1. Cochrane Database Syst Rev. 2015 Jan 28;1:CD010632. doi:
10.1002/14651858.CD010632.pub2.

¹⁸F-FDG PET for the early diagnosis of Alzheimer's disease dementia and other
dementias in people with mild cognitive impairment (MCI).

Smailagic N(1), Vacante M, Hyde C, Martin S, Ukoumunne O, Sachpekidis C.

Author information: 
(1)Institute of Public Health, University of Cambridge, Forvie Site, Robinson
Way, Cambridge, UK, CB2 0SR.

BACKGROUND: ¹⁸F-FDFG uptake by brain tissue as measured by positron emission
tomography (PET) is a well-established method for assessment of brain function in
people with dementia. Certain findings on brain PET scans can potentially predict
the decline of mild cognitive Impairment (MCI) to Alzheimer's disease dementia or
other dementias.
OBJECTIVES: To determine the diagnostic accuracy of the ¹⁸F-FDG PET index test
for detecting people with MCI at baseline who would clinically convert to
Alzheimer's disease dementia or other forms of dementia at follow-up.
SEARCH METHODS: We searched the Cochrane Register of Diagnostic Test Accuracy
Studies, MEDLINE, EMBASE, Science Citation Index, PsycINFO, BIOSIS previews,
LILACS, MEDION, (Meta-analyses van Diagnostisch Onderzoek), DARE (Database of
Abstracts of Reviews of Effects), HTA (Health Technology Assessment Database),
ARIF (Aggressive Research Intelligence Facility) and C-EBLM (International
Federation of Clinical Chemistry and Laboratory Medicine Committee for
Evidence-based Laboratory Medicine) databases to January 2013. We checked the
reference lists of any relevant studies and systematic reviews for additional
studies.
SELECTION CRITERIA: We included studies that evaluated the diagnostic accuracy of
¹⁸F-FDG PET to determine the conversion from MCI to Alzheimer's disease dementia 
or to other forms of dementia, i.e. any or all of vascular dementia, dementia
with Lewy bodies, and fronto-temporal dementia. These studies necessarily employ 
delayed verification of conversion to dementia and are sometimes labelled as
'delayed verification cross-sectional studies'.
DATA COLLECTION AND ANALYSIS: Two blinded review authors independently extracted 
data, resolving disagreement by discussion, with the option to involve a third
review author as arbiter if necessary. We extracted and summarised graphically
the data for two-by-two tables. We conducted exploratory analyses by plotting
estimates of sensitivity and specificity from each study on forest plots and in
receiver operating characteristic (ROC) space. When studies had mixed thresholds,
we derived estimates of sensitivity and likelihood ratios at fixed values (lower 
quartile, median and upper quartile) of specificity from the hierarchical summary
ROC (HSROC) models.
MAIN RESULTS: We included 14 studies (421 participants) in the analysis. The
sensitivities for conversion from MCI to Alzheimer's disease dementia were
between 25% and 100% while the specificities were between 15% and 100%. From the 
summary ROC curve we fitted we estimated that the sensitivity was 76% (95%
confidence interval (CI): 53.8 to 89.7) at the included study median specificity 
of 82%. This equates to a positive likelihood ratio of 4.03 (95% CI: 2.97 to
5.47), and a negative likelihood ratio of 0.34 (95% CI: 0.15 to 0.75). Three
studies recruited participants from the same Alzheimer's Disease Neuroimaging
Initiative (ADNI) cohort but only the largest ADNI study (Herholz 2011) is
included in the meta-analysis. In order to demonstrate whether the choice of ADNI
study or discriminating brain region (Chételat 2003) or reader assessment (Pardo 
2010) make a difference to the pooled estimate, we performed five additional
analyses. At the median specificity of 82%, the estimated sensitivity was between
74% and 76%. There was no impact on our findings. In addition to evaluating
Alzheimer's disease dementia, five studies evaluated the accuracy of ¹⁸F-FDG PET 
for all types of dementia. The sensitivities were between 46% and 95% while the
specificities were between 29% and 100%; however, we did not conduct a
meta-analysis because of too few studies, and those studies which we had found
recruited small numbers of participants. Our findings are based on studies with
poor reporting, and the majority of included studies had an unclear risk of bias,
mainly for the reference standard and participant selection domains. According to
the assessment of Index test domain, more than 50% of studies were of poor
methodological quality.
AUTHORS' CONCLUSIONS: It is difficult to determine to what extent the findings
from the meta-analysis can be applied to clinical practice. Given the
considerable variability of specificity values and lack of defined thresholds for
determination of test positivity in the included studies, the current evidence
does not support the routine use of ¹⁸F-FDG PET scans in clinical practice in
people with MCI. The ¹⁸F-FDG PET scan is a high-cost investigation, and it is
therefore important to clearly demonstrate its accuracy and to standardise the
process of ¹⁸F-FDG PET diagnostic modality prior to its being widely used. Future
studies with more uniform approaches to thresholds, analysis and study conduct
may provide a more homogeneous estimate than the one available from the included 
studies we have identified.

PMID: 25629415  [PubMed - in process]