Scolaris Content Display Scolaris Content Display

Study flow diagram.
Figures and Tables -
Figure 1

Study flow diagram.

Risk of bias and applicability concerns summary: review authors' judgements about each domain for each included study
Figures and Tables -
Figure 2

Risk of bias and applicability concerns summary: review authors' judgements about each domain for each included study

Forest plot of tests: 1 MCI to ADD by visual assessment from 2 to less than 4 years of follow‐up, 2 MCI to ADD by visual assessment from 1 to less than 2 years follow‐up, 3 MCI to ADD by SUVR at 1 to less than 2 years follow‐up, 4 MCI to any form of dementia.
Figures and Tables -
Figure 3

Forest plot of tests: 1 MCI to ADD by visual assessment from 2 to less than 4 years of follow‐up, 2 MCI to ADD by visual assessment from 1 to less than 2 years follow‐up, 3 MCI to ADD by SUVR at 1 to less than 2 years follow‐up, 4 MCI to any form of dementia.

MCI to ADD by visual assessment from 2 to less than 4 years of follow‐up.
Figures and Tables -
Test 1

MCI to ADD by visual assessment from 2 to less than 4 years of follow‐up.

MCI to ADD by visual assessment from 1 to less than 2 years follow‐up.
Figures and Tables -
Test 2

MCI to ADD by visual assessment from 1 to less than 2 years follow‐up.

MCI to ADD by SUVR at 1 to less than 2 years follow‐up.
Figures and Tables -
Test 3

MCI to ADD by SUVR at 1 to less than 2 years follow‐up.

MCI to any form of dementia.
Figures and Tables -
Test 4

MCI to any form of dementia.

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

Figures and Tables -
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
Table Tests. Data tables by test

Test

No. of studies

No. of participants

1 MCI to ADD by visual assessment from 2 to less than 4 years of follow‐up Show forest plot

1

47

2 MCI to ADD by visual assessment from 1 to less than 2 years follow‐up Show forest plot

1

401

3 MCI to ADD by SUVR at 1 to less than 2 years follow‐up Show forest plot

1

401

4 MCI to any form of dementia Show forest plot

1

5

Figures and Tables -
Table Tests. Data tables by test