A systematic review: 18F-FDG PET in the early diagnosis of degenerative diseases of the central nervous system

Neurodegenerative diseases include a broad group of disorders which are characterized by the presence of cognitive impairment. Alzheimer’s disease is the most prevalent and severe disorder and the most common cause of dementia. Three phases of Alzheimer's disease are recognized, asymptomatic, prodromal and the stage of dementia. 18F-FDG PET has been proposed for the diagnosis of Alzheimer's disease at the prodromal phase although discrepancies have been detected in the introduction of PET radiotracers into diagnostic criteria before the onset of dementia symptoms.

The authors have tried to assess the clinical and analytical validity, safety and clinical utility of 18F-FDG PET in the prodromal phase of Alzheimer's disease and his ability to predict the progression to dementia. Five (5) prospective studies and one (1) systematic review had outcomes regarding analytical and clinical validity, while no documents regarding the safety and efficacy of 18F-FDG PET was found. The literature published 2013-2016 was included in the search; QUADAS-2 tool  and AMSTAR tool were used for quality assessment of the prospective studies and of the systematic reviews, respectively.

In the systematic review studies, the sensitivity and the specificity for detection of people with a lesser cognitive impairment who developed Alzheimer's, dementia ranged 25%-100 % and 15%-100 %, respectively. 

Two studies applied visual evaluation of the PET scan; one of them reported 98% sensitivity and 41% specificity; two studies demonstrated values of accuracy between 53.6% and 68% and two studies reported positive predictive values 20%-60 % and negative predictive values 65.2%-95%. 

The automatized evaluation was reported in four studies, and DOR ranged from 1.74 to 28.2. Three studies reported ranges of values for sensitivity 61%-93%, for specificity from 23%-91%, the positive predictive value 36%-86% and a negative predictive value 73%-81%. 

Inter-rater agreement was presented in one study with a kappa index value of 0.89. No study analyzed the accuracy of technology for diagnosis of other neurodegenerative diseases and differential diagnosis of the AD, although four studies reported results for these conditions. 

Conclusions

• The evidence about the clinical and analytical validity of 18F-FDG PET in patients suffering from prodromal Alzheimer’s disease comes from one (1) systematic review of high quality and five (5) studies of moderate-low quality.
• The systematic review and prospective studies reported heterogeneity in results about clinical validity of 18F-FDG PET.
• One (1) study of high methodological quality, but low statistical power, reported poor clinical validity results of 18F-FDG PET. Three (3) studies of low quality reported discrepancies in results of clinical validity between studies which had several techniques of interpretation of PET scan.
• The evidence about the analytical validity comes from one small study (n=45) that showed a kappa value of k=0.89. This evidence was insufficient to prove concordance in the visual interpretation of images or concordance in software for automated translation.
• Results about safety and effectiveness of 18F-FDG PET were not identified. Thus, the clinical utility could not have been evaluated.
• The localized evidence showed uncertainties about the use of PET 18F-FDG for diagnosis in prodromal Alzheimer’s disease or for differential diagnosis for other neurodegenerative disorders.

See the full report in Spanish (with summary in English) here.

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