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 ◽  
...  

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.

2021 ◽  
Vol 17 (S5) ◽  
Author(s):  
Ester Esteban‐De Antonio ◽  
Alba Pérez‐Cordón ◽  
Silvia Gil ◽  
Amanda Cano ◽  
Adelina Orellana ◽  
...  

2020 ◽  
Vol 10 (2) ◽  
pp. 45 ◽  
Author(s):  
Valentina Bessi ◽  
Juri Balestrini ◽  
Silvia Bagnoli ◽  
Salvatore Mazzeo ◽  
Giulia Giacomucci ◽  
...  

Background: Some genes could interact with cardiovascular risk factors in the development of Alzheimer’s disease. We aimed to evaluate the interaction between ApoE ε4 status, Clock T3111C and Per2 C111G polymorphisms with cardiovascular profile in Subjective Cognitive Decline (SCD) and Mild Cognitive Impairment (MCI). Methods: We included 68 patients who underwent clinical evaluation; neuropsychological assessment; ApoE, Clock and Per2 genotyping at baseline; and neuropsychological follow-up every 12–24 months for a mean of 13 years. We considered subjects who developed AD and non-converters. Results: Clock T3111C was detected in 47% of cases, Per2 C111G in 19% of cases. ApoE ε4 carriers presented higher risk of heart disease; Clock C-carriers were more frequently smokers than non C-carriers. During the follow-up, 17 patients progressed to AD. Age at baseline, ApoE ε 4 and dyslipidemia increased the risk of conversion to AD. ApoE ε4 carriers with history of dyslipidemia showed higher risk to convert to AD compared to ApoE ε4− groups and ApoE ε4+ without dyslipidemia patients. Clock C-carriers with history of blood hypertension had a higher risk of conversion to AD. Conclusions: ApoE and Clock T3111C seem to interact with cardiovascular risk factors in SCD and MCI patients influencing the progression to AD.


2020 ◽  
Vol 77 (3) ◽  
pp. 1017-1024
Author(s):  
Seong Hee Ho ◽  
Dong-Won Yang

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.


2021 ◽  
pp. 1-7
Author(s):  
Wael K. Karameh ◽  
Ines Kortebi ◽  
Sanjeev Kumar ◽  
Damien Gallagher ◽  
Angela Golas ◽  
...  

ABSTRACT Objectives: To compare the prevalence of select cardiovascular risk factors (CVRFs) in patients with mild cognitive impairment (MCI) versus lifetime history of major depression disorder (MDD) and a normal comparison group using baseline data from the Prevention of Alzheimer’s Dementia with Cognitive Remediation plus Transcranial Direct Current Stimulation (PACt-MD) study. Design: Baseline data from a multi-centered intervention study of older adults with MCI, history of MDD, or combined MCI and history of MDD (PACt-MD) were analyzed. Setting: Community-based multi-centered study based in Toronto across 5 academic sites. Participants: Older adults with MCI, history of MDD, or combined MCI and history of MDD and healthy controls. Measurements: We examined the baseline distribution of smoking, hypertension and diabetes in three groups of participants aged 60+ years in the PACt-MD cohort study: MCI (n = 278), MDD (n = 95), and healthy older controls (n = 81). Generalized linear models were fitted to study the effect of CVRFs on MCI and MDD as well as neuropsychological composite scores. Results: A higher odds of hypertension among the MCI cohort compared to healthy controls (p < .05) was noted in unadjusted analysis. Statistical significance level was lost on adjusting for age, sex and education (p > .05). A history of hypertension was associated with lower performance in composite executive function (p < .05) and overall composite neuropsychological test score (p < .05) among a pooled cohort with MCI or MDD. Conclusions: This study reinforces the importance of treating modifiable CVRFs, specifically hypertension, as a means of mitigating cognitive decline in patients with at-risk cognitive conditions.


2020 ◽  
Vol 17 ◽  
Author(s):  
Hyung-Ji Kim ◽  
Jae-Hong Lee ◽  
E-nae Cheong ◽  
Sung-Eun Chung ◽  
Sungyang Jo ◽  
...  

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.


2019 ◽  
Vol Volume 15 ◽  
pp. 167-175 ◽  
Author(s):  
Oana Albai ◽  
Mirela Frandes ◽  
Romulus Timar ◽  
Deiana Roman ◽  
Bogdan Timar

2021 ◽  
Vol 79 (1) ◽  
pp. 401-414
Author(s):  
Max Toepper ◽  
Philipp Schulz ◽  
Thomas Beblo ◽  
Martin Driessen

Background: On-road driving behavior can be impaired in older drivers and particularly in drivers with mild cognitive impairment (MCI). Objective: To determine whether cognitive and non-cognitive risk factors for driving safety may allow an accurate and economic prediction of on-road driving skills, fitness to drive, and prospective accident risk in healthy older drivers and drivers with MCI, we examined a representative combined sample of older drivers with and without MCI (N = 74) in an observational on-road study. In particular, we examined whether non-cognitive risk factors improve predictive accuracy provided by cognitive factors alone. Methods: Multiple and logistic hierarchical regression analyses were utilized to predict different driving outcomes. In all regression models, we included cognitive predictors alone in a first step and added non-cognitive predictors in a second step. Results: Results revealed that the combination of cognitive and non-cognitive risk factors significantly predicted driving skills (R2adjusted = 0.30) and fitness to drive (81.2% accuracy) as well as the number (R2adjusted = 0.21) and occurrence (88.3% accuracy) of prospective minor at-fault accidents within the next 12 months. In all analyses, the inclusion of non-cognitive risk factors led to a significant increase of explained variance in the different outcome variables. Conclusion: Our findings suggest that a combination of the most robust cognitive and non-cognitive risk factors may allow an economic and accurate prediction of on-road driving performance and prospective accident risk in healthy older drivers and drivers with MCI. Therefore, non-cognitive risk factors appear to play an important role.


Author(s):  
Iván Galtier ◽  
Antonieta Nieto ◽  
María Mata ◽  
Jesús N. Lorenzo ◽  
José Barroso

ABSTRACT Objective: Subjective cognitive decline (SCD) and mild cognitive impairment (MCI) in Parkinson’s disease (PD) are considered as the risk factors for dementia (PDD). Posterior cortically based functions, such as visuospatial and visuoperceptual (VS-VP) processing, have been described as predictors of PDD. However, no investigations have focused on the qualitative analysis of the Judgment of Line Orientation Test (JLOT) and the Facial Recognition Test (FRT) in PD-SCD and PD-MCI. The aim of this work was to study the VS-VP errors in JLOT and FRT. Moreover, these variables are considered as predictors of PDD. Method: Forty-two PD patients and 19 controls were evaluated with a neuropsychological protocol. Patients were classified as PD-SCD and PD-MCI. Analyses of errors were conducted following the procedure described by Ska, Poissant, and Joanette (1990). Follow-up assessment was conducted to a mean of 7.5 years after the baseline. Results: PD-MCI patients showed a poor performance in JLOT and FRT total score and made a greater proportion of severe intraquadrant (QO2) and interquadrant errors (IQO). PD-SCD showed a poor performance in FRT and made mild errors in JLOT. PD-MCI and QO2/IQO errors were independent risk factors for PDD during the follow-up. Moreover, the combination of both PD-MCI diagnosis and QO2/IQO errors was associated with a greater risk. Conclusions: PD-MCI patients presented a greater alteration in VS-VP processing observable by the presence of severe misjudgments. PD-SCD patients also showed mild difficulties in VS-SP functions. Finally, QO2/IQO errors in PD-MCI are a useful predictor of PDD, more than PD-MCI diagnosis alone.


2021 ◽  
Vol 11 (1) ◽  
pp. 68
Author(s):  
Sara G. Aguilar-Navarro ◽  
Itzel I. Gonzalez-Aparicio ◽  
José Alberto Avila-Funes ◽  
Teresa Juárez-Cedillo ◽  
Teresa Tusié-Luna ◽  
...  

Mild cognitive impairment (MCI) (amnestic or non-amnestic) has different clinical and neuropsychological characteristics, and its evolution is heterogeneous. Cardiovascular risk factors (CVRF), such as hypertension, diabetes, or dyslipidemia, and the presence of the Apolipoprotein E ε4 (ApoE ε4) polymorphism have been associated with an increased risk of developing Alzheimer’s disease (AD) and other dementias but the relationship is inconsistent worldwide. We aimed to establish the association between the ApoE ε4 carrier status and CVRF on MCI subtypes (amnestic and non-amnestic) in Mexican older adults. Cross-sectional study including 137 older adults (n = 63 with normal cognition (NC), n = 24 with amnesic, and n = 50 with non-amnesic MCI). Multinomial logistic regression models were performed in order to determine the association between ApoE ε4 polymorphism carrier and CVRF on amnestic and non-amnestic-MCI. ApoE ε4 carrier status was present in 28.8% participants. The models showed that ApoE ε4 carrier status was not associated neither aMCI nor naMCI condition. The interaction term ApoE ε4 × CVRF was not statistically significant for both types of MCI. However, CVRF were associated with both types of MCI and the association remained statistically significant after adjustment by sex, age, and education level. The carrier status of the ApoE genotype does not contribute to this risk.


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