Systematic and Comparative Analysis of the Burden of Alzheimer´s Disease and Other Dementias in Mexico. Results at the National and Subnational Levels, 1990-2019.

INTRODUCTION: Dementias, including Alzheimer´s disease (AD), are one of the leading causes of disability and mortality in older people. It is a growing health problem in low- and middle-income countries, where epidemiological information is scarce and deficient. The aim of this study was to analyze the burden of AD and other dementias in Mexico from 1990 to 2019 by sex, subnational level, and age groups. METHODS: A secondary analysis was conducted using data from the 2019 Global Burden of Disease, Injury, and Risk Factors Study (GBD). Data on prevalence, incidence, mortality, years of life lost (YLL), years lived with disability (YLD), and disability-adjusted life years (DALY) due to AD and other dementias were obtained. A joinpoint regression analysis was performed to describe the changes in the trend of age-standardized DALY rates by AD and other dementias during the analysis period. RESULTS: AD and other dementias ranked second among neurological disorders producing the most DALY in Mexico. Between 1990 and 2019, prevalence and incidence increased by almost 203%. In 2019, the age-standardized rate per 100,000 inhabitants was: 512 for prevalence, 79.3 for incidence, 73.3 for YLD, 256.9 for YLL and 272.2 for DALY. Likewise, five states concentrated 39% of AD and other dementias cases: Ciudad de México, Estado de México, Veracruz, Jalisco and Puebla. Differences were also observed by sex and age groups. DISCUSSION: Given that the number of older adults in Mexico will significantly rise over the next few decades, AD and other dementias represent one of the most important health challenges. The fact that epidemiological and demographic transformations take place in Mexico in a very diverse way makes it difficult for the country to adequately plan for the growing demands of both people with AD and other dementias and their families.

Cardiac allografts from IL-4 knockout recipients: assessment of transplant arteriosclerosis and peripheral tolerance.

To study the role of IL-4 in tolerance induction and transplant arteriosclerosis, BALB/c hearts were transplanted into C57BL/6J wild-type or IL-4 knockout (IL-4(-/-)) recipients. A 30-day course of anti-CD4/8 mAb was used to induce long term graft survival. Primary graft survival was 50% (5 of 10) in IL-4(-/-) recipients comparable to 63% (5 of 8) in wild-type recipients. Mice with allografts surviving >80 days were tested for tolerance by challenge with a second donor or third party (CBA) heart. Secondary donor-strain heart grafts survived >30 days, but showed histologic evidence of ongoing alloimmune response. Third party hearts rejected rapidly. Although immunostaining and 32P RT-PCR assays showed no differences in the mononuclear cell infiltration and T cell activation between IL-4(-/-) and wild-type tolerant recipients, some monokines (IL-12, TNF-alpha, and allograft inflammatory factor-1) were up-regulated in grafts from IL-4(-/-) recipients. Computer-assisted analysis of elastin-stained vessels revealed that the severity of vascular thickening (percentage of luminal occlusion, mean +/- SD, n = 329) was similar in grafts from IL-4(-/-) (63.7 +/- 16.9%) and wild-type (69.5 +/- 17.6%) recipients. Thus, IL-4 deficiency did not alter primary or secondary graft survival, infiltration, or vascular thickening. The selective alterations in monokine expression suggests that alternative pathways are activated and may compensate in IL-4(-/-) mice.