Objective:To determine changes in the incidence of dementia between 1988 and 2015.Methods:This analysis was performed in aggregated data from individuals >65 years in seven population-based cohort studies in the United States and Europe from the Alzheimer Cohort Consortium. First, we calculated age- and sex-specific incidence rates for all-cause dementia, and then defined non-overlapping 5-year epochs within each study to determine trends in incidence. Estimates of change per 10-year interval were pooled and results are presented combined and stratified by sex.Results:Of 49,202 individuals, 4,253 (8.6%) developed dementia. The incidence rate of dementia increased with age, similarly for women and men, ranging from about 4 per 1,000 person years in individuals aged 65-69 years, to 65 per 1,000 person years for those aged 85-89 years. The incidence rate of dementia declined by 13% per calendar decade (95% CI: 7%-19%), consistently across studies, and somewhat more pronouncedly in men than in women (24% [95% CI 14%-32%] versus 8% [0%-15%]).Conclusion:The incidence rate of dementia in Europe and North America has declined by 13% per decade over the past 25 years, consistently across studies. Incidence is similar for men and women, although declines were somewhat more profound in men. These observations call for sustained efforts to finding the causes for this decline, as well as determining their validity in geographically and ethnically diverse populations.

No abstract

In this paper, we investigate evolutionary games with the invasion process updating rules on three simple non-directed graphs: the star, the circle and the complete graph. Here, we present an analytical approach and derive the exact solutions of the stochastic evolutionary game dynamics. We present formulae for the fixation probability and also for the speed of the evolutionary process, namely for the mean time to absorption (either mutant fixation or extinction) and then the mean time to mutant fixation. Through numerical examples, we compare the different impact of the population size and the fitness of each type of individual on the above quantities on the three different structures. We do this comparison in two specific cases. Firstly, we consider the case where mutants have fixed fitness r and resident individuals have fitness 1. Then, we consider the case where the fitness is not constant but depends on games played among the individuals, and we introduce a 'hawk-dove' game as an example.

Background: Quantifying changes in the levels of biological and cognitive markers prior to the clinical presentation of Alzheimer's disease (AD) will provide a template for understanding the underlying aetiology of the clinical syndrome and, concomitantly, for improving early diagnosis, clinical trial recruitment and treatment assessment. This study aims to characterise continuous changes of such markers and determine their rate of change and temporal order throughout the AD continuum. Methods: The methodology is founded on the development of stochastic models to estimate the expected time to reach different clinical disease states, for different risk groups, and synchronise short-term individual biomarker data onto a disease progression timeline. Twenty-seven markers are considered, including a range of cognitive scores, cerebrospinal (CSF) and plasma fluid proteins, and brain structural and molecular imaging measures. Data from 2014 participants in the Alzheimer's Disease Neuroimaging Initiative database is utilised. Results: The model suggests that detectable memory dysfunction could occur up to three decades prior to the onset of dementia due to AD (ADem). This is closely followed by changes in amyloid-β CSF levels and the first cognitive decline, as assessed by sensitive measures. Hippocampal atrophy could be observed as early as the initial amyloid-β accumulation. Brain hypometabolism starts later, about 14 years before onset, along with changes in the levels of total and phosphorylated tau proteins. Loss of functional abilities occurs rapidly around ADem onset. Neurofilament light is the only protein with notable early changes in plasma levels. The rate of change varies, with CSF, memory, amyloid PET and brain structural measures exhibiting the highest rate before the onset of ADem, followed by a decline. The probability of progressing to a more severe clinical state increases almost exponentially with age. In accordance with previous studies, the presence of apolipoprotein E4 alleles and amyloid-β accumulation can be associated with an increased risk of developing the disease, but their influence depends on age and clinical state. Conclusions: Despite the limited longitudinal data at the individual level and the high variability observed in such data, the study elucidates the link between the long asynchronous pathophysiological processes and the preclinical and clinical stages of AD.

This is the unspecified version of the paper.This version of the publication may differ from the final published version. Abstract It is known that in homogeneous populations the choice of the update rule is not critical in the evolutionary process. In this paper we investigate an evolutionary game between two strategies, A and B, interacting on a star graph considering four important update rules. We find explicit expressions for the fixation probability of any number of mutants placed at any position on the star, and the time to absorption (elimination or fixation of mutants) and fixation (absorption conditional on fixation occurring). For each of the update rules, we find appropriate conditions under which one strategy is favoured over the other. Considering the case where individuals have fixed fitness and a specific example of a Hawk-Dove game we then examine the effect of the update rule on the three quantities we study, and we show that in contrast with homogeneous populations, the choice of the update rule might be crucial for the evolutionary process in a non-homogeneous population. Permanent repository link