The Mediating Role of Cortical Atrophy on the Relationship between the Resilience Index and Cognitive Function: Findings from the Healthy Brain Initiative.

Background: Lifestyle factors are linked to differences in brain aging and risk for Alzheimer's disease, underscored by concepts like 'cognitive reserve' and 'brain maintenance'. The Resilience Index (RI), a composite of 6 factors (cognitive reserve, physical and cognitive activities, social engagement, diet, and mindfulness) provides such a holistic measure. Objective: This study aims to examine the association of RI scores with cognitive function and assess the mediating role of cortical atrophy. Methods: Baseline data from 113 participants (aged 45+, 68% female) from the Healthy Brain Initiative were included. Life course resilience was estimated with the RI, cognitive performance with Cognivue®, and brain health using a machine learning derived Cortical Atrophy Score (CAS). Mediation analysis probed the relationship between RI, cognitive outcomes, and cortical atrophy. Results: In age and sex adjusted models, the RI was significantly associated with CAS (ß= -0.25, p = 0.006) and Cognivue® scores (ß= 0.32, p < 0.001). The RI-Cognivue® association was partially mediated by CAS (ß= 0.07; 95% CI [0.02, 0.14]). Conclusions: Findings revealed that the collective effect of early and late-life lifestyle resilience factors on cognition are partially explained by their association with less brain atrophy. These findings underscore the value of comprehensive lifestyle assessments in understanding the risk and progression of cognitive decline and Alzheimer's disease in an aging population.

Emerging drugs for dementia with Lewy Bodies: a review of Phase II & III trials.

INTRODUCTION: Despite faster cognitive decline and greater negative impact on patients and family caregivers, drug development efforts in Dementia with Lewy Bodies (DLB) fall behind those for Alzheimer's Disease (AD). Current off-label drug DLB treatment options are limited to symptomatic agents developed to address cognitive deficits in AD, motor deficits in Parkinson's Disease, or behavioral symptoms in psychiatric disease. Aided by recent improvements in DLB diagnosis, a new focus on the development of disease-modifying agents (DMA) is emerging. AREAS COVERED: Driven by evidence supporting different pathological mechanisms in DLB and PDD, this review assesses the evidence on symptomatic drug treatments and describes current efforts in DMA development in DLB. Specifically, our goals were to: (1) review evidence supporting the use of symptomatic drug treatments in DLB; (2) review the current DMA pipeline in DLB with a focus on Phase II and III clinical trials; and (3) identify potential issues with the development of DMA in DLB. Included in this review were completed and ongoing drug clinical trials in DLB registered on ClinicalTrials.gov (no time limits set for the search) or disseminated at the 2023 international conference on Clinical Trials in AD. Drug clinical trials registered in non-US clinical trial registries were not included. EXPERT OPINION: Adoption of current symptomatic drug treatments used off-label in DLB relied on efficacy of benefits in other disorders rather than evidence from randomized controlled clinical trials. Symptoms remain difficult to manage. Several DMA drugs are currently being evaluated as either repurposing candidates or novel small molecules. Continued improvement in methodological aspects including development of DLB-specific outcome measures and biomarkers is needed to move the field of DMA drug development forward.

Impact of Emotions on Test of Variables of Attention(TOVA) Performance in a Pediatric Clinical Population: A Retrospective Study.

BACKGROUND: Continuous Performance Tests, like the Test of Variables of Attention (TOVA), are commonly used to assess attention processes in clinical settings. Although a few previous studies have explored the effects of emotions on the outcome of such tests, the results are scarce and contradictory at times. OBJECTIVE: Through this retrospective study, we  aimed to explore the correlation between performance on the TOVA and parent-reported emotional symptoms in youth. METHODS: We used preexisting datasets of Mood and Feelings Questionnaire, Screen for Child Anxiety Related Disorders, and Vanderbilt Attention-Deficit/Hyperactivity Disorder Diagnostic Rating Scale as well as preexisting results from the TOVA test from 216 patients aged between 8 and 18 years. Pearson's correlation coefficients, as well as linear regression models, were computed to examine the association between depressive and anxiety symptoms and the four indices of TOVA (response time variability, response time, commission errors, and omission errors). Additionally, we used generalized estimating equations to determine whether the reported emotional symptoms affect the TOVA outcome differently as the test progresses. RESULTS: Our results showed no significant effect of the reported emotional symptoms on the TOVA results even when controlling for sex or reported inattention and hyperactivity. CONCLUSION: TOVA results do not seem to be affected by emotional symptoms in youth. This being said, future studies should also explore other factors that can affect the performance on the TOVA, like motor disability, sleepiness, or neurodevelopmental disorders affecting cognitive abilities.