aMCI Patients Research Articles

F-18 ML-104 tau PET imaging in mild cognitive impairment.

This study was undertaken to evaluate the tau distribution patterns in patients with amnestic mild cognitive impairment (aMCI) using PET radiotracer F-18 ML-104. Thirty patients, clinically diagnosed as aMCI [mini mental state evaluation ≥24] in the neurology or geriatric memory clinics, were included in the study. Each aMCI patient underwent F-18 fluorodeoxyglucose and F-18 ML-104 tau PET. Standardized uptake value ratios for cortical gray matter regions were evaluated for F-18 ML-104 tau PET and compared with normal controls and with early Alzheimer's disease (AD) patients (used from a previous study). aMCI revealed significantly higher standardized uptake value ratios in both medial temporal cortices, precuneus and posterior cingulate cortices in comparison to normal controls and a significantly lesser binding in bilateral medial and lateral temporal, precuneus and posterior cingulate cortices in comparison to early AD. A negative correlation was noted between F-18 fluorodeoxyglucose uptake and F-18 ML-104 retention in the precuneus and posterior cingulate cortices in aMCI, while F-18 ML-104 retention and mini mental state evaluation scores revealed a moderate negative correlation in the posterior cingulate cortices. We could demonstrate a significant increase in cortical tau deposition in aMCI patients in comparison to normal controls, thus providing in vivo evidence of the underlying pathological process in this subgroup of patients with high probability of conversion to AD.

Impaired posterior cingulate cortex-parahippocampus connectivity is associated with episodic memory retrieval problems in amnestic mild cognitive impairment.

Episodic memory retention and retrieval decline are the most common impairments observed in amnestic mild cognitive impairment (aMCI) patients who progress to Alzheimer's disease (AD). Clinical electroencephalography research shows that patients with dementia due to AD exhibit a slowing of neural electrical activity in the parietal cortex. Memory research has further suggested that successful memory performance is associated with changes in a posterior cingulate-parahippocampal cortical network together with increased θ-γ oscillatory coupling, where θ oscillations act as carrier waves for γ oscillations, which contain the actual information. However, the neurophysiological link between the memory research and clinical studies investigating aMCI and AD is lacking. In this study, we look at brain activity in aMCI and how it relates to memory performance. We demonstrate decreased γ power in the posterior cingulate cortex and the left and right parahippocampus in aMCI patients in comparison to control participants. This goes together with reduced θ coherence between the posterior cingulate cortex and parahippocampus associated with altered memory performance aMCI patients in comparison to control participants. In addition, comparing patients with aMCI to control participants reveals an effect for θ-γ coupling for the posterior cingulate cortex, and the left and right parahippocampus. Taken together, our results show that parahippocampus and posterior cingulate cortex interact via θ-γ coupling, which is associated with memory recollection and is altered in aMCI patients, offering a potential candidate mechanism for memory decline in aMCI.

Preoperative Microbiomes and Intestinal Barrier Function Can Differentiate Prodromal Alzheimer's Disease From Normal Neurocognition in Elderly Patients Scheduled to Undergo Orthopedic Surgery.

ObjectiveEmerging evidence links perturbations in the microbiome to neurodegeneration in amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) and to surgical stress. In this study, we attempted to identify preoperative differences intestinal microbiota (IM) and barrier function between pAD [prodromal AD: Subjective cognitive decline (SCD) and aMCI] patients and normal neurocognition (NC) patients. Additionally, the potential associations between IM and barrier function, inflammation, and the clinical characteristics of pAD were evaluated.DesignEighty elderly patients scheduled to undergo orthopedic surgery were consecutively enrolled and grouped as NC, SCD, and aMCI following neuropsychological assessment. IM was determined by 16S rRNA MiSeq sequencing, and PICRUSt was used to predict functional shifts in IM. Furthermore, we investigated the association between IM and plasma claudin-1, occludin, LPS, systemic inflammatory cytokines, neuropsychological assessment, and clinical characteristics.ResultsThere was a lower Chao1 index in the SCD group (P = 0.004) and differences in beta diversity among the three groups (PCA: P = 0.026, PCoA: P= 0.004). The relative abundance of Bacteroidetes was higher in the SCD group (P = 0.016, P = 0.008), and Firmicutes were more enriched in the aMCI group than in the SCD group (P= 0.026). At the family level, the total abundance of Gram-negative bacteria was higher in the SCD group than in the aMCI group (P = 0.047), and the Christensenellaceae family was detected at lower levels in the SCD and aMCI groups than in the NC group (P= 0.039). At the genus level, the eleven short-chain fatty acid (SCFA)-producing bacteria exhibited differences among the three groups. PICRUSt analysis showed that the pathways involved in SCFA catabolism, biosynthesis, and adherent junctions were reduced in SCD patients, and lipid synthesis proteins were reduced in pAD patients. Meanwhile, elevated plasma LPS and CRP were observed in SCD patients, and higher plasma occludin in aMCI patients. The IM was correlated with plasma claudin-1, LPS, inflammatory factors, neuropsychological assessment, and clinical characteristics.ConclusionThe intestines of SCD and aMCI patients preoperatively exhibited IM dysbiosis and barrier dysfunction, and elevated plasma LPS and CRP were observed in SCD patients.

The Association Between Homocysteine and Memory in Older Adults.

Identifying modifiable risk factors for cognitive decline can reduce burden of dementia. We examined whether homocysteine was associated with memory performance, mediated by entorhinal volume, hippocampal volume, total gray matter volume, or white matter lesions, and moderated by APOE ɛ4 allele, B vitamins, creatinine, total cholesterol, or triglycerides. All 204 members of the Czech Brain Aging Study with subjective cognitive decline (SCD; n = 60) or amnestic mild cognitive impairment (aMCI; n = 144) who had valid data were included. Linear regression was used, followed by conditional process modeling to examine mediation and moderation. Controlling for age, sex, and education, higher homocysteine was related to poorer memory performance overall (b = -0.03, SE = 0.01, p = 0.017) and in participants with SCD (b = -0.06, SE = 0.03, p = 0.029), but less so in aMCI (b = -0.03, SE = 0.02, p = 0.074); though sensitivity analyses revealed a significant association when sample was reduced to aMCI patients with more complete cognitive data (who were also better functioning; b = -0.04, SE = 0.02, p = 0.022). Results were unchanged in fully adjusted models. Neither mediation by markers of brain integrity nor moderation by APOE ɛ4, B vitamins, creatinine, and cardiovascular factors were significant. Memory sub-analyses revealed that results for SCD were likely driven by non-verbal memory. The homocysteine-memory relationship was significant when hippocampal volume was below the median (b = -0.04, SE = 0.02, p = 0.046), but not at/above the median (p = 0.247). Higher homocysteine levels may adversely influence memory performance, which appears particularly apparent in those without cognitive impairment. Results appear to be independent of brain health, suggesting that homocysteine may represent a good target for intervention.

Disrupted White Matter Networks from Subjective Memory Impairment to Amnestic Mild Cognitive Impairment.

Subjective memory impairment (SMI) is a preclinical stage prior to amnestic mild cognitive impairment (aMCI) along with the Alzheimer's disease (AD) continuum. We hypothesized that SMI patients had white matter (WM) network disruptions similar to those in aMCI patients. We used diffusion-tensor magnetic resonance imaging and graph theory to construct, analyze, and compare the WM networks among 20 normal controls (NC), 20 SMI patients, and 20 aMCI patients. Compared with the NC group, the SMI group had significantly decreased global and local efficiency and an increased shortest path length. Moreover, similar to the aMCI group, the SMI group had lower nodal efficiency in regions located in the frontal and parietal lobes, limbic systems, and caudate nucleus compared to that of the NC group. Similar to aMCI patient, SMI patients exhibited WM network disruptions, and detection of these disruptions could facilitate the early detection of SMI.

An Effective Brain Imaging Biomarker for AD and aMCI: ALFF in Slow-5 Frequency Band.

As a potential brain imaging biomarker, amplitude of low frequency fluctuation (ALFF) has been used as a feature to distinguish patients with Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) from normal controls (NC). However, it remains unclear whether the frequency-dependent pattern of ALFF alterations can effectively distinguish the different phases of the disease. In the present study, 52 AD and 50 aMCI patients were enrolled together with 43 NC in total. The ALFF values were calculated in the following three frequency bands: classical (0.01-0.08 Hz), slow-4 (0.027-0.073 Hz) and slow-5 (0.01-0.027 Hz) for the three different groups. Subsequently, the local functional abnormalities were employed as features to examine the effect of classification among AD, aMCI and NC using a support vector machine (SVM). We found that the among-group differences of ALFF in the different frequency bands were mainly located in the left hippocampus (HP), right HP, bilateral posterior cingulate cortex (PCC) and bilateral precuneus (PCu), left angular gyrus (AG) and left medial prefrontal cortex (mPFC). When the local functional abnormalities were employed as features, we identified that the ALFF in the slow-5 frequency band showed the highest accuracy to distinguish among the three groups. These findings may deepen our understanding of the pathogenesis of AD and suggest that slow-5 frequency band may be helpful to explore the pathogenesis and distinguish the phases of this disease.

The Smart Aging Platform for Assessing Early Phases of Cognitive Impairment in Patients With Neurodegenerative Diseases.

Background: Smart Aging is a serious game (SG) platform that generates a 3D virtual reality environment in which users perform a set of screening tasks designed to allow evaluation of global cognition. Each task replicates activities of daily living performed in a familiar environment. The main goal of the present study was to ascertain whether Smart Aging could differentiate between different types and levels of cognitive impairment in patients with neurodegenerative disease.Methods: Ninety-one subjects (mean age = 70.29 ± 7.70 years)—healthy older adults (HCs, n = 23), patients with single-domain amnesic mild cognitive impairment (aMCI, n = 23), patients with single-domain executive Parkinson's disease MCI (PD-MCI, n = 20), and patients with mild Alzheimer's disease (mild AD, n = 25)—were enrolled in the study. All participants underwent cognitive evaluations performed using both traditional neuropsychological assessment tools, including the Mini-Mental State Examination (MMSE), Montreal Overall Cognitive Assessment (MoCA), and the Smart Aging platform. We analyzed global scores on Smart Aging indices (i.e., accuracy, time, distance) as well as the Smart Aging total score, looking for differences between the four groups.Results: The findings revealed significant between-group differences in all the Smart Aging indices: accuracy (p < 0.001), time (p < 0.001), distance (p < 0.001), and total Smart Aging score (p < 0.001). The HCs outperformed the mild AD, aMCI, and PD-MCI patients in terms of accuracy, time, distance, and Smart Aging total score. In addition, the mild AD group was outperformed both by the HCs and by the aMCI and PD-MCI patients on accuracy and distance. No significant differences were found between aMCI and PD-MCI patients. Finally, the Smart Aging scores significantly correlated with the results of the neuropsychological assessments used.Conclusion: These findings, although preliminary due to the small sample size, suggest the validity of Smart Aging as a screening tool for the detection of cognitive impairment in patients with neurodegenerative diseases.

Determining affected memory domains in patients with amnestic mild cognitive impairment using computerized and interactive tests

This study explores different episodic memory domains, namely object, temporal and spatial memory, affected in patients with a clinical diagnosis of single domain amnestic mild cognitive impairment (aMCI). 15 aMCI patients and 25 healthy controls were recruited and tested. Object, spatial, and temporal memory were tested using computerized tasks and again in interactive, real-world tasks. Controls outperformed patients on the object computerized task and showed a trend toward significance for the computerized spatial and temporal tasks, but there was no difference in spatial and temporal memory when using the interactive tasks, indicating the employment of compensatory mechanisms in patients to overcome some of the memory impairments associated with aMCI. These findings highlight that aMCI patients might delay seeking help due to compensatory mechanisms which mask their deficits in real-world situations.

Altered Frequency-Dependent Brain Activation and White Matter Integrity Associated With Cognition in Characterizing Preclinical Alzheimer's Disease Stages.

BackgroundSubjective cognitive decline (SCD), non-amnestic mild cognitive impairment (naMCI), and amnestic mild cognitive impairment (aMCI) are regarded to be at high risk of converting to Alzheimer’s disease (AD). Amplitude of low-frequency fluctuations (ALFF) can reflect functional deterioration while diffusion tensor imaging (DTI) is capable of detecting white matter integrity. Our study aimed to investigate the structural and functional alterations to further reveal convergence and divergence among SCD, naMCI, and aMCI and how these contribute to cognitive deterioration.MethodsWe analyzed ALFF under slow-4 (0.027–0.073 Hz) and slow-5 (0.01–0.027 Hz) bands and white matter fiber integrity among normal controls (CN), SCD, naMCI, and aMCI groups. Correlation analyses were further utilized among paired DTI alteration, ALFF deterioration, and cognitive decline.ResultsFor ALFF calculation, ascended ALFF values were detected in the lingual gyrus (LING) and superior frontal gyrus (SFG) within SCD and naMCI patients, respectively. Descended ALFF values were presented mainly in the LING, SFG, middle frontal gyrus, and precuneus in aMCI patients compared to CN, SCD, and naMCI groups. For DTI analyses, white matter alterations were detected within the uncinate fasciculus (UF) in aMCI patients and within the superior longitudinal fasciculus (SLF) in naMCI patients. SCD patients presented alterations in both fasciculi. Correlation analyses revealed that the majority of these structural and functional alterations were associated with complicated cognitive decline. Besides, UF alterations were correlated with ALFF deterioration in the SFG within aMCI patients.ConclusionsSCD shares structurally and functionally deteriorative characteristics with aMCI and naMCI, and tends to convert to either of them. Furthermore, abnormalities in white matter fibers may be the structural basis of abnormal brain activation in preclinical AD stages. Combined together, it suggests that structural and functional integration may characterize the preclinical AD progression.

Comprehensive classification models based on amygdala radiomic features for Alzheimer's disease and mild cognitive impairment.

The amygdala is an important part of the medial temporal lobe and plays a pivotal role in the emotional and cognitive function. The aim of this study was to build and validate comprehensive classification models based on amygdala radiomic features for Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI).For the amygdala, 3360 radiomic features were extracted from 97 AD patients, 53 aMCI patients and 45 normal controls (NCs) on the three-dimensional T1-weighted magnetization-prepared rapid gradient echo (MPRAGE) images. We used maximum relevance and minimum redundancy (mRMR) and least absolute shrinkage and selection operator (LASSO) to select the features. Multivariable logistic regression analysis was performed to build three classification models (AD-NC group, AD-aMCI group, and aMCI-NC group). Finally, internal validation was assessed.After two steps of feature selection, there were 5 radiomic features remained in the AD-NC group, 16 features remained in the AD-aMCI group and the aMCI-NC group, respectively. The proposed logistic classification analysis based on amygdala radiomic features achieves an accuracy of 0.90 and an area under the ROC curve (AUC) of 0.93 for AD vs. NC classification, an accuracy of 0.81 and an AUC of 0.84 for AD vs. aMCI classification, and an accuracy of 0.75 and an AUC of 0.80 for aMCI vs. NC classification.Amygdala radiomic features might be early biomarkers for detecting microstructural brain tissue changes during the AD and aMCI course. Logistic classification analysis demonstrated the promising classification performances for clinical applications among AD, aMCI and NC groups.

Effect of self-imagination on memory for older adults and aMCI patients

ABSTRACT Imagining an event from a personal perspective has been found to be able to enhance memory for words and sentences for healthy younger adults and brain-injured patients. However, little is known about how people with amnestic mild cognitive impairment (aMCI) respond to self-imagination, in comparison to healthy older adults. In the current study, participants were asked to process a group of objects using either a self-imagination approach or a baseline strategy in which the self was not heavily involved. Self-imagination shows a mnemonic advantage over the control strategy, though this pattern emerged more clearly for healthy older adults. Furthermore, suggestive evidence indicates that cognitive ability supports self-reference benefits for healthy older adults, but not aMCI patients. These findings extended previous research to reveal the effectiveness of self-imagination for older adults using pictorial stimuli and supported the viewpoint that aMCI could qualitatively change the way that cognitive resources are engaged.

Motor cortical excitability and paired-associative stimulation-induced plasticity in amnestic mild cognitive impairment and Alzheimer’s disease

ObjectiveSynaptopathy including alterations of synaptic plasticity (long-term potentiation, LTP) may precede neurodegeneration in Alzheimer’s disease (AD). We studied LTP-like corticospinal plasticity induced by paired-associative stimulation (PASLTP) in AD and its prodromal stage, amnestic mild cognitive impairment (aMCI). Methods15 AD and 15 aMCI patients, and 23 demographically matched healthy controls (HC) were included. Resting motor threshold (RMT) and stimulus intensity needed to evoke motor evoked potentials (MEP) of 1 mV (SI1mV) were obtained as single-pulse transcranial magnetic stimulation (TMS) measures of corticospinal excitability in a hand muscle at baseline, followed by PASLTP using standard methodology. MEP amplitude change after PASLTP normalized to baseline was defined as plasticity effect. All measures were repeated in two visits for examining test–retest reliability. ResultsSI1mV were lower in aMCI compared to HC, while there was no difference between AD and HC. RMT and SI1mV showed excellent test–retest reliability in all groups. PASLTP indiscriminately did not induce LTP-like plasticity in any of the groups, and expressed poor test–retest reliability. ConclusionsaMCI shows corticospinal hyperexcitability, consistent with glutamatergic excitotoxicity in early-stage AD. Possible abnormalities of LTP-like plasticity could not be reliably tested with the standard PASLTP protocol due to massive inter-subject variability even in HC, and poor test–retest reliability. SignificanceFindings indicate corticospinal hyperexcitability in prodromal AD, and reliability of single-pulse TMS measures for identifying such abnormality. In contrast, the standard PASLTP protocol may not be suitable for assessing LTP-like motor cortical plasticity, given its overall nil effect and poor test–retest reliability.

Microstructural and Cerebral Blood Flow Abnormalities in Subjective Cognitive Decline Plus: Diffusional Kurtosis Imaging and Three-Dimensional Arterial Spin Labeling Study.

Objective: To explore microstructural and cerebral blood flow (CBF) abnormalities in individuals with subjective cognitive decline plus (SCD plus) using diffusional kurtosis imaging (DKI) and three-dimensional (3D) arterial spin labeling (ASL).Methods: Twenty-seven patients with SCD plus, 31 patients with amnestic mild cognitive impairment (aMCI), and 33 elderly controls (ECs) were recruited and underwent DKI and 3D ASL using a GE 3.0-T MRI. Mean kurtosis (MK), fractional anisotropy (FA), mean diffusivity (MD), and CBF values were acquired from 24 regions of interest (ROIs) in the brain, including the bilateral hippocampal (Hip) subregions (head, body, and tail), posterior cingulate cortex (PCC), precuneus, dorsal thalamus subregions (anterior nucleus, ventrolateral nucleus, and medial nucleus), lenticular nucleus, caput nuclei caudati, white matter (WM) of the frontal lobe, and WM of the occipital lobe. Pearson's correlation analysis was performed to assess the relationships among the DKI-derived parameters, CBF values, and key neuropsychological tests for SCD plus.Results: Compared with ECs, participants with SCD plus showed a significant decline in MK and CBF values, mainly in the Hip head and PCC, and participants with aMCI exhibited more significant abnormalities in the MK and CBF values than individuals with ECs and SCD plus in multiple regions. Combined MK values showed better discrimination between patients with SCD plus and ECs than that obtained using CBF levels, with areas under the receiver operating characteristic (ROC) curve (AUC) of 0.874 and 0.837, respectively. Similarly, the AUC in discriminating SCD plus from aMCI patients obtained using combined MK values was 0.823, which was also higher than the combined AUC of 0.779 obtained using CBF values. Moreover, MK levels in the left Hip (h) and left PCC positively correlated with the auditory verbal learning test-delayed recall (AVLT-DR) score in participants with SCD plus. By contrast, only the CBF value in the left Hip head positively correlated with the AVLT-DR score.Conclusions: Our results provide new evidence of microstructural and CBF changes in patients with SCD plus. MK may be used as an early potential neuroimaging biomarker and may be a more sensitive DKI parameter than CBF at the very early stage of Alzheimer's disease (AD).

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.

Machine Learning for the Prediction of Amyloid Positivity in Amnestic Mild Cognitive Impairment

Amyloid-β (Aβ) evaluation in amnestic mild cognitive impairment (aMCI) patients is important for predicting conversion to Alzheimer's disease. However, Aβ evaluation through Aβ positron emission tomography (PET) is limited due to high cost and safety issues. We therefore aimed to develop and validate prediction models of Aβ positivity for aMCI using optimal interpretable machine learning (ML) approaches utilizing multimodal markers. We recruited 529 aMCI patients from multiple centers who underwent Aβ PET. We trained ML algorithms using a training cohort (324 aMCI from Samsung medical center) with two-phase modelling: model 1 included age, gender, education, diabetes, hypertension, apolipoprotein E genotype, and neuropsychological test scores; model 2 included the same variables as model 1 with additional MRI features. We used four-fold cross-validation during the modelling and evaluated the models on an external validation cohort (187 aMCI from the other centers). Model 1 showed good accuracy (area under the receiver operating characteristic curve [AUROC] 0.837) in cross-validation, and fair accuracy (AUROC 0.765) in external validation. Model 2 led to improvement in the prediction performance with good accuracy (AUROC 0.892) in cross validation compared to model 1. Apolipoprotein E genotype, delayed recall task scores, and interaction between cortical thickness in the temporal region and hippocampal volume were the most important predictors of Aβ positivity. Our results suggest that ML models are effective in predicting Aβ positivity at the individual level and could help the biomarker-guided diagnosis of prodromal AD.

Widespread white matter aberration is associated with the severity of apathy in amnestic Mild Cognitive Impairment: Tract-based spatial statistics analysis

Apathy is recognized as a prevalent behavioral symptom of amnestic Mild Cognitive Impairment (aMCI). In aMCI, apathy is associated with an increased risk and increases the risk of progression to Alzheimer’s Disease (AD). Previous DTI study in aMCI showed that apathy has been associated with white matter alterations in the cingulum, middle and inferior longitudinal fasciculus, fornix, and uncinate fasciculus. However, the underlying white matter correlates associated with apathy in aMCI are still unclear. We investigated this relationship using whole-brain diffusion tensor imaging (DTI). Twenty-nine aMCI patients and 20 matched cognitively healthy controls were included. Apathy severity was assessed using the Apathy Evaluation Scale Clinician version. We applied the tract-based spatial statistics analyses to DTI parameters: fractional anisotropy (FA), mean diffusivity, axial diffusivity, and radial diffusivity to investigate changes in white matter pathways associated with the severity of apathy. No significant difference was found in any of the DTI parameters between aMCI and the control group. In aMCI, higher severity of apathy was associated with lower FA in various white matter pathways including the left anterior part of inferior fronto-occipital fasciculus/uncinate fasciculus, genu and body of the corpus callosum, superior and anterior corona radiata, anterior thalamic radiation of both hemispheres and in the right superior longitudinal fasciculus/anterior segment of arcuate fasciculus (p < .05, TFCE-corrected) after controlling for age, gender and GDS non-apathy. A trend association was observed in the right posterior corona radiata and corticospinal tract/internal capsule, and bilateral forceps minor (p < .065, TFCE-corrected). In conclusion, in aMCI, severity of apathy is associated with aberrant white matter integrity in widely distributed pathways, within and between hemispheres.

Altered Neuroanatomical Asymmetries of Subcortical Structures in Subjective Cognitive Decline, Amnestic Mild Cognitive Impairment, and Alzheimer's Disease.

Individuals with subjective cognitive decline (SCD), defined by self-reported memory complaints but normal performance in objective neuropsychological tests, may be at higher risk of worsening or more frequent memory loss until conversion to Alzheimer's disease (AD) or related dementia. Asymmetry in two hemispheres is a cardinal character of human brain's structure and function, and altered brain asymmetry has also been connected with AD. This study aimed to determine whether the asymmetry of subcortical structures in individuals with SCD and amnestic mild cognitive impairment (aMCI) and AD patients are altered compared with normal controls (NC). We investigated neuroanatomical alterations in 35 SCD, 43 aMCI, and 41 AD subjects compared with 42 NC, focusing on asymmetrical changes in subcortical structures based on structural magnetic resonance images (sMRI). General linear model was conducted to test group differences, and partial correlation was used to model the interaction between asymmetry measurements and cognitive tests. Individuals with SCD (lateral ventricle and cerebellum-WM), aMCI patients (lateral ventricle, pallidum, hippocampus, amygdala, accumbens, and ventral DC), and AD patients (lateral-ventricle, cerebellum-cortical pallidum, thalamus, hippocampus, amygdala, accumbens, and ventral DC) exhibited significant altered neuroanatomical asymmetries of volume, surface area, and shape compared with NC. Significant associations between shape asymmetry and neuropsychological examinations were found in the hippocampus and accumbens. Altered neuroanatomical asymmetries of subcortical structures were significantly detected in SCD individuals and aMCI patients as well AD patients, and these specific asymmetry alterations are potential to be used as neuroimaging markers and for monitoring disease progression.

A Conformation Variant of p53 Combined with Machine Learning Identifies Alzheimer Disease in Preclinical and Prodromal Stages.

Early diagnosis of Alzheimer’s disease (AD) is a crucial starting point in disease management. Blood-based biomarkers could represent a considerable advantage in providing AD-risk information in primary care settings. Here, we report new data for a relatively unknown blood-based biomarker that holds promise for AD diagnosis. We evaluate a p53-misfolding conformation recognized by the antibody 2D3A8, also named Unfolded p53 (U-p532D3A8+), in 375 plasma samples derived from InveCe.Ab and PharmaCog/E-ADNI longitudinal studies. A machine learning approach is used to combine U-p532D3A8+ plasma levels with Mini-Mental State Examination (MMSE) and apolipoprotein E epsilon-4 (APOEε4) and is able to predict AD likelihood risk in InveCe.Ab with an overall 86.67% agreement with clinical diagnosis. These algorithms also accurately classify (AUC = 0.92) Aβ+—amnestic Mild Cognitive Impairment (aMCI) patients who will develop AD in PharmaCog/E-ADNI, where subjects were stratified according to Cerebrospinal fluid (CSF) AD markers (Aβ42 and p-Tau). Results support U-p532D3A8+ plasma level as a promising additional candidate blood-based biomarker for AD.

Subjective Sleep Quality in Amnestic Mild Cognitive Impairment Elderly and Its Possible Relationship With Plasma Amyloid-β.

Study objectivesTo investigate the extent to which sleep quality associated with plasma Aβ levels in amnestic mild cognitive impairment (aMCI) elderly.MethodsA total of 172 cognitively normal (NC) elderly and 133 aMCI elderly were included in this study. For the evaluation of sleep quality, the Pittsburgh Sleep Quality Index (PSQI) was used. Levels of plasma Aβ were determined by the sandwich enzyme-linked immunosorbent assay technique. Multivariable linear regression analysis was applied to evaluate associations between sleep quality and plasma Aβ levels after adjusting potential confounders.ResultsCompared to NC subjects, participants with aMCI had a higher global PSQI score (8.72 ± 3.87 vs. 7.10 ± 3.07, p < 0.001). The global PSQI score was positively associated with plasma Aβ42 level in the aMCI group (β = 0.063, 95% CI 0.001–0.125, and p = 0.049) but not in the NC group (p > 0.05). Additionally, a higher global PSQI score was associated with a higher plasma Aβ42/Aβ40 ratio in both NC (β = 0.010, 95% CI 0.003–0.016, and p = 0.003) and aMCI groups (β = 0.012, 95% CI 0.005–0.018, and p < 0.001). The association between global PSQI score and plasma Aβ42/Aβ40 ratio was stronger in individuals with aMCI relative to the NC subjects (β = 0.076 vs. 0.030, p for interaction = 0.023).ConclusionPoor sleep quality was associated with plasma Aβ42 and Aβ42/Aβ40 ratio, with a stronger effect among individuals with aMCI. A better understanding of the role of sleep in plasma Aβ levels in aMCI patients could lead to effective sleep-based intervention against the risk of Alzheimer’s disease.

Validity of the Clinical Dementia Rating Scale Sum of Boxes in Staging and Detection of Cognitive Impairment in Mexican Americans.

We evaluated the utility of the Clinical Dementia Rating Sum of Boxes score (CDR-SB) in staging and detecting amnestic-mild cognitive impairment (a-MCI) and Alzheimer's disease (AD) among Mexican Americans. Receiver operator curves were generated to evaluate the validity of the CDR-SB in staging and detecting a-MCI and AD in 1,073 Mexican Americans (758 controls, 163 a-MCI, and 152 AD). Optimal ranges of the CDR-SB were 0, 0.5-4, 4.5-8.0, 8.5-13 and 13.5-18 for staging the global CDR score of 0, 0.5, 1, 2, and 3, respectively. The CDR-SB ≥ 0.5 differentiated the a-MCI patients from the controls (sensitivity 100% and specificity 99.5%) and ≥ 2.0 distinguished the AD from a-MCI patients (sensitivity 83.6% and specificity 87.1%). These cutoffs were also appropriate for patients with ≤6 years of education. The CDR-SB is useful to detect and stage a-MCI and AD in Mexican Americans with diverse education levels.