Altered Vergence Eye Movements and Pupil Response of Patients with Alzheimer’s Disease and Mild Cognitive Impairment During an Oddball Task

2021 ◽  
pp. 1-13
Author(s):  
Elizabeth Carolina Jiménez ◽  
Alba Sierra-Marcos ◽  
August Romeo ◽  
Amin Hashemi ◽  
Oleksii Leonovych ◽  
...  

Background: Alzheimer’s disease (AD) is characterized by progressive deterioration of cognitive functions and may be preceded by mild cognitive impairment (MCI). Evidence shows changes in pupil and vergence responses related to cognitive processing of visual information. Objective: Here we test the hypothesis that MCI and AD are associated with specific patterns in vergence and pupil responses. Methods: We employed a visual oddball task. In the distractor condition (80%of the trials), a blue stimulus was presented whereas in the target condition (20%of trials) it was red. Participants (23 Controls, 33 MCI patients, and 18 AD patients) were instructed to press a button when a target appeared. Results: Participants briefly converged their eyes 200 ms after stimulus presentation. In controls, this transient peak response was followed by a delay response to targets but not to distractor stimuli. In the patient groups, delay responses to distractors were noticed. Consequently, the differential vergence response was strong in the control group, weak in the MCI group, and absent in the AD group. Pupils started to dilate 500–600 ms after the appearance of a target but slightly contracted after the presentation of a distractor. This differential pupil response was strongest in the AD group. Conclusion: Our findings support the idea of a role of vergence and pupil responses in attention and reveal altered responses in MCI and AD patients. Further studies should assess the value of vergence and pupil measurements as an objective support tool for early diagnosis of AD.

2020 ◽  
pp. 1-8
Author(s):  
Edith Labos ◽  
Edith Labos ◽  
Sofia Trojanowski ◽  
Karina Zabala ◽  
Miriam Del Rio ◽  
...  

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.


2020 ◽  
Author(s):  
Elizabeth R. Paitel ◽  
Marielle R. Samii ◽  
Kristy A Nielson

This systematic review examined whether event-related potentials (ERPs) during higher cognitive processing can detect subtle, early signs of neurodegenerative disease. Original, empirical studies retrieved from PsycINFO and PubMed were reviewed if they analyzed patterns in cognitive ERPs (150ms post-stimulus) differentiating mild cognitive impairment (MCI), Alzheimer’s disease (AD), or cognitively intact elders who carry AD risk through the Apolipoprotein-E ε4 allele (ε4+) from healthy older adult controls (HC). The 100 studies meeting inclusion criteria (MCI=47; AD=47; ε4+=6) analyzed N200, P300, N400, and occasionally, later components. While there was variability across studies, patterns of reduced amplitude and delayed latency were apparent in pathological aging, consistent with AD-related brain atrophy and cognitive impairment. These effects were particularly evident in advanced disease progression (i.e., AD > MCI) and in later ERP components measured during complex tasks. Although ERP studies in intact ε4+ elders are thus far scarce, a similar pattern of delayed latency was notable, along with a contrasting pattern of increased amplitude, consistent with compensatory neural activation. This limited work suggests ERPs might be able to index early neural changes indicative of future cognitive decline in otherwise healthy elders. As ERPs are also accessible and affordable relative to other neuroimaging methods, their addition to cognitive assessment might substantively enhance early identification and characterization of neural dysfunction, allowing opportunity for earlier differential diagnosis and targeting of intervention. To evaluate this possibility there is urgent need for well-powered studies assessing late cognitive ERPs during complex tasks, particularly in healthy elders at risk for cognitive decline.


2014 ◽  
Vol 20 (8) ◽  
pp. 836-847 ◽  
Author(s):  
Emily C. Edmonds ◽  
Lisa Delano-Wood ◽  
Douglas R. Galasko ◽  
David P. Salmon ◽  
Mark W. Bondi

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)


2021 ◽  
Vol 06 (03) ◽  
pp. 209-219
Author(s):  
Eleni G. Andreadou ◽  
Georgios Katsipis ◽  
Magda Tsolaki ◽  
Anastasia A. Pantazaki

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.


2021 ◽  
Vol 66 (2) ◽  
pp. 129-139
Author(s):  
S. A. Krynskiy ◽  
I. K. Malashenkova ◽  
D. P. Ogurtsov ◽  
N. A. Khailov ◽  
E. I. Chekulaeva ◽  
...  

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.


Author(s):  
A. de Mauléon ◽  
M. Soto ◽  
V. Kiyasova ◽  
J. Delrieu ◽  
I. Guignot ◽  
...  

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.


2020 ◽  
Author(s):  
Alexandra Grace Mitchell ◽  
Stephanie Rossit ◽  
Suvankar Pal ◽  
Michael Hornberger ◽  
Annie Warman ◽  
...  

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.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
T. J. Crawford ◽  
S. Taylor ◽  
D. Mardanbegi ◽  
M. Polden ◽  
T. W. Wilcockson ◽  
...  

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.


2020 ◽  
Vol 16 (12) ◽  
pp. 1143-1150 ◽  
Author(s):  
Eric X. Wei ◽  
Esther S. Oh ◽  
Aisha Harun ◽  
Matthew Ehrenburg ◽  
Qian-Li Xue ◽  
...  

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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