Introduction: Global estimates on numbers of persons in early stages of Alzheimer's disease (AD), including prodromal and preclinical, are lacking, yet are needed to inform policy decisions on preventive measures and planning for future therapies targeting AD pathology.
Methods:We synthesized the literature on prevalence across the AD continuum and derived a model estimating the number of persons, stratified by 5-year age groups, sex, and disease stage (AD dementia, prodromal AD, and preclinical AD).
Results:The global number of persons with AD dementia, prodromal AD, and preclinical AD were estimated at 32, 69, and 315 million, respectively. Together they constituted 416 million across the AD continuum, or 22% of all persons aged 50 and above.Discussion: Considering predementia stages, the number of persons with AD is much larger than conveyed in available literature. Our estimates are uncertain, especially for predementia stages in low-and middle-income regions where biomarker studies are missing.
Space Lab 3 (SL-3) was flown on Shuttle Challenger providing an opportunity to measure the effect of spaceflight on rat testes. Cannon developed the idea that organisms react to unfavorable conditions with highly integrated metabolic activities. Selye summarized the manifestations of physiological response to nonspecific stress and he pointed out that atrophy of the gonads always occurred. Many papers have been published showing the effects of social interaction, crowding, peck order and confinement. Flickinger showed delayed testicular development in subordinate roosters influenced by group numbers, social rank and social status. Christian reported increasing population size in mice resulted in adrenal hypertrophy, inhibition of reproductive maturation and loss of reproductive function in adults. Sex organ weights also declined. Two male dogs were flown on Cosmos 110 for 22 days. Fedorova reported an increase of 30 to 70% atypical spermatozoa consisting of tail curling and/or the absence of a tail.
Anterior pituitaries from "small" (250 g) and "large" (400 g) rats flown on the 7-day Spacelab 3 mission were pooled and trypsinized into two single-cell suspensions. Compared with ground-based controls, flight cells appeared to contain more intracellular growth hormone (GH) but release less GH over a 6-day culture period. After implantation into hypophysectomized rats, both sets of flight cells released only 50% of the GH compared with the control cells. Glands from large flight rats contained 44% somatotrophs compared with 37% for controls; small animals showed no difference. There were no striking differences in somatotroph ultrastructure between cells in the four groups. Western blot analysis indicated that there were no major differences in immunoactive GH variants. High-performance liquid chromatography fractionation of culture media indicated that small flight cells released much less of a high-molecular weight variant rich in GH bioactivity. The results suggest that GH cells from rats exposed to microgravity may experience secretory dysfunction. The possibility that this occurs directly at the pituitary cell level is discussed.
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