Early Stages Of Cognitive Impairment Research Articles

Feature selection using efficient fusion of Fisher Score and greedy searching for Alzheimer’s classification

Alzheimer’s disease is one of the deadly progressive neurodegenerative diseases among aged populations. But, the progression of the disease can be reduced by proper treatment of the disease during the early stages of cognitive impairment. The main objective of this study is to implement an efficient feature selection algorithm for the detection of Alzheimer’s patients at the baseline stage itself using multimodal data. In this paper, we propose an efficient fusion of Fisher Score ranking and greedy searching heuristic as feature selection criteria for Alzheimer’s prediction. The proposed algorithm provides a Balanced Classification Accuracy of 90% and 91% and Multi Area Under the Curve of 0.97, 0.98 using Support Vector Machine, K-Nearest Neighbor respectively for classifying Normal Controls, Mild Cognitive Impairment, and Alzheimer’s patients on Alzheimer’s Disease Neuroimaging Initiative-TADPOLE dataset at baseline visit itself. Moreover, the proposed algorithm also provides better sensitivity, specificity of 84%, 82.5% using Support Vector Machine, K-Nearest Neighbor for binary classification of Mild Cognitive Impairment, and Alzheimer’s patients on the Australian Imaging and Biomarker Lifestyle dataset also. Our results indicate that the proposed methodology with efficient feature selection is promising and can outperform the state of the art methods for early detection of Alzheimer’s.

A Comparison of Speech Features between Mild Cognitive Impairment and Healthy Aging Groups.

Background and PurposeLanguage dysfunction is a symptom common to patients with Alzheimer's disease (AD). Speech feature analysis may be a patient-friendly screening test for early-stage AD. We aimed to investigate the speech features of amnestic mild cognitive impairment (aMCI) compared to normal controls (NCs).MethodsSpoken responses to test questions were recorded with a microphone placed 15 cm in front of each participant. Speech samples delivered in response to four spoken test prompts (free speech test, Mini-Mental State Examination [MMSE], picture description test, and sentence repetition test) were obtained from 98 patients with aMCI and 139 NCs. Each recording was transcribed, with speech features noted. The frequency of the ten speech features assessed was evaluated to compare speech abilities between the test groups.ResultsAmong the ten speech features, the frequency of pauses (p=0.001) and mumbles (p=0.001) were significantly higher in patients with aMCI than in NCs. Moreover, MMSE score was found to negatively correlate with the frequency of pauses (r=−0.441, p<0.001) and mumbles (r=−0.341, p<0.001).ConclusionsFrequent pauses and mumbles reflect cognitive decline in aMCI patients in episodic and semantic memory tests. Speech feature analysis may prove to be a speech-based biomarker for screening early-stage cognitive impairment.

Balance and gait performance in older adults with early-stage cognitive impairment.

People with cognitive impairment are susceptible to fall. Previous studies regarding balance and gait enrolled patients with various severity of dementia. Quantification of the balance and gait performance of people with cognitive impairment may help identify their postural instability and fall risks. We investigated the differences in balance and gait among older adults with preserved cognition, amnestic mild cognitive impairment, and mild dementia due to Alzheimer's disease. Prospective observational study. Outpatient department of neurology or psychology. Older adults (aged ≥65 years) with independent gait were evaluated using the Mini-Mental State Examination and Clinical Dementia Rating scale. People with other neurological or musculoskeletal disorders were excluded. Participants were classified into three groups: 30 healthy controls, 30 mild cognitive impairment and 30 mild dementia. Balance were evaluated through functional test (Berg Balance Scale [BBS]) and laboratory test (posturography). Gait was assessed by wearable device. Muscle strength and mass were measured through grip force, calf circumstance, and body composition. The BBS (P=0.04), posturography of fall risk index (FR, P=0.01) and sensory integration indices in eyes open and firm surface (EOFIS, P=0.009), eyes open and foam surface (EOFOS, P=0.003) were substantially different among three groups. EOFIS and EOFOS indices of balance in mild dementia were significantly worse than in MCI. The gait speed (P=0.04) and stride length (P=0.04) were significantly different among three groups. The post-hoc analyses revealed that all above balance and gait indices in subjects with cognitive impairments were significantly worse than in healthy controls. The grip force, calf circumstance and body composition-muscle mass did not significantly differ among three groups. It is a piece of evidence that cognitive dysfunction, even in early stage of memory decline, may have some bad impact on balance and gait regardless of the effect of musculoskeletal problems. Understanding the difference of specific indices of balance and gait among different severity of cognitive impairments and healthy controls could help to develop better balance-oriented rehabilitation programs in older adults at early-stage cognitive impairment.

Determinants of early diagnosis of cognitive impairment in older Indian adults

AbstractBackgroundDiagnosis of cognitive impairment at an early stage is vital to the management of dementia like Alzheimer’s disease. Recent studies have proved that multi‐modal non‐pharmacological therapy does decrease the progression of cognitive decline in patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). In this study, we evaluated the determinants of presentation at an early stage of cognitive impairment, to our memory clinic.MethodPatients presenting with cognitive impairment were evaluated in our memory clinic. After reversible causes and depression were ruled out, patients were classified as those with early disease (SCD and MCI) or major neurocognitive decline (MNCD). A retrospective analysis of the data was done to evaluate the association of baseline characteristics (age, sex, education, region, occupation and cardiovascular diseases) with the stage of presentation of cognitive decline.ResultData of 415 patients, evaluated from 2017 to 2019, was analyzed. Reversible causes were identified in 29.2 % of the patients, including 24.1% with depression. SCD, MCI and MNCD were identified in 29.6%, 16.4%, and 24.8%, respectively. Demographic factors like male sex (p value &lt; 0.001), higher education (p value &lt; 0.001) and occupational skill (p value = 0.006), were significantly associated with early presentation to the memory clinic.ConclusionIn this study, we observed 65% of the patient presented at an early stage of cognitive decline (SCD and MCI). With development of possible disease modifying agents in near future, this can be an important stage of intervention. Female patients with lower educational and occupational status, associated with late presentation, can be an important target for screening.

Cerebrospinal fluid fatty acid binding protein 3: A screening biomarker for preclinical Alzheimer’s disease

AbstractBackgroundPreclinical Alzheimer’s disease (AD) is a silent, asymptomatic stage of AD, classified into three sub‐stages based on amyloid positivity, neuronal injury and presence of subtle cognitive decline. Pathophysiological biomarkers are needed to effectively screen cases of preclinical AD based on the specific stage. Fatty acid binding protein 3 (FABP3) is a biomarker of neuronal membrane disruption, associated with lipid dyshomeostasis. The current study evaluated the potential of cerebrospinal fluid (CSF) FAPB3, as a stage‐specific screening biomarker of preclinical AD.MethodThe levels of FABP3 were quantified in CSF samples of healthy participants (n = 159) from the Australian Imaging, Biomarkers and Lifestyle studying of ageing (AIBL), on the Meso Scale Discovery platform using Human FABP3 Kit (Meso Scale Diagnostics, USA). A sub‐set of participants, (n = 142) had undergone positron emission tomography (PET) brain amyloid imaging. These participants were dichotomised into PET amyloid positive (n = 49) and negative (n = 93) based on the PET derived standardized uptake value ratio (SUVR) cut‐off of 1.4. Diagnostic differences in CSF FABP3 levels were assessed among amyloid positive and negative participants. Cox proportional hazards model was used to identify individuals likely to progress to an early stage of cognitive impairment, by assessing the risk of conversion from clinical dementia rating (CDR) of 0 to CDR ≥ 0.5. CDR assessments were done over 4.5 years; participants who had at least two follow‐up assessments were included in the analysis.ResultCSF FABP3 levels were significantly higher in PET amyloid positive healthy participants as compared to negatives (p = 0.001). CSF FABP3 levels were significantly higher in healthy participants who converted from CDR 0 to CDR ≥ 0.5, over 4.5 years, against non‐converters (p = 0.039). In an unadjusted analyses, CSF levels of FABP3 significantly predicted the risk of conversion from CDR 0 to CDR ≥ 0.5, with a hazard ratio (HR) of 1.58 (CI 1.03‐2.43, p = 0.035).ConclusionFABP3 is a biomarker of early neurodegenerative changes, which can be used to screen cases of preclinical AD with asymptomatic amyloidosis, as well as identify individuals likely to progress to a clinical stage of AD.

Is the MMSE still effective for evaluating cognitive decline?

The Mini-Mental State Examination (MMSE) is a widely used screening tool for evaluating cognitive decline in various clinical settings. However, there is growing evidence that the MMSE may not be as effective in detecting early stages of cognitive impairment, such as mild cognitive impairment (MCI) or subjective cognitive decline (SCD). Several studies have suggested that the MMSE has lower sensitivity in detecting MCI compared to other neuropsychological tests, such as the Montreal Cognitive Assessment (MoCA) and the Addenbrooke’s Cognitive Examination (ACE-R). Additionally, the MMSE may not be sensitive enough to detect SCD, which is a subjective complaint of cognitive decline without objective impairment on neuropsychological tests. Despite these limitations, the MMSE remains a viable option for detecting major neurocognitive disorders, such as dementia, and it may still have a role in certain clinical contexts. Therefore, it is important to consider the specific context and purpose of the evaluation when selecting a screening tool for cognitive decline.

Associations of rest-activity patterns with amyloid burden, medial temporal lobe atrophy, and cognitive impairment.

BackgroundWe sought to investigate the possible associations of rest-activity patterns with cortical amyloid burden, medial temporal lobe (MTL) neurodegeneration, and cognitive function in patients in the early stage of cognitive impairment.MethodsRest-activity patterns were assessed in 100 participants (70 with mild cognitive impairment and 30 with mild dementia) using wrist actigraphy. All participants underwent 18F-flutemetamol positron emission tomography (PET) imaging to quantify cortical amyloid burden, structural brain magnetic resonance imaging (MRI) to quantify MTL grey matter volume, neuropsychological testing, and clinical diagnosis. We used multiple linear regression models adjusted for covariates, including demographics, diabetes, hypertension, depressive symptom, psychotropic medication, sleep medication, weekend effect, and apolipoprotein-ε allele status.FindingsAfter adjusting for possible confounders, we found that the midline estimation of statistic of rhythm (MESOR) associated positively with frontal/executive function (estimate = 1.17, standard error [SE] = 0.37, p = 0.002). The least active 5-h (L5) onset time associated positively with MTL grey matter volume and memory function (estimate = 1.24, SE = 0.33, p = 0.001, and estimate = 3.77, SE = 1.22, p = 0.003, respectively), particularly in amyloid-negative participants. Additional path analysis revealed that MTL grey matter volume partially mediated the association between L5 onset time and memory function in amyloid-negative participants.InterpretationDecreased MESOR and advanced L5 onset time may be useful as early signs of cognitive decline or MTL neurodegeneration. Furthermore, amyloid pathology may act as a moderator of the relationships between rest-activity patterns, neurodegeneration, and cognitive function.FundingKorea Centres for Disease Control and Prevention (#4845–303); National Research Foundation of Korea (2019M3C7A1031905, 2019R1A5A2026045).

The MemClin project: a prospective multi memory clinics study targeting early stages of cognitive impairment

BackgroundThere remains a lack of large-scale clinical studies of cognitive impairment that aim to increase diagnostic and prognostic accuracy as well as validate previous research findings. The MemClin project will amass large quantities of cross-disciplinary data allowing for the construction of robust models to improve diagnostic accuracy, expand our knowledge on differential diagnostics, strengthen longitudinal prognosis, and harmonise examination protocols across centres. The current article describes the Memory Clinic (MemClin) project’s study-design, materials and methods, and patient characteristics. In addition, we present preliminary descriptive data from the ongoing data collection.MethodsNine out of ten memory clinics in the greater Stockholm area, which largely use the same examination methods, are included. The data collection of patients with different stages of cognitive impairment and dementia is coordinated centrally allowing for efficient and secure large-scale database construction. The MemClin project rest directly on the memory clinics examinations with cognitive measures, health parameters, and biomarkers.ResultsCurrently, the MemClin project has informed consent from 1543 patients. Herein, we present preliminary data from 835 patients with confirmed cognitive diagnosis and neuropsychological test data available. Of those, 239 had dementia, 487 mild cognitive impairment (MCI), and 104 subjective cognitive impairment (SCI). In addition, we present descriptive data on visual ratings of brain atrophy and cerebrospinal fluid markers.ConclusionsBased on our current progress and preliminary data, the MemClin project has a high potential to provide a large-scale database of 1200–1500 new patients annually. This coordinated data collection will allow for the construction of improved diagnostic and prognostic models for neurodegenerative disorders and other cognitive conditions in their naturalistic setting.

Abstract P1-17-07: Objective measurement of cognitive impairment in breast cancer survivors who received chemotherapy with the use of novel computerized testing

Abstract Background: Breast cancer is the most common cancer in women worldwide. With early detection and advancement in treatment, majority of women diagnosed with breast cancer will be cured. Some of these breast cancer survivors report Cognitive Impairment (CI) also known as “chemo-brain” or “mental fog”, especially those who have received chemotherapy. Few studies using functional neuroimaging have been conducted to foresee possible neurological alterations that could be linked to CI but research in this area remains in its early stages. Cognivue ® is an FDA cleared medical device that helps in assessment of cognitive dysfunction using novel computerized technology and is reported to be useful in detecting early stages of CI. Methods: We conducted a pilot study at the Lipson Cancer Institute/Rochester General Hospital for evaluation of CI in patients with breast cancer who received curative chemotherapy within the last 12 months of enrollment and self-reported CI. We enrolled 23 female patients between ages 19 and 90 years. Patients were subjected to Mini Mental Status Examination (MMSE) and St. Louis University Mental Status examination (SLUMS) as well as Cognivue ® testing. MMSE and SLUMS were scored according to scoring range guidance and digital data was obtained from the Cognivue® software. Analysis was performed using correlations of numeric data, ANOVA with Tukey’s post-hoc tests for categorical data, and Positive/Negative Percent Agreement (PPA/NPA) analysis for comparison of all cognitive testing methods. Results: Cognivue ® provides higher sensitivity to evaluate CI than MMSE and SLUMS, mainly in detecting earlier stages of CI. The cognitive domains most affected were executive function, abstraction and memory. There was a statistically significant correlation between Cognivue/CI score and duration of chemotherapy (p = 0.02). Age, type of chemotherapy or hormonal status of breast cancer were not significantly related with CI. Conclusions: Cognivue appears to be beneficial in its ability to detect CI in breast cancer patients. Specifically, detection of impairment in executive function domain could be predictive of daily life activity issues in such patients post-chemotherapy. This study also provides a possibility of detecting early cognitive dysfunction as well as the potential to develop a predictive algorithm of early intervention strategies for better patient outcomes. Citation Format: Manasi M Godbole, Mukul Singal, Reina Benabou, Iqra Choudary, Mehul P Patel. Objective measurement of cognitive impairment in breast cancer survivors who received chemotherapy with the use of novel computerized testing [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-17-07.

Long-Short Term Neural Network Analysis of Center of Pressure of Gait

Detection of vascular dementia in early stages of cognitive impairment is difficult to do in a clinical setting since the earliest changes are often discrete and physiological in nature. One major aspect of this is gait patterns. This project utilizes force-sensing platforms, motion capture, and EMG sensors to unobtrusively collect biometric data from an individual's walking gait patterns. The data parameters gathered were center of pressure, gait phase and end of unloading/toe-ff events. By quantifying and analyzing machine learning algorithms, specifically deep learning time-series based models, onset patterns of vascular dementia are explored with an overarching goal of creating a system that will assist in understanding and diagnosing cases of vascular dementia. The proposed system provides a tool for which gait can be analyzed and compared over a long period of time and opens opportunity to increased personalization in health monitoring and disease diagnosis and provides an avenue to increase patient-centricity of medical care. Since gait is one of the early predictors of vascular dementia, we developed a long short-term neural network to predict the gait variations from which we can predict the onset of vascular dementia.

Upregulation of cannabinoid receptor type 2, but not TSPO, in senescence-accelerated neuroinflammation in mice: a positron emission tomography study

BackgroundMicroglial cells are activated in response to changes in brain homeostasis during aging, dementia, and stroke. Type 2 endocannabinoid receptors (CB2) and translocator protein 18 kD (TSPO) are considered to reflect distinct aspects of microglia-related neuroinflammatory responses in the brain. CB2 activation is considered to relate to the neuroprotective responses that may occur predominantly in the early stage of brain disorders such as Alzheimer’s disease, while an increase in TSPO expression tends to occur later during neuroinflammation, in a proinflammatory fashion. However, this information was deduced from studies with different animal samples under different experimental settings. In this study, we aimed to examine the early microglial status in the inflammation occurring in the brains of senescence-accelerated mouse prone 10 (SAMP10) mice, using positron emission tomography (PET) with CB2 and TSPO tracers, together with immunohistochemistry.MethodsFive- and 15-week-old SAMP10 mice that undergo neurodegeneration after 7 months of age were used. The binding levels of the TSPO tracer (R)-[11C]PK11195 and CB2 tracer [11C]NE40 were measured using PET in combination with immunohistochemistry for CB2 and TSPO. To our knowledge, this is the first study to report PET data for CB2 and TSPO at the early stage of cognitive impairment in an animal model.ResultsThe standard uptake value ratios (SUVRs) of [11C]NE40 binding were significantly higher than those of (R)-[11C]PK11195 binding in the cerebral cortical region at 15 weeks of age. At 5 weeks of age, the [11C]NE40 SUVR tended to be higher than the (R)-[11C]PK11195 SUVR. The (R)-[11C]PK11195 SUVR did not significantly differ between 5- and 15-week-old mice. Consistently, immunostaining analysis confirmed the upregulation of CB2, but not TSPO.ConclusionsThe use of the CB2 tracer [11C]NE40 and/or an immunohistochemical approach allows evaluation of the role of microglia in acute neuroinflammatory processes in the early stage of neurodegeneration. The present results provide in vivo evidence of different responses of two types of microglia to senescence-accelerated neuroinflammation, implying the perturbation of microglial balance by aging. Specific treatment for CB2-positive microglia might help ameliorate senescence-related neuroinflammation and the following neurodegeneration.

The Norwegian translation of the brief international cognitive assessment for multiple sclerosis (BICAMS)

BackgroundCognitive impairment is a common symptom in all stages of multiple sclerosis (MS), yet it is underreported and not routinely evaluated. The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) is a short and easily administered test battery for screening of cognitive impairment in MS that can be completed within 15 min and incorporated into routine clinical practice. The test battery consists of the oral version of the Symbols Digit Modalities Test (SDMT) and the initial learning trials of the California Verbal Learning Test 2nd edition (CVLT-II) and the Brief Visuospatial Memory Test Revised (BVMT-R). ObjectiveTo investigate if the Norwegian version of the BICAMS could identify cognitive impairment in early stages of MS and be used as part of routine follow-up procedures. MethodsA total of 65 relapsing-remitting MS (RRMS) patients and 68 healthy controls were examined with the BICAMS test battery. A randomly selected subset of 29 controls were retested 1–4 weeks after baseline. All participants were screened for anxiety and depression using the Hospital Anxiety and Depression Scale (HADS). ResultsThere were statistically significant differences between the patients with MS and the healthy controls on all three subtests, and the differences remained significant for the CVLT-II (p = 0.003) and BVMT-R (p = 0.011) after adjusting for education. There were no statistically significant correlations between BICAMS scores and anxiety and depression. SDMT and BVMT-R results in the control group at baseline and re-test were strongly correlated (r ≥ 0.70, p < 0.001), and CVLT-II achieved an adequate value of r = 0.60 (p = 0.001). On the SDMT, there was a statistically significant improvement between the two test-sessions. Cognitive impairment, defined as an abnormal test score on ≥1 subtest, was identified in 46.2% of the patient sample, whereas 15.4% were considered cognitively impaired on ≥2 subtests. ConclusionThis study supports that the Norwegian version of the BICAMS should be included as a screening procedure for cognitive impairment in Norwegian MS patients.

Episodic-Memory Performance in Machine Learning Modeling for Predicting Cognitive Health Status Classification.

Background:Memory dysfunction is characteristic of aging and often attributed to Alzheimer’s disease (AD). An easily administered tool for preliminary assessment of memory function and early AD detection would be integral in improving patient management.Objective:Our primary aim was to utilize machine learning in determining initial viable models to serve as complementary instruments in demonstrating efficacy of the MemTrax online Continuous Recognition Tasks (M-CRT) test for episodic-memory screening and assessing cognitive impairment.Methods:We used an existing dataset subset (n = 18,395) of demographic information, general health screening questions (addressing memory, sleep quality, medications, and medical conditions affecting thinking), and test results from a convenience sample of adults who took the M-CRT test. M-CRT performance and participant features were used as independent attributes: true positive/negative, percent responses/correct, response time, age, sex, and recent alcohol consumption. For predictive modeling, we used demographic information and test scores to predict binary classification of the health-related questions (yes/no) and general health status (healthy/unhealthy), based on the screening questions.Results:ANOVA revealed significant differences among HealthQScore groups for response time true positive (p = 0.000) and true positive (p = 0.020), but none for true negative (p = 0.0551). Both % responses and % correct had significant differences (p = 0.026 and p = 0.037, respectively). Logistic regression was generally the top-performing learner with moderately robust prediction performance (AUC) for HealthQScore (0.648–0.680) and selected general health questions (0.713–0.769).Conclusion:Our novel application of supervised machine learning and predictive modeling helps to demonstrate and validate cross-sectional utility of MemTrax in assessing early-stage cognitive impairment and general screening for AD.

Inflammation in mild cognitive impairment due to Parkinson's disease, Lewy body disease, and Alzheimer's disease.

Inflammation appears to play a role in the progression of neurodegenerative diseases. However, little is known about inflammation during early stages of cognitive decline or whether this differs in different disease groups. We sought to investigate this by assessing the inflammatory profile in patients with Parkinson disease with the early stages of cognitive impairment (PD-MCI), patients with prodromal Alzheimer disease (MCI-AD), prodromal Lewy body disease (MCI-LB), and controls. We obtained venous blood samples from participants with PD-MCI (n=44), PD-normal cognition (n=112), MCI-LB (n=38), MCI-AD (n=21), and controls (n=84). We measured 10 cytokines using Meso Scale Discovery V-Plex Plus including interferon gamma, interleukin (IL)-10, IL-12p70, IL-13, IL-1beta, IL-2, IL-4, IL-6, IL-8, and tumour necrosis factor alpha. High-sensitivity C-reactive protein was measured. There was a higher level of inflammation in patients with MCI-AD and MCI-LB compared with controls. PD noncognitively impaired had higher inflammatory markers than controls, but there was no difference between PD-MCI and controls. There was a decrease in inflammatory markers with increasing motor severity based on the Unified Parkinson's Disease Rating Scale. Inflammation may be involved in the onset of cognitive decline in patients with MCI-AD and MCI-LB but appears to be less prominent PD-MCI albeit in a small data set. This suggests that anti-inflammatory medications may have most benefit at the earliest stages of neurodegenerative diseases. For PD cases, this might be in advance of the development of MCI.

A divergent breakdown of neurocognitive networks in Parkinson's Disease mild cognitive impairment.

Cognitive decline is a major disabling feature in Parkinson's disease (PD). Multimodal imaging studies have shown functional disruption in neurocognitive networks related to cognitive impairment. However, it remains unknown whether these changes are related to gray matter loss, or whether they outline network vulnerability in the early stages of cognitive impairment. In this work, we intended to assess functional connectivity and graph theoretical measures and their relation to gray matter loss in Parkinson's disease with mild cognitive impairment (PD-MCI). We recruited 53 Parkinson's disease patients and classified them for cognitive impairment using Level-1 Movement Disorders Society-Task Force Criteria. Voxel-based morphometry, functional connectivity and graph theoretical measures were obtained on a 3-Tesla MRI scanner. Loss of gray matter was observed in the default mode network (bilateral precuneus), without a corresponding disruption of functional or graph theoretical properties. However, functional and graph theoretical changes appeared in salience network nodes, without evidence of gray matter loss. Global cognition and executive scores showed a correlation with node degree in the right anterior insula. We also found a correlation between visuospatial scores and right supramarginal gyrus node degree. Our findings highlight the loss of functional connectivity and topological features without structural damage in salience network regions in PD-MCI. They also underline the importance of multimodal hubs in the transition to mild cognitive impairment. This functional disruption in the absence of gray matter atrophy suggests that the salience network is a key vulnerable system at the onset of mild cognitive impairment in PD.

Associations of serum microRNA-20a, -27a, and -103a with cognitive function in a Japanese population: The Yakumo study

ObjectivesMicroRNAs (miRNAs) dysregulate gene expression by binding to target messenger RNAs, and play an important role in the pathogenesis of various diseases, including cancers, cardiovascular diseases and diabetes. Circulating miRNAs have increasingly been recognized as biomarkers for detecting and diagnosing those diseases. Few studies have investigated the association of circulating miRNA with the early stages of cognitive impairment, such as mild cognitive impairment, in the general population. The purpose of this study was to examine the association between cognitive function and several serum miRNAs levels related to amyloid precursor protein (APP) proteolysis in a Japanese general population who had never been diagnosed with dementia. MethodsWe conducted a cross-sectional study of 337 Japanese subjects (144 men, 193 women) who attended a health examination. The short form of the Mini-Mental State Examination (SMMSE) was used to assess cognitive function. Serum levels of 6 miRNAs (let-7d, miR-17, miR-20a, miR-27a, miR-34a, miR-103a) were measured by quantitative real-time polymerase chain reaction. ResultsMultivariable-adjusted odds ratios (ORs) for lower SMMSE score (SMMSE score < 28) were significantly increased in the lowest tertile of serum miR-20a (OR, 2.08; 95% confidence interval (CI), 1.09–4.04) and miR-103a (OR, 1.91; 95%CI, 1.00–3.69) compared to the highest tertile. Moreover, serum levels of miR-20a, -27a, and -103a were linearly and positively associated with SMMSE scores after adjustment for confounding factors. ConclusionLow serum levels of miR-20a, -27a, and -103a are independently associated with cognitive impairment.

The Changing Profile of Patients in a Geriatric Medicine Led Memory Clinic over 12 Years.

Memory clinics play an important role in enabling early dementia diagnosis and intervention. Few studies have investigated the changing patient profiles at memory clinics over time. We studied the trend of patient characteristics in a geriatric medicine-led memory clinic over 12 years to improve services and care to meet their needs. Data from 2340 first-visit patients seen at a memory clinic from 2005-2017 were extracted from a registered database and analysed. ANOVA, Pearson chi-square and non-parametric tests were used to describe and compare between patients with dementia (PWD) and patients with no dementia (PND). Data included diagnoses of dementia and mild cognitive impairment, age, education, MMSE scores and comorbidities. Patients averaged 77.2 ± 8.3 years of age with mean MMSE score of 16.2 ± 6.7. Those diagnosed with dementia were older (78.3 ± 7.9 years) and almost half (48.4%) had moderate or moderately severe dementia (FAST 5-6). Over time, there was a growing proportion of patients with mild cognitive impairment (MCI) and mild Alzheimer's dementia. Many PWD had co-morbidities of hypertension (65.9%), hyperlipidemia (55.1%), diabetes (33.5%) and 28.4% were frail. The findings call for services to better diagnose and manage patients at the earlier stages of cognitive impairment and provide holistic interventions for those with frailty and other co-morbidities. The continued rise in number of patients presenting to memory clinics provides impetus to expedite integration of tertiary-based memory clinics with primary and community care providers to better support PWD and their families.

Executive, emotional and physiological functioning in older drivers with mild cognitive impairment

Abstract Age-related changes and deterioration of cognitive skills affect older citizens’ attendance of everyday activities and considerably affect their independence and quality of life. Older people keep on driving for a long time and often even longer after deterioration occurs. Executive functioning is usually affected early in Alzheimer’s disease leading to the possibility that executive control might be affected before a probable diagnosis is possible. This study aimed to explore changes in executive control in drivers with Mild Cognitive Impairment (MCI) by using an existing fitness-to-drive assessment for older drivers taking also in consideration their current emotional and physiological functioning. Statistically significant difference was found in mean reaction time (msec) between control and MCI participants (F(1, 99) = 4.514, p = .036) in correct colour response for letters (mean difference: 101 msec). As such, early cognitive issues seem to relate more with phonological rather than numerical information that sometimes have higher demand in working memory and visual attention. This result implies that higher demanding driving tasks have an increased possibility to be affected even at early stages of cognitive impairment leading to increased proneness to accidents in complex driving scenarios (e.g. non-signalled intersections), when no effect on existing driving skills is still apparent.

Cell cycle reentry triggers hyperploidization and synaptic dysfunction followed by delayed cell death in differentiated cortical neurons

Cell cycle reentry followed by neuronal hyperploidy and synaptic failure are two early hallmarks of Alzheimer’s disease (AD), however their functional connection remains unexplored. To address this question, we induced cell cycle reentry in cultured cortical neurons by expressing SV40 large T antigen. Cell cycle reentry was followed by hyperploidy in ~70% of cortical neurons, and led to progressive axon initial segment loss and reduced density of dendritic PSD-95 puncta, which correlated with diminished spike generation and reduced spontaneous synaptic activity. This manipulation also resulted in delayed cell death, as previously observed in AD-affected hyperploid neurons. Membrane depolarization by high extracellular potassium maintained PSD-95 puncta density and partially rescued both spontaneous synaptic activity and cell death, while spike generation remained blocked. This suggests that AD-associated hyperploid neurons can be sustained in vivo if integrated in active neuronal circuits whilst promoting synaptic dysfunction. Thus, cell cycle reentry might contribute to cognitive impairment in early stages of AD and neuronal death susceptibility at late stages.

Memorization Test and Resting State EEG Components in Mild and Subjective Cognitive Impairment.

Mild (MCI) and Subjective Cognitive Impairment (SCI) are conditions at risk of developing Alzheimer's disease (AD). Differential between normal aging at early stages can be really challenging; available biomarkers need to be combined and can be quite invasive and expensive. The aim of this pilot study is to examine possible EEG alterations in MCI and SCI compared to controls, analyzing if a cognitive task could highlight early AD hallmarks. We recruited 11 MCI, 8 SCI and 7 healthy subjects as controls (CS), all matched for age and education. Neuropsychological assessment and EEG recording, at resting state and during a mental memory task, were performed. Classical spectral measures and nonlinear parameters were used to characterize EEGs. During cognitive task, α-band power reduction was found predominantly in frontal regions in SCI and CS, diffused to all regions in MCI; moreover, decreased EEG complexity was found in SCI compared to controls. The α -band power attenuation restricted to frontal regions in SCI during a free recall task (involving frontal areas), suggests that MCI patients compensate for encoding deficit by activating different brain networks to perform the same task. Furthermore, EEG complexity reduction - that has been found already in SCI - could be a possible early hallmark of AD. This study draws attention on the importance of nonlinear approach in EEG analysis and the potential role of cognitive task in highlighting EEG alterations at very early stages of cognitive impairment; EEG could therefore have a practical impact on dementia diagnosis.