Background: Anticholinergic medication use is linked with increased cognitive decline, dementia, falls and mortality, and their use should be limited in older people. Here we estimate the prevalence of anticholinergic use in England’s older population in 1991 and 2011, and describe changes in use by participant’s age, sex, cognition and disability.Methods: We compared data from participants aged 65+ years from the Cognitive Function and Ageing Studies (CFAS I and II), collected during 1990-1993 (N=7,635) and 2008-2011 (N=7,762). We estimated the prevalence of potent anticholinergic use (Anticholinergic Cognitive Burden [ACB] score=3) and average anticholinergic burden (sum of ACB scores), using inverse probability weights standardised to the 2011 UK population. These were stratified by age, sex, Mini-Mental State Examination score, and activities of daily living (ADL) or instrumental ADL (IADL) disability. Results: Prevalence of potent anticholinergic use increased from 5.7% (95% Confidence Interval [CI] 5.2-6.3%) of the older population in 1990-93 to 9.9% (9.3-10.7%) in 2008-11, adjusted odds ratio of 1.90 (95%CI 1.67 – 2.16). People with clinically significant cognitive impairment (MMSE [Mini Mental State Examination] 21 or less) were the heaviest users of potent anticholinergic in CFAS II (16.5% [95%CI 12.0-22.3%]). Large increases in the prevalence of the use medication with ‘any’ anticholinergic activity were seen in older people with clinically significant cognitive impairment (53.3% in CFAS I to 71.5% in CFAS II). Conclusions: Use of potent anticholinergic medications nearly doubled in England’s older population over 20 years with some of the greatest increases amongst those particularly vulnerable to anticholinergic side-effects.
Starch Synthase III plays a key role in starch biosynthesis and is highly expressed in developing wheat grains. To understand the contribution of SSIII to starch and grain properties, we developed wheat ssIIIa mutants in the elite cultivar Cadenza using in silico TILLING in a mutagenized population. SSIIIa protein was undetectable by immunoblot analysis in triple ssIIIa mutants carrying mutations in each homoeologous copy of ssIIIa (A, B and D). Loss of SSIIIa in triple mutants led to significant changes in starch phenotype including smaller A-type granules and altered granule morphology. Starch chain-length distributions of double and triple mutants indicated greater levels of amylose than sibling controls (33.8% of starch in triple mutants, and 29.3% in double mutants vs. 25.5% in sibling controls) and fewer long amylopectin chains. Wholemeal flour of triple mutants had more resistant starch (6.0% vs. 2.9% in sibling controls) and greater levels of non-starch polysaccharides; the grains appeared shrunken and weighed ~11% less than the sibling control which was partially explained by loss in starch content. Despite the elevation in resistant starch, the other effects on starch and grain properties may hamper the usefulness of ssIIIa mutants in breeding applications.
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