What is the diagnostic accuracy of ¹⁸F‐flutemetamol PET amyloid biomarker for predict progression to ADD in people with MCI?

Descriptive

Patient population

Participants diagnosed with MCI at the time of performing the test using any of the Petersen criteria or Winblad criteria or CDR = 0.5 or any of the 16 definitions included by Matthews (Matthews 2008).

Sources of referral

Not reported (n = 2)

MCI criteria

Petersen criteria (n = 2)

Sampling procedure

Unclear (n = 2)

Prior testing

The only testing prior to performing the ¹⁸F‐flutemetamol PET amyloid biomarker was the application of diagnostic criteria for identifying participants with MCI

Settings

Secondary care (n = 1)

Not reported (n = 1)

Index test

¹⁸F‐flutemetamol PET

Threshold pre‐specified at baseline

Yes (n=1)

Unclear (n=1)

Threshold interpretation

Visual (n = 1)

Quantitative (n = 1)

Thershold

SUVR (Standardised Uptake Volume ratio) of ROI: > 1.5 (n = 1)

Not specified: analytical visual approach of ROI: (n = 1)

¹⁸F‐flutemetamol retention region

Global cortex (n = 1)

Not reported (n = 1)

Reference Standard

For Alzheimer’s disease dementia:

NINCDS‐ADRDA (n = 1)

Unclear (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). Two studies (N = 252 participants) were included. Number of participants included in analysis: 243

Quality concerns

NCT01028053:

Patient selection and index test QUADAS‐2 domain: unclear risk of bias

Reference standard domain: low risk of bias

Flow and timing domain: high risk of bias

There were unclear concerns about applicability in the patient selection and index test domain.
Thurfjell 2012:

Patient selection and index test QUADAS‐2 domain: low risk of bias

Reference standard domain: unclear risk of bias

Flow and timing domain: high risk of bias.

There was unclear concern about applicability in the reference standard domain.

Limitations

Limited investigation of heterogeneity and sensitivity analysis due to an insufficient number of studies.

We were unable to evaluate progression from MCI to any other form of dementia (non‐ADD) or any form of dementia 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‐flutemetamol with visual assessment

1

81/224

64% (95% CI 53% to 75%)

69% (95% CI 60% to 76%)

36

13

20

¹⁸F‐flutemetamol with SUVR

1

9/19

89% (95% CI 52% to 100%)

80% (95% CI 44% to 97%)

47

5

11

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‐flutemetamol PET scan is not an accurate test for detecting progression from MCI to Alzheimer’s disease 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‐flutemetamol PET scan methodology in larger populations.