Recent studies have reported the presence of acetylcholine (ACh) receptor subtypes in bone tissue, and have demonstrated that inhibition of the ACh receptors has negative effects on bone mass and fracture healing capacity. However, little is known about the potential clinical effects that increased ACh signaling might have on bone. Accordingly, this study was designed to determine whether the use of acetylcholinesterase inhibitors (AChEIs), a group of drugs that stimulate ACh receptors and are used to treat Alzheimer's disease (AD), is associated with a decreased risk of hip fracture in AD patients. To accomplish this objective, a case-control analysis was performed using the AD population, aged above 75 years, based in the local health area of the Carlos Haya Hospital, in Malaga, Spain. The cases were 80 AD patients that suffered a hip fracture between January 2004 and December 2008. The controls were 2178 AD patients without hip fracture followed at our health care area during the same period of time. Compared with patients who did not use AChEIs, the hip fracture adjusted odds ratio (OR) for users of AChEIs was 0.42 (95% confidence interval [CI], 0.24-0.72), for users of rivastigmine was 0.22 (95% CI, 0.10-0.45), and for users of donepezil was 0.39 (95% CI, 0.19-0.76). Data were adjusted for the following parameters: body mass index, fall risk, smoking habits, cognition, dependence, degree of AD, comorbidity score, treatment with selective serotonin reuptake inhibitors, age, and gender. Our data suggests that use of AChEIs donepezil and rivastigmine is associated with a reduced risk of fractures in AD patients. Many elderly patients with AD disease who are at risk of developing osteoporosis may potentially benefit from therapy with the AChEIs donepezil and rivastigmine. ß
Abstract. Narrative evidence contained within historical documents and inscriptions provides an important record of climate variability for periods prior to the onset of systematic meteorological data collection. A common approach used by historical climatologists to convert such qualitative information into continuous quantitative proxy data is through the generation of ordinal-scale climate indices. There is, however, considerable variability in the types of phenomena reconstructed using an index approach and the practice of index development in different parts of the world. This review, written by members of the PAGES (Past Global Changes) CRIAS working group – a collective of climate historians and historical climatologists researching Climate Reconstructions and Impacts from the Archives of Societies – provides the first global synthesis of the use of the index approach in climate reconstruction. We begin by summarising the range of studies that have used indices for climate reconstruction across six continents (Europe, Asia, Africa, the Americas, and Australia) as well as the world's oceans. We then outline the different methods by which indices are developed in each of these regions, including a discussion of the processes adopted to verify and calibrate index series, and the measures used to express confidence and uncertainty. We conclude with a series of recommendations to guide the development of future index-based climate reconstructions to maximise their effectiveness for use by climate modellers and in multiproxy climate reconstructions.
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