18F-florbetapir PET scan for the early diagnosis of Alzheime | Figure 1
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18F-florbetapir PET scan for the early diagnosis of Alzheimer's disease dementia and other dementias
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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).
That 18F-florbetapir PET scans cannot be recommended for routine clinical use based on the currently available data.
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\ \ 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.](https://app.figure1.com/case-detail/36d33887-e9d8-4647-be17-a59e554efe03)
\ \ Why is improving screening for pulmonary tuberculosis in children important?\ Tuberculosis is one of the leading causes of death worldwide. Most children who die from tuberculosis are never diagnosed or treated. Screening may be useful to identify children with possible tuberculosis and refer them for further testing. As well, screening could be used to identify children without tuberculosis, who should be considered for preventive treatment. A false‐positive result means that children may undergo unnecessary testing and treatment and may not receive preventive treatment promptly. A false‐negative result means that children have tuberculosis, but may miss further testing to confirm the diagnosis.\ What is the aim of this review?\ To determine the accuracy of screening tests for active pulmonary tuberculosis in children in high‐risk groups, such as children with HIV and close contacts of people with tuberculosis.\ What was studied in this review?\ Screening tests were: one tuberculosis symptom; one or more of a combination of tuberculosis symptoms; the World Health Organization (WHO) four‐symptom screen (one or more of cough, fever, poor weight gain, or tuberculosis contact) in children with HIV, recommended at each healthcare visit; chest radiography (CXR); and Xpert MTB/RIF.\ What are the main results in this review?\ Nineteen studies assessed the following screening tests: one symptom (15 studies, 10,097 participants); more than one symptom (12 studies, 29,889 participants); CXR (10 studies, 7146 participants); and Xpert MTB/RIF (two studies, 787 participants).\ Symptom screening\ For every 1000 children screened, if 50 had tuberculosis according to the reference standard:\ One or more of cough, fever, or poor weight gain in tuberculosis contacts (composite reference standard (CRS) (4 studies)\ – 339 would screen positive, of whom 294 (87%) would not have tuberculosis (false positive).\ – 661 would screen negative, of whom 5 (1%) would have tuberculosis (false negative).\ One or more of cough, fever, or decreased playfulness in children under five, inpatient or outpatient (CRS) (3 studies)\ – 251 to 636 would screen positive, of whom 219 to 598 (87% to 94%) would not have tuberculosis (false positive).\ – 364 to 749 would screen negative, of whom 12 to 18 (2% to 3%) would have tuberculosis (false negative).\ One or more of cough, fever, poor weight gain, or tuberculosis close contact (WHO four‐symptom screen) in children with HIV, outpatient (CRS) (2 studies)\ – 88 would screen positive, of which 57 (65%) would not have tuberculosis (false positive).\ – 912 would screen negative, of which 19 (2%) would have tuberculosis (false negative).\ Abnormal CXR in tuberculosis contacts (CRS) (8 studies)\ – 63 would screen positive, of whom 19 (30%) would not have tuberculosis (false positive).\ – 937 would screen negative, of whom 6 (1%) would have tuberculosis (false negative).\ Xpert MTB/RIF in children, inpatient or outpatient microbiologic reference standard (MRS) (2 studies)\ – 31 to 69 would be Xpert MTB/RIF‐positive, of whom 9 to 19 (28% to 29%) would not have tuberculosis (false positive).\ – 969 to 931 would be Xpert MTB/RIF‐negative, of whom 0 to 28 (0% to 3%) would have tuberculosis (false negative).\ How reliable are the results of the studies in this review?\ Diagnosing tuberculosis in children is difficult. This may lead to screening tests appearing more or less accurate than they actually are. For Xpert MTB/RIF, there were few studies and children tested to be confident about results.\ Who do the results of this review apply to?\ Children at risk for pulmonary tuberculosis. Results likely do not apply to children in the general population. Studies mainly took place in countries with a high burden of tuberculosis.\ What are the implications of this review?\ In children who are tuberculosis contacts or living with HIV, screening tests using symptoms or CXR may be useful. However, symptoms and CXR formed part of the reference standard, which may falsely elevate the accuracy of the results. We urgently need better screening tests for tuberculosis in children to better identify children who should be considered for tuberculosis preventive treatment and to increase the timeliness of treatment in those with tuberculosis disease.\ How up‐to‐date is this review?\ To 14 February 2020.](https://app.figure1.com/case-detail/3ddb6053-b860-4568-abb0-8423deeed142)
\ \ Key points\ ‐ Psychological treatments based on cognitive behavioural therapy (which focuses on changing thoughts and behaviours) probably have small positive effects on depression, quality of life and daily activities in people with dementia or mild cognitive impairment (MCI).\ ‐ There is not enough evidence to know whether any psychological treatments are helpful for anxiety in people with dementia or MCI.\ ‐ More evidence is needed about different types of psychological treatments and which treatments may be best for which people.\ We found 29 studies that included 2599 people with dementia or MCI. Most of the evidence was about treatments based on cognitive behavioural therapy (CBT, which aims to alter thoughts and behaviours) and treatments aimed at supporting well‐being, which we called counselling and supportive therapies. We also found a very small number of studies about mindfulness‐based cognitive therapy and interpersonal therapy. The majority of studies looked at the effect on depression, but very few studies had anxiety as an outcome.\ The evidence suggests:\ ‐ CBT‐based treatments probably improve symptoms of depression, quality of life and ability to manage daily activities at the end of the treatment period in people with dementia or MCI, although the effects were small. We could not be sure about any effect on anxiety. There was some evidence that the effect on depression might depend on how severe the symptoms of depression were before the start of treatment, whether people had a diagnosis of dementia or MCI and what type of treatment was used, but more research would be needed to be sure about this.\ ‐ Supportive and counselling treatments may have no effect on symptoms of depression at the end of treatment and there was not enough evidence for us to know if there was any effect on anxiety.\ ‐ We cannot be sure about the effect of mindfulness‐based therapies or interpersonal therapy because there were very few studies of these treatments.\ There was limited information about unwanted effects associated with any of the treatments.\ We could be moderately certain about the small positive effects of CBT‐based treatments on depression, quality of life and daily activities, but were less certain about other results.](https://app.figure1.com/case-detail/8c1e9e3d-e248-4d5b-adda-97e1c724af81)
\ \ Observational studies following participants over many years have suggested that high blood pressure is associated with subsequent dementia or new problems with memory and thinking (cognitive impairment). It is important to establish if treating high blood pressure can reduce the risk of dementia and problems with memory and thinking. There is already clear evidence to support the treatment of high blood pressure after stroke. The evidence for treating high blood pressure in the absence of stroke was not as well established when this review protocol was written.\ Key findings\ We included 12 trials (30,412 participants) in this review. Treating high blood pressure with medicines may reduce the risk of dementia and problems with memory and thinking, but we were unable to confirm this using the data we have available. This may be due to shortcomings in the evidence available.\ Some participants had side effects from medications, such as falls, that led to them stopping the medications. This is also an important consideration.\ Limitations of the review\ We were unable to find evidence to confirm that treating high blood pressure with medicines will prevent future dementia or problems with memory and thinking. Based on the evidence available, all we can say is that the methods used in the studies we looked at were not sufficient to answer our study question. In practice, we want to know if treating high blood pressure in mid‐life reduces dementia and problems with memory and thinking in later life. These studies were too short in duration to answer this question. They tended to be designed to investigate heart attack and stroke as outcome measures, with memory and thinking tests added on, which means they were less likely to include the numbers of people with problems with memory and thinking necessary to reliably answer the question. In the studies comparing active medicines and placebo (inactive medicine), many people in the placebo groups ultimately did receive active medicine which further complicated the results.\ Antihypertensive treatment may prevent new problems with memory and thinking, or dementia, or both, despite the findings of this review. To be more confident in our conclusions, we would need studies that have more distinct treatment and placebo groups, and that treat participants starting at a younger age and with a longer follow‐up.](https://app.figure1.com/case-detail/a7e1d896-ee3b-4658-a734-f6e0691aa20a)
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