Forskningsartikler

Abstract:
Introduction: We investigated the effectiveness of the multicomponent learning, innovation, volunteer support, empowerment (LIVE) intervention on caregiver burden and care time in dyads of home-dwelling people with dementia and caregivers.

Method: A 24 month, multicenter, stepped-wedge trial, randomized dyads to receive the 6-month LIVE intervention by municipal coordinators (May 2019 to December 2021). Primary outcomes were caregiver burden assessed by Relative Stress Scale (RSS) and informal care time spent on personal activities assessed by Resource Utilization in Dementia Personal Activities of Daily Living (RUD-PADL). Analyses used an intention-to-treat.

Results: Two hundred eighty dyads were enrolled. Caregivers during the intervention period reported lower levels of RSS of 0.7 points (standard deviation [SD]: 0.8) compared to the caregivers in the control period. Caregivers during the intervention period reported more time spent on PADL of 11.7 hours/month (SD: 8.7) compared to caregivers during the control period; both were not statistically significant (P > 0.05).

Discussion: The LIVE intervention did not reduce caregiver burden or care time.

Trial registration: ClinicalTrials.gov NCT04043364.

Highlights: Two hundred eighty persons with dementia and caregivers were included in a stepped wedge randomized controlled trial. We used the learning, innovation, volunteer support, empowerment (LIVE) intervention. The LIVE intervention did not reduce caregiver burden or informal care time. The LIVE intervention improved the caregiver’s clinical global impression of change. Positive change was most pronounced for coordinator personalized support.

Line Iden Berge, Renira Corinne Angeles, Marie Hidle Gedde, Stein Erik Fæø, Janne Mannseth, Maarja Vislapuu, Natalie Genevieve Søyland Puaschitz, Eirin Hillestad, Dag Aarsland, Wilco Peter Achterberg, Heather Allore, Clive Ballard, Fan Li, Geir Selbæk, Ipsit Vihang Vahia & Bettina Sandgate Husebo

Abstract:
Introduction: The presence of psychosis in Alzheimer’s disease (AD) is suggested to be associated with distinct molecular and neuropathological profiles in the brain.

Methods: We assessed brain DNA methylation in AD donors with psychosis (AD+P) and without psychosis (AD-P) using the EPIC array. Weighted gene correlation network analysis identified modules of co-methylated genes in a discovery cohort (PITT-ADRC: N = 113 AD+P, N = 40 AD-P), with validation in an independent cohort (BDR: N = 79 AD+P, N = 117 AD-P), with Gene Ontology and cell-type enrichment analysis. Genetic data were integrated to identify methylation quantitative trait loci (mQTLs), which were co-localized with GWAS for related traits.

Results: We replicated one AD+P associated module, which was enriched for synaptic pathways and in excitatory and inhibitory neurons. mQTLs in this module co-localized with variants associated with schizophrenia and educational attainment.

Discussion: This represents the largest epigenetic study of AD+P to date, identifying pleiotropic relationships between AD+P and related traits.

Highlights: DNA methylation was assessed in the prefrontal cortex in subjects with AD+P and AD-P. WGCNA identified six modules of co-methylated loci associated with AD+P in a discovery cohort. One of the modules was replicated in an independent cohort. This module was enriched for synaptic genes and in excitatory and inhibitory neurons. mQTLs mapping to genes in the module co-localized with GWAS loci for schizophrenia and educational attainment.

Morteza Kouhsar, Luke Weymouth, Adam R Smith, Jennifer Imm, Claudia Bredemeyer, Yehani Wedatilake, Ali Torkamani, Sverre Bergh, Geir Selbæk, Jonathan Mill, Clive Ballard, Robert A Sweet, Julia Kofler, Byron Creese, Ehsan Pishva, Katie Lunnon