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

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.

Download Full-text

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

10.31487/j.ggr.2020.02.06 ◽

2020 ◽

pp. 1-8

Author(s):

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.

Download Full-text

Prospective predictors of decline v. stability in mild cognitive impairment with Lewy bodies or Alzheimer's disease

Psychological Medicine ◽

10.1017/s0033291720001130 ◽

2020 ◽

pp. 1-9

Author(s):

Calum A. Hamilton ◽

Fiona E. Matthews ◽

Paul C. Donaghy ◽

John-Paul Taylor ◽

John T. O'Brien ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Latent Class ◽

Lewy Bodies ◽

Cognitive Status ◽

Rapid Decline ◽

Visual Hallucinations ◽

Full Cohort

Abstract Background Mild cognitive impairment (MCI) may gradually worsen to dementia, but often remains stable for extended periods of time. Little is known about the predictors of decline to help explain this variation. We aimed to explore whether this heterogeneous course of MCI may be predicted by the presence of Lewy body (LB) symptoms in a prospectively-recruited longitudinal cohort of MCI with Lewy bodies (MCI-LB) and Alzheimer's disease (MCI-AD). Methods A prospective cohort (n = 76) aged ⩾60 years underwent detailed assessment after recent MCI diagnosis, and were followed up annually with repeated neuropsychological testing and clinical review of cognitive status and LB symptoms. Latent class mixture modelling identified data-driven sub-groups with distinct trajectories of global cognitive function. Results Three distinct trajectories were identified in the full cohort: slow/stable progression (46%), intermediate progressive decline (41%) and a small group with a much faster decline (13%). The presence of LB symptomology, and visual hallucinations in particular, predicted decline v. a stable cognitive trajectory. With time zeroed on study end (death, dementia or withdrawal) where available (n = 39), the same subgroups were identified. Adjustment for baseline functioning obscured the presence of any latent classes, suggesting that baseline function is an important parameter in prospective decline. Conclusions These results highlight some potential signals for impending decline in MCI; poorer baseline function and the presence of probable LB symptoms – particularly visual hallucinations. Identifying people with a rapid decline is important but our findings are preliminary given the modest cohort size.

Download Full-text

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

Current Alzheimer Research ◽

10.2174/1567205019666211227102706 ◽

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.

Download Full-text

Abstract MP18: Covid-19 Susceptibility and Mortality Among Individuals With Mild Cognitive Impairment, Alzheimer’s Disease and Related Dementias

Stroke ◽

10.1161/str.52.suppl_1.mp18 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Alan Pan ◽

Jennifer Meeks ◽

Thomas Potter ◽

Osman Khan ◽

Sudha Seshadri ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Clinical Laboratory ◽

Management Strategies ◽

High Risk Group ◽

Targeted Prevention ◽

Logistic Regression Models ◽

Comorbidity Burden

Introduction: We evaluated the burden of SARS-CoV-2 susceptibility and COVID-19 mortality associated with Mild Cognitive Impairment (MCI) or Dementia (MCID). Methods: We analyzed data from COVID-19 Outcomes Registry (CURATOR) at Houston Methodist; a tertiary healthcare system in greater Houston. All adult (≥ 18 years) patients tested for SARS-CoV-2 RNA in nasopharyngeal swabs were included. Utilizing validated ICD-10 codes (MCI, Alzheimer’s Disease, Vascular and Other Dementias) and use of MCID specific medications, we flagged patients with preexisting MCID. Logistic regression models were fitted to evaluate the odds of SARS-CoV-2 susceptibility and COVID-19 mortality associated with preexisting MCID. Odds ratios (OR) and 95% Confidence Intervals (CI) are reported. Results: Between March 3 and August 10, 2020; 86,614 individuals were tested, of whom 14,233 (16.4%) tested positive, with 4,473 (31.4%) hospitalizations, and 431 (9.6%) deaths. Overall 3,069 individuals had preexisting MCID; among whom 518 (16.9%) tested positive. Among all SARS-CoV-2 positive cases, MCID patients (vs. non MCID group) were older (79.9 vs. 47.3 years) and had higher overall comorbidity burden (median Charlson Comorbidity Index: 6 vs. 0), with higher proportion (%) of hypertension (90.3 vs. 39.0), heart failure (37.8 vs. 7.5), diabetes (69.3 vs. 28.2), and cancer (14.5 vs. 4.8). Mortality among MCID patients (vs. non MCID) was 22.3% vs. 8.6%. In fully adjusted models (demographics, comorbidities, clinical / laboratory parameters, complications, treatment and ICU admission), pre-existing MCID was independently associated with higher SARS-CoV-2 susceptibility, OR (CI) 1.62 (1.46-1.80) and in-hospital mortality OR (CI): 1.79 (1.23-2.61) among COVID-19 patients (graphic). Conclusions: Regardless of age, MCID is a potential risk factor for SARS-CoV-2 infection and COVID-19 mortality. Targeted prevention and management strategies are warranted for this high-risk group.

Download Full-text

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

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.688478 ◽

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.

Download Full-text

Subjective Cognitive Complaints Contribute to Misdiagnosis of Mild Cognitive Impairment

Journal of the International Neuropsychological Society ◽

10.1017/s135561771400068x ◽

2014 ◽

Vol 20 (8) ◽

pp. 836-847 ◽

Cited By ~ 98

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)

Download Full-text

Associations of Pulse and Blood Pressure with Hippocampal Volume by APOE and Cognitive Phenotype: The Alzheimer’s Disease Neuroimaging Initiative (ADNI)

Dementia and Geriatric Cognitive Disorders ◽

10.1159/000486955 ◽

2018 ◽

Vol 45 (1-2) ◽

pp. 66-78 ◽

Cited By ~ 3

Author(s):

Julius S. Ngwa ◽

Thomas V. Fungwe ◽

Oyonumo Ntekim ◽

Joanne S. Allard ◽

Sheree M. Johnson ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Blood Pressure ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Hippocampal Volume ◽

Cognitive Status ◽

Brain Volumes ◽

Using Data

Background: It is increasingly evident that high blood pressure can promote reduction in global and regional brain volumes. While these effects may preferentially affect the hippocampus, reports are inconsistent. Methods: Using data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), we examined the relationships of hippocampal volume to pulse pressure (PPR) and systolic (SBP) and diastolic (DBP) blood pressure according to apolipoprotein (APOE) ɛ4 positivity and cognitive status. The ADNI data included 1,308 participants: Alzheimer disease (AD = 237), late mild cognitive impairment (LMCI = 454), early mild cognitive impairment (EMCI = 254), and cognitively normal (CN = 365), with up to 24 months of follow-up. Results: Higher quartiles of PPR were significantly associated with lower hippocampal volumes (Q1 vs. Q4, p = 0.034) in the CN and AD groups, but with increasing hippocampal volume (Q1, p = 0.008; Q2, p = 0.020; Q3, p = 0.017; Q4 = reference) in the MCI groups. In adjusted stratified analyses among non-APOE ɛ4 carriers, the effects in the CN (Q1 vs. Q4, p = 0.006) and EMCI groups (Q1, p = 0.002; Q2, p = 0.013; Q3, p = 0.002; Q4 = reference) remained statistically significant. Also, higher DBP was significantly associated with higher hippocampal volume (p = 0.002) while higher SBP was significantly associated with decreasing hippocampal volume in the EMCI group (p = 0.015). Conclusion: Changes in PPR, SBP, and DBP differentially influenced hippocampal volumes depending on the cognitive and APOE genotypic categories.

Download Full-text

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

GSC Advanced Research and Reviews ◽

10.30574/gscarr.2021.6.3.0062 ◽

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.

Download Full-text

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

Voprosy Virusologii ◽

10.36233/0507-4088-32 ◽

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.

Download Full-text

Efficacy and Safety of Citicoline to Prevent Cognitive Deficiency Progression in First-Degree Relatives of Patients with Alzheimer’s Disease: Prospective Study

Psychiatry ◽

10.30629/2618-6667-2020-18-4-33-40 ◽

2020 ◽

Vol 18 (4) ◽

pp. 33-40

Author(s):

N. D. Seleznеva ◽

S. I. Gavrilova ◽

E. V. Ponomareva

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Prospective Study ◽

Cognitive Functioning ◽

Cognitive Dysfunction ◽

Cognitive Status ◽

First Degree Relatives ◽

Mild Cognitive Impairment Syndrome

Objective: study of the prolonged effects of a three-month course of therapy with citicoline, carried out three times for three years, to prevent the progression of cognitive deficit in 1st-degree relatives of patients with Alzheimer’s disease (AD).Study participants: the study involved first-degree relatives of patients with an established diagnosis of AD.Study design: an openlabel comparative three-year prospective study of the dynamics of cognitive status in two groups of relatives, one of whom received citicoline therapy (1st group), and the other did not (2nd group). The 1st group made up 48 relatives (11 — with mild cognitive impairment syndrome and 37 — with signs of minimal cognitive dysfunction). 32 relatives who had not received drug treatment for 3 years (8 of them had objectively confirmed signs of minimal cognitive dysfunction, in 24 people — cognitive functioning corresponded to the normal aging) were included to 2nd group. The groups did not have significant differences in demographic characteristics and distribution of the ApoE4(+) genotype carriers.Methods: clinical and psychological, psychometric, ApoE genotyping, statistical.Results: in the therapeutic group, a significant improvement in the cognitive status was found in 75.0% of the treated relatives with cognitive disfunction on most scales and tests, with the exception of the clock drawing test. In the group of relatives who did not receive drug therapy, there was a significant deterioration of cognitive functioning — in 2 cases with the formation of mild cognitive impairment syndrome, in 21 cases — with the appearance of minimal cognitive signs.Conclusion: the results of a three-year preventive course of citicoline therapy showed a significant positive effect of the drug on the cognitive status of the 1st degree relatives of AD patients who had signs of cognitive impairment that did not reach the level of dementia.

Download Full-text