amyloid Pet ◽  
Logistic Regression Models ◽  
E4 Allele

Background: The apolipoprotein E (APOE) ɛ4 allele is a well-known risk factor for AD and is associated with higher amyloid deposition and earlier dementia onset. However, the relationship between amyloid pathology and the most common APOE allele, ɛ3, has not been well studied. Objective: In this study, we aimed to identify the risk factors predicting amyloid PET positivity in patients with mild cognitive impairment (MCI) and APOE ɛ3/ɛ3 genotypes. Methods: We retrospectively reviewed the medical records of MCI patients with APOE ɛ3/ɛ3 genotypes who underwent amyloid PET scanning. Demographics, neuropsychological tests, and brain MRI were obtained. We analyzed which risk factors could affect amyloid PET positivity in MCI patients with APOE ɛ3/ɛ3 genotypes using logistic regression models. Results: We recruited 171 MCI patients with APOE ɛ3/ɛ3 genotypes in this study. Out of 171 patients, 49 patients (28.65%) showed positive results in the amyloid PET scans. In a multivariate logistic regression model, amyloid positivity was associated with frontal atrophy (OR = 2.63, p = 0.009), and CDR-SOB scores (OR = 2.46, p = 0.013). The odds ratio for amyloid PET positivity in patients older than and equal to 75 years with both frontal atrophy and CDR-SOB scores >1.0 was 3.63. Conclusion: Our study demonstrated that frontal atrophy, high CDR-SOB scores, and old age were risk factors associated with amyloid PET positivity in MCI with APOE ɛ3/ɛ3 genotypes.

Elucidating the risk factors for progression from amyloid-negative amnestic mild cognitive impairment to dementia

2020 ◽  
Vol 17 ◽  
Author(s):  
Hyung-Ji Kim ◽  
Jae-Hong Lee ◽  
E-nae Cheong ◽  
Sung-Eun Chung ◽  
Sungyang Jo ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Amnestic Mild Cognitive Impairment ◽  
Amyloid Pet ◽  
Clinical Progression ◽  
Amnestic Mci

Background: Amyloid PET allows for the assessment of amyloid β status in the brain, distinguishing true Alzheimer’s disease from Alzheimer’s disease-mimicking conditions. Around 15–20% of patients with clinically probable Alzheimer’s disease have been found to have no significant Alzheimer’s pathology on amyloid PET. However, a limited number of studies had been conducted this subpopulation in terms of clinical progression. Objective: We investigated the risk factors that could affect the progression to dementia in patients with amyloid-negative amnestic mild cognitive impairment (MCI). Methods: This study was a single-institutional, retrospective cohort study of patients over the age of 50 with amyloidnegative amnestic MCI who visited the memory clinic of Asan Medical Center with a follow-up period of more than 36 months. All participants underwent brain magnetic resonance imaging (MRI), detailed neuropsychological testing, and fluorine-18[F18]-florbetaben amyloid PET. Results: During the follow-up period, 39 of 107 patients progressed to dementia from amnestic MCI. In comparison with the stationary group, the progressed group had a more severe impairment in verbal and visual episodic memory function and hippocampal atrophy, which showed an Alzheimer’s disease-like pattern despite the lack of evidence for significant Alzheimer’s disease pathology. Voxel-based morphometric MRI analysis revealed that the progressed group had a reduced gray matter volume in the bilateral cerebellar cortices, right temporal cortex, and bilateral insular cortices. Conclusion: Considering the lack of evidence of amyloid pathology, clinical progression of these subpopulation may be caused by other neuropathologies such as TDP-43, abnormal tau or alpha synuclein that lead to neurodegeneration independent of amyloid-driven pathway. Further prospective studies incorporating biomarkers of Alzheimer’s diseasemimicking dementia are warranted.

scholarly journals Differential Methylation in APOE (Chr19; Exon Four; from 44,909,188 to 44,909,373/hg38) and Increased Apolipoprotein E Plasma Levels in Subjects with Mild Cognitive Impairment

2019 ◽  
Vol 20 (6) ◽  
pp. 1394 ◽  
Author(s):  
Oscar Mancera-Páez ◽  
Kelly Estrada-Orozco ◽  
María Mahecha ◽  
Francy Cruz ◽  
Kely Bonilla-Vargas ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Apolipoprotein E ◽  
Social History ◽  
Plasma Levels ◽  
Neuropsychological Testing ◽  
Logistic Regression Models ◽  
And Gender ◽  
Epigenetic Patterns ◽  
Risk Association

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.

scholarly journals Differential Methylation in APOE Genes (Chr19; exon four; from 44,909,188 to 44,909,373) and Increased Apolipoprotein E Plasmatic Levels in Subjects with Mild Cognitive Impairment”

2019 ◽  
Author(s):  
Oscar Mancera Páez ◽  
Kelly Estrada Orozco ◽  
Maria Fernanda Mahecha ◽  
Francy Cruz Sanabria ◽  
Kely Bonilla-Vargas ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Apolipoprotein E ◽  
Social History ◽  
Regression Models ◽  
Neuropsychological Testing ◽  
Logistic Regression Models ◽  
And Gender ◽  
Epigenetic Patterns ◽  
Risk Association

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 plasmatic apolipoprotein E (ApoE) levels as MCI biomarkers in Colombian subjects with MCI and controls. Methods: 100 participants were included (71% women, average age, 70 yrs., range 43-91). MCI was diagnosed by neuropsychological testing, medical and social history, activities of daily living, cognitive symptoms and neuroimaging. Multivariate logistic regression models adjusted by age and gender were performed to examine the risk association of MCI with plasma ApoE and APOE methylation Results: MCI was diagnosed in 41 subjects (average age, 66.5±9.6 yrs.) and compared with 59 controls. Elevated plasma ApoE and APOE methylation of CpGs 165, 190, and 198 were risk factors for MCI (P&lt;0.05). Higher CpG-227 methylation correlated with lower risk for MCI (P=0.002). Only CpG-227 was significantly correlated with plasmatic 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 can be used as potential biomarkers to identify early stages of MCI.

scholarly journals Subjective Cognitive Complaints in Newly-Diagnosed Parkinson’s Disease With and Without Mild Cognitive Impairment

2021 ◽  
Vol 15 ◽  
Author(s):  
Chenxi Pan ◽  
Jingru Ren ◽  
Ping Hua ◽  
Lei Yan ◽  
Miao Yu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Logistic Regression ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Status ◽  
Newly Diagnosed ◽  
Cognitive Complaints ◽  
Subjective Cognitive Complaints

Background: Subjective cognitive complaints (SCCs) and mild cognitive impairment (MCI) are common among patients with Parkinson’s disease (PD). However, the relationship between SCCs and MCI is not well understood. Herein, we aimed to investigate whether there are any differences in the prevalence and risk factors of SCCs between early PD patients with and without MCI.Methods: Overall, 108 newly diagnosed, untreated PD patients underwent comprehensive neuropsychological assessments. PD patients with mild cognitive impairment (PD-MCI) were diagnosed according to the MCI level II criteria. Furthermore, SCCs were measured with the Cognitive Complaints Interview (CCI). Logistic regression analysis, after adjusting for confounding variable, was performed in order to investigate risk factors of SCCs in PD-MCI patients and PD patients with normal cognition (PD-NC).Results: Furthermore, 42 (42.3%) participants reported SCCs and 53 (53.5%) participants were diagnosed with PD-MCI. The prevalence of SCCs in PD-MCI and PD-NC participants was 30.3% and 12.1%, respectively. Logistic regression analyses revealed that the presence of SCCs in PD-MCI group was significantly associated with Non-Motor Symptoms Questionnaire (NMSQ) score (OR = 1.340, 95%CI = 1.115−1.610, p = 0.002), while the presence of SCCs in PD-NC group was significantly associated with time of Stroop Color-Word Test card C (OR = 1.050, 95%CI = 1.009−1.119, p = 0.016).Conclusion: SCCs are frequent among patients with early PD. The prevalence and risk factor of SCCs are distinct in PD with and without MCI. These findings suggest that SCCs in early PD with different cognitive status appear to have different pathogenicity.

scholarly journals False Memory and Alzheimer’s Disease Pathology in Patients with Amnestic Mild Cognitive Impairment: A Study with Amyloid PET

2021 ◽  
pp. 172-180
Author(s):  
Eun-Ji Choi ◽  
Bum Joon Kim ◽  
Hyung-Ji Kim ◽  
Miseon Kwon ◽  
Noh Eul Han ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Logistic Regression ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
False Memory ◽  
Visual Recognition ◽  
Characteristic Curve ◽  
Amnestic Mild Cognitive Impairment ◽  
Amyloid Pet

<b><i>Introduction:</i></b> False memory, observed as intrusion errors or false positives (FPs), is prevalent in patients with Alzheimer’s disease, but has yet to be thoroughly investigated in patients with amnestic mild cognitive impairment (a-MCI) with Alzheimer’s disease pathology (ADP). We analyzed false versus veridical memory in individuals with a-MCI and measured the utility of false memory for ADP discrimination. <b><i>Methods:</i></b> Patients with a-MCI who received neuropsychological testing and amyloid PET were included. Patients were categorized into “with” and “without ADP” groups according to PET results. Memory tests assessed veridical and false memory, and the verity of patient responses was analyzed. A logistic regression model was used to evaluate false memory efficiency in discriminating ADP, and the sensitivity and specificity at the optimal level were estimated using the receiver-operating characteristic curve. <b><i>Results:</i></b> Thirty-seven ADP and 46 non-ADP patients were enrolled. The ADP group made more FPs in the recognition tests, and their response verity was significantly lower in every delayed memory test. No group difference, however, was observed in the veridical memory. The logistic regression analysis demonstrated that as the FPs increased, the risk of ADP increased 1.31 and 1.36 times in the verbal and visual recognition tests, respectively. The discriminatory accuracy of the FPs was estimated “low” to “moderate” in the visual and verbal recognition, respectively, with an optimal cutoff above 2.5. <b><i>Conclusion:</i></b> Increased false memory was the only feature to discriminate ADP from non-ADP in individuals with a-MCI. Further studies regarding false memory and its mechanism are warranted.

scholarly journals Vascular mild cognitive impairment and its relationship to hemoglobin A1c levels and apolipoprotein E genotypes in the Dominican Republic

2021 ◽  
Vol 15 (1) ◽  
pp. 69-78
Author(s):  
Martin Medrano ◽  
Gelanys Castro-Tejada ◽  
Rafael Lantigua ◽  
Gretel Silvestre ◽  
Sergio Diaz ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Dominican Republic ◽  
Apolipoprotein E ◽  
Cardiometabolic Risk ◽  
Hemoglobin A1c ◽  
Apoe Genotype ◽  
Cardiometabolic Risk Factors ◽  
Apolipoprotein E Genotypes

ABSTRACT. Dementia and vascular mild cognitive impairment (VaMCI) currently impose a tremendous human and economic burden on patients from aging populations and their families worldwide. Understanding the interplay of cardiometabolic risk factors and apolipoprotein E (APOE) may direct us to a more personalized medicine and preventative care in MCI and dementia. Objective: To evaluate the relationship of cardiometabolic risk factors with MCI and assess the APOE genotype’s role in an elderly cohort in the Dominican Republic. Methods: We studied a cohort of 180 participants 65 years of age and older using a combined assessment of cardiometabolic risk factors, neuropsychological battery tests, and APOE genotyping. We used the number of failed tests as a proxy to predict MCI. Results: We found that patients with the ε3-ε4 APOE genotype had 2.91 higher number of failed cognitive tests (p=0.027) compared to patients with the ε3-ε3 genotyped. The rate of test failures increased 10% (p=0.025) per unit increase in HbA1c percentage. Conclusions: Increased Hemoglobin A1c levels and ε3-ε4 APOE genotypes seem to have an association with the development of VaMCI.

scholarly journals BIOFACE: A Prospective Study of Risk Factors, Cognition, and Biomarkers in a Cohort of Individuals with Early-Onset Mild Cognitive Impairment. Study Rationale and Research Protocols

2021 ◽  
pp. 1-17
Author(s):  
Ester Esteban de Antonio ◽  
Alba Pérez-Cordón ◽  
Silvia Gil ◽  
Adelina Orellana ◽  
Amanda Cano ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Early Onset ◽  
Brain Mri ◽  
Point Of View ◽  
Non Invasive ◽  
History Of ◽  
Multimodal Biomarkers ◽  
A Prospective Study

Background: Mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) diagnosis is based on cerebrospinal fluid (CSF) or neuroimaging biomarkers. Currently, non-invasive and inexpensive blood-based biomarkers are being investigated, such as neuronal-derived plasma exosomes (NPEs). Neuroinflammation and early vascular changes have been described in AD pathogenesis and can be traced in plasma and NPEs. However, they have not been studied in early onset MCI (EOMCI). Objective: To describe the rationale, design, and baseline characteristics of the participants from the BIOFACE cohort, a two-year observational study on EOMCI conducted at Fundació ACE. The study goal is to characterize the different phenotypes from a clinical, neuropsychological, and biomarker point of view and to investigate the CSF and plasma proteomics as well as the role of NPEs as early biomarkers of AD. Methods: Participants underwent extended neurological and neuropsychological batteries, multimodal biomarkers including brain MRI, blood, saliva, CSF, anthropometric, and neuro-ophthalmological examinations. Results: Ninety-seven patients with EOMCI were recruited. 59.8%were women. Mean age at symptom onset was 57 years; mean MMSE was 28. First degree and presenile family history of dementia was present in 60.8%and 15.5%, respectively. Depressive and anxiety disorders along with vascular risk factors were the most frequent comorbidities. 29%of participants were APOE ɛ4 carriers, and 67%showed a CSF normal ATN profile. Conclusion: BIOFACE is a two-year study of clinical, cognition, and biomarkers that will shed light on the physiopathology and the potential utility of plasma and NPEs as non-invasive early diagnostic and prognostic biomarkers in people younger than 65 years.

scholarly journals Atrophy-centered subtyping of mild cognitive impairment

2020 ◽  
Author(s):  
Kichang Kwak ◽  
Kelly S. Giovanello ◽  
Martin Styner ◽  
Eran Dayan ◽  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Aging ◽  
Rating Scales ◽  
Gray Matter Volume ◽  
Brain Mri ◽  
Disease Free Survival ◽  
Amyloid Pet ◽  
Whole Brain ◽  
Mri Features

AbstractMild cognitive impairment (MCI) is considered as the transitional phase between normal cognitive aging and Alzheimer’s disease (AD). Nevertheless, trajectories of cognitive decline vary considerably among individuals with MCI. To address this heterogeneity, subtyping approaches have been developed, with the objective of identifying more homogenous subgroups and ultimately improving prognostic outcomes. To date, subtyping of MCI has been based primarily on cognitive performance measures, often resulting in indistinct boundaries between the proposed subgroups and limited validity. The degree to which markers of neurodegeneration such as brain atrophy can be used to subtype MCI into biologically and clinically meaningful subgroups remains unclear. Here we introduce and validate a data-driven subtyping method for MCI based solely upon measures of atrophy derived from structural magnetic resonance imaging (MRI). We trained a dense convolutional neural network to differentiate between patients with AD and age-matched cognitively normal (CN) subjects based on whole brain MRI features. We then deployed the trained model to classify individuals with MCI, as MCI-CN or MCI-AD, based on the degree to which their whole brain gray matter volume resembles CN-like or AD-like patterns. We subsequently validated the model-based subgroups using cognitive, clinical, fluid biomarker, and molecular neuroimaging data. Namely, we observed marked differences between the MCI-CN and MCI-AD groups in baseline and longitudinal cognitive and clinical rating scales, disease-free survival, cerebrospinal fluid (CSF) levels of amyloid beta and tau, fluorodeoxyglucose (FDG) and amyloid PET. Overall, the results suggest that patterns of atrophy in MCI are sufficiently distinct and heterogeneous, and can thus be used to subtype individuals into biologically and clinically meaningful subgroups.

scholarly journals Inequality in Social Support Associated With Mild Cognitive Impairment: A Cross-Sectional Study of Older (≥60 Years) Residents in Shanghai, China

2021 ◽  
Vol 9 ◽  
Author(s):  
Yuan Lu ◽  
Chaojie Liu ◽  
Sally Fawkes ◽  
Jia Ma ◽  
Yalin Liu ◽  
...  
Keyword(s):  
Social Support ◽  
Logistic Regression ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Regression Models ◽  
Income Group ◽  
Interaction Effects ◽  
Personal Income ◽  
Additive Interaction ◽  
Logistic Regression Models

Objective: Social support plays a critical role in the detection and management of mild cognitive impairment (MCI). However, socioeconomic inequalities exist in both social support and health care services. Our study aimed to compare the level of social support received by MCI patients in comparison with those without MCI and to determine its link with income.Methods: Secondary data analyses were performed. Social support was measured using the Duke Social Support Index (DSSI) and satisfaction ratings. Multivariate logistic regression models were constructed to determine the associations of personal income and MCI with social support after adjustment for variations in the sociodemographic and health characteristics of the respondents. The multiplicative and additive interaction effects of income and MCI were further examined through introducing the MCI*Income variable to the regression models and using the relative excess risk due to interaction (RERI) analysis, respectively.Results: The logistic regression models showed that the respondents with MCI had significantly lower social support as measured by the DSSI scores (AOR = 33.03, p &lt; 0.001) and satisfaction ratings (AOR = 7.48, p &lt; 0.001) compared with those without MCI. Similarly, social support decreased with lower personal income (p &lt; 0.001). There existed a significant multiplicative interaction effect between personal income and MCI on social support (AOR = 0.30–0.32, p &lt; 0.01). The gap in social support between those with and without MCI was higher in the higher income group compared with the lower income group (p &lt; 0.001). No significant additive interaction effects on social support were found between MCI and income.Conclusions: There are significant disparities in social support between people living with and without MCI. Such a gap is more profound in people with higher income. The inequality in social support associated with MCI may present a significant challenge to the successful implementation of community MCI detection and management.

Association of Neutrophil-Lymphocyte Ratio with Mild Cognitive Impairment in Elderly Chinese Adults: A Case-control Study

2020 ◽  
Vol 16 (14) ◽  
pp. 1309-1315
Author(s):  
Peilin An ◽  
Xuan Zhou ◽  
Yue Du ◽  
Jiangang Zhao ◽  
Aili Song ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Function ◽  
Predictive Values ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Elderly Chinese ◽  
Normal Cognitive Function ◽  
The Absolute

Background: Inflammation plays a significant role in the pathophysiology of cognitive impairment in previous studies. Neutrophil-lymphocyte ratio (NLR) is a reliable measure of systemic inflammation. Objective: The aim of this study was to investigate the association between NLR and mild cognitive impairment (MCI), and further to explore the diagnostic potential of the inflammatory markers NLR for the diagnosis of MCI in elderly Chinese individuals. Methods: 186 MCI subjects and 153 subjects with normal cognitive function were evaluated consecutively in this study. Neutrophil (NEUT) count and Lymphocyte (LYM) count were measured in fasting blood samples. The NLR was calculated by dividing the absolute NEUT count by the absolute LYM count. Multivariable logistic regression was used to evaluate the potential association between NLR and MCI. NLR for predicting MCI was analyzed using Receiver Operating Characteristic (ROC) curve analysis. Results: The NLR of MCI group was significantly higher than that of subjects with normal cognitive function (2.39 ± 0.55 vs. 1.94 ± 0.51, P < 0.001). Logistic regression analysis showed that higher NLR was an independent risk factor for MCI (OR: 4.549, 95% CI: 2.623-7.889, P < 0.001). ROC analysis suggested that the optimum NLR cut-off point for MCI was 2.07 with 73.66% sensitivity, 69.28% specificity, 74.48% Positive Predictive Values (PPV) and 68.36% negative predictive values (NPV). Subjects with NLR ≥ 2.07 showed higher risk relative to NLR < 2.07 (OR: 5.933, 95% CI: 3.467-10.155, P < 0.001). Conclusion: The elevated NLR is significantly associated with increased risk of MCI. In particular, NLR level higher than the threshold of 2.07 was significantly associated with the probability of MCI.

Sign in / Sign up

Export Citation Format

Share Document