scholarly journals The Effect of Traumatic Brain Injury on Alzheimer’s Disease and Cognitive Decline in Veterans and Non-Veterans

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 305-306
Author(s):  
Igor Akushevich ◽  
Arseniy Yashkin ◽  
Stanislav Kolpakov Nikitin ◽  
Julia Kravchenko
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Traumatic Brain Injury ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Brain Injury ◽  
Cognitive Decline ◽  
Cognitive Status ◽  
Risk Scores ◽  
Post Traumatic Stress

Abstract We assess the differences in the effect of traumatic brain injury (TBI) on the decline in cognitive status and the risk of Alzheimer’s disease and related dementia (AD/ADRD) between veteran and non-veteran respondents of the Health and Retirement Study (HRS) and measure the sensitivity of these differences to the incremental introduction of controls for associated risk factors. Three groups of AD/ADRD risk-related variables were used: i) demographic/socioeconomic factors, including gender, race, marital status, education, income, and the number of limitations in activities of daily living; ii) comorbidities, including co-existing depression/post-traumatic stress syndrome (PTSD), substance (alcohol, tobacco and/or prescription drug) abuse, diabetes mellitus, stroke, and heart failure; and iii) genetic factors, including the presence of at least one pair of the APOE4 allele and a series of polygenic risk scores associated with AD hallmarks. The dynamics of changes in cognitive impairment in response to TBI, PTSD, and mild cognitive impairment were validated against respective measures estimated using the Department of Defense Alzheimer’s Disease Neuroimaging Initiative (DoD-ADNI) data. The results of the analyses showed that TBI and PTSD were strongly associated with cognitive decline and the risks of AD/ADRD in both veteran and non-veteran subpopulations in HRS data and the difference between them was not statistically significant. Effect magnitude decreased with the addition of risk-related control variables but remained associated with the increased risks. Prevalence of mild cognitive impairment was associated with TBI at baseline in DoD-ADNI data, but no cognitive decline was observed during one year of follow-up.

Blink rate study in patients with Alzheimer's disease, Mild Cognitive Impairment and Subjective Cognitive Decline

2021 ◽  
Vol 19 ◽  
Author(s):  
Fabrizia D’Antonio ◽  
Maria Ilenia De Bartolo ◽  
Gina Ferrazzano ◽  
Micaela Sepe Monti ◽  
Letizia Imbriano ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Cognitive Status ◽  
Subjective Cognitive Decline ◽  
Blink Rate ◽  
Compensatory Mechanisms ◽  
Rate Study

Background: Blink rate (BR) is considered a marker of dopaminergic activity in humans. BR is increased in patients with Mild Cognitive Impairment (MCI), but no study has yet investigated whether BR changes with the progression of cognitive decline from MCI to Alzheimer’s disease (AD) and whether BR abnormalities are present in subjects with Subjective Cognitive Decline (SCD). Objective: The aim of our study was to assess BR in patients with AD, MCI, and SCD and to correlate BR with demographic and clinical features of cognitive decline. Methods: We enrolled 22 subjects with SCD, 23 with MCI, and 18 with AD and a group of 20 age-matched healthy controls (HCs). Cognitive function was assessed by testing global cognitive status and frontal, attentional, memory, verbal, and visuospatial functions. BR was measured by counting the number of blinks per minute. Results: MCI subjects had an increased BR (p<0.001), whereas AD subjects had a lower BR than HCs (p<0.05). Conversely, SCD subjects had a BR similar to HCs. No significant correlations emerged between neuropsychological scores and BR in SCD, MCI, and AD subjects. Conclusion: Increased BR in MCI likely reflects early compensatory mechanisms occurring before AD, whereas decreased BR in AD suggests dopaminergic system involvement in this condition.

scholarly journals Validity Evidence for the Research Category, “Cognitively Unimpaired – Declining,” as a Risk Marker for Mild Cognitive Impairment and Alzheimer’s Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Rebecca Langhough Koscik ◽  
Bruce P. Hermann ◽  
Samantha Allison ◽  
Lindsay R. Clark ◽  
Erin M. Jonaitis ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Operational Definition ◽  
Cognitive Status ◽  
Validity Evidence ◽  
Positron Emission ◽  
Clinically Significant

While clinically significant cognitive impairment is the key feature of the symptomatic stages of the Alzheimer’s disease (AD) continuum, subtle cognitive decline is now known to occur years before a clinical diagnosis of mild cognitive impairment (MCI) or dementia due to AD is made. The primary aim of this study was to examine criterion validity evidence for an operational definition of “cognitively unimpaired-declining” (CU-D) in the Wisconsin Registry for Alzheimer’s Prevention (WRAP), a longitudinal cohort study following cognition and risk factors from mid-life and on. Cognitive status was determined for each visit using a consensus review process that incorporated internal norms and published norms; a multi-disciplinary panel reviewed cases first to determine whether MCI or dementia was present, and subsequently whether CU-D was present, The CU-D group differed from CU-stable (CU-S) and MCI on concurrent measures of cognition, demonstrating concurrent validity. Participants who changed from CU-S to CU-D at the next study visit demonstrated greater declines than those who stayed CU-S. In addition, those who were CU-D were more likely to progress to MCI or dementia than those who were CU-S (predictive validity). In a subsample with positron emission tomography (PET) imaging, the CU-D group also differed from the CU-S and MCI/Dementia groups on measures of amyloid and tau burden, indicating that biomarker evidence of AD was elevated in those showing sub-clinical (CU-D) decline. Together, the results corroborate other studies showing that cognitive decline begins long before a dementia diagnosis and indicate that operational criteria can detect subclinical decline that may signal AD or other dementia risk.

scholarly journals Polygenic Risk Scoring is an Effective Approach to Predict Those Individuals Most Likely to Decline Cognitively Due to Alzheimer’s Disease

2020 ◽  
pp. 1-6
Author(s):  
P. Daunt ◽  
C.G. Ballard ◽  
B. Creese ◽  
G. Davidson ◽  
J. Hardy ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Risk Scores ◽  
Cognitively Normal ◽  
Polygenic Risk ◽  
Csf Biomarker ◽  
Risk Scoring

BACKGROUND: There is a clear need for simple and effective tests to identify individuals who are most likely to develop Alzheimer’s Disease (AD) both for the purposes of clinical trial recruitment but also for improved management of patients who may be experiencing early pre-clinical symptoms or who have clinical concerns. OBJECTIVES: To predict individuals at greatest risk of progression of cognitive impairment due to Alzheimer’s Disease in individuals from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) using a polygenic risk scoring algorithm. To compare the performance of a PRS algorithm in predicting cognitive decline against that of using the pTau/Aß1-42 ratio CSF biomarker profile. DESIGN: A longitudinal analysis of data from the Alzheimer’s Disease Neuroimaging Initiative study conducted across over 50 sites in the US and Canada. SETTING: Multi-center genetics study. PARTICPANTS: 515 subjects who upon entry to the study were diagnosed as cognitively normal or with mild cognitive impairment. MEASUREMENTS: Use of genotyping and/or whole genome sequencing data to calculate polygenic risk scores and assess ability to predict subsequent cognitive decline as measured by CDR-SB and ADAS-Cog13 over 4 years. RESULTS: The overall performance for predicting those individuals who would decline by at least 15 ADAS-Cog13 points from a baseline mild cognitive impairment in 4 years was 72.8% (CI:67.9-77.7) AUC increasing to 79.1% (CI: 75.6-82.6) when also including cognitively normal participants. Assessing mild cognitive impaired subjects only and using a threshold of greater than 0.6, the high genetic risk participant group declined, on average, by 1.4 points (CDR-SB) more than the low risk group over 4 years. The performance of the PRS algorithm tested was similar to that of the pTau/Aß1-42 ratio CSF biomarker profile in predicting cognitive decline. CONCLUSION: Calculating polygenic risk scores offers a simple and effective way, using DNA extracted from a simple mouth swab, to select mild cognitively impaired patients who are most likely to decline cognitively over the next four years.

Subjective Spatial Navigation Complaints - A Frequent Symptom Reported by Patients with Subjective Cognitive Decline, Mild Cognitive Impairment and Alzheimer's Disease

2018 ◽  
Vol 15 (3) ◽  
pp. 219-228 ◽  
Author(s):  
Jiri Cerman ◽  
Ross Andel ◽  
Jan Laczo ◽  
Martin Vyhnalek ◽  
Zuzana Nedelska ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Spatial Navigation ◽  
Subjective Cognitive Decline ◽  
Great Effort ◽  
Frequent Symptom ◽  
Normal Controls

Background: Great effort has been put into developing simple and feasible tools capable to detect Alzheimer's disease (AD) in its early clinical stage. Spatial navigation impairment occurs very early in AD and is detectable even in the stage of mild cognitive impairment (MCI). Objective: The aim was to describe the frequency of self-reported spatial navigation complaints in patients with subjective cognitive decline (SCD), amnestic and non-amnestic MCI (aMCI, naMCI) and AD dementia and to assess whether a simple questionnaire based on these complaints may be used to detect early AD. Method: In total 184 subjects: patients with aMCI (n=61), naMCI (n=27), SCD (n=63), dementia due to AD (n=20) and normal controls (n=13) were recruited. The subjects underwent neuropsychological examination and were administered a questionnaire addressing spatial navigation complaints. Responses to the 15 items questionnaire were scaled into four categories (no, minor, moderate and major complaints). Results: 55% of patients with aMCI, 64% with naMCI, 68% with SCD and 72% with AD complained about their spatial navigation. 38-61% of these complaints were moderate or major. Only 33% normal controls expressed complaints and none was ranked as moderate or major. The SCD, aMCI and AD dementia patients were more likely to express complaints than normal controls (p's<0.050) after adjusting for age, education, sex, depressive symptoms (OR for SCD=4.00, aMCI=3.90, AD dementia=7.02) or anxiety (OR for SCD=3.59, aMCI=3.64, AD dementia=6.41). Conclusion: Spatial navigation complaints are a frequent symptom not only in AD, but also in SCD and aMCI and can potentially be detected by a simple and inexpensive questionnaire.

scholarly journals Assessing visuo-constructive functions in patients with subjective cognitive decline, mild cognitive impairment and Alzheimer’s disease with the Vienna Visuo-Constructional Test 3.0 (VVT 3.0)

2021 ◽  
Author(s):  
Noel Valencia ◽  
Johann Lehrner
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Multinomial Logistic Regression ◽  
Subjective Cognitive Decline ◽  
Healthy Controls ◽  
Considerable Potential ◽  
Multinomial Logistic Regression Analysis

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.

Alexithymia in people with subjective cognitive decline, mild cognitive impairment, and mild Alzheimer’s disease

2017 ◽  
Vol 29 (6) ◽  
pp. 1105-1111 ◽  
Author(s):  
Mehmet Yuruyen ◽  
Fundan Engin Akcan ◽  
Gizem Cetiner Batun ◽  
Gozde Gultekin ◽  
Mesut Toprak ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Subjective Cognitive Decline

scholarly journals Subjective cognitive decline: The first clinical manifestation of Alzheimer's disease?

2016 ◽  
Vol 10 (3) ◽  
pp. 170-177 ◽  
Author(s):  
Adalberto Studart Neto ◽  
Ricardo Nitrini
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Clinical Manifestation ◽  
Neurodegenerative Disorder ◽  
Subjective Cognitive Decline ◽  
Subjective Memory ◽  
Increased Risk

ABSTRACT Background: Mild cognitive impairment is considered as the first clinical manifestation of Alzheimer's disease (AD), when the individual exhibits below performance on standardized neuropsychological tests. However, some subjects before having a lower performance on cognitive assessments already have a subjective memory complaint. Objective: A review about subjective cognitive decline, the association with AD biomarkers and risk of conversion to dementia. Methods: We performed a comprehensive non-systematic review on PubMed. The keywords used in the search were terms related to subjective cognitive decline. Results: Subjective cognitive decline is characterized by self-experience of deterioration in cognitive performance not detected objectively through formal neuropsychological testing. However, various terms and definitions have been used in the literature and the lack of a widely accepted concept hampers comparison of studies. Epidemiological data have shown that individuals with subjective cognitive decline are at increased risk of progression to AD dementia. In addition, there is evidence that this group has a higher prevalence of positive biomarkers for amyloidosis and neurodegeneration. However, Alzheimer's disease is not the only cause of subjective cognitive decline and various other conditions can be associated with subjective memory complaints, such as psychiatric disorders or normal aging. The features suggestive of a neurodegenerative disorder are: onset of decline within the last five years, age at onset above 60 years, associated concerns about decline and confirmation by an informant. Conclusion: These findings support the idea that subjective cognitive complaints may be an early clinical marker that precedes mild cognitive impairment due to Alzheimer's disease.

scholarly journals Neurobiological substrates underlying the effect of genomic risk for depression on the conversion of amnestic mild cognitive impairment

Brain ◽  
2018 ◽  
Vol 141 (12) ◽  
pp. 3457-3471 ◽  
Author(s):  
Jiayuan Xu ◽  
Qiaojun Li ◽  
Wen Qin ◽  
Mulin Jun Li ◽  
Chuanjun Zhuo ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Major Depressive Disorder ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Depressive Disorder ◽  
Genetic Variants ◽  
Amnestic Mild Cognitive Impairment ◽  
Risk Scores ◽  
Major Depressive

Abstract Depression increases the conversion risk from amnestic mild cognitive impairment to Alzheimer’s disease with unknown mechanisms. We hypothesize that the cumulative genomic risk for major depressive disorder may be a candidate cause for the increased conversion risk. Here, we aimed to investigate the predictive effect of the polygenic risk scores of major depressive disorder-specific genetic variants (PRSsMDD) on the conversion from non-depressed amnestic mild cognitive impairment to Alzheimer’s disease, and its underlying neurobiological mechanisms. The PRSsMDD could predict the conversion from amnestic mild cognitive impairment to Alzheimer’s disease, and amnestic mild cognitive impairment patients with high risk scores showed 16.25% higher conversion rate than those with low risk. The PRSsMDD was correlated with the left hippocampal volume, which was found to mediate the predictive effect of the PRSsMDD on the conversion of amnestic mild cognitive impairment. The major depressive disorder-specific genetic variants were mapped into genes using different strategies, and then enrichment analyses and protein–protein interaction network analysis revealed that these genes were involved in developmental process and amyloid-beta binding. They showed temporal-specific expression in the hippocampus in middle and late foetal developmental periods. Cell type-specific expression analysis of these genes demonstrated significant over-representation in the pyramidal neurons and interneurons in the hippocampus. These cross-scale neurobiological analyses and functional annotations indicate that major depressive disorder-specific genetic variants may increase the conversion from amnestic mild cognitive impairment to Alzheimer’s disease by modulating the early hippocampal development and amyloid-beta binding. The PRSsMDD could be used as a complementary measure to select patients with amnestic mild cognitive impairment with high conversion risk to Alzheimer’s disease.

scholarly journals Bayesian hidden Markov models for delineating the pathology of Alzheimer’s disease

2017 ◽  
Vol 28 (7) ◽  
pp. 2112-2124 ◽  
Author(s):  
Kai Kang ◽  
Jingheng Cai ◽  
Xinyuan Song ◽  
Hongtu Zhu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Markov Model ◽  
Cognitive Decline ◽  
Hidden Markov Model ◽  
Hidden Markov ◽  
Semiparametric Regression ◽  
Model Framework

Alzheimer’s disease is a firmly incurable and progressive disease. The pathology of Alzheimer’s disease usually evolves from cognitive normal, to mild cognitive impairment, to Alzheimer’s disease. The aim of this paper is to develop a Bayesian hidden Markov model to characterize disease pathology, identify hidden states corresponding to the diagnosed stages of cognitive decline, and examine the dynamic changes of potential risk factors associated with the cognitive normal–mild cognitive impairment–Alzheimer’s disease transition. The hidden Markov model framework consists of two major components. The first one is a state-dependent semiparametric regression for delineating the complex associations between clinical outcomes of interest and a set of prognostic biomarkers across neurodegenerative states. The second one is a parametric transition model, while accounting for potential covariate effects on the cross-state transition. The inter-individual and inter-process differences are taken into account via correlated random effects in both components. Based on the Alzheimer’s Disease Neuroimaging Initiative data set, we are able to identify four states of Alzheimer’s disease pathology, corresponding to common diagnosed cognitive decline stages, including cognitive normal, early mild cognitive impairment, late mild cognitive impairment, and Alzheimer’s disease and examine the effects of hippocampus, age, gender, and APOE-[Formula: see text] on degeneration of cognitive function across the four cognitive states.

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