Early Cognitive Impairment Research Articles

MRI or 18F-FDG PET for Brain Age Gap Estimation: Links to Cognition, Pathology, and Alzheimer Disease Progression.

Deviations of brain age from chronologic age, known as the brain age gap (BAG), have been linked to neurodegenerative diseases such as Alzheimer disease (AD). Here, we compare the associations of MRI-derived (atrophy) or 18F-FDG PET-derived (brain metabolism) BAG with cognitive performance, neuropathologic burden, and disease progression in cognitively normal individuals (CNs) and individuals with subjective cognitive decline (SCD) or mild cognitive impairment (MCI). Methods: Machine learning pipelines were trained to estimate brain age from 185 matched T1-weighted MRI or 18F-FDG PET scans of CN from the Alzheimer's Disease Neuroimaging Initiative and validated in external test sets from the Open Access of Imaging and German Center for Neurodegenerative Diseases-Longitudinal Cognitive Impairment and Dementia studies. BAG was correlated with measures of cognitive performance and AD neuropathology in CNs, SCD subjects, and MCI subjects. Finally, BAG was compared between cognitively stable and declining individuals and subsequently used to predict disease progression. Results: MRI (mean absolute error, 2.49 y) and 18F-FDG PET (mean absolute error, 2.60 y) both estimated chronologic age well. At the SCD stage, MRI-based BAG correlated significantly with beta-amyloid1-42 (Aβ1-42) in cerebrospinal fluid, whereas 18F-FDG PET BAG correlated with memory performance. At the MCI stage, both BAGs were associated with memory and executive function performance and cerebrospinal fluid Aβ1-42, but only MRI-derived BAG correlated with phosphorylated-tau181/Aβ1-42 Lastly, MRI-estimated BAG predicted MCI-to-AD progression better than 18F-FDG PET-estimated BAG (areas under the curve, 0.73 and 0.60, respectively). Conclusion: Age was reliably estimated from MRI or 18F-FDG PET. MRI BAG reflected cognitive and pathologic markers of AD in SCD and MCI, whereas 18F-FDG PET BAG was sensitive mainly to early cognitive impairment, possibly constituting an independent biomarker of brain age-related changes.

Virtual external stimulation promotes the transformation of the brain state from early mild cognitive impairment to health

AbstractNeurostimulation has emerged as a potential remedy for early mild cognitive impairment (EMCI). However, further exploration is needed on how external stimulation of brain regions promotes the transition of the brain state from EMCI to health and the selection of target locations. In this study, a functional magnetic resonance imaging dataset was used to evaluate the brain states of healthy individuals and patients with EMCI to explore the probabilistic metastable substate space, identifying abnormal manifestations of EMCI. Stimulation targets were then identified and stimulated to achieve complete controllability of the effective connection network for EMCI. A whole‐brain model successfully fitted the brain state of the patients with EMCI based on diffusion tensor imaging data. Based on this whole‐brain model, stimulation of the hippocampus, medial frontal gyrus, suboccipital gyrus, and fusiform gyrus can promote the transformation of the brain state from EMCI to health. The findings reveal the underlying brain mechanisms of cognitive decline in patients with EMCI and the stimulation targets of the neural mechanisms of EMCI restoration, which could help in designing more effective therapeutic interventions for EMCI.

Impact of early cognitive impairment on outcome trajectory in patients with intracerebral hemorrhage.

To assess the prevalence and factors associated with early cognitive impairment in intracerebral hemorrhage (ICH) patients and to describe short-term recovery trajectories among ICH patients with early cognitive impairment. We prospectively enrolled ICH patients without baseline dementia in our institutions. Cognitive function was assessed using mini-mental state examination (MMSE), and functional outcome was evaluated at discharge, 3, and 6 months after symptoms onset using the modified Rankin Scale (mRS). We used multinomial logistic regression models to investigate potential risk factors and generalized linear models to analyze the functional outcome data. Out of 181 patients with ICH, 167 were included in the final analysis. Early cognitive impairment occurred in 60.48% of patients with ICH. Age (odds ratio [OR] per 1-year increase, 1.037; 95% confidence interval [CI], 1.003-1.071; p = 0.034), National Institutes of Health Stroke Scale (NIHSS) score (OR per 1-point increase, 1.146; 95% CI, 1.065-1.233; p < 0.001) and lobar ICH location (OR, 4.774; 95% CI, 1.810-12.593; p = 0.002) were associated with early cognitive impairment in ICH patients. Patients with ≥10 years of education were less likely to experience early cognitive impairment (OR, 0.323; 95% CI, 0.133-0.783; p = 0.012). Participants with early cognitive impairment had a higher risk of poor outcome (OR, 4.315; 95% CI, 1.503-12.393; p = 0.005) than those without. Furthermore, there was a significantly faster functional recovery rate for those without early cognitive impairment compared with those with at 3 and 6 months (p < 0.05). Early cognitive impairment was prevalent and associated with poor outcomes in ICH patients, which decelerated short-term functional recovery.

Histidine-containing dipeptide supplementation improves delayed recall: a systematic review and meta-analysis.

Histidine-containing dipeptides (carnosine, anserine, beta-alanine and others) are found in human muscle tissue and other organs like the brain. Data in rodents and humans indicate that administration of exogenous carnosine improved cognitive performance. However, RCTs results vary. To perform a systematic review and meta-analysis of randomized controlled trials (RCTs) of histidine-containing dipeptide (HCD) supplementation on cognitive performance in humans to assess its utility as a cognitive stabiliser. OVID Medline, Medline, EBM Reviews, Embase, and Cumulative Index to Nursing and Allied Health Literature databases from 1/1/1965 to 1/6/2022 for all RCT of HCDs were searched. 2653 abstracts were screened, identifying 94 full-text articles which were assessed for eligibility. Ten articles reporting the use of HCD supplementation were meta-analysed. The random effects model has been applied using the DerSimonian-Laird method. HCD treatment significantly increased performance on Wechsler Memory Scale (WMS) -2 Delayed recall (Weighted mean difference (WMD) (95% CI (CI)) = 1.5 (0.6, 2.5), P < .01). Treatment with HCDs had no effect on Alzheimer's Disease Assessment Scale-Cognitive (WMD (95% CI) = -0.2 (-1.1, 0.7), P = .65, I2 = 0%), Mini-Mental State Examination (WMD (95% CI) = 0.7 (-0.2, 1.5), P = .14, I2 = 42%), The Wechsler Adult Intelligence Scale (WAIS) Digit span Backward (WMD (95% CI) = 0.1 (-0.3, 0.5), P = .51, I2 = 0%), WAIS digit span Forward (WMD (95% CI) = 0.0 (-0.3, 0.4), P = .85, I2 = 33%) and the WMS-1 Immediate recall (WMD (95% CI) = .7 (-.2, 1.5), P = .11, I2 = 0%). The effect on delayed recall remained in subgroup meta-analysis performed on studies of patients without mild cognitive impairment (MCI), and in those without MCI where average age in the study was above 65. HCD, supplementation improved scores on the Delayed recall examination, a neuropsychological test affected early in Alzheimer's disease. Further studies are needed in people with early cognitive impairment with longer follow-up duration and standardization of carnosine doses to delineate the true effect. PROSPERO registration no. CRD42017075354.

Association Between Acoustic Features and Brain Volumes: the Framingham Heart Study.

Although brain magnetic resonance imaging (MRI) is a valuable tool for investigating structural changes in the brain associated with neurodegeneration, the development of non-invasive and cost-effective alternative methods for detecting early cognitive impairment is crucial. The human voice has been increasingly used as an indicator for effectively detecting cognitive disorders, but it remains unclear whether acoustic features are associated with structural neuroimaging. This study aims to investigate the association between acoustic features and brain volume and compare the predictive power of each for mild cognitive impairment (MCI) in a large community-based population. The study included participants from the Framingham Heart Study (FHS) who had at least one voice recording and an MRI scan. Sixty-five acoustic features were extracted with the OpenSMILE software (v2.1.3) from each voice recording. Nine MRI measures were derived according to the FHS MRI protocol. We examined the associations between acoustic features and MRI measures using linear regression models adjusted for age, sex, and education. Acoustic composite scores were generated by combining acoustic features significantly associated with MRI measures. The MCI prediction ability of acoustic composite scores and MRI measures were compared by building random forest models and calculating the mean area under the receiver operating characteristic curve (AUC) of 10-fold cross-validation. The study included 4,293 participants (age 57 ± 13 years, 53.9% women). During 9.3±3.7 years follow-up, 106 participants were diagnosed with MCI. Seven MRI measures were significantly associated with more than 20 acoustic features after adjusting for multiple testing. The acoustic composite scores can improve the AUC for MCI prediction to 0.794, compared to 0.759 achieved by MRI measures. We found multiple acoustic features were associated with MRI measures, suggesting the potential for using acoustic features as easily accessible digital biomarkers for the early diagnosis of MCI.

Long-Term Krill Oil Administration Alleviated Early Mild Cognitive Impairment in APP/PS1 Mice.

Alzheimer's disease is an age-dependent neurodegenerative disorder. Mounting studies focus on the improvement of advanced cognitive impairment by dietary nutrients. Krill oil (KO), a rich source of DHA/EPA and astaxanthin, is effective in improving cognitive function. The study mainly investigates the protective effects of long-term KO administration on early cognitive impairment. Results show that 2 months KO administration (50 and 100mgkg-1 BW) can dramatically promote learning and memory abilities. Mechanism studies demonstrate that KO reduces amyloid β concentration by regulating the amyloidogenic pathway, inhibits neuro-inflammation via regulating TLR4-NLRP3 signaling pathway, and prevents neuron injure. KO supplementation also enhances gut barrier integrity, reduces serum lipopolysaccharide leakage, and alters the gut microbiota by reducing Helicobacteraceae, Lactobacillaceae proportion, increasing Dubosiella and Akkermansia relative abundance. Particularly, a significant increase of isovaleric acid, propionic acid, and acetic acid levels is observed after KO supplementation. Correlation analysis shows that short-chain fatty acids (SCFAs), gut microbiota, and cognitive function are strongly correlated. The results reveal that KO relieves early mild cognitive impairment possibly for its role in mediating the gut microbiome-SCFAs-brain axis. Thus, KO may provide potential intervention strategies to prevent cognitive impairment in the early stages through the microbiota-gut-brain axis.

Exploring the Potential of the Corpus Callosum Area as a Predictive Marker for Impaired Information Processing in Multiple Sclerosis

Early cognitive impairment (CI) detection is crucial in multiple sclerosis (MS). However, it can progress silently regardless of relapse activity and reach an advanced stage. We aimed to determine whether the corpus callosum area (CCA) is a sensitive and feasible marker for CI in MS compared to other neuroimaging markers. We assessed cognitive function in 77 MS patients using the Symbol Digit Modalities Test, Paced Auditory Serial Additions Task, Wechsler Adult Intelligence Scale-IV, and Wechsler Memory Scale-Revised. The neuroimaging markers included manually measured CCA, two diffusion tensor imaging markers, and nine volumetric measurements. Apart from volumes of the hippocampus and cerebellum, ten markers showed a significant correlation with all neuropsychological tests and significant differences between the groups. The normalized CCA demonstrated a moderate-to-strong correlation with all neuropsychological tests and successfully differentiated between the CI and cognitively normal groups with 80% sensitivity and 83% specificity. The marker had a large area under the curve and a high Youden index (0.82 and 0.63, respectively) and comparability with established cognitive markers. Therefore, the normalized CCA may serve as a reliable marker for CI in MS and can be easily implemented in clinical practice, providing a supportive diagnostic tool for CI in MS.

A post hoc analysis of Projected Retained Ability Scores (PRAS) for the longitudinal assessment of cognitive functioning in patients with neuronopathic mucopolysaccharidosis II receiving intrathecal idursulfase-IT

BackgroundNorm-based scores used to assess cognitive ability have clinical value when describing functioning of patients with neuronopathic disorders compared with unaffected, same-age peers. However, they have limitations when used to assess change in cognitive ability between two timepoints, especially in children with severe cognitive decline. Calculation of Projected Retained Ability Scores (PRAS) is a novel method developed to characterize absolute change in norm-based ability test scores. In this analysis, PRAS were calculated post hoc for children with mucopolysaccharidosis II (MPS II; Hunter syndrome) and early cognitive impairment in a 52-week phase 2/3 randomized controlled trial (RCT) and its extension study of intrathecal idursulfase (idursulfase-IT). Patients completing the first year of the extension after receiving idursulfase-IT in the RCT and extension (n = 32 of 34 enrolled) or the extension only (n = 15 of 15 enrolled) were categorized according to changes in Differential Ability Scales, Second Edition, General Conceptual Ability (DAS-II GCA) scores and PRAS at 1 and 2 years. Analyses were conducted in the overall population and a subpopulation aged < 6 years at baseline (idursulfase-IT in the RCT and extension [n = 27] and extension only [n = 12]).ResultsPRAS methodology differentiated patients with decreases in DAS-II GCA scores into three separate categories reflecting below-average cognitive growth rates, plateauing cognitive development, and deteriorating cognitive functioning. After 1 year in the RCT, 72.4% of patients who initiated idursulfase-IT had above-average or average cognitive growth rates in DAS-II GCA scores compared with 53.3% of those who did not receive idursulfase-IT; 6.9% versus 20.0% experienced deteriorating cognitive functioning. Similar results were seen in children aged < 6 years: 76% (idursulfase-IT group) versus 50% (no idursulfase-IT) had above-average or average cognitive growth rates in DAS-II GCA scores; 4% versus 17% had deteriorating cognitive functioning. The difference in the distributions of cognitive categories at 1 year in children aged < 6 years was significant (p = 0.048). At 2 years, the proportions of patients in different cognitive categories were more similar between treatment groups.ConclusionsPRAS methodology may help to differentiate changes in cognitive development in MPS II, and therefore may represent a valuable addition to existing approaches for interpreting changes in cognitive scores over time.Trial Registration: ClinicalTrials.gov NCT02055118 (registration date: 4 February 2014) and NCT02412787 (registration date: 9 April 2015).

76 Baseline Frontoparietal Gray Matter Volume Predicts Executive Function Performance at 24-Months in Early and Late Mild Cognitive Impairment

Objective:To examine the relationships between baseline gray matter volumes, diagnostic status, and executive function performance at 24-month follow-up, and the relative importance of predictors of executive function in a cohort of non-demented older adults.Participants and Methods:The study sample included 147 participants from the Alzheimer’s Disease Neuroimaging Initiative (mean age = 70.6, SD = 6.4; mean education = 17 years, SD = 2.4). At baseline, 49 participants were diagnosed as cognitively normal (CN), 60 as early mild cognitive impairment (EMCI), and 38 as late mild cognitive impairment (LMCI). Magnetic resonance imaging (MRI) data were collected at baseline. A composite score of executive function and FreeSurfer-derived gray matter regions-of-interest (ROI; whole brain, superior frontal gyrus, middle frontal gyrus, inferior frontal gyrus, orbitofrontal cortex, anterior cingulate cortex, superior parietal lobule, inferior parietal lobule, hippocampus) were examined. Hierarchical linear regression models were employed to assess whether brain volume predicted executive function at 24-month follow-up and interaction effects between baseline ROI volume and diagnostic status. Age, gender, education, Mini-Mental State Examination scores, and APOE-e4 allele status were included as control variables in each model. Relative importance metrics, which quantifies an individual regressor’s contribution to a multiple regression model, were computed using the Lindemen, Merenda, and Gold (lmg) method to assess the relative contribution of each variable in predicting executive function performance.Results:Across all participants, baseline gray matter ROI volume accounted for a significant amount of variance in executive function at 24-months after accounting for control variables. Specifically, anterior cingulate cortex and superior parietal lobule accounted for an additional 7% and 6% of variance in executive function at 24-months. Significant brain region X diagnostic status interaction effects were observed in executive function performance at 24-months. Relative importance metrics within each group indicated that age is the most important predictor of executive function at 24-months for CN, anterior cingulate cortex is most important for EMCI, and Mini-Mental Examination score is most important for LMCI.Conclusions:Our findings implicate frontoparietal gray matter regions as significant predictors of executive function performance at 24-months, and that this relationship is moderated by diagnostic status. Our results indicate that the value of specific variables to predict executive function performance varies based on diagnostic status. Specifically, anterior cingulate cortex was a significant predictor of executive function performance across all participants and was the most important variable in predicting performance in the earliest stage of mild cognitive impairment. These results support previous studies examining gray matter correlates of executive function and extend the literature by exploring predictors of executive function in early and late stages of mild cognitive impairment.

56 Predictors of Finger Tapping Variability in Older Adults Evaluated for a Neurodegenerative Memory Disorder

Objective:Patients with early Alzheimer Disease (AD) and Mild Cognitive Impairment of the Amnestic type (MCI-A) have been reported to show large variability of tapping scores. Factors that contribute to that variability remain undetermined. This preliminary study aimed to identify predictors of finger tapping variability in older adults evaluated for a neurodegenerative memory disorder. Based on earlier research with normally functioning adults, we predicted that the number of “invalid” tapping responses (i.e. failure of the index finger to adequately lift off the tapping key once it is depressed to produce the next number on a mechanical counter) and the female gender would predict finger tapping variability, but age and educational level would not predict variability.Participants and Methods:This preliminary study included 4 groups of participants, comprised of 8 healthy controls (HC, 3 males; 73±7years); 12 persons with subjective memory complaints (SMC, 3 males; 69±5 years); 12 with MCI-A (7 males; 76±5 years) and 7 early AD (5 males; 75±6years). All participants were administered a modified version of the Halstead Finger Tapping Test (HFTT). Mean, range of tapping score (i.e. a measure of variability), and number of invalid taps across 7 trials in each hand were calculated. ANOVA was performed for the HFTT metrics with the main effect of group. Tukey HSD tests were used for post hoc comparisons between groups. Multiple regression analysis was performed to determine the degree to which the number of invalid tapping responses, sex, age, and educational level predicted finger tapping variability using all 4 groups.Results:Mean tapping score did not vary significantly across groups in the dominant [F (3, 35) = 0.633, p = 0.599] or non-dominant [F (3, 35) = 2.345, p = 0.090] hand. Range score approached a significant difference between groups in the dominant hand [F (3, 35) = 2.745, p = 0.058], with a clear significant effect of group on range score in the non-dominant hand [F (3, 35) = 4.078, p = 0.014]. Range score in the nondominant hand was significantly higher in the AD compared to SMC (p = 0.018) and HC (p = 0.024). Regression analysis revealed statistically significant findings for the dominant hand (R2 = 0.327, F (4, 34) = 4.130, p = 0.008) and for the non-dominant hand (R2 = 0.330, F (4, 34) = 4.180, p = 0.007). For both the dominant and non-dominant hands, number of invalid taps significantly predicted range score (ß = 0.453, p = 0.044, and ß = 0.498, p = 0.012, respectively). Sex, age, and education years did not predict range scores.Conclusions:Variability of finger tapping in patients evaluated for neurodegenerative memory disorders and aged matched controls is predicted by the number of invalid tapping responses (comprising over 30% of the variance), but not by demographic variables in this clinical sample. Neurodegenerative disorders may eliminate a sex effect.

MRI Visible Perivascular Spaces and the Risk of Incident Mild Cognitive Impairment in a Community Sample.

Magnetic resonance imaging (MRI) visible perivascular spaces (PVS) are associated with the risk of incident dementia but their association with the early stages of cognitive impairment remains equivocal. We examined the association between MRI visible PVS and the risk of incident mild cognitive impairment (MCI) in the community-based Framingham Heart Study (FHS). FHS participants aged at least 50 years free of stroke, cognitive impairment, and dementia at the time of MRI were included. PVS were rated according to severity in the basal ganglia and centrum semiovale (CSO) using established criteria. Cox regression analyses were used to relate PVS to incident MCI adjusted for demographic and cardiovascular variables. The mean age of the sample (1,314 participants) at MRI was 68 years (SD, 9; 54% women). There were 263 cases of incident MCI over a median 7.4 years follow-up (max, 19.8 years). MCI risk increased with higher PVS severity in the CSO. Relative to persons with the lowest severity rating, persons with the highest severity rating in the CSO had a higher risk of incident MCI (hazard ratio [HR] = 2.55; 95% confidence interval [CI], 1.48-4.37; p = 0.0007). In secondary analysis, this association seemed stronger in women. Risk of incident MCI was nominally higher for participants with the highest severity grade of PVS in the basal ganglia, though not statistically significant relative to the lowest grade (HR = 2.19; 95% CI, 0.78-6.14; p = 0.14). PVS burden in the CSO may be a risk marker for early cognitive impairment.

In person versus remote cognitive rehabilitation in patients with subjective cognitive decline or neurocognitive disorders: what factors drive patient's preference?

To date, there is still a lack of consensus for identifying the ideal candidate for cognitive telerehabilitation (TR). The main goal of the present study is to identify the factors associated to the preference for either TR or in-person cognitive training (CT) programs in older adults at risk of dementia or with early cognitive impairment. A sample of 56 participants with subjective cognitive decline or neurocognitive disorders eligible for CT were enrolled at the Dementia Research Center and Neurorehabilitation Unit of IRCCS Mondino Foundation. All individuals underwent a baseline assessment to capture their complete profile, including cognitive reserve and lifestyle habits, sociodemographic characteristics, cognitive functioning, and mental health. Patients were then asked their preference for TR or in-person CT, before being randomized to either treatment as per protocol procedures. Statistical analyses included explorative descriptive approach, logistic regression, and non-parametric models to explore the overall contribution of each variable. The two (TR and in-person) preference groups were similar for cognitive functioning and mental health status. Socio-demographic and lifestyle profiles seem to be the most important factors to influence the preference in terms of the area under the curve (AUC) of the models. The two preference groups differed in terms of socio-demographic characteristics (e.g., level of technological skills, age, and distance from the clinic). Furthermore, participants who selected the TR modality of CT had significantly higher levels of cognitive reserve and adopted more protective lifestyle habits (e.g., regular physical activity, Mediterranean diet) when compared to those who preferred in-person CT. These findings highlight that the preference to receive CT delivered by TR or in person is a complex issue and is influenced by a variety of factors, mostly related to lifestyle habits and sociodemographic characteristics. Availability of profiles of patients that may be more attracted to one or the other modality of TR may help promote shared decision-making to enhance patient experience and outcomes.

Mutation in the FUS nuclear localisation signal domain causes neurodevelopmental and systemic metabolic alterations.

Variants in the ubiquitously expressed DNA/RNA-binding protein FUS cause aggressive juvenile forms of amyotrophic lateral sclerosis (ALS). Most FUS mutation studies have focused on motor neuron degeneration; little is known about wider systemic or developmental effects. We studied pleiotropic phenotypes in a physiological knock-in mouse model carrying the pathogenic FUSDelta14 mutation in homozygosity. RNA sequencing of multiple organs aimed to identify pathways altered by the mutant protein in the systemic transcriptome, including metabolic tissues, given the link between ALS-frontotemporal dementia and altered metabolism. Few genes were commonly altered across all tissues, and most genes and pathways affected were generally tissue specific. Phenotypic assessment of mice revealed systemic metabolic alterations related to the pathway changes identified. Magnetic resonance imaging brain scans and histological characterisation revealed that homozygous FUSDelta14 brains were smaller than heterozygous and wild-type brains and displayed significant morphological alterations, including a thinner cortex, reduced neuronal number and increased gliosis, which correlated with early cognitive impairment and fatal seizures. These findings show that the disease aetiology of FUS variants can include both neurodevelopmental and systemic alterations.

Further evaluation of narrative description as a measure of cognitive function in Alzheimer's disease.

The narrative description (ND) test objectively measures the ability to understand and describe visual scenes. As subtle differences in speech occur early in cognitive decline, we analyzed linguistic features for their utility in detecting cognitive impairment and predicting downstream decline. Participants (n = 52) with normal cognition to mild dementia performed the ND test (watched twenty 30-s video clips and described the visual content). Cognitive function was followed for up to 5 years. We computed simple linguistic features such as content efficiency, speech rate, and part of speech and unique word counts. We examined (a) relationships between cognitive status and ND score and linguistic features; (b) ability to discriminate early cognitive impairment from normal cognition using ND score and linguistic features; and (c) whether ND score and linguistic features were associated with future cognitive functional decline. Many of the linguistic-feature metrics were related to cognitive status. Many of the linguistic features could distinguish between the cognitively normal group and the mild cognitive impairment (MCI) and Dementia groups. The area under the curve (AUC) for ND score alone was 0.74, with a nonsignificant increase to 0.78 when adding mean word length. Among participants with subjective cognitive decline (SCD) at the first visit, a smaller number of words plus more interjections or a lower ND score at baseline were predictive of future cognitive decline. While many linguistic features were associated with cognitive status, and some were able to detect early cognitive impairment or predictive of future cognitive decline, all the features we tested seem to have been captured by the ND score. Thus, adding linguistic measures to the ND test score did not add to its value in assessing current or predicting future cognitive status. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Can you find it? Novel oddity detection task for the early detection of Alzheimer's disease.

We aimed to develop a measure to specifically assess the functioning of the perirhinal cortex (PRC), a brain structure affected very early in Alzheimer's disease (AD) pathology. In this novel task, participants were shown arrays of six complex figures and had to identify the "odd-one." The pilot study included 50 normal controls (NCs) and 50 patients in very early stages of AD. Participants completed the task and received MRI scanning. Best differentiating items were determined and applied in a validation study including 25 NCs, 27 early-stage AD patients, and 26 patients with major depression. Logistic regression models investigated if task performance predicted group membership. Task performance was then related to whole-brain gray matter integrity. As proof of concept, cortical thickness values of four regions of interest (ROIs; e.g., medial PRC and entorhinal cortex [ERC]) were compared between the groups. The associations of task performance and cortical thickness of the ROIs were investigated using linear models. Task performance showed good discriminative ability between early-stage AD patients and NCs. Whole-brain analyses revealed four significant clusters (p < .001) with peak voxels in parahippocampal regions including PRC and ERC. ROI analyses showed distinctly reduced cortical thickness in the AD group compared to both other groups in the medial PRC and ERC (p ≤ .001). Task performance modeled by ROI cortical thickness did not achieve significant results. Although further validation is needed, especially with age-matched participant groups, these findings indicate that the task detects early cognitive impairment related to AD. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Advances in Folic Acid Biosensors and Their Significance in Maternal, Perinatal, and Paediatric Preventive Medicine.

Auxotrophic primates like human beings rely on exogenous dietary vitamin B9 supplementation to meet their metabolic demands. Folates play a crucial role in nucleotide synthesis and DNA methylation. Maternal folate deficiency causes several pregnancy-related complications, perinatal defects, and early childhood cognitive impairments. New evidence suggests excess FA is a potential risk factor resulting in unfavourable genomic and epigenomic alterations. Thus, it is essential to revisit the need to consistently monitor maternal folate levels during pregnancy. Yet, to date, no point-of-care folate-monitoring biosensor is commercially available. Here, we critically appraise the advances in folate biosensors to understand the translational gaps in biosensor design. Further, our review sheds light on the potential role of folate biosensors in strengthening maternal, perinatal, and child healthcare.

Fine-Grained and Multiple Classification for Alzheimer's Disease With Wavelet Convolution Unit Network.

In this article, we propose a novel wavelet convolution unit for the image-oriented neural network to integrate wavelet analysis with a vanilla convolution operator to extract deep abstract features more efficiently. On one hand, in order to acquire non-local receptive fields and avoid information loss, we define a new convolution operation by composing a traditional convolution function and approximate and detailed representations after single-scale wavelet decomposition of source images. On the other hand, multi-scale wavelet decomposition is introduced to obtain more comprehensive multi-scale feature information. Then, we fuse all these cross-scale features to improve the problem of inaccurate localization of singular points. Given the novel wavelet convolution unit, we further design a network based on it for fine-grained Alzheimer's disease classifications (i.e., Alzheimer's disease, Normal controls, early mild cognitive impairment, late mild cognitive impairment). Up to now, only a few methods have studied one or several fine-grained classifications, and even fewer methods can achieve both fine-grained and multi-class classifications. We adopt the novel network and diffuse tensor images to achieve fine-grained classifications, which achieved state-of-the-art accuracy for all eight kinds of fine-grained classifications, up to 97.30%, 95.78%, 95.00%, 94.00%, 97.89%, 95.71%, 95.07%, 93.79%. In order to build a reference standard for Alzheimer's disease classifications, we actually implemented all twelve coarse-grained and fine-grained classifications. The results show that the proposed method achieves solidly high accuracy for them. Its classification ability greatly exceeds any kind of existing Alzheimer's disease classification method.

Edge‐centric functional network reveals new spatiotemporal biomarkers of early mild cognitive impairment

AbstractMost neuroimaging studies of the pathogenesis of early mild cognitive impairment (EMCI) rely on a node‐centric network model, which only calculates correlations between brain regions. Considering the interaction of low‐order correlations between pairs of brain regions, we use an edge‐centric network model to study high‐order functional network correlations. Here, we compute edge time series (eTS) to obtain overlapping communities and study the relationship between subnetworks and communities in space. Then, based on the overlapping communities, we calculate the normalized entropy to measure the diversity of each node. Next, we compute the high‐amplitude co‐fluctuation of the eTS to explore the pattern of brain activity with temporal precision. Our results show that the normal control and EMCI patients differ in brain regions, subnetworks, and the whole brain. In particular, entropy values show a gradual decrease, and brain network co‐fluctuation increases with disease progression. Our study is the first to investigate the pathogenesis of EMCI from the perspective of spatiotemporal flexibility and cognitive diversity based on high‐order edge connectivity, further characterizing brain dynamics and providing new insights into the search for biomarkers of EMCI.

A blunted TH17 cytokine signature in women with mild cognitive impairment: insights from inflammatory profiling of a community-based cohort of older adults.

People with dementia have an increase in brain inflammation, caused in part by innate and adaptive immune cells. However, it remains unknown whether dementia-associated diseases alter neuro-immune reflex arcs to impact the systemic immune system. We examined peripheral immune cells from a community-based cohort of older adults to test if systemic inflammatory cytokine signatures associated with early stages of cognitive impairment. Human peripheral blood mononuclear cells were cultured with monocyte or T-cell-targeted stimuli, and multiplex assays quantitated cytokines in the conditioned media. Following T-cell-targeted stimulation, cells from women with cognitive impairment produced lower amounts of TH17 cytokines compared with cells from cognitively healthy women, while myeloid-targeted stimuli elicited similar amounts of cytokines from cells of both groups. This TH17 signature correlated with the proportion of circulating CD4+ and CD8+ T cells and plasma glial fibrillary acidic protein and neurofilament light concentrations. These results suggest that decreases in TH17 cytokines could be an early systemic change in women at risk for developing dementia. Amelioration of TH17s cytokines in early cognitive impairment could, in part, explain the compromised ability of older adults to respond to vaccines or defend against infection.

Tau-PET abnormality as a biomarker for Alzheimer's disease staging and early detection: a topological perspective.

Alzheimer's disease can be detected early through biomarkers such as tau positron emission tomography (PET) imaging, which shows abnormal protein accumulations in the brain. The standardized uptake value ratio (SUVR) is often used to quantify tau-PET imaging, but topological information from multiple brain regions is also linked to tau pathology. Here a new method was developed to investigate the correlations between brain regions using subject-level tau networks. Participants with cognitive normal (74), early mild cognitive impairment (35), late mild cognitive impairment (32), and Alzheimer's disease (40) were included. The abnormality network from each scan was constructed to extract topological features, and 7 functional clusters were further analyzed for connectivity strengths. Results showed that the proposed method performed better than conventional SUVR measures for disease staging and prodromal sign detection. For example, when to differ healthy subjects with and without amyloid deposition, topological biomarker is significant with P < 0.01, SUVR is not with P > 0.05. Functionally significant clusters, i.e. medial temporal lobe, default mode network, and visual-related regions, were identified as critical hubs vulnerable to early disease conversion before mild cognitive impairment. These findings were replicated in an independent data cohort, demonstrating the potential to monitor the early sign and progression of Alzheimer's disease from a topological perspective for individual.