Background: Fatigue and cognitive complaints are the most frequent persistent symptoms in patients after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study aimed to assess fatigue and neuropsychological performance and investigate changes in the thickness and volume of gray matter (GM) and microstructural abnormalities in the white matter (WM) in a group of patients with mild-to-moderate coronavirus disease 2019 (COVID-19).Methods: We studied 56 COVID-19 patients and 37 matched controls using magnetic resonance imaging (MRI). Cognition was assessed using Montreal Cognitive Assessment and Cambridge Neuropsychological Test Automated Battery, and fatigue was assessed using Chalder Fatigue Scale (CFQ-11). T1-weighted MRI was used to assess GM thickness and volume. Fiber-specific apparent fiber density (FD), free water index, and diffusion tensor imaging data were extracted using diffusion-weighted MRI (d-MRI). d-MRI data were correlated with clinical and cognitive measures using partial correlations and general linear modeling.Results: COVID-19 patients had mild-to-moderate acute illness (95% non-hospitalized). The average period between real-time quantitative reverse transcription polymerase chain reaction-based diagnosis and clinical/MRI assessments was 93.3 (±26.4) days. The COVID-19 group had higher total CFQ-11 scores than the control group (p < 0.001). There were no differences in neuropsychological performance between groups. The COVID-19 group had lower FD in the association, projection, and commissural tracts, but no change in GM. The corona radiata, corticospinal tract, corpus callosum, arcuate fasciculus, cingulate, fornix, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus, and uncinate fasciculus were involved. CFQ-11 scores, performance in reaction time, and visual memory tests correlated with microstructural changes in patients with COVID-19.Conclusions: Quantitative d-MRI detected changes in the WM microstructure of patients recovering from COVID-19. This study suggests a possible brain substrate underlying the symptoms caused by SARS-CoV-2 during medium- to long-term recovery.

We aimed to investigate changes in olfactory bulb volume and brain network in the white matter (WM) in patients with persistent olfactory disfunction (OD) following COVID-19. A cross-sectional study evaluated 38 participants with OD after mild COVID-19 and 24 controls, including Sniffin' Sticks identification test (SS-16), MoCA, and brain magnetic resonance imaging. Network-Based Statistics (NBS) and graph theoretical analysis were used to explore the WM. The COVID-19 group had reduced olfactory bulb volume compared to controls. In NBS, COVID-19 patients showed increased structural connectivity in a subnetwork comprising parietal brain regions. Regarding global network topological properties, patients exhibited lower global and local efficiency and higher assortativity than controls. Concerning local network topological properties, patients had reduced local efficiency (left lateral orbital gyrus and pallidum), increased clustering (left lateral orbital gyrus), increased nodal strength (right anterior orbital gyrus), and reduced nodal strength (left amygdala). SS-16 test score was negatively correlated with clustering of whole-brain WM in the COVID-19 group. Thus, patients with OD after COVID-19 had relevant WM network dysfunction with increased connectivity in the parietal sensory cortex. Reduced integration and increased segregation are observed within olfactory-related brain areas might be due to compensatory plasticity mechanisms devoted to recovering olfactory function.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder primarily characterized by memory loss and cognitive decline, which significantly impacts patients’ quality of life and imposes substantial emotional, practical, and economic burdens on their families. As the most common cause of senile dementia, AD currently affects approximately 50 million people worldwide, with projections indicating a threefold increase by 2050 due to rising life expectancy and an aging global population. Diagnosis of AD remains challenging. Neuroimaging techniques reveal atrophy in critical brain regions, particularly in the cortex, hippocampus, and limbic system, which are essential substrates for memory, personality changes, and other cognitive functions. The hallmark molecular changes associated with AD include the accumulation of β-amyloid plaques and the formation of tau protein tangles. Several underlying mechanisms contribute to neuron loss, such as oxidative stress, neuroinflammation, microbial dysbiosis, and insulin resistance. In this context, exosomes—small extracellular vesicles that facilitate cell communication—transport proteins, DNA, mRNA, and non-coding RNA (ncRNA), all of which play a significant role in the neurobiology of AD. Furthermore, emerging research indicates that exosomal ncRNAs may serve as promising biomarkers for AD, offering the possibility of improved diagnostic precision. This review explores the potential of exosomal ncRNAs—specifically circular RNAs and microRNAS—as non-invasive biomarkers for AD, highlighting recent advances and future directions in translational studies.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder primarily characterized by memory loss and cognitive decline, which significantly impacts patients' quality of life and imposes substantial emotional, practical, and economic burdens on their families. As the most common cause of senile dementia, AD currently affects approximately 50 million people worldwide, with projections indicating a threefold increase by 2050 due to rising life expectancy and an aging global population. Diagnosis of AD remains challenging. Neuroimaging techniques reveal atrophy in critical brain regions, particularly in the cortex, hippocampus, and limbic system, which are essential substrates for memory, personality changes, and other cognitive functions. The hallmark molecular changes associated with AD include the accumulation of β-amyloid plaques and the formation of tau protein tangles. Several underlying mechanisms contribute to neuron loss, such as oxidative stress, neuroinflammation, microbial dysbiosis and insulin resistance. In this context, exosomes − small extracellular vesicles that facilitate cell communication − transport proteins, DNA, mRNA, and non-coding RNA (ncRNA), all of which play a significant role in the neurobiology of AD. Furthermore, emerging research indicates that exosomal ncRNAs may serve as promising biomarkers for AD, offering the possibility of improved diagnostic precision. This review explores the potential of exossomal ncRNAs as non-invasive biomarkers for AD, focusing on recent advances and future directions in translational studies.

The glymphatic system has been proposed as a brain-wide pathway that promotes the exchange between cerebrospinal and interstitial fluids and facilitates the clearance of metabolic waste products, including amyloid-β and tau proteins. Diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) has emerged as a non-invasive magnetic resonance imaging technique proposed to indirectly assess glymphatic-related fluid dynamics. This systematic review evaluated the methodological consistency and clinical applicability of the ALPS index in neurodegenerative diseases. A structured search of PubMed (MEDLINE) and Web of Science identified human studies published up to January 2026 investigating DTI-ALPS in neurodegenerative conditions. Data regarding study populations, MRI acquisition parameters, image-processing methods, statistical approaches, and clinical associations were extracted and synthesized. Ten studies met the inclusion criteria. Across studies, lower ALPS index values were generally associated with cognitive impairment, amyloid burden, and disease severity, particularly in Alzheimer’s disease. Several studies incorporated multimodal biomarkers, including amyloid positron emission tomography and cerebrospinal fluid markers, thereby improving the biological interpretation of DTI-ALPS findings. However, substantial methodological heterogeneity was identified across studies, including variability in region-of-interest placement, diffusion acquisition protocols, and image-processing pipelines. Furthermore, the interpretation of diffusivity metrics as direct measures of glymphatic flow remains controversial. Current evidence suggests that DTI-ALPS may represent a promising non-invasive imaging marker of glymphatic-related alterations; however, its biological specificity and clinical applicability remain insufficiently established. Standardized acquisition protocols, harmonized analytical pipelines, and longitudinal multicenter studies are required to clarify its role in neurodegenerative disease research.