This patient had a $40,000 USD workup including both invasiv | Figure 1

This patient had a $40,000 USD workup including both invasive and non-invasive tests. Her diagnosis of Myasthenia Gravis (MG) was made by a clever physician with an ice cube. Placing an ice cube on the patient’s eyelids for 30 to 60 seconds transiently improves ptosis in MG. The decreased temperature reduces activity of cholinesterase, resulting in increased acetylcholine concentration and improved transmission. Diagnostic tests like this are ideal because they are fast, painless, and inexpensive, with good sensitivity and specificity.

Thank you @drbob for sharing this case. #top2015

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Evidence for Cholinesterase Inhibitors in Vascular Dementia

Review question

What is the evidence for cholinesterase inhibitors (medicines designed to improve memory and thinking in people with dementia), when used with people who have vascular dementia?

Background

Vascular dementia (or vascular cognitive impairment) is a term used when a person has problems with memory and thinking that are caused by a disruption of blood supply. There are few drug treatments for vascular dementia.

In this review, we evaluated three drugs from the cholinesterase inhibitor family, donepezil, rivastigmine, and galantamine. These medications are widely used in Alzheimer's dementia but may also be useful in people with vascular dementia. Previous reviews of these cholinesterase inhibitor drugs could not draw definitive conclusions for people with vascular dementia.

Purpose of this review

We wanted to learn whether cholinesterase inhibitors benefit people with vascular dementia. We were interested in their effects on memory, thinking, and daily functioning. We wanted to learn of any harms associated with these drugs.

As some time has passed since the previous reviews, we wanted to update them by searching for new studies. We combined the three previous reviews on donepezil, rivastigmine, and galantamine into one review.

What we did

We searched for studies that described the effects of donepezil, rivastigmine, and galantamine for people with vascular dementia. We searched databases of scientific studies and contacted drug manufacturers and experts in vascular dementia. Our search is current to 19 August 2020.

To be included in our review, studies had to randomly assign people with vascular dementia to treatment with a cholinesterase inhibitor, or a dummy pill (placebo) and then compare the two groups. Studies comparing one cholinesterase inhibitor against another were also included. We combined the results of the included studies for each medicine to estimate how effective they were and how likely they were to cause side effects. We assessed how well the studies were conducted and how credible the results were.

We did not find studies which compared different cholinesterase inhibitors with each other. To see whether the different cholinesterase inhibitor drugs differed in their effects, we used a technique called network meta‐analysis, which can provide an idea of how the medicines might perform if they were compared head‐to‐head.

What we found

We found 8 studies including a total of 4373 people with vascular dementia (or vascular cognitive impairment). The studies tested the drug donepezil at two different doses (5mg and 10mg daily), against each other and against placebo. Rivastigmine and galantamine were tested against placebo only. Rivastigmine is available as a skin patch, but the studies only tested the pill version. All eight studies evaluated participants when they first started taking the medicine or placebo and again six months later. Different tests were used to measure the effects. All studies included tests of memory, thinking, and reported side effects.

People taking donepezil or galantamine had better scores on memory and thinking tests than people taking placebo, but the benefits were modest and may not be large enough to be evident in daily life. There was no evidence of a difference for rivastigmine, but the evidence was less certain, and the doses taken by some participants may have been too low to show an effect. We found evidence that when compared to placebo, side effects such as nausea and diarrhea were more common in people taking donepezil 10mg and galantamine, but probably not donepezil 5mg. We were unable to draw conclusions about side effects of rivastigmine from the studies.

Summary

No vascular dementia trials comparing the different cholinesterase inhibitors against each other have been conducted. Using the information from the individual studies, we made indirect assessments of how the drugs would perform if tested head‐to‐head. The results suggested that donepezil 10 mg had the greatest effect on memory and thinking, but caused more side effects than donepezil 5 mg or galantamine. There were only a small number of studies for each drug. Certainty in the results varied between drugs and between outcomes, from high to very low certainty. The studies showed only a small benefit at most; however, in the absence of any other treatments, people living with dementia may still wish to consider the use of these drugs.