Positron emission tomography in combination with computed tomography (PET/CT) in minimal cognitive impairment and dementias

PICHON RIVIERE, A.; AUGUSTOVSKI, F.; GARCIA MARTI, S.; GLUJOVSKY, D.; ALCARAZ, A.; LOPEZ, A.; BARDACH, A.; CIAPPONI, A; REY-ARES, L.; ROJAS, J

Documento de Evaluación de Tecnologías Sanitarias

IECS

Año: 2012 p. 1 - 30

1668-2793

Dementia is a progressive clinical syndrome and is non reversible to some extent. Alzheimer´s disease is its most common manifestation representing approximately two thirds of all the cases. At present, diagnosis is based on a careful history taking, physical, neurological and mental examination as well as complementary lab tests and neurologic imaging exams both computed tomography (CT) and magnetic resonance (MRI). It has been many years since the use of PET in combination with computed tomography (PET/CT) has been proposed in patients with dementia, especially in Alzheimer´s disease (AD) which would be of substantial importance to be able to early diagnose this disease and consequently lead to improvement in health and quality of life results in subjects with AD and other dementias.TechnologyPositron Emission Tomography (PET) is a nuclear medicine imaging procedure that uses radioactive contrast agents to capture and measure biochemical processes taking place within tissues. PET may be complemented with other imaging procedures such as radiographies, computed tomography (CT) or MRI, among others. As with other nuclear medicine procedures, PET defines the disease in terms of quantitative abnormal regional chemistry. Simply, this PET technique is a highly specialized process that uses radiolabeled substances of mean short life to assess the level of metabolic activity and perfusion in several human body organs and systems. In combination with CT scan it allows to reconstruct the image both from the metabolic and the structural functional perspective.PurposeThe purpose of this report is to assess the diagnostic and/or prognostic usefulness of PET in combination with CT (PET/CT) in patients with minimal cognitive impairment (MCI) and neurodegenerative dementias.MethodsA bibliographic search was carried out on the main databases: DARE, NHS EED, on Internet general search engines, in health technology evaluation agencies and health sponsors. Priority was given to the inclusion of systematic reviews; controlled, randomized clinical trials (RCTs); health technology assessments and economic evaluations; clinical practice guidelines and coverage policies of other health systems.ResultsPET in patients with mild to moderate dementiaDiagnostic and prognostic usefulnessThirty-two studies evaluated the use of PET in patients with mild to moderate dementia. Nineteen of them were aimed at evaluating the specificity and sensitivity of PET in the differential diagnosis of patients with AD versus other dementias and the remaining 13 assessed patients with AD versus control subjects. One study evaluated the role of PET/CT to predict progression of cognitive impairment in affected patients.The most important ones, due to methodological features including the study multicenter design and the number of included patients, refer to a study that analyzed the diagnostic usefulness of PET in 129 patients referred for evaluation of mild, moderate and severe dementia. PET was compared with the clinical diagnostic criteria for dementia, which also included the conduct of complementary studies to rule out other etiologies in the dementia process. The study found 75% sensitivity for the diagnosis of DA, 88% for its moderate form and 92% for its severe form. Another multicenter study conducted on 284 patients that compared the test with the clinical and complementary information for the diagnosis of dementia as well as with anatomopathological data found 94% sensitivity and 73% specificity for AD diagnosis and 95% and 71% for dementia episodes respectively. Another multicenter study including 548 patients evaluated the usefulness of PET in differentiating AD from other neurodegenerative dementias. PET showed a diagnostic accuracy of 96% in differentiating patients with cognitive impairment from those without impairment, with no differences in accuracy as to the mild and moderate/stage of dementia. In the diagnosis of DA, its sensitivity was 90% with a 71% specificity while it was approximately 88% (85-99% CI 95%) and 73% (18-86% CI 95%), respectively. One study evaluated the prognostic role of PET in patients with dementia; this technique showed a 91% sensitivity (85-97% 95% CI) and a 75% specificity (64-86% 95% CI) for predicting which patients would progress to cognitive impairment from those who would not in the following months. The rest of the studies are described in the full text of this report.PET/CT in patients with MCIAlthough several studies included patients with mild cognitive impairment, only two carried out the stratified analysis of this population. One longitudinal study on 30 patients with MCI showed a 92% sensitivity and a 89% specificity of PET using 18 FDG in early AD diagnosis in patients with MCI, while the other study which included 39 patients with probable AD and 40 healthy subjects, reported a 94% sensitivity and 99% specificity respectively for MCI diagnosis.PET/CT in patients with dementia under 65 years old and rapidly progressing dementiasNo studies distinctly evaluating this group of patients and the diagnostic/prognostic value of PET/CT were found.Coverage PoliciesMany health sponsors do not cover the diagnostic use of PET in AD while the American Academy of Neurology states that although PET seems to be promising, more quality evidence is required to determine the actual role that it might have in the diagnosis of dementias.ConclusionsAlthough studies have shown a high sensitivity as well as specificity, this is not significantly higher than the one obtained with the method currently used in the clinical practice. Considering that the sensitivity of the clinical criteria for dementia diagnosis as well as the differential diagnosis is approximately 80%-90%, it is difficult that this procedure (PET/CT) may further improve the diagnostic process and, if so, it might be at the expense of a low marginal benefit and a very high cost; therefore the evidence on this field and the precise determination of its usefulness in this process should be determined before endorsing the use of this technology in dementias.