MCI Group Research Articles

Plasma phosphorylated tau181 outperforms [18F] fluorodeoxyglucose positron emission tomography in the identification of early Alzheimer disease.

This study was undertaken to compare the performance of plasma p-tau181 with that of [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) in the identification of early biological Alzheimer disease (AD). We included 533 cognitively impaired participants from the Alzheimer's Disease Neuroimaging Initiative. Participants underwent PET scans, biofluid collection, and cognitive tests. Receiver operating characteristic analyses were used to determine the diagnostic accuracy of plasma p-tau181 and [18F]FDG-PET using clinical diagnosis and core AD biomarkers ([18F]florbetapir-PET and cerebrospinal fluid [CSF] p-tau181) as reference standards. Differences in the diagnostic accuracy between plasma p-tau181 and [18F]FDG-PET were determined by bootstrap-based tests. Correlations of [18F]FDG-PET and plasma p-tau181 with CSF p-tau181, amyloid β (Aβ) PET, and cognitive performance were evaluated to compare associations between measurements. We observed that both plasma p-tau181 and [18F]FDG-PET identified individuals with positive AD biomarkers in CSF or on Aβ-PET. In the MCI group, plasma p-tau181 outperformed [18F]FDG-PET in identifying AD measured by CSF (p = 0.0007) and by Aβ-PET (p = 0.001). We also observed that both plasma p-tau181 and [18F]FDG-PET metabolism were associated with core AD biomarkers. However, [18F]FDG-PET uptake was more closely associated with cognitive outcomes (Montreal Cognitive Assessment, Mini-Mental State Examination, Clinical Dementia Rating Sum of Boxes, and logical memory delayed recall, p < 0.001) than plasma p-tau181. Overall, although both plasma p-tau181 and [18F]FDG-PET were associated with core AD biomarkers, plasma p-tau181 outperformed [18F]FDG-PET in identifying individuals with early AD pathophysiology. Taken together, our study suggests that plasma p-tau181 may aid in detecting individuals with underlying early AD.

AROMHA Brain Health Test: A Remote Olfactory Assessment as a Screen for Cognitive Impairment.

Cost-effective, noninvasive screening methods for preclinical Alzheimer's disease (AD) and other neurocognitive disorders remain an unmet need. The olfactory neural circuits develop AD pathological changes prior to symptom onset. To probe these vulnerable circuits, we developed the digital remote AROMHA Brain Health Test (ABHT), an at-home odor identification, discrimination, memory, and intensity assessment. The ABHT was self-administered among cognitively normal (CN) English and Spanish speakers (n=127), participants with subjective cognitive complaints (SCC; n=34), and mild cognitive impairment (MCI; n=19). Self-administered tests took place remotely at home under unobserved (among interested CN participants) and observed modalities (CN, SCC, and MCI), as well as in-person with a research assistant present (CN, SCC, and MCI). Olfactory performance was similar across observed and unobserved remote self-administration and between English and Spanish speakers. Odor memory, identification, and discrimination scores decreased with age, and olfactory identification and discrimination were lower in the MCI group compared to CN and SCC groups, independent of age, sex, and education. The ABHT revealed age-related olfactory decline, and discriminated CN older adults from those with cognitive impairment. Replication of our results in other populations would support the use of the ABHT to identify and monitor individuals at risk for developing dementia.

Lateral Thinking: Pathway Specific Neurodegeneration of the Cortical Cholinergic System in Alzheimer's Disease.

Atrophy of the nucleus basalis of Meynert (NBM) is an early indicator of Alzheimer's disease (AD). However, reduced integrity of the NBM white matter tracts may be more relevant for cognitive impairment and progression to dementia than NBM volume. Research is needed to compare differences in NBM volume and integrity of the lateral and medial NBM tracts across early and later stages of AD progression. 187 participants were included in this study who were either healthy controls (HC; n=50) or had early mild cognitive impairment (EMCI; n=50), late MCI (LMCI; n=37), or AD (n=50). NBM volume was calculated using voxel-based morphometry and mean diffusivity (MD) of the lateral and medial NBM tracts were extracted using probabilistic tractography. Between group differences in NBM volume and tract MD were compared using linear mixed models controlling for age, sex, and either total intracranial volume or MD of a control mask, respectively. Associations between NBM volume and tract MD with executive function, memory, language, and visuospatial function were also analysed. NBM volume was smallest in AD followed by LMCI (p<0.0001), with no difference between EMCI and HC. AD had highest MD for both tracts compared to all other groups (p<0.001). Both MCI groups had higher lateral tract MD compared to HC (p<0.05). Medial tract MD was higher in LMCI (p=0.008), but not EMCI (p=0.09) compared to HC. Higher lateral tract MD was associated with executive function (p=0.001) and language (p=0.02). Integrity of the lateral NBM tract is most sensitive to the earliest stages of AD and should be considered an important therapeutic target for early detection and intervention.

The role of cognitive flexibility on higher level executive functions in mild cognitive impairment and healthy older adults

BackgroundMild Cognitive Impairment (MCI) is a preclinical condition between healthy and pathological aging, which is characterized by impairments in executive functions (EFs), including cognitive flexibility. According to Diamond’s model, cognitive flexibility is a core executive function, along with working memory and inhibition, but it requires the development of these last EFs to reach its full potential. In this model, planning and fluid intelligence are considered higher-level EFs. Given their central role in enabling individuals to adapt their daily life behavior efficiently, the goal is to gain valuable insight into the functionality of cognitive flexibility in a preclinical form of cognitive decline. This study aims to investigate the role of cognitive flexibility and its components, set-shifting and switching, in MCI. The hypotheses are as follows: (I) healthy participants are expected to perform better than those with MCI on cognitive flexibility and higher-level EFs tasks, taking into account the mediating role of global cognitive functioning; (II) cognitive flexibility can predict performance on higher-level EFs (i.e., planning and fluid intelligence) tasks differently in healthy individuals and those diagnosed with MCI.MethodsNinety participants were selected and divided into a healthy control group (N = 45; mean age 64.1 ± 6.80; 66.6% female) and an MCI group (N = 45; mean age 65.2 ± 8.14; 40% female). Cognitive flexibility, fluid intelligence, planning, and global cognitive functioning of all participants were assessed using standardized tasks.ResultsResults indicated that individuals with MCI showed greater impairment in global cognitive functioning and EFs performance. Furthermore, the study confirms the predictive role of cognitive flexibility for higher EFs in individuals with MCI and only partially in healthy older adults.

Depressive Symptoms Are Not Associated with Predementia Cerebrospinal Fluid Amyloid Pathology

Introduction: Depressive symptoms are associated with Alzheimer’s disease (AD), but their neurobiological and neuropsychological correlates remain poorly understood. We investigate if depressive symptoms are associated with amyloid (Aβ) pathology and cognition in predementia AD. Methods: We included subjective cognitive decline (SCD, n = 160) and mild cognitive impairment (MCI, n = 192) from the dementia disease initiation cohort. Depressive symptoms were assessed using the Geriatric Depression Scale (GDS-15). Aβ pathology was determined using cerebrospinal fluid (CSF) Aβ42/40 ratio. Associations between depressive symptoms and cognition were assessed with logistic regression. Results: Only the Aβ negative MCI group (MCI-Aβ−) was associated with depressive symptoms (odds ratio [OR] = 2.65, p = 0.005). Depressive symptoms were associated with worse memory in MCI-Aβ− (OR = 0.94, p = 0.039), but with better performance in MCI-Aβ+ (OR = 1.103, p = 0.001). Conclusion: Our results suggest that depressive symptoms in MCI are neither associated with Aβ pathology, nor AD-associated memory impairment. However, memory impairment in non-AD MCI may relate to depressive symptoms.

Comparison of Right Ventricular Outflow Tract Reconstruction Techniques on Mid-Term Pulmonic Valve Fate.

Introduction: The pulmonic valve-sparing technique (PVS) is an emerging approach of right ventricular outflow tract reconstruction in tetralogy of Fallot (TOF) correction aimed at reducing the incidence of pulmonic regurgitation (PR) and the need for subsequent reintervention. This study aims to compare the long-term occurrence of moderate to severe PR/stenosis (PR/PS) between three different approaches. Patients and Methods: We conducted a retrospective cohort study involving 173 patients who underwent TOF correction at Chiang Mai University hospital between January 2006 and December 2016. The patients were divided into three groups: transannular patch (TAP; n = 88, 50.9%), monocusp insertion (MCI; n = 40, 23.1%), and PVS (n = 45, 26%). The study assessed freedom from moderate to severe PR/PS. Results: The median overall follow-up time was 79.8 months (interquartile range: 50.7-115.5 months. The PVS exhibited larger PV Z-score (-2.6 ± 2.3 mm, P < .001), with predominantly tricuspid morphology (64.4%). The PVS had significantly shorter median ventilator time, intensive care unit stay, hospital stay, and longer median follow-up time. Postoperative moderate-severe PR was lower in the PVS group (P < .001), with no significant difference in PS (P = .356) and complications among the groups. Freedom from moderate-severe PR/PS was longer in the MCI group (2.8, 0.2-42.3 months vs 30.9, 0.2-50.9 months, respectively). Multivariable analysis showed TAP and MCI had a higher risk of developing moderate-severe PR (hazard ratio [HR] 2.51; 95% confidence interval [CI] 1.23-5.13 vs HR 1.41; 95%CI 0.59-3.38) but lower risk of moderate-severe PS (HR 0.14; 95%CI 0.02-0.9 vs HR 0.39; 95%CI 0.05-3.19). Conclusion: Pulmonic valve-sparing reconstruction showed promise in preventing late moderate-severe PR in patients with favorable PV anatomy. However, it should be noted that this technique is associated with a higher incidence of PS.

Mitochondrial dysfunction is associated with cognitive impairment in adults with OSA without dementia

Study objectivesIncreased reactive oxygen species associated with loss of mitochondrial function affect synaptic activity, which is an important mechanism underlying cognitive decline. This study assesses the role of mitochondrial proteins in neuron-derived exosomes (NDEs) on cognitive impairment in patients with obstructive sleep apnea (OSA) without dementia. MethodsAnalyses were conducted in 268 study participants with complete polysomnography data, cognitive tests, and important clinical data available. NDEs were isolated immunochemically for enzyme-linked immunosorbent assay quantification of mitochondrial proteins, i.e., humanin and mitochondrial open reading frame of the 12S rRNA-c (MOTS-c), and synaptic protein, i.e., neurogranin (NRGN). A mediation analysis of the relationship between sleep parameters and cognition was performed using humanin, MOTS-c, and NRGN values as a mediating factor. Twenty-two patients with moderate to severe OSA who received CPAP therapy were followed up, and humanin, MOTS-c and NRGN levels were reassessed after 1 year of treatment. ResultsAll participants were divided into the OSA + MCI group (n = 91), OSA-MCI group (n = 89), MCI group (MCI without OSA) (n = 38) and control group (normal cognitive state without OSA) (n = 50). The mean CD63-normalized NDE levels of humanin, MOTS-c, and NRGN in the OSA + MCI group were higher than those in the OSA-MCI and control groups. The NDE levels of humanin, MOTS-c, and NRGN in the MCI group were lower than those in controls. The odds of cognitive impairment in patients with OSA were higher with higher NDE levels of humanin, MOTS-c, and NRGN (odds ratio (OR): 2.100, 95 % confidence interval (CI): 1.646–2.679, P < 0.001; OR: 5.453, 95 % CI: 3.112–9.556, P < 0.001; OR: 3.115, 95 % CI: 2.163–4.484, P < 0.001). The impaired cognitive performance was associated with higher NDE levels of humanin (β: 0.505, SE: 0.048, P < 0.001), MOTS-c (β: 0.580, SE: 0.001, P < 0.001), and NRGN (β: 0.585, SE: 0.553, P < 0.001). The relationship between sleep parameters (mean SaO2 and T90) and MoCA scores was mediated by the NDE levels of humanin, MOTS-c, and NRGN with the proportion of mediation varying from 35.33 % to 149.07 %. Receiver operating characteristic curve revealed an area under the curve of 0.905 for humanin, 0.873 for MOTS-c, and 0.934 for NRGN to predict MCI in OSA patients without dementia. Increased humanin, MOTS-c, and NRGN levels significantly decreased after CPAP treatment. ConclusionsMitochondrial dysfunction is implicated in cognitive impairment in OSA patients without dementia, and mainly mediates the association between intermittent hypoxia and cognitive impairment in adults with OSA without dementia. Mitochondrial dysfunction can be partially reversible by CPAP treatment. Mitochondrial proteins can be used as markers of cognitive impairment in patients with OSA.

Prospective study to evaluate radioactive iodine of 20 mCi vs 10–15 mCi in Graves’ disease

ObjectivesTo assess whether increasing radioactive iodine dose can increase treatment efficacy in Graves’ disease.MethodsA prospective study was conducted, including 106 patients receiving 20 mCi (740 MBq) radioactive iodine (RAI), compared with a retrospective data, including 113 patients receiving 10–15 mCi (370–555 MBq) RAI. Remission and failure rates were evaluated at 6 months post-RAI. Statistical analysis was performed using logistic regression and Kaplan–Meier curves.ResultsPatients receiving 20 mCi RAI demonstrated a significantly higher remission rate compared to the 10–15 mCi group (82.1% vs 66.4%, p = 0.009). Median time to remission was shorter in the 20 mCI group (3 vs 4 months, p = 0.002). Hypothyroidism at 6 months was more prevalent in the 20 mCi group (67% vs 53%, p = 0.03). Larger thyroid size (> 60 g) was associated with treatment failure (p = 0.02).ConclusionsHigher dosage (20 mCi) RAI showed superior efficacy in achieving remission compared to lower dosages (10–15 mCi) in Graves’ disease treatment.

A novel speech analysis algorithm to detect cognitive impairment in a Spanish population.

Early detection of cognitive impairment in the elderly is crucial for diagnosis and appropriate care. Brief, cost-effective cognitive screening instruments are needed to help identify individuals who require further evaluation. This study presents preliminary data on a new screening technology using automated voice recording analysis software in a Spanish population. Data were collected from 174 Spanish-speaking individuals clinically diagnosed as cognitively normal (CN, n = 87) or impaired (mild cognitive impairment [MCI], n = 63; all-cause dementia, n = 24). Participants were recorded performing four common language tasks (Animal fluency, alternating fluency [sports and fruits], phonemic "F" fluency, and Cookie Theft Description). Recordings were processed via text-transcription and digital-signal processing techniques to capture neuropsychological variables and audio characteristics. A training sample of 122 subjects with similar demographics across groups was used to develop an algorithm to detect cognitive impairment. Speech and task features were used to develop five independent machine learning (ML) models to compute scores between 0 and 1, and a final algorithm was constructed using repeated cross-validation. A socio-demographically balanced subset of 52 participants was used to test the algorithm. Analysis of covariance (ANCOVA), covarying for demographic characteristics, was used to predict logistically-transformed algorithm scores. Mean logit algorithm scores were significantly different across groups in the testing sample (p < 0.01). Comparisons of CN with impaired (MCI + dementia) and MCI groups using the final algorithm resulted in an AUC of 0.93/0.90, with overall accuracy of 88.4%/87.5%, sensitivity of 87.5/83.3, and specificity of 89.2/89.2, respectively. Findings provide initial support for the utility of this automated speech analysis algorithm as a screening tool for cognitive impairment in Spanish speakers. Additional study is needed to validate this technology in larger and more diverse clinical populations.

Assessing the cognitive decline of people in the spectrum of AD by monitoring their activities of daily living in an IoT-enabled smart home environment: a cross-sectional pilot study.

Assessing functional decline related to activities of daily living (ADLs) is deemed significant for the early diagnosis of dementia. As current assessment methods for ADLs often lack the ability to capture subtle changes, technology-based approaches are perceived as advantageous. Specifically, digital biomarkers are emerging, offering a promising avenue for research, as they allow unobtrusive and objective monitoring. A study was conducted with the involvement of 36 participants assigned to three known groups (Healthy Controls, participants with Subjective Cognitive Decline and participants with Mild Cognitive Impairment). Participants visited the CERTH-IT Smart Home, an environment that simulates a fully functional residence, and were asked to follow a protocol describing different ADL Tasks (namely Task 1 - Meal, Task 2 - Beverage and Task 3 - Snack Preparation). By utilizing data from fixed in-home sensors installed in the Smart Home, the identification of the performed Tasks and their derived features was explored through the developed CARL platform. Furthermore, differences between groups were investigated. Finally, overall feasibility and study satisfaction were evaluated. The composition of the ADLs was attainable, and differentiation among the HC group compared to the SCD and the MCI groups considering the feature "Activity Duration" in Task 1 - Meal Preparation was possible, while no difference could be noted between the SCD and the MCI groups. This ecologically valid study was determined as feasible, with participants expressing positive feedback. The findings additionally reinforce the interest and need to include people in preclinical stages of dementia in research to further evolve and develop clinically relevant digital biomarkers.

Decreased levels of hydrogen sulfide in the hypothalamic paraventricular nucleus contribute to sympathetic hyperactivity induced by cerebral infarction.

Paroxysmal sympathetic hyperactivity (PSH) is a common clinical feature secondary to ischemic stroke (IS), but its mechanism is poorly understood. We aimed to investigate the role of H2S in the pathogenesis of PSH. IS patients were divided into malignant (MCI) and non-malignant cerebral infarction (NMCI) group. IS in rats was induced by the right middle cerebral artery occlusion (MCAO). H2S donor (NaHS) or inhibitor (aminooxy-acetic acid, AOAA) were microinjected into the hypothalamic paraventricular nucleus (PVN). Compared with the NMCI group, patients in the MCI group showed PSH, including tachycardia, hypertension, and more plasma norepinephrine (NE) that was positively correlated with levels of creatine kinase, glutamate transaminase, and creatinine respectively. The 1-year survival rate of patients with high plasma NE levels was lower. The hypothalamus of rats with MCAO showed increased activity, especially in the PVN region. The levels of H2S in PVN of the rats with MCAO were reduced, while the blood pressure and renal sympathetic discharge were increased, which could be ameliorated by NaHS and exacerbated by AOAA. NaHS completely reduced the disulfide bond of NMDAR1 in PC12 cells. The inhibition of NMDAR by MK-801 microinjected in PVN of rats with MCAO also could lower blood pressure and renal sympathetic discharge. In conclusion, PSH may be associated with disease progression and survival in patients with IS. Decreased levels of H2S in PVN were involved in regulating sympathetic efferent activity after cerebral infarction. Our results might provide a new strategy and target for the prevention and treatment of PSH.

Neuropsychiatric symptoms and brain morphology in patients with mild cognitive impairment, cerebrovascular disease and Parkinson disease: A cross sectional and longitudinal study.

Neuropsychiatric symptoms (NPS) increase risk of developing dementia and are linked to various neurodegenerative conditions, including mild cognitive impairment (MCI due to Alzheimer's disease [AD]), cerebrovascular disease (CVD), and Parkinson's disease (PD). We explored the structural neural correlates of NPS cross-sectionally and longitudinally across various neurodegenerative diagnoses. The study included individuals with MCI due to AD, (n=74), CVD (n=143), and PD (n=137) at baseline, and at 2-years follow-up (MCI due to AD, n=37, CVD n=103, and PD n=84). We assessed the severity of NPS using the Neuropsychiatric Inventory Questionnaire. For brain structure we included cortical thickness and subcortical volume of predefined regions of interest associated with corticolimbic and frontal-executive circuits. Cross-sectional analysis revealed significant negative correlations between appetite with both circuits in the MCI and CVD groups, while apathy was associated with these circuits in both the MCI and PD groups. Longitudinally, changes in apathy scores in the MCI group were negatively linked to the changes of the frontal-executive circuit. In the CVD group, changes in agitation and nighttime behavior were negatively associated with the corticolimbic and frontal-executive circuits, respectively. In the PD group, changes in disinhibition and apathy were positively associated with the corticolimbic and frontal-executive circuits, respectively. The observed correlations suggest that underlying pathological changes in the brain may contribute to alterations in neural activity associated with MBI. Notably, the difference between cross-sectional and longitudinal results indicates the necessity of conducting longitudinal studies for reproducible findings and drawing robust inferences.

Neuropsychiatric symptoms and ApoE genotype in older adults without dementia: a cross-sectional study.

The ApoE genotype and neuropsychiatric symptoms (NPS) are known risk factors for cognitive decline in older adults. However, the interaction between these variables is still unclear. The aim of this study was to determine the association between the presence of the ApoE ε4 allele and the occurrence of NPS in older adults without dementia. In this cross-sectional investigation we determined the apolipoprotein E (ApoE) genotype of 74 older adults who were either cognitively normal (20.3% / Clinician Dementia Rating Scale (CDR): 0) or had mild cognitive impairment (MCI: 79.7% / CDR: 0.5). We used a comprehensive cognitive assessment protocol, and NPS were estimated by the Neuropsychiatric Inventory-Clinician Rating Scale (NPI-C), Mild Behavioural Impairment-Checklist (MBI-C), Hamilton Rating Scale for Depression (HAM-D), and Apathy Inventory. ApoE ε4 carriers had higher MBI-C total scores than ApoE ε4 noncarriers. Correlations between NPS and ApoE genotype were observed for two NPI-C domains, although in opposite directions: the ApoE ε4 allele was associated with a 1.8 unit decrease in the estimated aberrant motor disturbance score and with a 1.3 unit increase in the estimated appetite/eating disorders score. All fitted models were significant, except for the one fitted for the domain delusions from the NPI-C. Among individuals with amnestic MCI, ε4 carriers presented higher depression score (HAM-D) than noncarriers; in turn, ε4 noncarriers exhibited higher aggression score (NPI-C) than ε4 carriers. Our analyses showed associations between NPS and the presence of the ApoE ε4 allele in two NPI-C domains, despite the sample size. Furthermore, compared to noncarriers, the presence of the ApoE ε4 correlated positively with appetite/eating disorders and negatively with aberrant motor disturbance domain. Examination of the amnestic MCI group displayed significant, although weak, associations. Therefore, ε4 carriers exhibited higher depression scores according to the HAM-D scale compared to ε4 noncarriers. Conversely, ε4 noncarriers had higher scores in the aggression domain of the NPI-C than ε4 carriers.

Epigenome-wide DNA methylation analysis of late-stage mild cognitive impairment.

Background: Patients with late-stage mild cognitive impairment (LMCI) have a higher risk of progression to Alzheimer's disease (AD) than those with early-stage mild cognitive impairment (EMCI). However, previous studies have often pooled EMCI and LMCI patients into a single MCI group, with limited independent investigation into the pathogenesis of LMCI. Methods: In this study, we employed whole-genome methylation association analysis to determine the differences in peripheral blood methylation profiles between 663 cognitive aging (CN) and 554 LMCI patients. Results: Our results revealed 2,333 differentially methylated probes (DMPs) and 85 differentially methylated regions (DMRs) specific to LMCI. The top hit methylation sites or regions were associated with genes such as SNED1, histone deacetylases coding gene HDACs, and HOX and ZNF gene family. The DNA methylations upregulated the expression of HDAC4, HDAC8, and HOX family genes HOXC5 and HOXC9, but they downregulated the expression of SNED1, ADCYAP1, and ZNF family genes ZNF415 and ZNF502. Gene Ontology (GO) and KEGG analysis showed that the genes associated with these methylation sites were predominantly related to the processes of addiction disorders, neurotransmission, and neurogenesis. Out of the 554 LMCI patients included in this study, 358 subjects (65%) had progressed to AD. Further association analysis between the LMCI subjects with a stable course (sLMCI) and those who progressed to AD (pLMCI) indicated that the methylation signal intensities of HDAC6, ZNF502, HOXC5, HOXC6, and HOXD8 were associated with increased susceptibility to AD. Protective effects against progression to AD were noticed when the methylation of SNED1 and ZNF727 appeared in LMCI patients. Conclusion: Our findings highlight a substantial number of LMCI-specific methylated biomarkers that differ from those identified in previous MCI case-control studies. These biomarkers have the potential to contribute to a better understanding of the pathogenesis of LMCI.

Urine metabolomics phenotyping and urinary biomarker exploratory in mild cognitive impairment and Alzheimer's disease.

Alzheimer's disease is a prevalent disease with a heavy global burden and is suggested to be a metabolic disease in the brain in recent years. The metabolome is considered to be the most promising phenotype which reflects changes in genetic, transcript, and protein profiles as well as environmental effects. Aiming to obtain a comprehensive understanding and convenient diagnosis of MCI and AD from another perspective, researchers are working on AD metabolomics. Urine is more convenient which could reflect the change of disease at an earlier stage. Thus, we conducted a cross-sectional study to investigate novel diagnostic panels. We first enrolled participants from China-Japan Friendship Hospital from April 2022 to November 2022, collected urine samples and conducted an LC-MS/MS analysis. In parallel, clinical data were collected and clinical examinations were performed. After statistical and bioinformatics analyzes, significant risk factors and differential urinary metabolites were determined. We attempt to investigate diagnostic panels based on machine learning including LASSO and SVM. Fifty-seven AD patients, 43 MCI patients and 62 CN subjects were enrolled. A total of 2,140 metabolites were identified among which 125 significantly differed between the AD and CN groups, including 46 upregulated ones and 79 downregulated ones. In parallel, there were 93 significant differential metabolites between the MCI and CN groups, including 23 upregulated ones and 70 downregulated ones. AD diagnostic panel (30 metabolites+ age + APOE) achieved an AUC of 0.9575 in the test set while MCI diagnostic panel (45 metabolites+ age + APOE) achieved an AUC of 0.7333 in the test set. Atropine, S-Methyl-L-cysteine-S-oxide, D-Mannose 6-phosphate (M6P), Spiculisporic Acid, N-Acetyl-L-methionine, 13,14-dihydro-15-keto-tetranor Prostaglandin D2, Pyridoxal 5'-Phosphate (PLP) and 17(S)-HpDHA were considered valuable for both AD and MCI diagnosis and defined as hub metabolites. Besides, diagnostic metabolites were weakly correlated with cognitive functions. In conclusion, the procedure is convenient, non-invasive, and useful for diagnosis, which could assist physicians in differentiating AD and MCI from CN. Atropine, M6P and PLP were evidence-based hub metabolites in AD.

CROSS-SECTIONAL AND LONGITUDINAL ASSOCIATIONS BETWEEN SLEEP DISTURBANCES, DEPRESSIVE AND ANXIETY SYMPTOMS

Abstract Introduction Older adults often experience elevated sleep disturbances, depressive and anxiety symptoms. However, the role of sleep disturbances in explaining individual variability in depressive and anxiety symptoms among older adults is poorly understood. Methods The sample was derived from the National Social Life, Health, and Aging Project, a nationally representative longitudinal study among American older adults. MCI was defined as Montreal Cognitive Assessment scored less than 23. Subjective insomnia symptoms and objective sleep measures (total sleep time, wake after sleep onset, percentage sleep) obtained from actigraphy were used. Validated measures on depressive and anxiety symptoms were collected both at round 2(N=645) and round 3(N=456). Multiple regressions were conducted to establish cross-sectional and longitudinal associations between sleep disturbances, depressive and anxiety symptoms. Results Cross-sectionally, compared to cognitively intact older adults, severe insomnia symptoms were associated with poorer depressive symptoms(B=0.40, p&amp;lt; 0.01) in older adults with MCI. Severe insomnia symptoms were associated with poorer anxiety symptoms(B=0.13, p&amp;lt; 0.01) in older adults, and no interaction effects were found by MCI groups. Longitudinally, insomnia symptoms at round 2 were associated with poorer depressive symptoms and poorer anxiety symptoms in older adults at round 3, but no interaction effects were found by MCI groups. No significant relationships were found between objective sleep disturbances and depressive/anxiety symptoms both cross-sectionally and longitudinally. Conclusions The findings provide further insight into insomnia symptoms that may be associated with increased risks for developmental depressive and anxiety symptoms. These data suggest that targeting insomnia treatment may confer long-term mental health benefits.

PREVALENCE OF METABOLIC COMORBIDITIES AMONG COGNITIVELY NORMAL AND IMPAIRED WHITE AND AFRICAN AMERICANS

Abstract Assessing comorbidities associated with a MCI diagnosis is crucial for diagnostic accuracy and for understanding the role of comorbidities in cognitive decline. In this study of amnestic (aMCI) and non-amnestic (naMCI) MCI participants and persons with normal cognition (CN), we compared the prevalence of three primary comorbidities: Hypertension (HTN), Hyperlipidemia (HLD), and Diabetes Mellitus (DM) across African American and White populations using Chi-squares. Participant data (N = 9,342, 17% African American) were available through the National Alzheimer’s Coordinating Center and included: CN (n = 5,963; MOCA mean=27), aMCI (2,694; MOCA=22), and naMCI (685; MOCA=24) with diagnosis and data per their first Uniform Data Set (Version 3) visit. Significant differences in the distribution of HTN, HLD, and DM were found among the diagnostic groups for the total cohort and racial groups, separately; however, diagnostic differences across races were not always consistent. The relative rates of DM and HLD across the diagnostic groups for both races were generally similar, though higher percentages were seen in African Americans (25% of African Americans, 10% of Whites). As for HTN (52% of African Americans, 39% of Whites), however, the distributions differ across the diagnostic groups and race (%yes for diagnosis; White Americans: CN 35%, aMCI 47%, naMCI 44%; African Americans: CN 66%, aMCI 70%, naMCI 79%, p&amp;lt; 0.001). These findings highlight the importance of considering the contributions of both race and diagnosis when evaluating the role of comorbid factors and metabolic disorders in NC and MCI groups, in particular when considering blood pressure-related measures.

USE OF EYE TRACKING TECHNOLOGY TO DETECT MILD COGNITIVE IMPAIRMENT

Abstract Early detection of dementia is key to helping individuals and their families cope. Use of eye tracking technology to measure eye movements could provide an objective and sensitive measure of cognitive impairment (Hodgson et al, 2019; Wang et al, 2020). In this pilot study, we predicted that eye tracking metrics differ between people with diagnosed MCI and those of healthy controls. Eleven veterans (≥ 55 years) being seen at the San Francisco VA Health Care System who either had a confirmed diagnosis of MCI or had subjective memory complaints and scored lower than a 26 on the MoCA participated. Their results were compared to that of a previously collected control sample (n = 41) (Liston et al, 2017). Participants completed a five-minute visual tracking test with 48 trials based on a classic step-ramp visual tracking paradigm that was administered on a PC computer with a camera and eye tracking capability. The visual tracking test yields 10 z-scored eye tracking metrics that are summarized in a single scalar summary score. Receiver operating characteristics (ROC) were computed and compared to the control sample. The summary score of the MCI group (median: -2.2) differed significantly from the healthy control sample (median: 0.0), which yielded a significant sensitivity of the test to presence or absence of MCI (ROC area = 0.94, p &amp;lt; .001). Although we view the results as preliminary due to the small sample size, results suggest that use of eye tracking technology may be a viable option for MCI detection.

Association between erythrocyte membrane fatty acids and gut bacteria in obesity-related cognitive dysfunction

Obesity increases the risk of cognitive impairment and dementia, and the gut microbiota can affect brain cognitive function and obesity through a variety of pathways such as the gut-brain axis. This study aimed to discover how fatty acid affect cognitive function by regulating intestinal flora in obesity. Obese subjects were recruited for cognitive function assessment, and participants were divided into obese group with cognitive impairment (MCI, n = 49) and obese cognitively normal group (Non_MCI, n = 55). In the erythrocyte membrane, the proportion of polyunsaturated fatty acids (PUFA), linoleic acid (C18:2 n-6) and arachidonic acid (C20:4 n-6) and n-6/n-3 ratio was higher in the MCI group than in the Non_MCI group. However, the α-linolenic acid (C18:3 n-3) percentage of the erythrocyte membrane was lower in the MCI group. We found that Coriobacteriales_Incertae_Sedis was positively correlated with erythrocyte membrane C20:4 n-6 and n-6 PUFA and negatively correlated with cognitive scores in obese patients. In addition, several of the functional pathways we predicted were significantly different in the MCI and Non_MCI groups. Higher levels of n-6/n-3 polyunsaturated fatty acids ratio in the erythrocyte membranes may influence the inflammatory response in the organism causing obesity induced cognitive damage. Moreover, high levels of n-6/n-3 polyunsaturated fatty acids ratio may also affect the intestinal flora of obese patients, which in turn may affect the cognitive function of obese patients.

Correlation between long-term glycemic variability and cognitive function in middle-aged and elderly patients with type 2 diabetes mellitus: a retrospective study.

To investigate the correlation between long-term glycemic variability and cognitive function in middle-aged and elderly patients with type 2 diabetes mellitus (T2DM). This retrospective analysis includes 222 patients hospitalized at Second Affiliated Hospital of Anhui Medical University from June 2021 to June 2023. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). All patients were categorized into the MCI group and the non-MCI group based on their MoCA score. Long-term blood glucose fluctuations were measured using glycated hemoglobin A1c standard deviation (HbA1c-SD) and fasting plasma glucose standard deviation (FPG-SD). The study compared general clinical data, blood biochemical indicators, and glycemic variability indicators between the two groups. The differences between the groups were compared using t-test, Chi-Square Test, or Mann-Whitney U test. Kendall's correlation analysis, multivariate logistic regression analysis and ROC curve correlation analysis were further used to analyze the correlation and diagnostic power. The differences in age, MoCA scores, MMSE scores, HOMA-β, HbA1c-M, HbA1c-SD, FPG-M, FPG-SD, eGFR, Smoking, GLP-1RA and SGLT-2i usage were statistically significant between the two groups (P<0.05). Kendall's correlation analysis showed that age, HbA1c-M, HbA1c-SD, FPG-M, and FPG-SD was negatively correlated with MoCA scores; meanwhile, the HOMA-β, and eGFR was positively correlated with MoCA scores. Multiple logistic regression analysis revealed that HbA1c-SD, FPG-SD and Smoking were risk factors for cognitive dysfunction, while eGFR, GLP-1RA and SGLT-2i usage was a protective effect. The area under the curve (AUC) values for predicting MCI prevalence were 0.830 (95% CI [0.774-0.877], P<0.001) for HbA1c-SD, 0.791 (95% CI [0.655-0.808], P<0.001) for FPG-SD, and 0.698 (95% CI [0.633-0.757], P<0.001) for eGFR. The optimal diagnostic values were 0.91, 1.32, and 74.81 ml/min/1.73 m2 for HbA1c-SD, FPG-SD, and eGFR, respectively. Cognitive function in middle-aged and elderly T2DM patients is influenced by long-term blood glucose variability, with poorer cognitive function observed in individuals with higher blood glucose variability. The impact of HbA1c-SD on MCI exhibited a greater magnitude compared to that of PFG-SD and smoking. Additionally, renal function, GLP-1RA and SGLT-2i usage exert positive effects on cognitive function.