Structural connectivity modifications following deep brain stimulation of the subcallosal cingulate and nucleus accumbens in severe anorexia nervosa.

PURPOSE: Anorexia nervosa (AN) is a mental health disorder characterized by significant weight loss and associated medical and psychological comorbidities. Conventional treatments for severe AN have shown limited effectiveness, leading to the exploration of novel interventional strategies, including deep brain stimulation (DBS). However, the neural mechanisms driving DBS interventions, particularly in psychiatric conditions, remain uncertain. This study aims to address this knowledge gap by examining changes in structural connectivity in patients with severe AN before and after DBS. METHODS: Sixteen participants, including eight patients with AN and eight controls, underwent baseline T1-weigthed and diffusion tensor imaging (DTI) acquisitions. Patients received DBS targeting either the subcallosal cingulate (DBS-SCC, N = 4) or the nucleus accumbens (DBS-NAcc, N = 4) based on psychiatric comorbidities and AN subtype. Post-DBS neuroimaging evaluation was conducted in four patients. Data analyses were performed to compare structural connectivity between patients and controls and to assess connectivity changes after DBS intervention. RESULTS: Baseline findings revealed that structural connectivity is significantly reduced in patients with AN compared to controls, mainly regarding callosal and subcallosal white matter (WM) tracts. Furthermore, pre- vs. post-DBS analyses in AN identified a specific increase after the intervention in two WM tracts: the anterior thalamic radiation and the superior longitudinal fasciculus-parietal bundle. CONCLUSIONS: This study supports that structural connectivity is highly compromised in severe AN. Moreover, this investigation preliminarily reveals that after DBS of the SCC and NAcc in severe AN, there are WM modifications. These microstructural plasticity adaptations may signify a mechanistic underpinning of DBS in this psychiatric disorder.

Cognitive and quality-of-life related factors of body mass index (BMI) improvement after deep brain stimulation in the subcallosal cingulate and nucleus accumbens in treatment-refractory chronic anorexia nervosa.

BACKGROUND: Up to 20% of the cases of anorexia nervosa (AN) are chronic and treatment-resistant. Recently, the efficacy of deep brain stimulation (DBS) for severe cases of AN has been explored, with studies showing an improvement in body mass index and other psychiatric outcomes. While the effects of DBS on cognitive domains have been studied in patients with other neurological and psychiatric conditions so far, no evidence has been gathered in AN. METHODS: Eight patients with severe, chronic, treatment-resistant AN received DBS either to the nucleus accumbens (NAcc) or subcallosal cingulate (SCC; four subjects on each target). A comprehensive battery of neuropsychological and clinical outcomes was used before and 6-month after surgery. FINDINGS: Although Body Mass Index (BMI) did not normalise, statistically significant improvements in BMI, quality of life, and performance on cognitive flexibility were observed after 6 months of DBS. Changes in BMI were related to a decrease in depressive symptoms and an improvement in memory functioning. INTERPRETATION: These findings, although preliminary, support the use of DBS in AN, pointing to its safety, even for cognitive functioning; improvements of cognitive flexibility are reported. DBS seems to exert changes on cognition and mood that accompany BMI increments. Further studies are needed better to determine the impact of DBS on cognitive functions.

Cognitive outcome after stereo-electroencephalography-guided radiofrequency thermocoagulation in temporal lobe epilepsy.

OBJECTIVE: Stereo-electroencephalography (SEEG)-guided radiofrequency thermocoagulation (RFTC) is being used incrementally in the invasive diagnosis of epilepsy. There is currently a lack of information regarding the potential cognitive consequences of the extended use of this technique. This work describes, for the first time, the cognitive outcomes after RFTC in patients with temporal lobe epilepsy (TLE), evaluated longitudinally and using a control group. METHODS: Forty-eight adult patients with drug-resistant unilateral TLE (30 RFTC-treated patients and 18 controls) were evaluated using a comprehensive neuropsychological protocol at baseline. In the RFTC group, two follow-up assessments were performed at 3 months and 1 year. The control group was reevaluated after 1 year. Two analyses were performed: 1) group-level analyses, in which linear mixed models were applied according to TLE lateralization (intragroup and intergroup [RFTC vs control] comparisons), and 2) individual-level analyses, in which the Reliable Change Index (RCI) algorithm was developed and a 90% CI (cutoff ± 1.64) was used to describe neuropsychological outcomes at 1 year post-RFTC. A memory subanalysis was performed in hippocampal RFTC patients (25/30). A Spearman coefficient study was conducted to determine the correlation between cognitive change and thermocoagulated contacts. RESULTS: Left- and right-sided TLE patients treated with RFTC showed cognitive preservation at baseline. At a group level, the short-term evaluation, including verbal and visual memory, language, and executive functions, showed preservation in these domains and no significant differences compared with baseline. In the long-term follow-up assessment (1 year after RFTC), no significant intragroup changes were found, nor were significant changes found in comparison with the control group. The RCI algorithm showed that significant individual cognitive losses and gains were infrequent. Three patients presented with naming deficits, only 1 (3.3%) of whom showed a clinically significant deficit. Significant gains were more prevalent in executive function tests with a speed component (4/20 left-sided RFTC patients). Twenty-five of the 30 (83%) patients were treated with hippocampal RFTC. No patients experienced significant loss in verbal delayed memory in the left-sided RFTC sample or in visual delayed memory in the right-sided RFTC sample. The correlations between cognitive change and RFTC contacts were mostly nonsignificant. CONCLUSIONS: In the group-level comparisons, discernible cognitive impairment following RFTC was not evidenced. The majority of patients did not exhibit significant individual declines during the 1-year follow-up period. Notably, the procedural intervention yielded no substantial repercussions on memory functioning following hippocampal RFTC. These findings underscore the evidence supporting the cognitive preservation associated with SEEG-guided RFTC.

Blood Biomarkers of Alzheimer's Disease and Cognition: A Literature Review.

Recent advances in blood-based biomarkers of Alzheimer's Disease (AD) show great promise for clinical applications, offering a less invasive alternative to current cerebrospinal fluid (CSF) measures. However, the relationships between these biomarkers and specific cognitive functions, as well as their utility in predicting longitudinal cognitive decline, are not yet fully understood. This descriptive review surveys the literature from 2018 to 2023, focusing on the associations of amyloid-ß (Aß), Total Tau (t-Tau), Phosphorylated Tau (p-Tau), Neurofilament Light (NfL), and Glial Fibrillary Acidic Protein (GFAP) with cognitive measures. The reviewed studies are heterogeneous, varying in design and population (cognitively unimpaired, cognitively impaired, or mixed populations), and show results that are sometimes conflicting. Generally, cognition positively correlates with Aß levels, especially when evaluated through the Aß42/Aß40 ratio. In contrast, t-Tau, p-Tau, Nfl, and GFAP levels typically show a negative correlation with cognitive performance. While p-Tau measures generally exhibit stronger associations with cognitive functions compared to other biomarkers, no single blood marker has emerged as being predominantly linked to a specific cognitive domain. These findings contribute to our understanding of the complex relationship between blood biomarkers and cognitive performance and underscore their potential utility in clinical assessments of cognition.

Effects of COVID-19 Pandemic Confinement in Patients With Cognitive Impairment.

Introduction: State of emergency caused by COVID-19 pandemic and subsequent lockdown hit Spain on 14th March 2020 and lasted until 21st June 2020. Social isolation measures were applied. Medical attention was focused on COVID-19. Primary and social care were mainly performed by telephone. This exceptional situation may affect especially vulnerable patients such as people living with dementia. Our aim was to describe the influence of restrictive measures on patients living with mild cognitive decline and dementia evaluating SARS-CoV2 infection, changes in routines, cognitive decline stage, neuropsychiatric symptoms, delirium, falls, caregiver stress, and access to sanitary care. Materials and Methods: We gathered MCI and dementia patients with clinical follow-up before and after confinement from DegMar registry (Hospital del Mar). A telephone ad-hoc questionnaire was administered. Global status was assessed using CDR scale. Changes in neuropsychiatric symptoms were assessed by Neuropsychiatric Inventory (NPI) and retrospective interview for pre-confinement base characteristics. Results: We contacted a total of 60 patients, age 75.4 years ± 5,192. 53.3% were women. Alzheimer's Disease (41.7%) and Mild Cognitive Impairment (25%) were the most prevalent diagnosis. Remaining cases included different dementia disorders. A total of 10% of patients had been diagnosed with SARS-CoV-2. During confinement 70% of patients abandoned previous daily activities, 60% had cognitive worsening reported by relatives/caretakers, 15% presented delirium episodes, and 13% suffered increased incidence of falls. Caregivers reported an increased burden in 41% cases and burnout in 11% cases. 16% reported difficulties accessing medical care, 33% received medical phone assistance, 20% needed emergency care and 21% had changes in psychopharmacological therapies. Neuropsychiatric profile globally worsened (p < 0.000), also in particular items like agitation (p = 0.003), depression (p < 0.000), anxiety (p < 0.000) and changes in appetite (p = 0.004). Conclusion: SARS-CoV2-related lockdown resulted in an important effect over social and cognitive spheres and worsening of neuropsychiatric traits in patients living with mild cognitive decline and dementia. Although the uncertainty regarding the evolution of the pandemic makes strategy difficult, we need to reach patients and caregivers and develop adequate strategies to reinforce and adapt social and health care.

A Randomized Trial of Deep Brain Stimulation to the Subcallosal Cingulate and Nucleus Accumbens in Patients with Treatment-Refractory, Chronic, and Severe Anorexia Nervosa: Initial Results at 6 Months of Follow Up.

BACKGROUND: The main objective of this study was to assess the safety and efficacy of deep brain stimulation (DBS) in patients with severe anorexia nervosa (AN). METHODS: Eight participants received active DBS to the subcallosal cingulate (SCC) or nucleus accumbens (NAcc) depending on comorbidities (affective or anxiety disorders, respectively) and type of AN. The primary outcome measure was body mass index (BMI). RESULTS: Overall, we found no significant difference (p = 0.84) between mean preoperative and postoperative (month 6) BMI. A BMI reference value (BMI-RV) was calculated. In patients that received preoperative inpatient care to raise the BMI, the BMI-RV was defined as the mean BMI value in the 12 months prior to surgery. In patients that did not require inpatient care, the BMI-RV was defined as the mean BMI in the 3-month period before surgery. This value was compared to the postoperative BMI (month 6), revealing a significant increase (p = 0.02). After 6 months of DBS, five participants showed an increase of ≥10% in the BMI-RV. Quality of life was improved (p = 0.03). Three cases presented cutaneous complications. CONCLUSION: DBS may be effective for some patients with severe AN. Cutaneous complications were observed. Longer term data are needed.

Treatment Design and Rationale for a Randomized Trial of Prophylactic Cranial Irradiation With or Without Hippocampal Avoidance for SCLC: PREMER Trial on Behalf of the Oncologic Group for the Study of Lung Cancer/Spanish Radiation Oncology Group-Radiation Oncology Clinical Research Group.

BACKGROUND: Prophylactic cranial irradiation (PCI) is part of the usual treatment in most patients with small-cell lung cancer (SCLC) and response after treatment of the primary tumor. Clinical evidence suggests that radiation dose received by the hippocampus during whole brain radiotherapy might play a role in radiation-induced neurocognitive decline. PATIENTS AND METHODS: This study is a multicenter phase III trial (NCT02397733) randomizing SCLC patients after informed consent, to receive standard PCI treatment or PCI with hippocampus avoidance (PCI-HA) by using intensity modulated radiation therapy or volumetric modulated arc therapy. The primary objective is assessment of hippocampus-dependent memory functioning and safety after PCI with or without hippocampus sparing by the Free and Cued Selective Reminding Test. Secondary objectives are assessment of other neurotoxicity/quality of life, radiological brain abnormalities on magnetic resonance images, and evaluation of the incidence and location of brain metastases after PCI-HA compared with standard PCI. The originally planned sample size (n = 150) has been calculated to detect a 50% difference in the 3-month delayed recall score between the 2 treatment arms, with a statistical power of 80% (ß = 20%) and a significance level of 5% (α = 5%), with a maximum loss to follow-up of 10%. CONCLUSION: This study is an important step in introducing a new therapeutic approach to patients with SCLC candidates for PCI.

One-Year Reference Norms of Cognitive Change in Spanish Old Adults: Data from the NEURONORMA Sample.

OBJECTIVE: Serial cognitive assessments are useful for many purposes, such as monitoring cognitive decline or evaluating the result of an intervention. In order to determine if an observed change is reliable and meaningful, longitudinal reference data from non-clinical samples are needed. Since neuropsychological outcomes are affected by language and cultural background, cognitive tests should be adapted, and country-based norms collected. The lack of cross-sectional normative data for Spanish population has been partially remediated, but there is still a need of reliable change norms. This paper aims to give an initial response to this need by providing several reliable change indices (RCI) for 1-year follow-up in a Spanish sample. METHOD: A longitudinal observational study was designed. A total of 122 healthy subjects over age 50 were evaluated twice (M = 369.5, SD= 10.7 days) with the NEURONORMA battery. Scores changes were analyzed, and simple discrepancy scores, standard deviation indices, RCI, and standardized regression-based scores were calculated. RESULTS: Significant improvements were observed in variables related to memory, both verbal and visual, visuospatial function, and the completion time of complex problems. Reference tables for several RCI are provided for their use in clinical settings. CONCLUSIONS: Our results confirm the existence of heterogeneous practice effects after 1 year, and support the recommendation of using reliable change norms to avoid misdiagnosis in repeated assessments. This study provides with initial, preliminary norms of cognitive change for its use in Spanish elders. Further studies on larger samples and different inter-visit intervals are still needed.