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.