School of Medicine

Alopecia areata is thought to be a T-cell mediated and cytokine mediated autoimmune disease that results in non-scarring hair loss. Poliosis has been described as a localized depigmentation of hair caused by a deficiency of melanin in hair follicles. A 57-year-old man with a history of alopecia areata developed white hair regrowth in areas of previous hair loss. We retrospectively reviewed the medical literature using PubMed, searching: (1) alopecia areata and (2) poliosis. Poliosis may be associated with autoimmune diseases including alopecia areata, as described in our case. However, it is also reported in patients who have cutaneous lesions, genetic syndromes, infections, medication use, and trauma. Hair regrowth following alopecia areata may be associated with poliosis. We hypothesize that the incidence of poliosis in areas of previous alopecia areata-related hair loss may be greater than reflected in the published literature.

The Adolescent Brain Cognitive Development® (ABCD) Study provides a unique opportunity to investigate developmental processes in a large, diverse cohort of youths, aged approximately 9-10 at baseline and assessed annually for 10 years. Given the size and complexity of the ABCD Study, researchers analyzing its data will encounter a myriad of methodological and analytical considerations. This review provides an examination of key concepts and techniques related to longitudinal analyses of the ABCD Study data, including: (1) characterization of the factors associated with variation in developmental trajectories; (2) assessment of how level and timing of exposures may impact subsequent development; (3) quantification of how variation in developmental domains may be associated with outcomes, including mediation models and reciprocal relationships. We emphasize the importance of selecting appropriate statistical models to address these research questions. By presenting the advantages and potential challenges of longitudinal analyses in the ABCD Study, this review seeks to equip researchers with foundational knowledge and tools to make informed decisions as they navigate and effectively analyze and interpret the multi-dimensional longitudinal data currently available.

The two-times higher prevalence of Alzheimer's disease (AD) in females versus males is well-known; however, there are also sex/gender differences in clinical presentation and diagnostic accuracy that are less examined but equally important to understand in terms of improving early detection, intervention and disease tracking in each sex/gender. This review explores how these disparities in clinical presentation manifest across the AD continuum, with a focus on the earlier stages of preclinical AD and mild cognitive impairment (MCI). We summarize evidence indicating that female's verbal memory advantage may mask early cognitive decline, leading to delayed MCI diagnosis and limiting opportunities for early intervention. Conversely, females demonstrate steeper cognitive decline at later disease stages compared to males. These patterns align with the cognitive reserve theory, suggesting female's verbal memory strength may act as a domain-specific resilience factor. Lastly, this review emphasizes the need for sex-sensitive diagnostic tools to improve early detection accuracy and equity in clinical practice.

Cannabis use disorder (CUD) is associated with sexually dimorphic behavioral and neurobiological effects, but sex differences in a broader sampling of brain structures in CUD assessed relative to normative reference values have not been examined. Here, we assessed sex differences in brain regions measured via 3 T MRI in 72 adults (50 males, 22 females) with CUD. T1-weighted images, segmented via FreeSurfer, were used to derive Normative Morphometry Imaging Statistics z-scores (accounting for age, sex, intracranial volume, and image quality). Z-scores were then compared between sexes and associated with behavioral data. We found that average z-scores were within normative ranges for both sexes. There were no sex differences in total brain, cerebral white matter, and subcortical gray matter z-scores, but total cortical thickness z-scores were greater in females. Fourteen cortical regions surrounding the central and lateral sulci had greater z-scores in females than in males, but the medial orbitofrontal cortex z-score was greater in males. Of these regions, 3 were positively correlated with cannabis-related problems. Findings suggest sexual dimorphism in brain structure in CUD primarily in the frontal, medial parietal, and superior temporal lobes, with some association with cannabis-related problems even in the context of normative brain structure. Future research is needed to clarify causal mechanisms of morphometric differences in CUD.

People living with HIV (HIV+) are roughly twice as likely to smoke cigarettes (Smok+) as the general population. With the advent of effective antiretroviral therapies, it is increasingly important to understand the effects of chronic HIV infection and cigarette smoking on brain function and cognition since HIV+ individuals have heightened neuroinflammation and cognitive deficits even with such therapies. Based on prior studies demonstrating that smoking reduces a marker for neuroinflammation in HIV- individuals, we hypothesized that HIV+/Smok+ individuals would have less neuroinflammation and better cognitive control than HIV+/Smok- individuals. Fifty-nine participants (HIV-/Smok- [n = 16], HIV-/Smok+ [n=14], HIV+/Smok- [n = 18], and HIV+/Smok+ [n = 11]) underwent baseline eligibility tests, positron emission tomography (PET) scanning to determine levels of a marker for neuroinflammation, and assessment of cognitive control with the reverse-translated 5-choice continuous performance test (5C-CPT), with smokers having smoked to satiety prior to testing. For the PET data, a significant effect of smoking status on whole brain (WB) standardized uptake value (SUV) was found between HIV+/Smok+ and HIV+/Smok- participants (due to 18.8% lower WB SUV in the HIV+/Smok+ group). HIV+/Smok- participants exhibited a mean 13.5% higher WB SUV than HIV-/Smok- participants. For the 5C-CPT, HIV+/Smok+ participants performed significantly better than HIV+/Smok- participants (d prime), and HIV+/Smok- participants performed worse than HIV-/Smok- participants. Thus, HIV+/Smok+ individuals demonstrated lower levels of the neuroinflammation marker and better cognitive control than HIV+/Smok- individuals. Given that HIV+ individuals whose HIV is well-controlled can still have chronic neurocognitive complications, study results suggest possible paths for future research into nicotine-related treatments to prevent such complications.

OBJECTIVE: To examine the spectrum and severity of cognitive symptoms in veterans with migraine, traumatic brain injury (TBI), or both; and to evaluate the extent to which psychiatric conditions contribute to the relationship of migraine and TBI with cognitive symptoms. BACKGROUND: Migraine contributes significantly to global disability, with veterans facing additional burdens due to high comorbidity of TBI and psychiatric conditions. Understanding the intersection of these conditions is crucial for improving veterans health-care outcomes. METHODS: This observational study used self-reported data from 338,217 veterans enrolled in the Million Veteran Program (MVP) to assess cognitive symptoms using the Medical Outcomes Study Cognitive Functioning Scale Revised (MOS-Cog-R) and psychiatric conditions in veterans with migraine only, TBI only, both, or neither. RESULTS: Of the participants, 30,080/338,217 (8.9%) veterans reported migraine, 31,906/338,217 (9.4%) reported TBI, and 7828/338,217 (2.3%) reported both migraine and TBI. Veterans with only migraine or only TBI reported similar levels of cognitive symptoms (M = 74.19, standard deviation [SD] = 25.18; M = 73.87, SD = 24.98, respectively), which were substantially higher than veterans without these conditions (M = 62.52, SD = 27.90). Veterans with both conditions reported the most cognitive symptoms (M = 83.01, SD = 22.13) and psychiatric conditions (depression = 5041/7828 [64.4%], anxiety = 3735/7828 [47.7%], post-traumatic stress disorder = 4243/7828 [54.2%]). The association of migraine and TBI with cognitive symptoms persisted beyond the influence of psychiatric conditions (B = -2.20, standard error = -0.36, p < 0.001). CONCLUSION: Veterans with migraine reported cognitive challenges analogous to veterans with TBI, indicating a need for careful attention to cognitive symptoms in veterans with migraine. Further, the associations of migraine and TBI with cognitive symptoms in veterans were not explained by psychiatric conditions. These findings encourage future research to elucidate the association between self-reported and objective cognitive symptoms and to identify factors, including environmental exposure and genetic influences, contributing to cognitive impairment to optimize the assessment and treatment of veterans with migraine.

This multi-ancestry meta-analysis of genome-wide association studies (GWAS) investigated the genetic factors underlying chronic back pain (CBP) in a sample from the Million Veteran Program comprised of 553,601 Veterans of African (19.2%), European (72.6%), and Hispanic (8.2%) ancestry. The results revealed novel (N = 67) and known (N = 20) genome-wide significant loci associated with CBP, with 43 independent variants replicating in a non-overlapping contemporary meta-GWAS of the spinal pain dorsalgia phenotype. The most significant novel variant was rs12533005 (chr7:114416000, p = 1.61 × 10-20, OR = 0.96 (95% CI: 0.95-0.97), EA = C, EAF = 0.39), in an intron of the FOXP2 gene. In silico functional characterization revealed enrichment in brain and pituitary tissues. Mendelian randomization analysis of 62 variants for CBP-MVP revealed 48 with causal links to dorsalgia. Notably, four genes (INPP5B, DRD2, HTT, SLC30A6) associated with these variants are targets of existing drugs. Our findings more than double the number of previously reported genetic predictors across all spinal pain phenotypes.

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