scholarly journals Visually guided reaching in Alzheimer's disease and mild cognitive impairment

2020 ◽  
Author(s):  
Alexandra Grace Mitchell ◽  
Stephanie Rossit ◽  
Suvankar Pal ◽  
Michael Hornberger ◽  
Annie Warman ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Posterior Parietal Cortex ◽  
Peripheral Vision ◽  
Control Group ◽  
Optic Ataxia ◽  
Individual Level ◽  
Radial Depth

Recent evidence has implicated areas within the posterior parietal cortex (PPC), as among the first to show pathophysiological changes in Alzheimer’s disease. Focal brain damage to the PPC can cause optic ataxia, a specific deficit in reaching to peripheral targets. Visuomotor deficits in optic ataxia are often only detected when reaching to objects in peripheral vision, therefore this condition can often go unnoticed. The present study investigated whether peripheral misreaching is a feature of Alzheimer’s disease. Reaching ability was assessed in individuals with a clinical diagnosis of mild-to-moderate Alzheimer’s and mild cognitive impairment (MCI), compared to a control group of healthy, older adults. Participants were required to reach to targets presented in central vision or in the periphery using two reaching tasks; one in the lateral plane and another presented in radial depth. Case-control comparisons identified 1/10 MCI and 3/17 Alzheimer’s patients with severe peripheral reaching deficits at the individual level, but group-level comparisons did not find significantly higher peripheral reaching error in neither Alzheimer’s nor MCI groups. However, exploratory analyses showed significantly increased reach duration in both Alzheimer’s and MCI groups relative to controls. We conclude that Alzheimer’s disease may lead to a visuomotor impairment that is compensated for by a slowing down of the reach movement to maintain accuracy. However, these findings suggest that peripheral reaching deficits similar to what is observed in optic ataxia are unlikely to be a common feature of Alzheimer’s disease.

scholarly journals Using a Digital Neuro Signature to measure longitudinal individual-level change in Alzheimer’s disease: the Altoida large cohort study

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Irene B. Meier ◽  
Max Buegler ◽  
Robbert Harms ◽  
Azizi Seixas ◽  
Arzu Çöltekin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Disease Risk ◽  
Intraindividual Variability ◽  
Cognitive Test ◽  
Individual Level ◽  
Level Change ◽  
Neuropsychological Assessments

AbstractConventional neuropsychological assessments for Alzheimer’s disease are burdensome and inaccurate at detecting mild cognitive impairment and predicting Alzheimer’s disease risk. Altoida’s Digital Neuro Signature (DNS), a longitudinal cognitive test consisting of two active digital biomarker metrics, alleviates these limitations. By comparison to conventional neuropsychological assessments, DNS results in faster evaluations (10 min vs 45–120 min), and generates higher test-retest in intraindividual assessment, as well as higher accuracy at detecting abnormal cognition. This study comparatively evaluates the performance of Altoida’s DNS and conventional neuropsychological assessments in intraindividual assessments of cognition and function by means of two semi-naturalistic observational experiments with 525 participants in laboratory and clinical settings. The results show that DNS is consistently more sensitive than conventional neuropsychological assessments at capturing longitudinal individual-level change, both with respect to intraindividual variability and dispersion (intraindividual variability across multiple tests), across three participant groups: healthy controls, mild cognitive impairment, and Alzheimer’s disease. Dispersion differences between DNS and conventional neuropsychological assessments were more pronounced with more advanced disease stages, and DNS-intraindividual variability was able to predict conversion from mild cognitive impairment to Alzheimer’s disease. These findings are instrumental for patient monitoring and management, remote clinical trial assessment, and timely interventions, and will hopefully contribute to a better understanding of Alzheimer’s disease.

scholarly journals Cognitive Skills Questionnaire: Comparative Results in Elderly Population without Cognitive Deficit, Mild Cognitive Impairment and Alzheimer's Disease

2020 ◽  
pp. 1-8
Author(s):  
Edith Labos ◽  
Edith Labos ◽  
Sofia Trojanowski ◽  
Karina Zabala ◽  
Miriam Del Rio ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Skills ◽  
Cognitive Disorders ◽  
Cognitive Disorder ◽  
Screening Tools ◽  
Control Group ◽  
Cognitive Complaint

The increase in consultations for changes and/or cognitive complaints in the elderly, together with the current interest in epidemiological research in this context creates the need for screening tools for cognitive assessment to enable the detection of early deficits. Evidence shows its predictive value in the development of dementia disease. This study aims at displaying the results of a Cognitive Skills Questionnaire (CSQ) in a patient population with mild cognitive impairment (MCI) and Alzheimer’s disease (AD), both compared with a control group (CG) with no cognitive disorder and verifying its sensitivity and specificity in order to identify risk patients with cognitive disorder. Participants and Methods: A total of 208 participants were evaluated, out of which 60 had MCI, 46 had AD and a remaining group of 102 subjects who had no cognitive disorder. All participants were administrated the CSQ and a battery of neuropsychological proofs. We analysed the statistical data using ANOVA, Student’s t-test, Tuckey test, ROC curve and principal components analysis. A multiple regression analysis was carried out so as to single out those questions which better differentiated the studied groups. Results: The CSQ showed significant differences between the CG and both groups of patients (AD p> 0.01 and MCI p> 0.05). It was established a cut-off point of 17.5 in the CSQ total score with a sensitivity of 93% and a specificity of 91.3%. Conclusion: The CSQ could eventually allow us to identify patients with cognitive disorders and those others with a cognitive complaint greater than expected. Thus, this questionnaire could be a useful testing and counselling tool in health primary attention.

scholarly journals Permutation Entropy and Statistical Complexity in Mild Cognitive Impairment and Alzheimer’s Disease: An Analysis Based on Frequency Bands

Entropy ◽  
2020 ◽  
Vol 22 (1) ◽  
pp. 116 ◽  
Author(s):  
Ignacio Echegoyen ◽  
David López-Sanz ◽  
Johann H. Martínez ◽  
Fernando Maestú ◽  
Javier M. Buldú
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Frequency Band ◽  
Local Level ◽  
Permutation Entropy ◽  
Frequency Bands ◽  
Individual Level ◽  
Statistical Complexity

We present one of the first applications of Permutation Entropy (PE) and Statistical Complexity (SC) (measured as the product of PE and Jensen-Shanon Divergence) on Magnetoencephalography (MEG) recordings of 46 subjects suffering from Mild Cognitive Impairment (MCI), 17 individuals diagnosed with Alzheimer’s Disease (AD) and 48 healthy controls. We studied the differences in PE and SC in broadband signals and their decomposition into frequency bands ( δ , θ , α and β ), considering two modalities: (i) raw time series obtained from the magnetometers and (ii) a reconstruction into cortical sources or regions of interest (ROIs). We conducted our analyses at three levels: (i) at the group level we compared SC in each frequency band and modality between groups; (ii) at the individual level we compared how the [PE, SC] plane differs in each modality; and (iii) at the local level we explored differences in scalp and cortical space. We recovered classical results that considered only broadband signals and found a nontrivial pattern of alterations in each frequency band, showing that SC does not necessarily decrease in AD or MCI.

scholarly journals Subjective Cognitive Complaints Contribute to Misdiagnosis of Mild Cognitive Impairment

2014 ◽  
Vol 20 (8) ◽  
pp. 836-847 ◽  
Author(s):  
Emily C. Edmonds ◽  
Lisa Delano-Wood ◽  
Douglas R. Galasko ◽  
David P. Salmon ◽  
Mark W. Bondi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cluster Analysis ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Control Group ◽  
Cognitive Complaints ◽  
Informant Report ◽  
Cognitive Problems ◽  
Subjective Cognitive Complaints

AbstractSubjective cognitive complaints are a criterion for the diagnosis of mild cognitive impairment (MCI), despite their uncertain relationship to objective memory performance in MCI. We aimed to examine self-reported cognitive complaints in subgroups of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) MCI cohort to determine whether they are a valuable inclusion in the diagnosis of MCI or, alternatively, if they contribute to misdiagnosis. Subgroups of MCI were derived using cluster analysis of baseline neuropsychological test data from 448 ADNI MCI participants. Cognitive complaints were assessed via the Everyday Cognition (ECog) questionnaire, and discrepancy scores were calculated between self- and informant-report. Cluster analysis revealed Amnestic and Mixed cognitive phenotypes as well as a third Cluster-Derived Normal subgroup (41.3%), whose neuropsychological and cerebrospinal fluid (CSF) Alzheimer’s disease (AD) biomarker profiles did not differ from a “robust” normal control group. This cognitively intact phenotype of MCI participants overestimated their cognitive problems relative to their informant, whereas Amnestic MCI participants with objective memory impairment underestimated their cognitive problems. Underestimation of cognitive problems was associated with positive CSF AD biomarkers and progression to dementia. Overall, there was no relationship between self-reported cognitive complaints and objective cognitive functioning, but significant correlations were observed with depressive symptoms. The inclusion of self-reported complaints in MCI diagnostic criteria may cloud rather than clarify diagnosis and result in high rates of misclassification of MCI. Discrepancies between self- and informant-report demonstrate that overestimation of cognitive problems is characteristic of normal aging while underestimation may reflect greater risk for cognitive decline. (JINS, 2014, 20, 1–12)

scholarly journals Bacterial rhamnolipids (RLs) in saliva of Alzheimer's disease and Mild Cognitive Impairment patients and correlation with neuroinflammation and cognitive state

2021 ◽  
Vol 06 (03) ◽  
pp. 209-219
Author(s):  
Eleni G. Andreadou ◽  
Georgios Katsipis ◽  
Magda Tsolaki ◽  
Anastasia A. Pantazaki
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Mental State ◽  
Biological Fluids ◽  
Pilot Trial ◽  
Control Group ◽  
Cognitive State ◽  
Cox 2

Alzheimer’s disease (AD) is increasingly affecting the aging population and the estimated prevalence reaches 50 million people worldwide. The need for the discovery of new biomarkers for AD diagnosis is urgent and especially in biological fluids other than cerebrospinal fluid (CSF), as its collection is invasive. Arguments are numerous that chronic bacterial infections might be considered as one of the possible causes of AD. Rhamnolipids (RLs) are bacterial virulence factors, suspicious for dysfunctions and disorders including AD. The aim of this pilot trial was to investigate RLs levels in saliva of Mild Cognitive Impairment (MCI) and AD patients with indirect ELISA. Specifically, salivary RLs were determined in 30 AD patients, 24 MCI patients and 15 cognitively healthy individuals and were found elevated in AD and MCI patients compared to those of the control group. The established biomarkers of AD, tau and Aβ42 amyloid, and the inflammatory markers cyclooxygenases (COX-1 and COX-2) were also determined, to evaluate their possible interdependence from RLs levels. Levels of RLs positively correlate with COX-2 levels and negatively with the mental state according to Mini–Mental State Examination (MMSE) score of donors. Multilinear regression verified the tight interrelation of RLs with COX-2 in saliva of MCI and AD patients. The results of this study stand by the hypothesis of inflammatory involvement in AD and indicate that RLs could be suggested as eventual biomarkers for AD diagnosis using saliva as biological fluid.

scholarly journals Herpesvirus infections and immunological disturbances in patients with different stages of Alzheimer’s disease

2021 ◽  
Vol 66 (2) ◽  
pp. 129-139
Author(s):  
S. A. Krynskiy ◽  
I. K. Malashenkova ◽  
D. P. Ogurtsov ◽  
N. A. Khailov ◽  
E. I. Chekulaeva ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Clinical Stage ◽  
Memory Loss ◽  
Control Group ◽  
Immunological Parameters ◽  
Humoral And Cellular Immunity

Introduction. Alzheimer’s disease (AD) is a multifactorial disease that leads to a progressive memory loss, visualspatial impairments, emotional and personality changes. As its earliest pre-dementia clinical stage, amnestic mild cognitive impairment syndrome (aMCI) is currently considered. Neuroinflammation plays a role in the development and progression of aMCI and the initial stage of AD, which can be supported by immunological disorders of a systemic character. Study of factors, including infections, influencing immune disorders and systemic inflammatory response in patients with aMCI, is of great importance.The aim of this study was to obtain new data on the possible role of herpesvirus infections in the development and progression of aMCI.Material and methods. 100 patients with aMCI diagnosis, 45 patients with AD, 40 people from the control group were enrolled into the study. The frequency of DNA detection of herpesviruses (Epstein–Barr virus (EBV), human herpesviruses (HHV) type 6 and 7, cytomegalovirus (CMV)), the levels of viral load and the serological markers of herpesvirus infections (IgG to HHV-1, IgG to CMV) were determined. Immunological studies included an assessment of the level of the main pro-inflammatory and anti-inflammatory cytokines, and indicators of humoral and cellular immunity.Results. The study found an increased detection rate of EBV in saliva and a higher level of EBV DNA in saliva in aMCI and AD than in the control group. A relationship between the presence of active EBV infection and changes in immunological parameters in patients with aMCI were found. It was also discovered that the level of IgG antibodies to CMV is associated with the stage of AD.Discussion. The results indicate a possible role of EBV- and CMV-induced infections in the development of immunological changes which are typical for mild cognitive impairment and in the progression of AD. Conclusion. The obtained data can be important for prognostic methods addressing AD development, including its pre-dementia stage, and for new approaches to individualized treatment and prevention.

scholarly journals THE ROSAS COHORT: A PROSPECTIVE, LONGITUDINAL STUDY OF BIOMARKERS FOR ALZHEIMER’S DISEASE. STRATEGY, METHODS AND INITIAL RESULTS

2017 ◽  
pp. 1-11
Author(s):  
A. de Mauléon ◽  
M. Soto ◽  
V. Kiyasova ◽  
J. Delrieu ◽  
I. Guignot ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Urine Samples ◽  
Control Group ◽  
Dementia Of Alzheimer’S Type ◽  
Blood And Urine Samples ◽  
Baseline Characteristics

Objective: The aims of the Research Of biomarkers in Alzheimer’s diseaSe (ROSAS) study were to determine the biofluid and imaging biomarkers permitting an early diagnosis of Alzheimer’s disease and better characterisation of cognitive and behavioural course of the pathology. This paper outlines the overall strategy, methodology of the study, baseline characteristics of the population and first longitudinal results from the ROSAS cohort. Methods: Longitudinal prospective monocentric observational study performed at the Alzheimer’s disease Research centre in Toulouse. A total of 387 patients were studied and analyzed in 3 groups: 184 patients with dementia of Alzheimer’s type, 96 patients with memory disorders without dementia (Mild Cognitive Impairment) and 107 patients without abnormal memory tests (control group), and were followed up during 4 years. Patient’s sociodemographic characteristics, risk factors, medical conditions, previous and current medications, neuropsychological assessment and overall cognitive status were recorded. Blood and urine samples were collected at every year, Magnetic Resonance Imaging were performed at inclusion, after one year of follow-up and at the end of the study. Results: At baseline, three different groups of the cohort differed interestingly in age, level of education, and in percentage of ApoEε4 carriers whereas the history of cardiovascular and endocrine pathologies were similar among the groups. During the follow-up period (3-4 years) 42 mild cognitive impairment patients (43.8%) progressed to dementia, 7 controls progressed into mild cognitive impairment and 1 patient in the control group converted from mild cognitive impairment group to dementia of Alzheimer’s type group. During the first year of follow up, the incidence of progression from mild cognitive impairment to dementia of Alzheimer’s type was 12.7 per 100, during the second year 33.9 per 100 and 46.7 per 100 for the third year. Conclusion: This paper presents the baseline characteristics of the unique French prospective monocenter study in which the natural course of dementia of Alzheimer’s type was evaluated. Future analysis of blood and urine samples collection from the ROSAS study will permit to identify possible biofluid biomarkers predicting the early stages of the dementia of Alzheimer’s type and risk of progression from Mild Cognitive Impairment to Alzheimer’s disease.

scholarly journals TMS-EEG Biomarkers of Amnestic Mild Cognitive Impairment Due to Alzheimer’s Disease: A Proof-of-Concept Six Years Prospective Study

2021 ◽  
Vol 13 ◽  
Author(s):  
Florinda Ferreri ◽  
Andrea Guerra ◽  
Luca Vollero ◽  
David Ponzo ◽  
Sara Määtta ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Sensorimotor Cortex ◽  
Amnestic Mild Cognitive Impairment ◽  
Additional Parameter ◽  
Sensorimotor Network ◽  
Individual Level ◽  
Gamma Frequency

Background: Early and affordable identification of subjects with amnestic mild cognitive impairment (aMCI) who will convert to Alzheimer’s disease (AD) is a major scientific challenge.Objective: To investigate the neurophysiological hallmarks of sensorimotor cortex function in aMCI under the hypothesis that some may represent the plastic rearrangements induced by neurodegeneration, hence predictors of future conversion to AD. We sought to determine (1) whether the sensorimotor network shows peculiar alterations in patients with aMCI and (2) if sensorimotor network alterations predict long-term disease progression at the individual level.Methods: We studied several transcranial magnetic stimulation (TMS)-electroencephalogram (EEG) parameters of the sensorimotor cortex in a group of patients with aMCI and followed them for 6 years. We then identified aMCI who clinically converted to AD [prodromal to AD-MCI (pAD-MCI)] and those who remained cognitively stable [non-prodromal to AD-MCI (npAD-MCI)].Results: Patients with aMCI showed reduced motor cortex (M1) excitability and disrupted EEG synchronization [decreased intertrial coherence (ITC)] in alpha, beta and gamma frequency bands compared to the control subjects. The degree of alteration in M1 excitability and alpha ITC was comparable between pAD-MCI and npAD-MCI. Importantly, beta and gamma ITC impairment in the stimulated M1 was greater in pAD-MCI than npAD-MCI. Furthermore, an additional parameter related to the waveform shape of scalp signals, reflecting time-specific alterations in global TMS-induced activity [stability of the dipolar activity (sDA)], discriminated npAD-MCI from MCI who will convert to AD.Discussion: The above mentioned specific cortical changes, reflecting deficit of synchronization within the cortico-basal ganglia-thalamo-cortical loop in aMCI, may reflect the pathological processes underlying AD. These changes could be tested in larger cohorts as neurophysiological biomarkers of AD.

scholarly journals The Effects of Previous Error and Success in Alzheimer’s Disease and Mild Cognitive Impairment

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
T. J. Crawford ◽  
S. Taylor ◽  
D. Mardanbegi ◽  
M. Polden ◽  
T. W. Wilcockson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Reaction Times ◽  
Control Group ◽  
Future Performance ◽  
Negative Effect ◽  
Saccadic Reaction Times ◽  
Previous Error

AbstractThis work investigated in Alzheimer’s disease dementia (AD), whether the probability of making an error on a task (or a correct response) was influenced by the outcome of the previous trials. We used the antisaccade task (AST) as a model task given the emerging consensus that it provides a promising sensitive and early biological test of cognitive impairment in AD. It can be employed equally well in healthy young and old adults, and in clinical populations. This study examined eye-movements in a sample of 202 participants (42 with dementia due to AD; 65 with mild cognitive impairment (MCI); 95 control participants). The findings revealed an overall increase in the frequency of AST errors in AD and MCI compared to the control group, as predicted. The errors on the current trial increased in proportion to the number of consecutive errors on the previous trials. Interestingly, the probability of errors was reduced on the trials that followed a previously corrected error, compared to the trials where the error remained uncorrected, revealing a level of adaptive control in participants with MCI or AD dementia. There was an earlier peak in the AST distribution of the saccadic reaction times for the inhibitory errors in comparison to the correct saccades. These findings revealed that the inhibitory errors of the past have a negative effect on the future performance of healthy adults as well as people with a neurodegenerative cognitive impairment.

Increased Prevalence of Vestibular Loss in Mild Cognitive Impairment and Alzheimer’s Disease

2020 ◽  
Vol 16 (12) ◽  
pp. 1143-1150 ◽  
Author(s):  
Eric X. Wei ◽  
Esther S. Oh ◽  
Aisha Harun ◽  
Matthew Ehrenburg ◽  
Qian-Li Xue ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Conditional Logistic Regression ◽  
Vestibular Function ◽  
Cognitive Status ◽  
Control Group ◽  
Vestibular Loss ◽  
Logistic Regression Models

Background/Aims:: Recent evidence has shown that Alzheimer’s Disease (AD) patients have reduced vestibular function relative to healthy controls. In this study, we evaluated whether patients with Mild Cognitive Impairment (MCI) also have reduced vestibular function relative to controls, and compared the level of vestibular impairment between MCI and AD patients. Methods:: Vestibular physiologic function was assessed in 77 patients (26 MCI, 51 AD) and 295 matched controls using 3 clinical vestibular tests. The association between vestibular loss and cognitive impairment was evaluated using conditional logistic regression models. Results:: Individuals with vestibular impairment had a 3 to 4-fold increased odds of being in the MCI vs. control group (p-values < 0.05). MCI patients had a level of vestibular impairment that was intermediate between controls and AD. Conclusion:: These findings suggest a dose-response relationship between vestibular loss and cognitive status, and support the hypothesis that vestibular loss contributes to cognitive decline.

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