Summary of findings'. 'Diagnostic test accuracy of ¹⁸F‐florbetapir to predict the progression to ADD, any other form of dementia (non‐ADD) or any form of dementia in people with MCI.

What is the diagnostic accuracy of 18F‐florbetapir PET amyloid biomarker for predict progression to ADD, any other form of dementia (non‐ADD) or any form of dementia in people with MCI?
Descriptive
Patient population	Participants diagnosed with MCI at time of performing the test using any of the Petersen criteria or Winblad criteria or CDR = 0.5 or any 16 definitions included by Matthews (Matthews 2008).
Sources of referral	Not reported (n = 2) Mixed (memory clinics, newspaper ads, radio, and other public media campaigns) (n = 1)
MCI criteria	ADNI criteria, CDR 0.5 criterion was included (n = 2) CIND (cognitive impairment not dementia) (Matthews 2008) (n = 1)
Sampling procedure	Unclear (n = 3)
Prior testing	The only testing prior to performing the 18F‐florbetapir PET amyloid biomarker was the application of diagnostic criteria for identifying participants with MCI
Settings	Community and institutionalised (n = 1) Not reported (n = 2)
Index test	18F‐florbetapir PET
Threshold prespecified at baseline	Yes (n = 3)
Threshold interpretation	Visual (n = 3) Quantitative (n = 1)
Threshold	Visual: Increased tracer uptake reduced or absent white matter/gray matter contrast in at least one cortical (frontal, parietal, temporal, occipital) region detectable on more than two adjacent scan slices (n = 1) Amyloid burden based on successive levels of florbetapir retention from from 0 (no amyloid) to 4 (high levels of cortical amyloid). The median of the three visual scores was used to dichotomize participants into Aβ (‐) (score, 0 to 1 point) and Aβ (+) (score, 2 to 4 points) (n = 2) SUVR (Standardised Uptake Volume ratio): > 1.11 (n = 1)
18F‐florbetapir retention region	Global cortex (n = 1)
Reference Standard	Alzheimer’s disease dementia: NINCDS‐ADRDA (n = 1) Unclear (n = 1) Any form of dementia: DSM‐IV criteria for dementia (n = 1)
Target condition	Progression from MCI to Alzheimer’s disease dementia or any other forms of dementia (non‐ADD) or any form of dementia
Included studies	Prospectively well‐defined cohorts with any accepted definition of MCI (as above). Three studies (N = 458 participants) were included. Number of participants included in analysis: 453.
Quality concerns	The participant selection and reference standard QUADAS‐2 domain: unclear risk of bias. The index test domain: low risk of bias in all three included studies. The flow and timing domain: high risk of bias in the two included studies. Unclear concerns about applicability in the reference standard domain in all three included studies.
Limitations	Limited investigation of heterogeneity and sensitivity analysis due to insufficient number of studies. We were unable to evaluate progression from MCI to any other form of dementia (non‐ADD) due to lack of included studies.
Test	Studies	Cases/Participants	Sensitivity	Specificity	Consequences in a cohort of 100
					Proportion converting1	Missed cases2	Overdiagnosed2
Alzheimer's disease dementia
18F‐florbetapir by visual assessment from one to less than two years of follow‐up (Schreiber 2015)	1	61/401	89% (95% CI 78% to 95%)	58% (95% CI 53% to 64%)	15	2	36
18F‐florbetapir by quantitative assessment from one to less than two years of follow‐up (Schreiber 2015)	1	61/401	87% (95% CI 76% to 94%)	51% (95% CI 45% to 56%)	15	2	42
18F‐florbetapir by visual assessment from two to less than four years of follow‐up (Doraiswamy 2014)	1	9/47	67% (95% CI 30% to 93%)	71% (95% CI 54% to 85%)	19	6	23
Any form of dementia
18F‐florbetapir by visual assessment from one to less than two years of follow‐up (Kawas 2013)	1	3/5	67% (95% CI 9% to 99%)	50% (95% CI 1% to 99%)	60	20	20
Investigation of heterogeneity and sensitivity analysis: The planned investigations were not possible due to the limited number of studies available for each analysis.
Conclusions:18F‐florbetapir PET scan is not an accurate test for detecting progression from MCI to Alzheimer’s disease dementia or any form of dementia. The strength of the evidence was weak because of considerable variation in study methods, unclear methodological quality due to poor reporting, and high risk of bias due to possible conflict of interest. There is a need for conducting studies using standardised 18F‐florbetapir PET scan methodology in larger populations.

^{1. Proportion converting to ADD or any form of dementia in each included study.}

^{2. Missed and overdiagnosed numbers were computed using the proportion converting to the target condition. 
 ADD: Alzheimer's disease dementia
 ADNI: Alzheimer's Disease Neuroimaging Initiative
 CDR: Clinical dementia rating
 CIND: Cognitive impairment not dementia
 DSM‐IV: Diagnostic and Statistical Manual of Mental Disorders (4th ed.)
 MCI: Mild cognitive impairment
 NINCDS‐ADRDA: National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association
 QUADAS‐2: Quality Assessment of Diagnostic Accuracy Studies
 SUVR: Standardised uptake value ratio}