scholarly journals Analysis of cognitive performance and polymorphisms of SORL1, PVRL2, CR1, TOMM40, APOE, PICALM, GWAS_14q, CLU, and BIN1 in patients with mild cognitive impairment and cognitively healthy controls

Author(s):  
F. Cruz-Sanabria ◽  
K. Bonilla-Vargas ◽  
K. Estrada ◽  
O. Mancera ◽  
E. Vega ◽  
...  
2009 ◽  
Vol 21 (6) ◽  
pp. 1072-1080 ◽  
Author(s):  
Yong M. Shi ◽  
Hong Zhou ◽  
Zhi J. Zhang ◽  
Hui Yu ◽  
Feng Bai ◽  
...  

ABSTRACTBackground: The genetic region coding for low-density lipoprotein receptor-related protein1 (LRP1) is considered an intriguing susceptibility locus for Alzheimer's disease (AD). Amnestic mild cognitive impairment (aMCI) is characterized by episodic memory impairment and represents the prodromal stage of AD. Our aim in this study is to investigate the relationship between LRP1 genetic variation and aMCI, and the influence of LRP1 on cognitive performance.Methods: We performed a case-control association study analyzing five polymorphisms in LRP1 gene by TaqMan Assays-on-Demand SNP Genotyping. All samples were derived from Chinese subjects (109 cases, 104 healthy controls) and assessed using multi-dimension neuropsychological instruments.Results: We identified haplotypes within the region containing the LRP1 gene. Of these, haplotype TAA (T: rs1800194; A: rs11837145; A: rs10876967) was significantly associated with aMCI, being over-represented in aMCI versus healthy controls. Haplotype TAA was associated with poor performance on episodic memory in all subjects.Conclusions: This study confirms the association between genetic variants in LRP1 and aMCI. Moreover, we have identified a relationship between LRP1 genetic variation and specific aspects of neurocognitive function. Our convergent results suggest that LRP1 plays an important role in cognitive function and possibly in the pathogenesis of aMCI.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Manfred Berres ◽  
Andreas U. Monsch ◽  
René Spiegel

Abstract Background The Placebo Group Simulation Approach (PGSA) aims at partially replacing randomized placebo-controlled trials (RPCTs), making use of data from historical control groups in order to decrease the needed number of study participants exposed to lengthy placebo treatment. PGSA algorithms to create virtual control groups were originally derived from mild cognitive impairment (MCI) data of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. To produce more generalizable algorithms, we aimed to compile five different MCI databases in a heuristic manner to create a “standard control algorithm” for use in future clinical trials. Methods We compared data from two North American cohort studies (n=395 and 4328, respectively), one company-sponsored international clinical drug trial (n=831) and two convenience patient samples, one from Germany (n=726), and one from Switzerland (n=1558). Results Despite differences between the five MCI samples regarding inclusion and exclusion criteria, their baseline demographic and cognitive performance data varied less than expected. However, the five samples differed markedly with regard to their subsequent cognitive performance and clinical development: (1) MCI patients from the drug trial did not deteriorate on verbal fluency over 3 years, whereas patients in the other samples did; (2) relatively few patients from the drug trial progressed from MCI to dementia (about 10% after 4 years), in contrast to the other four samples with progression rates over 30%. Conclusion Conventional MCI criteria were insufficient to allow for the creation of well-defined and internationally comparable samples of MCI patients. More recently published criteria for MCI or “MCI due to AD” are unlikely to remedy this situation. The Alzheimer scientific community needs to agree on a standard set of neuropsychological tests including appropriate selection criteria to make MCI a scientifically more useful concept. Patient data from different sources would then be comparable, and the scientific merits of algorithm-based study designs such as the PGSA could be properly assessed.


2021 ◽  
Author(s):  
Noel Valencia ◽  
Johann Lehrner

Summary Background Visuo-Constructive functions have considerable potential for the early diagnosis and monitoring of disease progression in Alzheimer’s disease. Objectives Using the Vienna Visuo-Constructional Test 3.0 (VVT 3.0), we measured visuo-constructive functions in subjective cognitive decline (SCD), mild cognitive impairment (MCI), Alzheimer’s disease (AD), and healthy controls to determine whether VVT performance can be used to distinguish these groups. Materials and methods Data of 671 participants was analyzed comparing scores across diagnostic groups and exploring associations with relevant clinical variables. Predictive validity was assessed using Receiver Operator Characteristic curves and multinomial logistic regression analysis. Results We found significant differences between AD and the other groups. Identification of cases suffering from visuo-constructive impairment was possible using VVT scores, but these did not permit classification into diagnostic subgroups. Conclusions In summary, VVT scores are useful indicators for visuo-constructive impairment but face challenges when attempting to discriminate between several diagnostic groups.


Author(s):  
Filipe Godinho ◽  
Carolina Maruta ◽  
Cláudia Borbinha ◽  
Isabel Pavão Martins

BMJ Open ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. e046879
Author(s):  
Bernhard Grässler ◽  
Fabian Herold ◽  
Milos Dordevic ◽  
Tariq Ali Gujar ◽  
Sabine Darius ◽  
...  

IntroductionThe diagnosis of mild cognitive impairment (MCI), that is, the transitory phase between normal age-related cognitive decline and dementia, remains a challenging task. It was observed that a multimodal approach (simultaneous analysis of several complementary modalities) can improve the classification accuracy. We will combine three noninvasive measurement modalities: functional near-infrared spectroscopy (fNIRS), electroencephalography and heart rate variability via ECG. Our aim is to explore neurophysiological correlates of cognitive performance and whether our multimodal approach can aid in early identification of individuals with MCI.Methods and analysisThis study will be a cross-sectional with patients with MCI and healthy controls (HC). The neurophysiological signals will be measured during rest and while performing cognitive tasks: (1) Stroop, (2) N-back and (3) verbal fluency test (VFT). Main aims of statistical analysis are to (1) determine the differences in neurophysiological responses of HC and MCI, (2) investigate relationships between measures of cognitive performance and neurophysiological responses and (3) investigate whether the classification accuracy can be improved by using our multimodal approach. To meet these targets, statistical analysis will include machine learning approaches.This is, to the best of our knowledge, the first study that applies simultaneously these three modalities in MCI and HC. We hypothesise that the multimodal approach improves the classification accuracy between HC and MCI as compared with a unimodal approach. If our hypothesis is verified, this study paves the way for additional research on multimodal approaches for dementia research and fosters the exploration of new biomarkers for an early detection of nonphysiological age-related cognitive decline.Ethics and disseminationEthics approval was obtained from the local Ethics Committee (reference: 83/19). Data will be shared with the scientific community no more than 1 year following completion of study and data assembly.Trial registration numberClinicalTrials.gov, NCT04427436, registered on 10 June 2020, https://clinicaltrials.gov/ct2/show/study/NCT04427436.


2017 ◽  
Vol 24 (2) ◽  
pp. 176-187 ◽  
Author(s):  
Shanna L. Burke ◽  
Miriam J. Rodriguez ◽  
Warren Barker ◽  
Maria T Greig-Custo ◽  
Monica Rosselli ◽  
...  

AbstractObjectives:The aim of this study was to determine the presence and severity of potential cultural and language bias in widely used cognitive and other assessment instruments, using structural MRI measures of neurodegeneration as biomarkers of disease stage and severity.Methods:Hispanic (n=75) and White non-Hispanic (WNH) (n=90) subjects were classified as cognitively normal (CN), amnestic mild cognitive impairment (aMCI) and mild dementia. Performance on the culture-fair and educationally fair Fuld Object Memory Evaluation (FOME) and Clinical Dementia Rating Scale (CDR) between Hispanics and WNHs was equivalent, in each diagnostic group. Volumetric and visually rated measures of the hippocampus entorhinal cortex, and inferior lateral ventricles (ILV) were measured on structural MRI scans for all subjects. A series of analyses of covariance, controlling for age, depression, and education, were conducted to compare the level of neurodegeneration on these MRI measures between Hispanics and WNHs in each diagnostic group.Results:Among both Hispanics and WNH groups there was a progressive decrease in volume of the hippocampus and entorhinal cortex, and an increase in volume of the ILV (indicating increasing atrophy in the regions surrounding the ILV) from CN to aMCI to mild dementia. For equivalent levels of performance on the FOME and CDR, WNHs had greater levels of neurodegeneration than did Hispanic subjects.Conclusions:Atrophy in medial temporal regions was found to be greater among WNH than Hispanic diagnostic groups, despite the lack of statistical differences in cognitive performance between these two ethnic groups. Presumably, unmeasured factors result in better cognitive performance among WNH than Hispanics for a given level of neurodegeneration. (JINS, 2018,24, 176–187)


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