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.

Neighborhood greenspace and neighborhood income associated with white matter grade worsening: Cardiovascular Health Study.

INTRODUCTION: We examined whether a combined measure of neighborhood greenspace and neighborhood median income was associated with white matter hyperintensity (WMH) and ventricle size changes. METHODS: The sample included 1260 cognitively normal ≥ 65-year-olds with two magnetic resonance images (MRI; ≈ 5 years apart). WMH and ventricular size were graded from 0 (least) to 9 (most) abnormal (worsening = increase of ≥1 grade from initial to follow-up MRI scans). The four-category neighborhood greenspace-income measure was based on median neighborhood greenspace and income values at initial MRI. Multivariable logistic regression tested associations between neighborhood greenspace-income and MRI measures (worsening vs. not). RESULTS: White matter grade worsening was more likely for those in lower greenspace-lower income neighborhoods than higher greenspace-higher income neighborhoods (odds ratio = 1.73; 95% confidence interval = 1.19-2.51). DISCUSSION: The combination of lower neighborhood income and lower greenspace may be a risk factor for worsening white matter grade on MRI. However, findings need to be replicated in more diverse cohorts. HIGHLIGHTS: Population-based cohort of older adults (≥ 65 years) with greenspace and MRI dataCombined measure of neighborhood greenspace and neighborhood income at initial MRIMRI outcomes included white matter hyperintensities (WMH) and ventricular sizeLongitudinal change in MRI outcomes measured approximately 5 years apartWorsening WMH over time more likely for lower greenspace-lower income neighborhoods.

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.

Mindfulness and Care Experience in Family Caregivers of Persons Living with Dementia.

Background: Greater mindfulness, the practice of awareness and living in the moment without judgement, has been linked to positive caregiving outcomes in dementia caregivers and its impact attributed to greater decentering and emotion regulation abilities. Whether the impact of these mindfulness-based processes varies across caregiver subgroups is unclear. Objective: Analyze cross-sectional associations between mindfulness and caregiver psychosocial outcomes, considering different caregiver and patient characteristics. Methods: A total of 128 family caregivers of persons living with Alzheimer's disease and related disorders were assessed on several mindfulness measures (i.e., global; decentering, positive emotion regulation, negative emotion regulation) and provided self-reported appraisals of caregiving experience; care preparedness; confidence, burden, and depression/anxiety. Bivariate relationships between mindfulness and caregiver outcomes were assessed with Pearson's correlations and stratified by caregiver (women versus men; spouse versus adult child) and patient (mild cognitive impairment (MCI) versus Dementia; AD versus dementia with Lewy bodies; low versus high symptom severity) characteristics. Results: Greater mindfulness was associated with positive outcomes and inversely associated with negative outcomes. Stratification identified specific patterns of associations across caregiver groups. Significant correlations were found between all mindfulness measures and caregiving outcomes in male and MCI caregivers while the individual mindfulness component of positive emotion regulation was significantly correlated to outcomes in most caregiver groups. Conclusion: Our findings support a link between caregiver mindfulness and improved caregiving outcomes and suggest directions of inquiry into whether the effectiveness of dementia caregiver-support interventions may be improved by targeting specific mindfulness processes or offering a more inclusive all-scope approach depending on individual caregiver or patient characteristics.