OBJECTIVE: Alzheimer\'s dementia (AD) is a slowly progressing neurodegenerative disease, characterized by beta-amyloid deposition and neurofibrillary tangles. Peripheral atherosclerosis may deteriorate these processes via endothelial cell dysfunction and microvascular impairment. Cilostazol - a phosphodiesterase 3 inhibitor - is a standard treatment for peripheral arterial occlusive disease and a potential treatment for preserving cognitive function in AD patients. We aimed to determine whether cilostazol is beneficial in AD patients with peripheral arterial occlusive disease by evaluating Cognitive Abilities Screening Instrument (CASI) domains.
METHODS: We conducted a retrospective case-control study of 62 AD patients in Taiwan. Thirty-one patients had peripheral arterial occlusive disease and were receiving cilostazol plus acetylcholinesterase inhibitors (AchEIs) or N-methyl d-aspartate antagonists, whereas 31 others were receiving AchEIs. Therapeutic responses were measured using neuropsychological assessments. The CASI was administered at baseline and 12 months later; different domains were analyzed between the groups using univariate and multivariate analyses.
RESULTS: Age, sex, education duration, ApoE ε4 gene status, and initial Mini-Mental State Examination scores were not different between the two groups. Except for fluency, no CASI domains showed a statistical difference between the groups. A significant difference was observed in category fluency (P = 0.010). In the logistic regression analysis, after adjusting for covariate effects, category fluency still showed a significant difference between the groups (P = 0.013).
CONCLUSIONS: In AD patients with peripheral arterial occlusive disease who have received Food and Drug Administration-approved pharmacotherapy, cilostazol, as an antiplatelet, may help to preserve general cognitive function, with significant preservation in category fluency. Geriatr Gerontol Int 2023; 23: 194-199.

Acetylcholinesterase inhibitors (AChEIs) are used off-label, in both adult and pediatric patients, to help further neuro-recovery after traumatic brain injury (TBI). Evidence is limited and piecemeal. This review describes how TBI affects the cholinergic system and consolidates evidence supporting or refuting the use of AChEIs following TBI.
NCBI MEDLINE search included all articles published through March 2021 on AChEI use in acute and post-acute adult TBI rehabilitation (treatment began <90 days or ≥90 days since injury, respectively), and in pediatric TBI rehabilitation. Further, we checked ClinicalTrials.gov for ongoing trials using AChEIs for TBI rehabilitation in the United States.
27 original articles from NCBI Medline, published through March 2021, were included. The use of AChEIs following TBI in acute and post-acute rehabilitation settings, in both adult and pediatric patients, along with medication side effects, is discussed.
Most studies showed benefits with only moderate effect sizes because of small sample sizes. Reported side effects are minimal and stop soon after AChEIs is discontinued. Conclusions are limited by paucity of research; but fortunately, a large randomized controlled trial is ongoing, and more are needed to truly determine the efficacy of AChEIs in helping with recovery from TBI.

Cardiovascular diseases remain a major cause of morbidity and mortality worldwide. Cardiovascular diseases such as acute myocardial infarction, ischaemia/reperfusion injury and heart failure are associated with cardiac autonomic imbalance characterized by sympathetic overactivity and parasympathetic withdrawal from the heart. Increased parasympathetic activity by electrical vagal nerve stimulation has been shown to provide beneficial effects in the case of cardiovascular diseases in both animals and patients by improving autonomic function, cardiac remodelling and mitochondrial function. However, clinical limitations for electrical vagal nerve stimulation exist because of its invasive nature, costly equipment and limited clinical validation. Therefore, novel therapeutic approaches which moderate parasympathetic activities could be beneficial for in the case of cardiovascular disease. Acetylcholinesterase inhibitors inhibit acetylcholinesterase and hence increase cholinergic transmission. Recent studies have reported that acetylcholinesterase inhibitors improve autonomic function and cardiac function in cardiovascular disease models. Despite its potential clinical benefits for cardiovascular disease patients, the role of acetylcholinesterase inhibitors in acute myocardial infarction and heart failure remediation remains unclear. This article comprehensively reviews the effects of acetylcholinesterase inhibitors on the heart in acute myocardial infarction and heart failure scenarios from in vitro and in vivo studies to clinical reports. The mechanisms involved are also discussed in this review.

Due to the well-defined risks of abrupt discontinuation of certain psychiatric medications, such as withdrawal and worsening symptoms, guideline recommendations describe evidence-based strategies for tapering some psychiatric medications, such as antidepressants. Despite widespread use of acetylcholinesterase inhibitor (ACHEI) therapy in the management of dementia, guideline recommendations for discontinuation of these therapies are very inconsistent. Specifically, studies and evidence-based recommendations for discontinuing ACHEIs in patients with dementia with Lewy bodies (DLB) are severely lacking. This deficit is problematic in that emerging reports suggest several adverse outcomes, such as worsening cognition and behavioral symptoms, are associated with abrupt switching and discontinuation of ACHEI therapy in this population. A case of rapid cognitive and functional decline following both abrupt switch and discontinuation of donepezil in a patient diagnosed with DLB is presented. A literature review of outcomes following changes in ACHEI therapy in DLB is also presented.

UNASSIGNED: Abrupt withdrawal of pharmacological therapies for myasthenia gravis can exacerbate muscle weakness and even trigger myasthenic crisis. Such medications should ideally be continued, but how this can be achieved in patients approaching the end of life, particularly when enteral administration is compromised, has not been defined.
UNASSIGNED: An 83-year-old man with a history of generalized myasthenia gravis and palliative metastatic anal adenocarcinoma was admitted to his local hospital with general decline, where he was considered by more than one physician to be actively dying from his cancer. In the days preceding admission, the patient had not taken his medications consistently, including the acetylcholinesterase inhibitor, pyridostigmine, for the management of his myasthenia gravis.
UNASSIGNED: Reintroduction of the patient\'s usual myasthenia therapy improved his clinical condition to the point where he was no longer thought to be dying. When enteral administration of pyridostigmine was no longer possible, the patient was successfully converted to neostigmine, which was administered as a continuous subcutaneous infusion.
UNASSIGNED: Undertreated myasthenia gravis can lead to a rapid deterioration in a patient\'s clinical condition, and such patients may be mistakenly diagnosed as dying. Undertreated myasthenia gravis should therefore be considered as a potentially reversible cause of acute deterioration, especially in patients with complex comorbidities. The use of neostigmine as a continuous subcutaneous infusion may have a role in the management of such patients, particularly when enteral administration of acetylcholinesterase inhibitors is no longer possible.

The objective of this study was to analyze the effect of acetylcholinesterase inhibitors (AChEIs) on the risk of osteoporotic fractures in Alzheimer patients. A nested case-control study was conducted on 1190 cases and 4760 controls. The use of AChEIs was found to decrease the risk of osteoporotic fractures in these patients.
The objective of this study is to estimate the extent to which the use of AChEIs is associated with a reduction in the risk of osteoporotic fractures.
A nested case-control study was conducted using data from the UK Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) database (1998-2013). The study cohort consisted of Alzheimer\'s Disease (AD) patients aged ≥ 65 years with no previous history of osteoporotic fractures at cohort baseline. Cases were individuals who suffered an osteoporotic fracture during the study period, whereas controls were subject who did not experience any osteoporotic fractures during the same period. Controls were drawn from the population time at risk while being matched to the cases in respect to age, sex, up-to-standard follow-up in the CPRD, calendar time, and duration of AD (control-to-case ratio: 4-to-1). Information on the use of AChEIs and the relevant potential confounders was ascertained from the CPRD database for all the cases and controls.
We identified 1190 cases and 4760 controls. Compared to non-users, any use of AChEIs prior to the fracture was associated with a reduction in the fracture risk [adjusted odds ratio (OR) 0.80 (confidence interval (CI) 95%, 0.70-0.91)]. The use of AChEIs corresponding to a proportion of days covered of 0.8-1.0 was associated with a lower osteoporotic fracture risk compared to non-use [adjusted OR 0.76 (CI 95%, 0.66-0.87)].
In this study using large primary care databases, the use and treatment adherence to AChEIs were associated with a decreased risk of osteoporotic fractures in elderly AD patients.

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Congenital myopathies are a clinically and genetically heterogeneous group of disorders characterized by early onset hypotonia, weakness and characteristic, but not pathognomonic, structural abnormalities in muscle fibres. The clinical features overlap with muscular dystrophies, myofibrillar myopathies, neurogenic conditions and congenital myasthenic syndromes. We describe a case of cap myopathy with myasthenic features due to a mutation in the TPM2 gene that responded to anticholinesterase therapy. We also review other published cases of congenital myopathies with neuromuscular transmission abnormalities. This report expands the spectrum of congenital myopathies with secondary neuromuscular transmission defects. The recognition of these cases is important since these conditions can benefit from treatment with drugs enhancing neuromuscular transmission.