Hypothalamic subregion alterations in anorexia nervosa and obesity: Association with appetite-regulating hormone levels.

OBJECTIVE: Anorexia nervosa (AN) and obesity are weight-related disorders with imbalances in energy homeostasis that may be due to hormonal dysregulation. Given the importance of the hypothalamus in hormonal regulation, we aimed to identify morphometric alterations to hypothalamic subregions linked to these conditions and their connection to appetite-regulating hormones. METHODS: Structural magnetic resonance imaging (MRI) was obtained from 78 patients with AN, 27 individuals with obesity and 100 normal-weight healthy controls. Leptin, ghrelin, and insulin blood levels were measured in a subsample of each group. An automated segmentation method was used to segment the hypothalamus and its subregions. Volumes of the hypothalamus and its subregions were compared between groups, and correlational analysis was employed to assess the relationship between morphometric measurements and appetite-regulating hormone levels. RESULTS: While accounting for total brain volume, patients with AN displayed a smaller volume in the inferior-tubular subregion (ITS). Conversely, obesity was associated with a larger volume in the anterior-superior, ITS, posterior subregions (PS), and entire hypothalamus. There were no significant volumetric differences between AN subtypes. Leptin correlated positively with PS volume, whereas ghrelin correlated negatively with the whole hypothalamus volume in the entire cohort. However, appetite-regulating hormone levels did not mediate the effects of body mass index on volumetric measures. CONCLUSION: Our results indicate the importance of regional structural hypothalamic alterations in AN and obesity, extending beyond global changes to brain volume. Furthermore, these alterations may be linked to changes in hormonal appetite regulation. However, given the small sample size in our correlation analysis, further analyses in a larger sample size are warranted. PUBLIC SIGNIFICANCE: Using an automated segmentation method to investigate morphometric alterations of hypothalamic subregions in AN and obesity, this study provides valuable insights into the complex interplay between hypothalamic alterations, hormonal appetite regulation, and body weight, highlighting the need for further research to uncover underlying mechanisms.

Gait decline while dual-tasking is an early sign of white matter deterioration in middle-aged and older adults.

Loss of white matter integrity (WMI) is associated with gait deficits in middle-aged and older adults. However, these deficits are often only apparent under cognitively demanding situations, such as walking and simultaneously performing a secondary cognitive task. Moreover, evidence suggests that declining executive functions (EF) are linked to gait decline, and their co-occurrence may point to a common underlying pathology, i.e., degeneration of shared brain regions. In this study, we applied diffusion tensor imaging (DTI) and a standardized gait assessment under single- and dual-tasking (DT) conditions (walking and subtracting) in 74 middle-aged and older adults without any significant gait or cognitive impairments to detect subtle WM alterations associated with gait decline under DT conditions. Additionally, the Trail Making Test (TMT) was used to assess EF, classify participants into three groups based on their performance, and examine a possible interaction between gait, EF, and WMI. Gait speed and subtracting speed while dual-tasking correlated significantly with the fractional anisotropy (FA) in the bilateral anterior corona radiata (highest r = 0.51/p < 0.0125 FWE-corrected). Dual-task costs (DTC) of gait speed correlated significantly with FA in widespread pathways, including the corpus callosum, bilateral anterior and superior corona radiata, as well as the left superior longitudinal fasciculus (highest r = -0.47/p < 0.0125 FWE-corrected). EF performance was associated with FA in the left anterior corona radiata (p < 0.05); however, EF did not significantly mediate the effects of WMI on DTC of gait speed. There were no significant correlations between TMT and DTC of gait and subtracting speed, respectively. Our findings indicate that gait decline under DT conditions is associated with widespread WM deterioration even in middle-aged and older adults without any significant gait or cognitive impairments. However, this relationship was not mediated by EF.

Distinct Relationship Between Cognitive Flexibility and White Matter Integrity in Individuals at Risk of Parkinson's Disease.

BACKGROUND AND OBJECTIVE: Executive dysfunction is the most common cognitive impairment in Parkinson's disease (PD), occurring even in its early stages. In our study, we applied diffusion tensor imaging (DTI) to investigate white matter integrity and its association with a specific executive function such as cognitive flexibility in individuals with risk factors for PD. METHODS: We examined 50 individuals with risk factors for developing PD and 24 healthy controls from the TREND (Tübinger Evaluation of Risk Factors for Early Detection of Neurodegeneration) study including neuropsychological evaluation and DTI. Cognitive flexibility was assessed using the trail making test (TMT). Tract based spatial statistics (TBSS) were employed to assess white matter abnormalities and their correlation with cognitive flexibility. RESULTS: TMT performance correlated with mean and axial diffusivity in several white matter regions, predominantly in the frontoparietal white matter. These effects were stronger in PD risk persons (PD-RP) than in controls as evidenced by a significant group interaction. White matter integrity and TMT performance did not significantly differ across groups. CONCLUSION: Based on our results, PD-RP do no exhibit white matter changes or impaired cognitive flexibility. However, specific executive functions in PD-RP are more related to white matter alterations than in healthy older adults.