RESUMO
Age at onset of Alzheimer's disease is highly variable, and its modifiers (genetic or environmental) could act through epigenetic changes, such as DNA methylation at CpG sites. DNA methylation is also linked to ageing-the strongest Alzheimer's disease risk factor. DNA methylation age can be calculated using age-related CpGs and might reflect biological ageing. We conducted a clinical, genetic and epigenetic investigation of a unique Ashkenazi Jewish family with monozygotic triplets, two of whom developed Alzheimer's disease at ages 73 and 76, while the third at age 85 has no cognitive complaints or deficits in daily activities. One of their offspring developed Alzheimer's disease at age 50. Targeted sequencing of 80 genes associated with neurodegeneration revealed that the triplets and the affected offspring are heterozygous carriers of the risk APOE ε4 allele, as well as rare substitutions in APP (p.S198P), NOTCH3 (p.H1235L) and SORL1 (p.W1563C). In addition, we catalogued 52 possibly damaging rare variants detected by NeuroX array in affected individuals. Analysis of family members on a genome-wide DNA methylation chip revealed that the DNA methylation age of the triplets was 6-10 years younger than chronological age, while it was 9 years older in the offspring with early-onset Alzheimer's disease, suggesting accelerated ageing.
Assuntos
Doença de Alzheimer/genética , Epigênese Genética/genética , Trigêmeos/genética , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Senilidade Prematura/genética , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Apolipoproteínas E/genética , DNA/genética , Metilação de DNA , Feminino , Variação Genética , Genótipo , Heterozigoto , Humanos , Judeus , Doenças Neurodegenerativas/diagnóstico por imagem , Doenças Neurodegenerativas/patologia , Linhagem , Tomografia Computadorizada de Emissão de Fóton Único , Tomografia Computadorizada por Raios XRESUMO
Although a few papers documented benefits of group therapeutic activities for individuals with dementia, there is a dearth of studies that have investigated the effects of group activities on persons with dementia. This paper introduces a theoretical framework of studying group therapeutic recreational activity, the Comprehensive Process Model of Group Engagement, and an assessment tool, the Group Observational Measurement of Engagement (GOME). We also report the psychometric properties of this assessment. One hundred and four persons with dementia took part in ten different group activities, with each activity conducted twice at random order so that 20 activities were observed for each group of participants. Following each group activity, research and therapeutic recreation staff members used the GOME assessment to independently rate participants on individual-level measures of attendance duration and engagement, and group level measures (e.g., positive and negative interactions among group members). Reliability and validity analyses comparing observer ratings for each group activity on the individual-level measures of attendance and engagement showed good psychometric properties. Different measures collected on a group level differed with respect to their psychometric quality. We present a theoretical framework to understand group engagement and present measures that could be used in future research and practice.