Individuals with Alzheimer's disease tend to be less aware o | Figure 1

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Individuals with Alzheimer's disease tend to be less aware of their own cognitive deficits as the disease progresses - here is an excerpt from a subjective memory questionnaire given to a patient with AD (image 1) and the patient's spouse (image 2). This patient had a Mini Mental State Exam score of 22/30 and a clinical dementia rating of 1.0 and had progressed from MCI to AD within the past year.

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In people with mild cognitive impairment (MCI), does using a 18F PET scan with florbetapir predict the progression to Alzheimer's disease dementia (ADD) and other dementias?

Cochrane Review; 3 studies (453 participants with MCI).
Key findings:

• At follow-up of 1.6 years, the scan correctly classified 89% of the participants who progressed to ADD but only 58% of the participants who did not progress to ADD. This means that in a group of 100 people with MCI, 15% of whom will develop ADD, we would expect 13 of 15 people to have a positive result and the other 2 participants to be falsely negative. Also 49 people who will not develop ADD would have a negative result, but 36 people who will not develop ADD would have a positive result (false positives).
• In a study that followed up people for 3 years, the scan correctly classified 67% of people who progressed to ADD and 71% who did not progress to ADD. This means in a group of 100 people with MCI, 19 of whom will develop ADD, we would expect 13 people to have a positive result of the scan and 6 people to have a falsely negative result. Also 58 of 81 participants who will not progress to ADD would have a negative result, but 23 people who will not develop ADD would have a positive result (false positives).
• The 18F-florbetapir PET scans cannot be recommended for routine clinical use based on the currently available data.

In people with mild cognitive impairment (MCI), does using a 18F PET scan with florbetaben predict progression to Alzheimer's disease dementia (ADD) and other dementias?

Cochrane Review; 1 study (45 participants with MCI); funded by the test manufacturer.
Key findings:

• Based on only one study, the 18F-florbetaben PET scan, as a single test with visual assessment, correctly classified 100% of the participants who will progress to ADD and 83% of the participants who did not progress to ADD at four years follow-up. This means in a cohort with 100 participants with MCI, 47 of whom will progress to ADD, we would expect that all those 47 MCI participants would test positive with the 18F-florbetaben scan and that 0 participants would be falsely negative (i.e. none of the 47 participants would have a negative test and yet progress to ADD). In addition, we would expect 44 of 53 participants who did not progress to ADD to be 18F-florbetaben-negative and 9 to be falsely positive (i.e. 9 of the 53 participants would have a positive test but not progress to ADD).
• The small size of the included study lowered our confidence on these estimates of accuracy. It is possible that the test is considerably less accurate than these results suggest.
• 18F-florbetaben imaging is a promising test to predict the progression from MCI to ADD; but more studies are needed.

The dietary supplement Souvenaid for preventing dementia or delaying cognitive decline in people with Alzheimer's disease

Review question
We investigated whether people with mild cognitive impairment (MCI) due to Alzheimer's disease (AD) can reduce their risk of developing dementia with a patented dietary supplement called Souvenaid. We also investigated the effect of Souvenaid on memory or other thinking skills, ability to carry out daily activities, and side effects in people with MCI or any stage of dementia due to AD.
Background
Alzheimer's disease is a brain disease. It is the commonest cause of dementia among older people. A person is said to have dementia when there has been a decline in their memory and thinking skills which is severe enough to stop them being fully independent in all their daily activities. Because AD develops slowly, it is also possible to pick up symptoms before dementia is fully developed. This pre‐dementia stage, when people with AD have a detectable decline in memory and thinking skills but are still able to manage their usual activities independently, is known as mild cognitive impairment due to AD, or 'prodromal' AD.
Souvenaid is a patented mix of vitamins and minerals (Fortasyn Connect™) which was designed to improve brain function in AD. It is a drink which is to be taken once a day. It is intended to be consumed under medical supervision, in addition to the usual diet.
Search for evidence
We systematically searched for randomised controlled trials (RCTs) which were published up to June 2020 and which compared treatment with Souvenaid for at least 16 weeks with treatment with a dummy supplement (a placebo). For the comparison to be fair, it had to be decided randomly whether each participant was given Souvenaid or the placebo.
Key results

• We found three RCTs with a total of 1097 participants to include in the review. Two of the trials investigated Souvenaid in people with dementia over a treatment period of 24 weeks. One of these included 527 participants with mild‐to‐moderate dementia due to AD and the other included 259 participants with mild dementia due to AD. The third trial investigated the use of Souvenaid for two years in 311 people with prodromal AD.
• We considered all of the trials to be well‐designed, but because of differences between them in the severity of the participants' symptoms and in the way the researchers measured their results, we were not able to combine the data numerically from the single trials. All the results we report are therefore based on single trials, which leads us to have only moderate confidence in the findings of this review. This means that results could be changed by further research.
• We found that people with prodromal AD who took Souvenaid daily for two years were probably no more or less likely than those taking placebo to develop dementia.
• Souvenaid probably had little or no effect on measures of memory or other thinking skills in people with prodromal AD (after two years of treatment) or with mild or mild‐to‐moderate dementia due to AD (after 24 weeks of treatment). It also probably had little or no effect on the ability of people with mild or mild‐to‐moderate dementia due to AD to manage everyday activities (again after 24 weeks).
• Two studies used an outcome scale which combined memory and thinking skills with practical skills (described as a combined cognitive‐functional outcome). There was probably a small benefit of Souvenaid on this outcome among people with prodromal AD who took Souvenaid for two years. However, there was probably little or no effect of Souvenaid on this outcome among people with mild‐to‐moderate AD dementia who took it for 24 weeks.
• There were only a few adverse events reported in the trials, and it was not possible to know whether any of them were side effects of Souvenaid.
  Study funding sources
  Two studies were funded by the manufacturer of Souvenaid. The third study (in prodromal AD) was funded by European grants.

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