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.

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.

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.