Form Of Mild Cognitive Impairment Research Articles

PET imagining in Alzheimer’s disease

Purpose. The purpose of this article is to explore the potential of positron emission tomography (PET) in early diagnosis of Alzheimer's disease (AD), monitoring of disease progression and assessment of treatment effectiveness. And also, to become familiar with advantages and disadvantages of application of various radiopharmaceuticals.
 Materials and methods. The material for the study was the scientific results of publications in professional scientific journals of the leading countries of the world of scientific and clinical activity over the past 10 years on the clinical significance of hybrid radiation imaging methods in the diagnosis and treatment of patients with AD. The study involved the use of PET radiation imaging methods in Alzheimer's disease.
 Results. The efficacy of PET at different stages of AD has been demonstrated. The advantages and disadvantages of using different PET techniques and different radiopharmaceuticals are discussed. PET, unlike other biomarkers, is able to assess the prevalence of lesions, evaluate progression and make a prediction of the further course of the disease.
 Conclusions. Positron emission tomography in patients with AD is an effective diagnostic technique that can be used at different stages from the prodromal period in the form of mild cognitive impairment to assessing the progression or effectiveness of treatment in numerous clinical trials.

Item‐based scoring and serial position of words generated during the Category Fluency Test: differences between controls and MCI subtypes

AbstractBackgroundThe order in which words are recalled during the 1‐minute Category Fluency Test (CFT) can be informative about the integrity of the underlying semantic memory (SM) system. Typically, the first entries tend to be easier exemplars and, as the category is explored in more depth during the course of the minute, words generated tend to become more difficult. We hypothesised that an item‐based scoring method that quantifies this increase in difficulty will help identify the semantic feature(s) most sensitive to the loss of SM integrity observed in people with a form of mild cognitive impairment (MCI).MethodTwo‐hundred participants (age: 58.68 ± 12.08 years) were sub‐divided into four clinical diagnostic groups: 50 healthy controls, 50 individuals with amnestic MCI, 50 individuals with non‐amnestic MCI and 50 individuals with subjective cognitive complaints but no objective deficits. No differences in age, years of education or gender existed across the four groups. All participants were administered a 1‐minute CFT (two categories: animals and fruits). Individual performance was scored word‐by‐word according to nine semantic features: age of acquisition, frequency, prevalence, recognition time, valence, arousal, dominance, sensorimotor interaction and concreteness. Correlation coefficients (Spearman’s rho) were calculated between each feature and the serial position of each word within the list. Correlations were then converted to z‐scores and analysed across the four groups with Kruskal‐Wallis one‐way analyses of variance.ResultThe z‐converted correlation between serial position and dominance was the only one differing across groups (at a p = 0.009). Bonferroni‐corrected post‐hoc tests showed a difference between healthy controls and individuals with amnestic MCI (p = 0.008). The decline in word dominance was significantly steeper in the group of amnestic MCI (z = ‐0.322) than in controls (z = ‐0.199).ConclusionThe study of SM is relevant to characterising the clinical mechanisms of normal and abnormal ageing. A procedure that focuses on CFT words difficulty and order of recall can complement classic methods that are typically used to detect loss of SM integrity. This pilot study indicates that ‘dominance’ is a semantic feature that might help characterise loss of SM integrity in individuals with amnestic MCI.

Olfactory Mucosal Cells of Individuals with Alzheimer’s Disease Display Alterations Similar to the Alzheimer Brain

AbstractBackgroundA sense of smell is orchestrated in the first place by the cells of the olfactory mucosa (OM), located in the rooftop of the nasal cavity. Impairments in olfaction are implicated in aging but also in Alzheimer’s disease (AD). Here, we describe the observed alterations in cultures of OM cells derived from individuals with late‐onset AD or amnestic form of mild cognitive impairment (MCI) when compared to OM cells derived from their cognitively healthy control subjects.MethodPrimary cultures of OM cells were harvested from biopsies of OM derived from cognitively healthy individuals and individuals with late‐onset AD or amnestic MCI and cultured in vitro. First, the cell types present in cultures of OM cells and genes differentially expressed between the OM cells derived from control subjects and individuals AD or MCI OM were assessed by single cell RNA‐sequencing (scRNA‐seq). Next, a total RNA‐seq was applied to a larger cohort of samples. The results of total and scRNA‐seq were further validated with various functional in vitro assays including inductively coupled plasma mass spectrometry (ICP‐MS) and measurements of intracellular ATP levels.ResultThe scRNA‐seq unveiled a total of five distinct cell populations in OM cell cultures. A total of 240 previously AD‐related genes were found to be differentially expressed between the AD and control OM cell cultures. Similarly, the MCI OM cells harbored 224 differentially expressed genes when compared to OM cells derived from their control subjects. Common for both AD and MCI OM cells were the alterations in genes related to mitochondrial function when compared to controls. Additionally, the ICP‐MS revealed increased levels of zinc, calcium and sodium in the AD OM cells in comparison to the OM cells derived from cognitively healthy subjects.ConclusionThe results implicate the role of olfactory mucosa as a site displaying early alterations related to Alzheimer’s disease.

Biotypes of Central Nervous System Complications in People With Human Immunodeficiency Virus: Virology, Immunology, and Neuropathology.

Despite viral suppression with antiretroviral therapy (ART), people with human immunodeficiency virus (HIV) continue to experience central nervous system (CNS) complications, primarily in the form of mild cognitive impairment and mental health disorders (eg, depression, anxiety, other neuropsychiatric problems). The multifactorial pathogenesis and heterogeneity of mechanisms likely underlying CNS complications must be addressed in the development of preventive interventions and effective treatments. The biotyping approach has previously been useful to define phenotypes of other CNS diseases based on underlying mechanisms and could be translated to the field of neuroHIV. The purpose of the Biotype Workshop series, and the Virology, Immunology and Neuropathology Working Group in particular, is to capitalize on current and new technologies and guide future research efforts using the wealth of available immunological, virologic, and neuropathological data collected from people with HIV on and off ART.

Ginkgo biloba Extract EGb 761 in the Treatment of Patients with Mild Neurocognitive Impairment: A Systematic Review.

Many clinical trials testing Ginkgo biloba extract EGb 761 in patients with mild forms of cognitive impairment were conducted before widely accepted terms and diagnostic criteria for such conditions were available. This makes it difficult to compare any results from earlier and more recent trials. The objective of this systematic review was to provide a descriptive overview of clinical trials of EGb 761 in patients who met the diagnostic criteria for mild neurocognitive disorder (mild NCD) according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5). MEDLINE, PubMed and EMBASE were searched for randomized, placebo-controlled double-blind trials of EGb 761 in mild impairment of cognitive functioning. All trials involving patients who met retrospectively applied diagnostic criteria for mild NCD were included. Trials of primary prevention of dementia and trials of combinations of medical treatments were excluded. Among 298 records found in databases and 76 further records related to EGb 761 in references of systematic reviews, 9 reports on clinical trials involving 946 patients met the pre-specified criteria for inclusion. Beneficial effects of EGb 761 were seen in neuropsychological tests (8 of 9 studies), scales for neuropsychiatric symptoms (3 of 3 studies), geriatric rating scales (1 of 2 studies) and global ratings of change (1 of 1 study). Significant effects were found in several domains of cognition (memory, speed of processing, attention and executive functioning). Among the neuropsychiatric symptoms, depression (2 of 3 studies) and anxiety (1 of 1 study) were significantly improved. No differences between EGb 761 treatment and placebo were seen with regard to the rates of adverse events. The included studies demonstrate treatment benefits of Ginkgo biloba extract EGb 761, mainly on cognitive deficits and neuropsychiatric symptoms, in patients with mild NCD. The drug was safe and well tolerated.

Issues of diagnosis and treatment of mild cognitive impairment

Cognitive impairment refers to frequent disorders in the elderly and senile, and their prevalence increases with age significantly. Non-dementia cognitive disorders mean a spectrum of changes in the cognitive sphere that precede the development of dementia over the course of many months and even years. Mild forms of cognitive impairment (MCI) are the most studied type of pre-dementia conditions, which in most cases represent a prodromal stage of disorders progressing over time to a dementia syndrome. Early identification of individuals with MCI is important because timely diagnosis of these disorders is expanding the potential impact of the secondary prevention and therapeutic intervention, which can delay or even prevent the onset of professional and social maladaptation due to development of dementia. The article considers the historical issues of studying these disorders, presents the modern principles of their classification and diagnostic criteria. A clinical observation of a patient with a polyfunctional non-amnestic type MCI syndrome is provided. The features of cognitive disorders typical for chronic cerebrovascular insufficiency, such as mental retardation, impaired activity arrangement, difficulties with generalisation in relative preservation of memory and orientation in combination with emotional and affective disorders are described. The authors discuss issues of treatment of MCI syndrome, which should be comprehensive and include the correction of all vascular risk factors, non-drug (regular physical activity, cognitive training) and pharmacological treatments aimed at improving cognitive performance. The article describes the possibilities of modern neuroprotective and symptomatic therapy of cognitive impairment, showing the role of choline alfoscerate in the treatment of MCI.

Convergent and divergent oscillatory aberrations during visuospatial processing in HIV-related cognitive impairment and Alzheimer's disease.

Adults with HIV frequently develop a form of mild cognitive impairment known as HIV-associated neurocognitive disorder (HAND), but presumably cognitive decline in older persons with HIV could also be attributable to Alzheimer's disease (AD). However, distinguishing these two conditions in individual patients is exceedingly difficult, as the distinct neural and neuropsychological features are poorly understood and most studies to date have only investigated HAND or AD spectrum (ADS) disorders in isolation. The current study examined the neural dynamics underlying visuospatial processing using magnetoencephalography (MEG) in 31 biomarker-confirmed patients on the ADS, 26 older participants who met criteria for HAND, and 31 older cognitively normal controls. MEG data were examined in the time-frequency domain, and a data-driven approach was utilized to identify the neural dynamics underlying visuospatial processing. Both clinical groups (ADS/HAND) were significantly less accurate than controls on the task and exhibited stronger prefrontal theta oscillations compared to controls. Regarding disease-specific alterations, those with HAND exhibited stronger alpha oscillations than those on the ADS in frontoparietal and temporal cortices. These results indicate both common and unique neurophysiological alterations among those with ADS disorders and HAND in regions serving visuospatial processing and suggest the underlying neuropathological features are at least partially distinct.

Imaging Cognitive Impairment and Impulse Control Disorders in Parkinson's Disease

Dementia and mild forms of cognitive impairment as well as neuropsychiatric symptoms (i. e., impulse control disorders) are frequent and disabling non-motor symptoms of Parkinson's disease (PD). The identification of changes in neuroimaging studies for the early diagnosis and monitoring of the cognitive and neuropsychiatric symptoms associated with Parkinson's disease, as well as their pathophysiological understanding, are critical for the development of an optimal therapeutic approach. In the current literature review, we present an update on the latest structural and functional neuroimaging findings, including high magnetic field resonance and radionuclide imaging, assessing cognitive dysfunction and impulse control disorders in PD.

Preventing Loss of Independence through Exercise (PLIÉ): A Pilot Trial in Older Adults with Subjective Memory Decline and Mild Cognitive Impairment.

Background:Preventing Loss of Independence through Exercise (PLIÉ) is a group movement program initially developed for people with mild-to-moderate dementia that integrates principles from several well-established traditions to specifically address the needs of people with cognitive impairment.Objective:To investigate whether PLIÉ would benefit cognitive and behavioral outcomes and functional brain connectivity in older adults with milder forms of cognitive impairment.Methods:Participants (≥55 y) with subjective memory decline (SMD) or mild cognitive impairment (MCI) were assessed with tests of cognitive and physical function, self-report questionnaires, and resting state functional magnetic resonance imaging (rs-fMRI) on a 3 Tesla scanner before and after participating in twice weekly PLIÉ classes for 12 weeks at the San Francisco Veterans Affairs Medical Center.Results:Eighteen participants completed the pre-post intervention pilot trial. We observed significant improvements on the Alzheimer’s Disease Assessment Scale cognitive subscale (ADAS-cog; effect size 0.34, p = 0.002) and enhanced functional connections between the medial prefrontal cortex (mPFC) and other nodes of the default mode network (DMN) after PLIÉ. Improvements (i.e., lower scores) on ADAS-cog were significantly correlated with enhanced functional connectivity between the mPFC and left lateral parietal cortex (Spearman’s ρ= –0.74, p = 0.001) and between the mPFC and right hippocampus (Spearman’s ρ= –0.83, p = 0.001). After completing PLIÉ, participants reported significant reductions in feelings of social isolation and improvements in well-being and interoceptive self-regulation.Conclusion:These preliminary findings of post-PLIÉ improvements in DMN functional connectivity, cognition, interoceptive self-regulation, well-being and reduced feelings of social isolation warrant larger randomized, controlled trials of PLIÉ in older adults with SMD and MCI.

Severity and treatment of cognitive impairment

With an increase in life expectancy in the population, the proportion of people with cognitive impairment (CI) increases. Modern neurology focuses on the milder forms of CI: moderate, mild, and subjective CI, which are more promising in terms of successful treatment and slowing down their progression. Age is the leading risk factor for CI, the prevalence of which in the general population of people aged over 65 years reaches 10–15%. The primary role in CI development is played by Alzheimer's disease, cerebrovascular diseases, mixed vascular-neurodegenerative process, and other types of neurodegenerative diseases, and all of them share some pathophysiological mechanisms. Correction of vascular risk factors plays a leading role in the treatment of pre-dementia stages of CI. The possibilities of using nimodipine in the therapy of CI are analyzed.

MO204CHRONIC KIDNEY DISEASE, SLEEPINESS, MILD COGNITIVE IMPAIRMENT AND FINE MOTOR CONTROL

Abstract Background and Aims Chronic kidney disease (CKD) is a systemic condition because it modifies all organs' function due to an imbalance in plasma volume, electrolytes, hormones, and proteins. Indeed, at the nervous system level, mild cognitive impairment (MCI), sleep disorders and depression often accompany CKD. MCI partially explains the low quality of life of CKD patients, comparable to that of metastatic cancer patients. Mild Cognitive Impairment (MCI) has a high prevalence in this cohort (27-62%). Nevertheless, scattered literature data suggest that CKD patients can also have poor motor control, evidenced by a higher risk of falls, postural instability, reduced gait speed. In this cohort, few data are available regarding the motor circuits called central pattern generators, which control physiological tremor. Specifically, uraemic encephalopathy accentuates physiological tremor, which is regulated by central and peripheral oscillators. Overall, subtle changes in motor control often accompany other forms of MCI. Therefore, this study aimed at evaluating the effects of chronic kidney disease on cognitive and motor functions using up-to-date technologies to record physiological tremor and innovative data analysis. Method This retrospective case-control study enrolled 313 patients (139 controls, 79 CKD patients stage III-IV, 35 kidney transplant (Tx), 60 dialysis (HD) patients). These groups were comparable for age and weight. Creatininemia, azotemia, LDL, HDL, hemoglobin, and proteinuria were used for correlative analyses. We evaluated the chronotype using the Morningness-Eveningness Questionnaire (MEQ) and the degree of sleepiness using the Epworth Sleepiness Scale (ESS). Cognitive impairment was assessed by the Montreal Cognitive Assessment test (MoCA). Cognitive domains of the MoCA score were projected onto brain regions using CerebroViz library in R and a new transformation matrix derived from fMRI literature data. UMAP algorithm was used to identify patients' subgroups. The physiological tremor was recorded on patients maintaining the dominant arm extended using the smartphone App Phyphox. The tremor frequency spectrum was extracted by Fourier analysis. Results The sleepiness score (ESS) was significantly increased in HD (ESS = 5±0.4) compared to the healthy controls (ESS= 4±0.41) whereas was not significantly modified in CKD patients (3.24± 0.32). The chronotype was also not significantly different among the various groups. The mean score of the MoCA test was significantly lower in CKD, Tx, and HD groups (CKD MoCA =24.5±0.3; Tx MoCA =25.4±0.6; HD MoCA =24.6±0.7) than controls (MoCA score=28±0.1). A different pattern of impairment in the cognitive domains of MoCA was evidenced in the various groups using the CerebroViz projection and UMAP tools. MoCA score was inversely correlated with proteinuria (Pearson coefficient=-0.47; p<0.05). The higher frequencies of the physiological tremor (11-13 Hz) were significantly more represented in Tx patients compared to controls (p<0.05). Conversely, the lower frequencies (1-4 Hz) were significantly less represented in the HD group compared to controls (p<0.05). The peak frequency was inversely correlated with age in all patients (Pearson coefficient= -0.45; p<0.05) and inversely associated with azotemia levels, particularly in HD patients (Pearson coefficient=0.43; p<0.05). Conclusion Our results suggest that CKD patients present altered cognitive and motor control patterns, linked in part to the proteinuria level, suggesting a pathogenetic role of endothelial dysfunction. The characteristic motor, sleepiness and cognitive patterns of HD patients might be due to the arteriovenous fistula or the other peculiarities of these patients. These results might help identify new early markers of brain dysfunction in these patients, with the possibility of delaying or reversing cognitive decay.

Reduced rank multinomial logistic regression in Markov chains with application to cognitive data.

Finite Markov chains are useful tools for studying transitions among health states; these chains can be complex consisting of a mix of transient and absorbing states. The transition probabilities, which are often affected by covariates, can be difficult to estimate due to the presence of many covariates and/or a subset of transitions that are rarely observed. The purpose of this article is to show how to estimate the effect of a subset of covariates of interest after adjusting for the presence of multiple other covariates by applying multidimensional dimension reduction to the latter. The case in which transitions within each row of the one-step transition probability matrix are estimated by multinomial logistic regression is discussed in detail. Dimension reduction for the adjustment covariates involves estimating the effect of the covariates by a product of matrices iteratively; at each iteration one matrix in the product is fixed while the second is estimated using either standard software or nonlinear estimation, depending on which of the matrices in the product is fixed. The algorithm is illustrated by an application where the effect of at least one Apolipoprotein-E (APOE) gene allele on transition probability is estimated in a Markov Chain that includes adjustment for eight covariates and focuses on transitions from normal cognition to several forms of mild cognitive impairment, with possible absorption into dementia. Data were drawn from annual cognitive assessments of 649 participants enrolled in the BRAiNS cohort at the University of Kentucky's Alzheimer's Disease Research Center.

Living With Cognitive Impairment in China: Exploring Dyadic Experiences Through a Person-Centered Care Lens.

China has experienced a substantial increase in the number of older adults with dementia and milder forms of cognitive impairment. Being spouses of Persons with cognitive impairment (PWCI) and living with them for several decades does not necessarily mean that it is easier for them to provide person-centered care and maintain a valued and healthy relationship. The current study explored how elements of PCC, as operationalized by the Senses Framework, operate or fail to operate in the dyadic experiences of PWCI and their spousal care partners within the socio-cultural context of China. Our findings suggest that PWCI and their spouses experience the six senses through the person-centeredness in their daily interactions with each other. It also indicated successes and challenges to being person-centered early in the disease and identified their unmet needs as well as barriers and facilitators to improve their well-being.

Assessment Of Cardiorespiratory Fitness In Older Adults With Cognitive Impairment

Interest in the potential benefits of physical activity (PA) and exercise on cognition in late life has grown exponentially in the past decade. Peak oxygen uptake (VO2) is one of the most widely used metrics of physical fitness. The most accurate measure of VO2 is cardiopulmonary testing (CPX); however, this method may not be easily accessible in many settings nor appropriate for all populations, including older adults. Self-report measures of PA are easily administered and readily available, yet these measures rely on an accurate recall of past activity. This may be difficult for older adults with even mild forms of cognitive impairment. Identifying alternative methods that accurately estimate a patient’s physical fitness are essential. PURPOSE: To evaluate the use of multiple measures of physical fitness in a sample of older adults with amnestic Mild Cognitive Impairment (aMCI). METHODS: The sample included 105 older adults who were diagnosed with aMCI (93.3% male, aged = 71.2 ± 9.2 years). Measures of physical fitness included CPX, 6-minute walk test (6MWT), and the Yale Physical Activity Survey (YPAS). Analysis included comparison of the sub-maximal measures of physical fitness (6MWT) and self-report measures (YPAS) with directly-measured cardiorespiratory fitness on key measures on physiologic measures of fitness (e.g., peak VO2, resting blood pressure (BP), BMI). RESULTS: The 6MWT demonstrated a stronger correlation with directly-measured peak VO2 (r = 0.62, p = 0.00) compared to YPAS. The YPAS activity dimensions summary index (composed of questions on vigorous activity, leisurely walking, moving, sitting, and standing) correlated marginally with VO2max (r = 0.28; P = 0.01). The YPAS index of vigorous activity was slightly correlated with VO2max (r = 0.21; P = 0.03). CPX was inversely correlated with BMI (r=-0.21; P=0.03) and non-significantly with resting BP. Resting BP and BMI was not significantly associated with 6MWT nor the YPAS indices. CONCLUSION: The present analysis suggests that even mild forms of cognitive impairment impact the validity of self-report measures of physical fitness. Sub-maximal tests of aerobic capacity, such as the 6MWT, provide more accurate estimates of cardiorespiratory fitness and are easily administered in a variety of settings in which older adults receive health care.

Cognitive Impairment and Dementia in Parkinson's Disease

Cognitive decline is common in Parkinson's disease (PD) and is a leading cause of reduced quality of life. Cognitive difficulty seen early in the course of PD takes the form of mild cognitive impairment (MCI-PD), and Parkinson's disease dementia (PDD) is nearly universal in the late stages of the disease. Although most people with MCI-PD will progress to PDD, the two entities have significant differences in terms of underlying pathophysiology as well as cognitive profiles and management strategies. The most important contributor to MCI-PD is frontostriatal dopamine depletion, whereas the major cause of PDD is Lewy body pathology spreading to the neocortex plus, in many cases, comorbid Alzheimer's pathology. Management strategies for both MCI-PD and PDD are limited. The best approach for MCI-PD is a combination of cognitive rehabilitation and appropriate titration of dopaminergic therapy, and the medications used in treatment of Alzheimer's disease appear to have a modest benefit for patients with PDD. [ Psychiatr Ann . 2020;50(3):100–106.]

Cognitive Function, Access to Kidney Transplantation, and Waitlist Mortality Among Kidney Transplant Candidates With or Without Diabetes

Intact cognition is generally a prerequisite for navigating through and completing evaluation for kidney transplantation. Despite kidney transplantation being contraindicated for those with severe dementia, screening for more mild forms of cognitive impairment before referral is rare. Candidates may have unrecognized cognitive impairment, which may prolong evaluation, elevate mortality risk, and hinder access to kidney transplantation. We estimated the burden of cognitive impairment and its association with access to kidney transplantation and waitlist mortality. Prospective cohort study. 3,630 participants (January 2009 to June 2018) with cognitive function measured (by the Modified Mini-Mental State Examination [3MS]) at kidney transplantation evaluation at 1 of 2 transplantation centers. Cognitive impairment (3MS score<80). Listing, waitlist mortality, and kidney transplantation. We estimated the adjusted chance of listing (Cox regression), risk for waitlist mortality (competing-risks regression), and kidney transplantation rate (Poisson regression) by cognitive impairment. Given potential differences in cause of cognitive impairment among those with and without diabetes, we tested whether these associations differed by diabetes status using a Wald test. At evaluation, 6.4% of participants had cognitive impairment, which was independently associated with 25% lower chance of listing (adjusted HR, 0.75; 95% CI, 0.61-0.91); this association did not differ by diabetes status (Pinteraction=0.07). There was a nominal difference by diabetes status for the association between cognitive impairment and kidney transplantation rate (Pinteraction=0.05), while the association between cognitive impairment and waitlist mortality differed by diabetes status kidney transplantation rates (Pinteraction=0.02). Among candidates without diabetes, those with cognitive impairment were at 2.47 (95% CI, 1.31-4.66) times greater risk for waitlist mortality; cognitive impairment was not associated with this outcome among candidates with diabetes. Single measure of cognitive impairment. Cognitive impairment is associated with a lower chance of being placed on the waitlist, and among patients without diabetes, with increased mortality on the waitlist. Future studies should investigate whether implementation of screening for cognitive impairment improves these outcomes.

Abnormalities of saccadic eye movements in dementia due to Alzheimer's disease and mild cognitive impairment.

Background: There is increasing evidence that people in the early stages of Alzheimer’s disease (AD) have subtle impairments in cognitive inhibition that can be detected by using relatively simple eye-tracking paradigms, but these subtle impairments are often missed by traditional cognitive assessments. People with mild cognitive impairment (MCI) are at an increased likelihood of dementia due to AD. No study has yet investigated and contrasted the MCI subtypes in relation to eye movement performance. Methods: In this work we explore whether eye-tracking impairments can distinguish between patients with the amnesic and the non-amnesic variants of MCI. Participants were 68 people with dementia due to AD, 42 had a diagnosis of aMCI, and 47 had a diagnosis of naMCI, and 92 age-matched cognitively healthy controls. Results: The findings revealed that eye-tracking can distinguish between the two forms of MCI. Conclusions: The work provides further support for eye-tracking as a useful diagnostic biomarker in the assessment of dementia.

A parameter-efficient deep learning approach to predict conversion from mild cognitive impairment to Alzheimer's disease

Some forms of mild cognitive impairment (MCI) are the clinical precursors of Alzheimer's disease (AD), while other MCI types tend to remain stable over-time and do not progress to AD. To identify and choose effective and personalized strategies to prevent or slow the progression of AD, we need to develop objective measures that are able to discriminate the MCI patients who are at risk of AD from those MCI patients who have less risk to develop AD. Here, we present a novel deep learning architecture, based on dual learning and an ad hoc layer for 3D separable convolutions, which aims at identifying MCI patients who have a high likelihood of developing AD within 3 years.Our deep learning procedures combine structural magnetic resonance imaging (MRI), demographic, neuropsychological, and APOe4 genetic data as input measures. The most novel characteristics of our machine learning model compared to previous ones are the following: 1) our deep learning model is multi-tasking, in the sense that it jointly learns to simultaneously predict both MCI to AD conversion as well as AD vs. healthy controls classification, which facilitates relevant feature extraction for AD prognostication; 2) the neural network classifier employs fewer parameters than other deep learning architectures which significantly limits data-overfitting (we use ∼550,000 network parameters, which is orders of magnitude lower than other network designs); 3) both structural MRI images and their warp field characteristics, which quantify local volumetric changes in relation to the MRI template, were used as separate input streams to extract as much information as possible from the MRI data. All analyses were performed on a subset of the database made publicly available via the Alzheimer's Disease Neuroimaging Initiative (ADNI), (n = 785 participants, n = 192 AD patients, n = 409 MCI patients (including both MCI patients who convert to AD and MCI patients who do not covert to AD), and n = 184 healthy controls).The most predictive combination of inputs were the structural MRI images and the demographic, neuropsychological, and APOe4 data. In contrast, the warp field metrics were of little added predictive value. The algorithm was able to distinguish the MCI patients developing AD within 3 years from those patients with stable MCI over the same time-period with an area under the curve (AUC) of 0.925 and a 10-fold cross-validated accuracy of 86%, a sensitivity of 87.5%, and specificity of 85%. To our knowledge, this is the highest performance achieved so far using similar datasets. The same network provided an AUC of 1 and 100% accuracy, sensitivity, and specificity when classifying patients with AD from healthy controls. Our classification framework was also robust to the use of different co-registration templates and potentially irrelevant features/image portions.Our approach is flexible and can in principle integrate other imaging modalities, such as PET, and diverse other sets of clinical data. The convolutional framework is potentially applicable to any 3D image dataset and gives the flexibility to design a computer-aided diagnosis system targeting the prediction of several medical conditions and neuropsychiatric disorders via multi-modal imaging and tabular clinical data.

Discriminative capacity and construct validity of the Clock Drawing Test in Mild Cognitive Impairment and Alzheimer’s disease

Objectives: The aim of this study was to analyze the psychometric and diagnostic properties of the Clock Drawing Test (CDT), scored according to the Babins, Rouleau, and Cahn scoring systems, for Mild Cognitive Impairment (MCI) and Alzheimer’s disease (AD) screening, and develop corresponding cutoff scores. Additionally, we assessed the construct validity of the CDT through exploratory and confirmatory factor analysis.Methods: We developed a cross-sectional study of ambulatory MCI and AD patients, divided in two clinical groups (450 MCI and 250 mild AD patients) and a normal control group (N = 400). All participants were assessed with the CDT, Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) for convergent validity.Results: The selected scoring systems presented adequate validity and reliability values. The proposed cutoff scores showed 60 to 65% sensitivity and 58 to 62% specificity to identify MCI patients. The corresponding values for AD were 84 to 90% sensitivity and 76 to 78% specificity. Exploratory and confirmatory factor analysis revealed that the Babins scoring system had good construct validity and allowed us to propose a three-factor model for this system.Conclusions: Our results confirmed the complexity of the CDT and support it as a cognitive screening instrument particularly sensitive to AD. The use of the CDT with MCI patients should be interpreted with more caution due to the lower sensitivity and specificity for milder forms of cognitive impairment.

The association between asymptomatic and mild neurocognitive impairment and adherence to antiretroviral therapy among people living with human immunodeficiency virus.

BackgroundAsymptomatic cognitive impairment in human immunodeficiency virus (HIV)-infected patients has recently been recognised as part of HIV-associated neurocognitive disorders. This has been implicated as one of the causes of poor adherence to antiretroviral therapy (ART).ObjectiveTo assess the association between neurocognitive impairment (asymptomatic and mild forms) and adherence to ART.MethodsThis was a cross-sectional survey involving 218 participants consecutively sampled from those attending the HIV treatment clinic at Aga Khan University Hospital in Nairobi. Data collected included quantitative primary data on pre-defined baseline characteristics, neurocognitive assessment by Montreal Cognitive Assessment (MoCA) tool (Appendix 1), instrumental activities of daily living by Lawton score and objective and subjective adherence measures by medication possession ratio (MPR) and simplified medication adherence questionnaire (SMAQ) (see Appendix 2). Univariate and bivariate analyses were conducted to determine the strengths of association between predictor and the outcome variables.ResultsAmong the 218 participants in the study, a total of 69% had asymptomatic to mild neurocognitive impairment as assessed by the MoCA tool, while a total of 66% were determined as being adherent to ART by objective measures (by MPR) compared to subjective rates of 77% as assessed by SMAQ. However, no statistically significant association was observed between the presence of asymptomatic or mild neurocognitive impairment and likelihood of adherence to ART (p > 0.05).ConclusionEven though asymptomatic and mild forms of cognitive impairment are prevalent in the population studied, there was no significant association between cognitive impairment and adherence to treatment.