Prevalence of memory impairment 2000-2015 in Sao Paolo, Brazil

in Alzheimer's and Dementia: the Journal of the Alzheimer's Association (2020), 16

Background: Decreases in prevalence of memory impairment and dementia over the last two decades have been observed in different countries for cohorts entering older age. We sought to explore the changes ... [more ▼]

Background: Decreases in prevalence of memory impairment and dementia over the last two decades have been observed in different countries for cohorts entering older age. We sought to explore the changes in prevalence of cognitive impairment across four waves of the Health, Welfare and Aging survey (SABE) with data collected in Sao Paolo, Brazil, in 2000, 2006, 2010, and 2015. Method: Mini Mental State Exam (MMSE) scores and covariate values were available for 5,191 respondents (62.4% female) aged 60 to 99 across four waves. Cognitive impairment was defined as having <=12 points on a 19-point abbreviated version of the MMSE. Age group, educational attainment (no formal schooling, primary, secondary, post-secondary), self-reported heart disease, stroke, diabetes, hypertension, and BMI (<18.5, 18.5-24.9, 25-29.9, 30+) were adjusted for. Result: In more recent waves, prevalence of cognitive impairment was higher for respondents aged 60-64 years (9.0% in 2015 vs. 4.6% in 2000), 65-69 years (9.7% in 2015 vs. 5.8% in 2006) and 70-74 years (13.9% in 2015 vs. 5.8% in 2006). Between 2015 and 2000, respondents were increasingly more likely to report some formal education (90.8% vs. 75.3%), secondary (17.6% vs. 7.3%) or postsecondary education (11.4% vs. 4.3%). Respondents were increasingly more likely to report hypertension (66.5% vs. 54.2%), diabetes (28.7% vs. 17.8%), and be overweight/obese (74.1% vs. 58.9%). In age-adjusted logistic regressions, respondents in 2015 were more likely to show cognitive impairment compared to 2000 (OR 1.84, CI 1.20-2.82). Conclusion: SABE respondents showed higher prevalence of cognitive impairment in 2015 compared to respondents of the same age in earlier waves, but differences disappeared after adjusting for chronic disease burden and educational attainment. [less ▲]

IDENTIFICATION OF A RARE GENE VARIANT THAT IS ASSOCIATED WITH FAMILIAL ALZHEIMER DISEASE AND REGULATES APP EXPRESSION

in Alzheimer's and Dementia: the Journal of the Alzheimer's Association (2017), 13(7, Supplement), 648

Background Genetic mutations leading to familial forms of Alzheimer disease (AD) have so far been reported for a few genes including APP, PSEN1 and PSEN2, UNC5C, PLD3, ABCA7, TTC3, and possibly ADAM10 ... [more ▼]

Background Genetic mutations leading to familial forms of Alzheimer disease (AD) have so far been reported for a few genes including APP, PSEN1 and PSEN2, UNC5C, PLD3, ABCA7, TTC3, and possibly ADAM10. With the advent of whole exome and whole genome sequencing approaches new genes and mutations are likely to be identified. Methods We analyzed the genetic cause of AD in a large multiplex family with an autosomal-dominant pattern of inheritance with LOAD. The family lacked pathogenic mutations of known AD genes. We performed whole-genome sequencing (WGS) in six family members (two affected and four unaffected) and prioritized rare, potential damaging, variants that segregated with disease. Variants were further characterized by subsequent molecular analyzes in human brain and cell culture models. Results We identified a single rare nonsynonymous variant co-segregating with AD. The mutation inhibits pro-protein cleavage and the formation of the active enzyme, thus leading to a loss-of-function of the gene. We further found a strong negative correlation between the identified gene and APP gene expression in human brain and in cells over-expressing the gene. The negative regulation of APP expression was only observed for the wt gene, but not for mutated forms, thus causing beside the loss of enzyme function a decoupling of both APPexpression and subsequent beta-amyloid formation. The identity of the gene will be presented on the conference. Conclusions This novel pathway strongly supports a causative association of the identified gene with the pathogenesis of AD. [less ▲]