Neurodegeneration and aging are pressing issues with significant personal, economic, ethical, and social consequences. However, the underlying biological mechanisms of these conditions remain largely unknown, making the development of effective treatments challenging. The difficulty in early detection and diagnosis of neurodegenerative diseases further compounds the issue. Recent advancements in genetics, genomics, and brain imaging technology hold great promise for improving our understanding of neurodegeneration and aging, as well as the development of personalized medicine and new drugs and therapies. Addressing these challenges will require a multi-disciplinary and collaborative approach from researchers in various fields. This Special Issue offers valuable insights and perspectives on this critical area of research, which can help advance our understanding and improve the health and well-being of our aging population.

We present a case of untreated type II odontoid fracture, which evolved in severe dislocation 18 months later. Delayed dislocations in untreated type II odontoid fractures are already reported in literature. The singularity of our case is that CT-scan showed signs of fusion in the right C1-C2 articulation, which could have required a more complex surgical procedure to realign the upper cervical spine. Surprisingly, a CT scan performed in the extension position showed complete mobility of C1 and allowed us to perform a one stage posterior fixation. We want to highline both the importance of treating an Anderson type II fracture to prevent dislocation (acute or delayed), and the possibility to perform a flexion-extension CT scan to project a better surgical plan.

Background: Adolescence is a critical developmental stage for the emergence of major depressive disorder (MDD). Structural and diffusion neuroimaging studies have highlighted the anterior cingulate cortex (ACC) as a key region implicated in emotion regulation, stress reactivity, and mood processing. However, few studies have examined whether microstructural characteristics of the ACC, reflected by mean diffusivity (MD) within gray matter–white matter (GM–WM) contrast regions, are associated with depression in early adolescence. Objective: To examine whether mean diffusivity (MD) within the GM–WM contrast of the left caudal anterior cingulate cortex (ACC) is associated with a past diagnosis of MDD among adolescents in the Adolescent Brain Cognitive Development (ABCD) Study, after accounting for demographic, socioeconomic, and adversity-related factors. Methods: Data were drawn from adolescents with diffusion MRI–derived mean diffusivity measures and diagnostics. The independent variable was mean diffusivity (MD) of the GM–WM contrast in the left caudal ACC. The primary outcome was past MDD diagnosis based on structured psychiatric assessments. Covariates included age, sex, socioeconomic status (SES), and exposure to adverse childhood experiences (ACEs). Logistic regression models tested the association between ACC MD and past MDD. A secondary model evaluated the relationship between ACC MD and past suicide attempt. Results: Mean diffusivity of the left caudal ACC was associated with the odds of past MDD, independent of age, sex, SES, and adversity exposure. In contrast, ACC mean diffusivity was not associated with a history of suicide attempt. Conclusions: Increased mean diffusivity in the caudal ACC may indicate microstructural alterations associated with depressive vulnerability in adolescence. ACC tissue integrity may serve as a sensitive neural correlate of early-onset depression.

Early-onset neurodegenerative diseases (EO-NDs), such as early-onset Alzheimer’s disease (EOAD), Parkinson’s disease (EOPD), and familial amyotrophic lateral sclerosis (fALS), often stem from monogenic causes and manifest before typical age thresholds. These disorders frequently feature disrupted mitochondrial function and heightened oxidative stress, which together accelerate neuronal damage and degeneration. In this work, the author performs a comprehensive analysis of the literature and data related to mitochondrial dysfunction and redox imbalance in EO-NDs. Bibliometric trends were assessed using R-based tools on PubMed datasets, highlighting keyword networks and publication surges in recent years. Publicly available RNA-seq datasets from GEO and SRA were examined, with example DESeq2 analysis illustrating altered mitochondrial gene expression in EO-ND patient-derived samples. Network modeling of redox pathways using Python’s networkx demonstrates how oxidative stress can propagate through metabolic networks. Together, these computational approaches reinforce that mitochondrial DNA mutations, impaired electron transport chain (ETC) function, and reactive oxygen species (ROS) accumulation play central roles in EO-ND pathogenesis. The discussion further evaluates why antioxidant clinical trials have largely failed and how emerging therapies such as gene replacement, antisense oligonucleotides, and mitochondrial biogenesis modulators may provide more effective interventions.