A Cochrane review on brain 18F-FDG PET in dementia: limitations and future perspectives

[18F]FDG PET is a well-established method for the evaluation
of patients with suspected Alzheimer's disease (AD) and other
neurodegenerative diseases [1]. This tool has the unique ability
to estimate the local cerebral metabolic rate of glucose
consumption (CMRgl), thus providing information on the distribution
of neuronal death and synapse dysfunction in vivo
[2]. Clinically, [18F]FDG PET plays a major role in the early
and differential diagnosis of dementia due to AD by showing
specific disease patterns of hypometabolism, reflecting neuronal
dysfunction in affected brain regions even in the earliest
stages of the disease [1]. However, the role of [18F]FDG PET
in identifying patients affected by AD but who are still at the
stage of mild cognitive impairment (MCI) is less established.
Although various studies have indicated a high predictive value
in this population, appropriate standardization approaches
(i.e. semiquantification methods, observer-independent analyses,
identification of cut-off values) and the value of [18F]FDG
PET in comparison to amyloidosis biomarkers are still a matter
of debate.
Recently, a Cochrane review was published with the objective
of determining the diagnostic accuracy of [18F]FDG PET
for identifying subjects with MCI who will clinically convert
toADor other dementias [3]. The authors concluded that there
is no evidence supporting routine clinical use of [18F]FDG
PET to identify those patients with MCI who will develop
AD. For several reasons, we do not agree with the authors of
this Cochrane review that existing data on the value of FDG
PET in MCI supports such a categorical conclusion. Indeed,
clear variability in diagnostic performance of [18F]FDG PET
is found in the literature, as correctly reported in the Cochrane
review. This variability, however, is not exclusively attributable
to the method itself, but rather can be explained by a
number of factors concerning study design, definitions of
MCI itself and data analysis procedures.
We would like to highlight some of these factors in greater
detail, because we believe that knowledge on these issues may
be necessary to correctly interpret the available literature and
to appreciate the diagnostic value of [18F]FDG PET in MCI.