Lewy body disease (LBD) and Alzheimer’s disease (AD) are the most common causes of cognitive decline and dementia and are associated with characteristic alterations in resting-state electroencephalographic (rsEEG) activity. This multicenter exploratory study investigated periodic and aperiodic rsEEG features in patients with cognitive decline due to Lewy body disease (LBCD) and Alzheimer’s disease (ADCD), compared with cognitively unimpaired older adults (Nold), and examined the clinical relevance of these markers in LBCD. A total of 140 LBCD, 135 ADCD, and 118 Nold datasets from the PDWAVES archive underwent spectral parameterization to decompose rsEEG power spectra (1–30 Hz) into periodic peaks and aperiodic background activity. Both clinical groups showed a significant slowing of the individual alpha frequency (IAF), more pronounced in LBCD, along with reduced periodic alpha and beta power reflected in a lower vigilance index. The aperiodic exponent was elevated in both groups, and the aperiodic offset was also higher in LBCD, suggesting steeper spectral profiles consistent with increased inhibitory cortical tone. Within the LBCD group, poorer cognition was associated with higher low-frequency alpha power, whereas better cognition was predicted by higher high-frequency alpha power. A reduced vigilance index was associated with the presence of visual hallucinations, while no associations emerged for other symptoms. These findings suggest that combined periodic and aperiodic rsEEG features may provide relevant markers of altered vigilance regulation in LBCD. Future studies should evaluate whether these EEG markers can inform targeted interventions, such as neuromodulatory or audiovisual stimulation, to stabilize quiet-vigilance states and improve clinical outcomes. Panel A shows the spectral parameterization of rsEEG activity into periodic and aperiodic components. Panel B summarizes the main group differences in key rsEEG markers across LBCD, ADCD, and Nold participants. Panel C shows the topographical associations between the vigilance index and cognition and visual hallucinations in LBCD; colors reflect the direction and strength of the associations. For the visual hallucinations map, negative log-odds indicate lower odds of hallucinations for higher vigilance index values, whereas positive log-odds indicate higher odds; values around ± 1.5 correspond approximately to odds ratios of 0.22 and 4.5, respectively. Abbreviations: rsEEG, resting-state electroencephalography; LBCD, cognitive decline due to Lewy body disease; ADCD, cognitive decline due to Alzheimer’s disease; Nold, cognitively unimpaired older adults; IAF, individual alpha frequency; MMSE, Mini-Mental State Examination; p, standardized regression coefficient; log-odds, logistic regression coefficient.

Lipid droplets (LDs) are key organelles involved in lipid storage, energy metabolism, and stress adaptation, and their altered dynamics have been increasingly implicated in cancer, including Acute Lymphoblastic Leukemia (ALL). In this study, we employ Holographic Tomography in Flow Cytometry (HTFC) to perform an extensive label-free, high-throughput, and three dimensional (3D) characterization of LDs in ALL lymphocytes. We measure thousands of lymphocytes belonging to three B-ALL and three T-ALL cell lines. By avoiding any fluorescent marker, we segment LDs based on the sole refractive index (RI) contrast. Then, we perform a statistically significant analysis of both whole cells and intracellular LDs, by measuring morphological and biophysical parameters derived from the 3D RI distributions. Our approach provides for the first time a comprehensive label-free 3D mapping of LDs inside different cell lines of ALL lymphocytes. The resulting statistical characterization represents a first step toward organelle-level phenotyping in leukemia and points to the potential of HTFC for future non-invasive metabolic profiling in hematologic malignancies.

OBJECTIVE:We evaluated the accuracy of standard machine learning (ML) algorithms in predicting 1-year cognitive decline in Alzheimer's disease patients with mild cognitive impairment (ADMCI) using resting-state electroencephalographic (rsEEG) biomarkers enriched with APOE genotype, sex, age, and educational attainment data. METHODS:The study analyzed datasets from 63 ADMCI patients obtained from an international archive. The ML algorithms included Simple Logistic Regression, Model Trees, Logistic Regression, K-nearest neighbor, and Support Vector Machine. Input features comprised lobar rsEEG source activities across delta (<4 Hz) to alpha (≈10-12 Hz) bands, cerebrospinal fluid (CSF Aβ1-42/p-tau), and structural magnetic resonance imaging (sMRI) biomarkers. Cognitive decline was assessed over a 1-year follow-up ("stable" vs. "decliner") based on Mini-Mental State Examination (MMSE) scores. RESULTS:The four independent ML algorithms accurately predicted changes in the MMSE score over a 1-year follow-up, with accuracies of 77-78% in ADMCI participants aged ≥ 70 years and 74-77% in those aged < 70 years. CONCLUSIONS AND SIGNIFICANCE:These findings suggest that rsEEG biomarkers in ADMCI patients may not only reveal underlying pathophysiological mechanisms affecting cortical arousal and vigilance but also hold predictive value for cognitive outcomes.

INTRODUCTION:We evaluated whether the brain glymphatic drainage function estimated by the diffusion tensor imaging along the perivascular space (DTI-ALPS) index relates to white matter (WM) integrity, Alzheimer's disease (AD) neuropathology, resting-state electroencephalogram (rsEEG) alpha rhythms underpinning quiet vigilance, and cognitive decline in mild cognitive impairment (MCI). METHODS:Clinical, neuroimaging, and rsEEG data were analyzed in matched mild cognitive impairment due to AD (ADMCI) and MCI not due to AD (noADMCI) participants. DTI-ALPS index and aperiodic and periodic components of the rsEEG power spectra were calculated following standard pipelines. RESULTS:Lower DTI-ALPS index was associated with higher AD neuropathology and WM lesions, lower periodic rsEEG alpha rhythms, and worse cognition in patients with ADMCI and noADMCI as a whole population, with the ADMCI (over noADMCI) group showing lower DTI-ALPS index, greater AD neuropathology, and lower periodic rsEEG alpha rhythms. CONCLUSIONS:The DTI-ALPS index may capture glymphatic system impairment linked to AD neuropathology, vigilance dysfunction, and cognitive decline in MCI.

Non-small-cell lung cancer (NSCLC) is one of the most frequent cancer types and is responsible for the majority of cancer-related deaths worldwide. For this reason, initial diagnosis, prognosis, and targeted therapy of NSCLC represent very attractive areas of study. Aptamers are single-stranded nucleic acids (RNA or DNA) generated through Systematic Evolution of Ligands by Exponential Enrichment (SELEX); they are able to bind to a molecular target with high affinity and specificity. Thanks to their intrinsic nucleic acid properties, they can be easily modified and optimized to enhance target binding and their half-life; moreover, they exhibit no immunogenicity and toxicity. Due to this, many aptamers have just been selected against NSCLC biomarkers and provide specific imaging agents to improve the diagnosis of this type of cancer. However, despite the promising results in preclinical studies, the application of aptamers in NSCLC diagnosis is still in its early stages, mainly due to the limited literature in the research world, the dominance of antibodies in the pharmaceutical market and the challenge of target identification. Consequently, this appears to be a temporary issue, and aptamers could see increasing application in the future; thus, we performed a review aimed at summarizing current knowledge on the new promising DNA and RNA aptamer-based molecules for NSCLC diagnosis. All studies from 2000 were included and investigated. Our findings showed that several DNA and RNA aptamers are promising diagnostic tools for NSCLC management.

Magnetic resonance imaging based on chemical exchange saturation transfer (MRI-CEST) has emerged as a powerful imaging technique for mapping physiological parameters, such as tissue pH, with high spatial resolution. This study explores the pH-responsive performance of a novel peptide-based CEST agent, selected among several candidates, when compared with the established contrast agent iopamidol. The selected hLys containing pentapeptide showed enhanced sensitivity and biocompatibility while maintaining an excellent CEST response. In vivo MRI studies further assessed its applicability for tumor pH imaging. The results demonstrate that the selected peptide-based agent displays good CEST contrast variations in response to pH changes, highlighting its potential as a pH-responsive CEST agent. The assessed pH values were very similar to those obtained upon the administration of iopamidol, a well-established pH-CEST agent. Notably, this result was obtained by administering a mass dose of contrast agent that is about 8-fold less than that used in the case of iopamidol. These findings pave the way for the development of peptide-derived MRI probes for noninvasive tumor microenvironment assessment.

Herein, we reported the use of Intraoperative-Contrast Enhanced Ultrasonography (Io-CEUS) during Robotic Assisted Thoracic Surgery (RATS) for identification of malignant lung nodule that was missed during previous operation. Pre-operative CT scan with 3D reconstruction defined the prompt position of the target lesion within S8 segment of right lower lobe and the anatomic landmarks as the distance from interlobar fissure and diaphragm. The lesion was then successfully detected by Io-CEUS. The different arterial enhancement observed during wash-in (hyperenhancement) and wash-out (hypo-enhancement) phases helped to differentiate the nodule from lung parenchyma. The lesion was resected by mechanical stapler and frozen section analysis diagnosed metastasis from colon carcinoma. Post-operative course was unremarkable; patient was discharged on post-operative day 3.

CircRNAs are covalently closed ncRNAs originating through back splicing; their expression is finely regulated, displaying specific patterns across different cell types, tissues, and developmental stages. While the molecular functions of circRNAs are not completely elucidated, their regulatory involvement in physiological processes is well established, alongside their dysregulation in several human disorders. These features, together with their higher stability compared to other ncRNAs, make this class of molecules promising theragnostic agents, particularly in biomarker discovery. Accordingly, it is crucial to develop and standardize experimental strategies that improve circRNA analysis, ensuring accurate and effective isolation of these molecules. In biomarker discovery, selecting the appropriate biological matrix is critical; whole blood is often preferred for its accessibility and minimally invasive collection. Because circRNAs are present in human peripheral blood and show promise as disease theragnostic biomarkers, we established a preliminary workflow tailored to isolate and analyze circRNAs from whole blood. The promising effectiveness and robustness of this workflow were demonstrated by qPCR analysis, suggesting highly reproducible detection and reliability in isolating and analyzing circRNAs. This, together with their stability and specific expression profiles, supports the utility of circRNAs in biomarker discovery and advanced circRNA research and contributes to accelerating their future integration into theragnostic applications in clinical settings.

OBJECTIVES:This exploratory study tested the hypothesis that Huntington's disease (HD) is characterized by distinct abnormalities in resting-state electroencephalographic (rsEEG) rhythms compared to Alzheimer's disease (AD). METHODS:Clinical and rsEEG data were collected from 35 patients with HD, 81 patients with AD, and 102 healthy controls (HC). The rsEEG cortical source activations from 30 electrodes were estimated using eLORETA and were harmonized across clinical sites. RESULTS:Compared to the HC group, both the HD and AD groups showed widespread increases in rsEEG delta source activation and decreases in alpha source activation, with the HD patients exhibiting the most pronounced frontal effects. In patients with HD, those abnormal rsEEG source activations were associated with cognitive, motor, and functional deficits. CONCLUSIONS:Patients with HD were characterized by a particular slowing of frontal rsEEG rhythms associated with clinically relevant variables. SIGNIFICANCE:A topographically widespread slowing of cortical oscillatory activity was observed in both HD and AD groups, with a particularly pronounced frontal effect in HD, which may predict a greater impact on the sleep-wake cycle. These observations should be considered exploratory and need validation in future studies with enhanced vigilance monitoring during longer rsEEG recordings.

Emerging evidence highlights the involvement of skeletal muscle in the pathogenesis of amyotrophic lateral sclerosis (ALS), through mechanisms involving inflammation and mitochondrial dysfunction in skeletal muscle fibers. The 18 kDa translocator protein (TSPO) is primarily expressed on the outer mitochondrial membrane, is implicated in inflammation, and serves as both a biomarker and a therapeutic target for neuroinflammation. This study investigated whether PET imaging targeting the TSPO, immunohistochemistry, and confocal microscopy can characterize skeletal muscle inflammation and muscular fiber damage in SOD1-G93A ALS transgenic mice. High-resolution PET/CT imaging with [18F]DPA-714 was employed to assess TSPO expression in the triceps brachii of SOD1-G93A mice at mild (age range: 98-112 days; Clinical Score (CS) range:1-1.5) and moderate-severe (age range: 120-137 days; CS range: 2-4) symptomatic stages. To support PET data, TSPO was analyzed by immunohistochemistry and confocal microscopy in the triceps skeletal muscle obtained from mild and moderate-severe SOD1-G93A mice. Inflammatory and anti-inflammatory macrophage cells in skeletal muscle tissues were detected by immunofluorescence. PET/CT revealed a progressive, significant increase of [18F]DPA-714 uptake in SOD1-G93A triceps brachii in mild and moderate-severe stages. Immunohistochemistry and confocal microscopy confirmed increased TSPO expression in the degenerating muscle fibers and in infiltrating macrophage cells. In vivo studies of TSPO expression in ALS-affected skeletal muscles may provide valuable insights into muscle inflammation and mitochondrial involvement during disease progression. In addition, TSPO and PET/CT imaging with [18F]DPA-714 might represent a noninvasive and promising diagnostic biomarker for detecting early muscle pathology in ALS.

Patients with mild cognitive impairment due to Alzheimer’s disease (ADMCI) typically show abnormally high delta (<4 Hz) and low alpha (8–12 Hz) rhythms measured from resting-state eyes-closed electroencephalographic (rsEEG) activity. Here, we hypothesized that the abnormalities in rsEEG activity may be greater in ADMCI patients than in those with MCI not due to AD (noADMCI). Furthermore, they may be associated with the diagnostic cerebrospinal fluid (CSF) amyloid–tau biomarkers in ADMCI patients. An international database provided clinical–demographic–rsEEG datasets for cognitively unimpaired older (Healthy; N = 45), ADMCI (N = 70), and noADMCI (N = 45) participants. The rsEEG rhythms spanned individual delta, theta, and alpha frequency bands. The eLORETA freeware estimated cortical rsEEG sources. Posterior rsEEG alpha source activities were reduced in the ADMCI group compared not only to the Healthy group but also to the noADMCI group (p < 0.001). Negative associations between the CSF phospho-tau and total tau levels and posterior rsEEG alpha source activities were observed in the ADMCI group (p < 0.001), whereas those with CSF amyloid beta 42 levels were marginal. These results suggest that neurophysiological brain neural oscillatory synchronization mechanisms regulating cortical arousal and vigilance through rsEEG alpha rhythms are mainly affected by brain tauopathy in ADMCI patients.

Estimating the volume of brain structures and white matter lesions has been demonstrated to be crucial as diagnostic markers of dementia. In this context, employing accelerated MR sequences could be particularly suitable for deploying comfortable imaging protocols. The aims of the study are twofold. First, the quality of accelerated structural and FLAIR sequences will be evaluated using conventional sequences as a comparative reference. Second, their concordance in the estimation of diagnostic markers will be assessed. Forty-six dementia patients underwent brain 3T MR protocol, including conventional and accelerated 3D T1w and 3D FLAIR sequences. The image quality was assessed using peak signal-to-noise ratio, structural similarity index measure, and mean squared error. The intraclass correlation and the Dice similarity coefficients were used to compare the markers. The quality assessment showed high agreement between accelerated and conventional sequences. Excellent concordance was demonstrated in the quantification of brain structures and white matter lesions. The results demonstrate the reliability of diagnostic markers of dementia derived from accelerated MR sequences, thereby supporting their use in clinical practice.

INTRODUCTION:Whether Alzheimer's disease pathology involves white matter pathways connecting the locus coeruleus (LC) to the entorhinal cortex (EC) is unclear. In this cross-sectional observational study, we investigated the microstructural integrity of the LC-EC pathway in relation to amyloid, tau, and neurodegeneration (ATN) biomarkers along the cognitive spectrum from normal cognition to dementia. METHODS:One hundred twenty-four participants underwent clinical assessment, diffusion-weighted imaging, structural magnetic resonance imaging (N), amyloid (A), and tau (T) positron emission tomography. Diffusivity indices were assessed in the LC-EC tract using a probabilistic atlas, and linear models were used to assess associations with ATN markers and cognition. RESULTS:Differences in LC-EC microstructural parameters were observed in participants with Braak stage > I versus Braak 0 (p < 0.020), N+ versus N- (p < 0.001), and cognitively impaired versus unimpaired (p < 0.019). LC-EC mean diffusivity was associated with Mini-Mental State Examination score even after accounting for ATN markers (p = 0.015). DISCUSSION:Our results suggest that LC-EC diffusivity provides complementary information over ATN biomarkers in explaining cognitive impairment. HIGHLIGHTS:Locus coeruleus-entorhinal cortex (LC-EC) tract microstructure is associated with tau and especially neurodegeneration markers. LC-EC tract microstructure is more sensitive to tau pathology and neurodegeneration than tracts commonly affected in Alzheimer's disease. LC-EC diffusivity measures provide complementary information over amyloid, tau, and neurodegeneration (ATN) biomarkers.

We aimed to investigate the effects of an isoenergetic multifactorial diet, previously shown to reduce liver and pancreatic fat content, compared with a monounsaturated fatty acid (MUFA)-rich diet, on plasma apolipoprotein C-III (ApoC-III) levels and their relationship with ectopic fat and beta cell function in people with type 2 diabetes. In this randomised controlled, parallel group study, 36 individuals with type 2 diabetes (20 men, 16 women), aged 35–75 years, were assigned to an 8 week intervention with either an isoenergetic MUFA-rich diet (n=16) or a multifactorial diet rich in MUFA, polyunsaturated fats, fibre, polyphenols and vitamins (n=20). Fasting and postprandial (3 h test meal reflecting the assigned diet) plasma glucose, insulin and ApoC-III concentrations were measured before and after the intervention. Beta cell function was assessed as the insulin-to-glucose total AUC ratio. Liver and pancreatic fat content were quantified using magnetic resonance techniques. Compared with the MUFA diet, the multifactorial diet led to a decrease (8 week minus baseline) in fasting ApoC-III levels (−0.006 ± 0.040 vs +0.007 ± 0.048 g/l, p=0.070) and postprandial ApoC-III AUC (−1.34 ± 6.01 vs +1.60 ± 5.56 g/l × 180 min, p=0.043). Regardless of dietary intervention, changes in fasting ApoC-III positively correlated with changes in liver fat (r=0.357, p=0.032) and pancreatic fat (r=0.385, p=0.020). Both fasting and postprandial ApoC-III changes were inversely correlated with beta cell function (r=−0.384, p=0.026; r=−0.402, p=0.018, respectively). A multifactorial diet significantly reduced plasma ApoC-III levels in individuals with type 2 diabetes. Independent of dietary intervention, lower ApoC-III levels were associated with reduced liver and pancreatic fat accumulation and improved beta cell function. ClinicalTrials.gov NCT03380416

BACKGROUND:Colon cancer and pancreatic ductal adenocarcinoma are among the most aggressive tumors for which therapeutic options are limited. Both cancers share common features, such as some KRAS pathogenic variants and common epidemiology. The integration of multidimensional datasets by combining machine learning and bioinformatics approaches could provide deeper insights into the intricate KRAS-related networks underlying cancer progression and unveil novel biomarkers and potential therapeutic targets. This study aimed to uncover colon and pancreatic cancers that shared transcriptional changes closely related to KRAS missense mutations. METHODS:Feature Selection (FS) technique and Qiagen's Ingenuity Pathway Analysis (IPA) were used to combine DNA-Seq and RNA-Seq data from mutant and wild-type (WT) KRAS colon and pancreatic tumor samples. RESULTS:From the FS, we prioritized 70 genes (54 protein-coding genes and 16 ncRNA-coding genes) that were able to discriminate between WT and mutated KRAS patients. These genes were involved in KRAS signaling and other related processes, such as EMT signaling, glycolysis, apical junction, Wnt/beta-catenin signaling, and IL-2/STAT5 signaling. Using IPA, we identified a top-scoring network of 19 upregulated genes in both tumor types stratified into mutant KRAS and WT KRAS samples. For a set of genes, qRT-PCR performed on colon and pancreatic representative cancer cell lines showed concordant expression trends when comparing colon-dominant KRAS mutants versus WT KRAS and dominant pancreatic KRAS mutants versus WT KRAS, as expected according to in silico analyses. CONCLUSIONS:Our findings may provide insight into the common transcriptional signatures potentially underlying colon and pancreatic KRAS-mutant cancers. However, further studies are needed to elucidate the diagnostic and prognostic value of targets identified as common features in our study.

Huntington's disease (HD) differs from Alzheimer's disease (AD) in its clinical presentation, particularly regarding vigilance, with notable motor, functional, and cognitive impairments that may be mirrored in resting-state electroencephalographic (rsEEG) rhythms. To evaluate this hypothesis, clinical and rsEEG data were gathered from age-, sex-, and education-matched groups, including HD patients ( N  = 29), AD patients ( N  = 24), and healthy older participants (Nold, N = 29). EEG sources were computed using eLORETA software. The findings are as follows: (1) Compared to the Nold participants, both AD and HD patients exhibited higher widespread delta source activities (with HD > AD); (2) HD patients with the most pronounced motor deficits showed very high delta and theta source activities across widespread cortical regions; (3) HD patients with the most severe cognitive deficits exhibited lower alpha and higher delta source activities in widespread cortical regions; and (4) HD patients with the most significant functional deficits displayed very high delta source activities in widespread cortical regions. These findings indicate that in HD patients during quiet wakefulness, disruptions in cortical neural synchronization at delta and alpha frequencies are distinctly linked to cognitive, motor, and functional impairments. This underscores a unique interaction between the cholinergic and dopaminergic systems, which likely modulates the generation of alpha and delta source activities.

Splenomegaly is a quite common clinical feature of Philadelphia (Ph) negative chronic myeloproliferative neoplasms (MPNs) and its presence may, in some cases, drives treatment decision. Most importantly, palpable splenomegaly is a minor criterion for both pre-fibrotic/early primary myelofibrosis and primary myelofibrosis (PMF) diagnosis, even if clinical assessment by physical examination is poorly reliable and accurate. On the other hand, despite the International Working Group-Myeloproliferative Neoplasms Research and Treatment and European LeukemiaNet guidelines defined spleen response criteria by palpation, they also recognized the highly subjective nature of spleen size assessment by physical examination, and recommended objective confirmation of volume reduction via computed tomography or magnetic resonance imaging (MRI). In particular, spleen volume (SV) reduction of at least 35

In this "centenary" paper, an expert panel revisited Hans Berger's groundbreaking discovery of human restingstate electroencephalographic (rsEEG) alpha rhythms (8-12 Hz) in 1924, his foresight of substantial clinical applications in patients with "senile dementia," and new developments in the field, focusing on Alzheimer's disease (AD), the most prevalent cause of dementia in pathological aging. Clinical guidelines issued in 2024 by the US National Institute on Aging-Alzheimer's Association (NIA-AA) and the European Neuroscience Societies did not endorse routine use of rsEEG biomarkers in the clinical workup of older adults with cognitive impairment. Nevertheless, the expert panel highlighted decades of research from independent workgroups and different techniques showing consistent evidence that abnormalities in rsEEG delta, theta, and alpha rhythms (< 30 Hz) observed in AD patients correlate with wellestablished AD biomarkers of neuropathology, neurodegeneration, and cognitive decline. We posit that these abnormalities may reflect alterations in oscillatory synchronization within subcortical and cortical circuits, inducing cortical inhibitory-excitatory imbalance (in some cases leading to epileptiform activity) and vigilance dysfunctions (e.g., mental fatigue and drowsiness), which may impact AD patients' quality of life. Berger's vision of using EEG to understand and manage dementia in pathological aging is still actual.

This study investigated microstructural features of the locus coeruleus to entorhinal cortex pathway (LC-EC) in relation to amyloid (A), tau (T), neurodegeneration (N) markers and cognitive impairment in memory clinic patients. 124 participants were recruited from the Geneva Memory Clinic (n=30 cognitively unimpaired – CU; n=80 MCI and n=14 dementia - CI) and underwent clinical assessment, 3T MRI scan including diffusion weighted imaging, amyloid PET, and tau PET. Diffusivity indices (fractional anisotropy - FA, mean, axial and radial diffusivities - MD, AxD, RD) were assessed in the LC-EC pathway using a probabilistic atlas. A, T, N markers were assessed both as continuous and dichotomous measures. Differences in LC-EC microstructure according to ATN markers and diagnosis were assessed with ANOVA models (FDR correction). Linear regression models were used to test whether LC-EC pathway microstructure predicted cognitive impairment independently of ATN markers. Lower FA (p=0.020) and higher MD, RD and AxD (p<0.005) was observed in participants with tau positivity in the EC (T EC +, Braak stage ≥1) compared to tau negative subjects (T EC -). Higher MD, RD and AxD was observed in neurodegeneration positive (N+, medial temporal atrophy) versus negative (N-) participants (p<0.001), and CI versus CU (p<0.016). There was no difference in LC-TE microstructure between amyloid positive (A+) and negative (A-) subjects (p>0.05) nor between tau positive (T+; Braak stage ≥4) and negative (T-) subjects (p>0.05). The regression model showed that RD of the LC-EC tract was associated with clinical diagnosis and mini mental state examination score independently of ATN markers (p<0.05). Our results indicate that LC-EC microstructural measures, specifically RD, are sensitive in detecting CI and provide complementary information over ATN biomarkers. Associations with T suggest that LC-TE microstructural alterations show regional specificity in the EC.