Caregivers' perspectives and experiences of withdrawing acetylcholinesterase inhibitors and memantine in advanced dementia: a qualitative analysis of an online discussion forum.

BACKGROUND: There is considerable uncertainty surrounding the medications used to delay the progression of dementia, especially their long-term efficacy and when to withdraw treatment with these agents. Current research regarding the optimal use of antidementia medication is limited, contributing to variability in practice guidelines and in clinicians' prescribing practices. Little is currently known about the experiences encountered by caregivers of people with dementia after antidementia medication is withdrawn. AIM: To investigate the experiences and perspectives of carers and family members when antidementia medications (cholinesterase inhibitors and/or memantine) are stopped, by analysing archived threads and posts of an online discussion forum for people affected by dementia. METHODS: Archived discussions from Talking Point, an online discussion forum hosted by the Alzheimer's Society UK, were searched for threads discussing antidementia medication withdrawal and relevant threads were analysed thematically using the Framework method. Participant demographics were not established due to usernames which ensured anonymity. RESULTS: Four key themes emerged: (1) expectations about withdrawal, (2) method of withdrawal, (3) clinical condition on withdrawal, and (4) the effect of withdrawal on caregivers. CONCLUSIONS: Online discussion forums such as Talking Point provide dementia carers with an outlet to seek help, offer advice and share experiences with other members. The study findings highlight the complexity surrounding optimising dementia pharmacotherapy and antidementia medication withdrawal, highlighting the need for treatment to be person-centred and highly individualised.

Nesca, a novel neuronal adapter protein, links the molecular motor kinesin with the pre-synaptic membrane protein, syntaxin-1, in hippocampal neurons.

Vesicular transport in neurons plays a vital role in neuronal function and survival. Nesca is a novel protein that we previously identified and herein describe its pattern of expression, subcellular localization and protein-protein interactions both in vitro and in vivo. Specifically, a large proportion of Nesca is in tight association with both actin and microtubule cytoskeletal proteins. Nesca binds to F-actin, microtubules, ßIII and acetylated α-tubulin, but not neurofilaments or the actin-binding protein drebrin, in in vitro-binding assays. Nesca co-immunoprecipitates with kinesin heavy chain (KIF5B) and kinesin light-chain motors as well as with the synaptic membrane precursor protein, syntaxin-1, and is a constituent of the post-synaptic density. Moreover, in vitro-binding assays indicate that Nesca directly binds KIF5B, kinesin light-chain and syntaxin-1. In contrast, Nesca does not co-immunoprecipitate with the kinesin motors KIF1B, KIF3A nor does it bind syntaxin-4 or the synaptosome-associated protein 25 kDa (SNAP-25) in vitro. Nesca expression in neurons is highly punctuate, co-stains with syntaxin-1, and is found in fractions containing markers of early endosomes and Golgi suggesting that it is involved in vesicular transport. Collectively, these data suggest that Nesca functions as an adapter involved in neuronal vesicular transport including vesicles containing soluble N-ethylmaleimide sensitive factor attachment protein receptors that are essential to exocytosis.

Incidence of in-hospital mortality or nonfatal myocardial infarction or nonfatal stroke in 216 diabetics and 552 nondiabetics undergoing percutaneous coronary intervention with stenting.

We investigated the incidence of in-hospital mortality or nonfatal myocardial infarction or nonfatal stroke in 216 patients with diabetes mellitus and in 552 patients without diabetes mellitus (68% men and 32% women, mean age 66 +/- 14 y) who underwent percutaneous coronary intervention with stenting. Symptomatic chest pain was present in 95% of diabetics and in 95% of nondiabetics. Unstable symptoms were present in 67% of diabetics and in 68% of nondiabetics. Aspirin was used in 99% of diabetics and nondiabetics. Clopidogrel was used in 98% of diabetics and nondiabetics. Beta blockers were used in 85% of diabetics and nondiabetics. Lipid-lowering drugs were used in 96% of diabetics and in 95% of nondiabetics. In-hospital mortality occurred in 2 of 216 diabetics (0.9%) and in 2 of 552 nondiabetics (0.4%), P not significant. In-hospital mortality or nonfatal myocardial infarction or nonfatal stroke occurred in 3 of 216 diabetics (1.4%) and in 6 of 552 nondiabetics (1.1%), P not significant.