Abstract: Eleven studies (1117 participants) met our inclusion criteria. These consisted of six case-control studies, two retrospective cohort studies and three prospective cohort studies. Three studies used single-headed camera SPECT while the remaining eight used multiple-headed camera SPECT. Study design and methods varied widely. Overall, participant selection was not well described and the studies were judged as having either high or unclear risk of bias. Often the threshold used to define a positive SPECT result was not predefined and the results were reported with knowledge of the reference standard. Concerns regarding applicability of the studies to the review question were generally low across all three domains (participant selection, index test and reference standard). Sensitivities and specificities for differentiating FTD from non-FTD ranged from 0.73 to 1.00 and from 0.80 to 1.00, respectively, for the three multiple-headed camera studies. Sensitivities were lower for the two single-headed camera studies; one reported a sensitivity and specificity of 0.40 (95% confidence interval (CI) 0.05 to 0.85) and 0.95 (95% CI 0.90 to 0.98), respectively, and the other a sensitivity and specificity of 0.36 (95% CI 0.24 to 0.50) and 0.92 (95% CI 0.88 to 0.95), respectively. Eight of the 11 studies which used SPECT to differentiate FTD from Alzheimer's disease used multiple-headed camera SPECT. Of these studies, five used a case-control design and reported sensitivities of between 0.52 and 1.00, and specificities of between 0.41 and 0.86. The remaining three studies used a cohort design and reported sensitivities of between 0.73 and 1.00, and specificities of between 0.94 and 1.00. The three studies that used single-headed camera SPECT reported sensitivities of between 0.40 and 0.80, and specificities of between 0.61 and 0.97. At present, we would not recommend the routine use of rCBF SPECT in clinical practice because there is insufficient evidence from the available literature to support this. Further research into the use of rCBF SPECT for differentiating FTD from other dementias is required. In particular, protocols should be standardised, study populations should be well described, the threshold for 'abnormal' scans predefined and clear details given on how scans are analysed. More prospective cohort studies that verify the presence or absence of FTD during a period of follow up should be undertaken.

Plain-language summary: We searched many databases for all papers with FTD and rCBF SPECT as their focus. These papers were reviewed independently by several researchers. After application of inclusion and exclusion criteria, eleven studies including 299 individuals with FTD were available for this review. The studies were published over a 21-year period, with a study size ranging from 27 to 363 participants, mainly recruited from University clinics, tertiary referral centres or memory clinics. Of the 11 studies, three used single-headed (single detector) gamma cameras, a method no longer used in clinical practice today. Evidence is current to June 2013. The majority of studies were at high risk of bias due to insufficient details on how participants were selected and how the rCBF SPECT scans were conducted and analysed. The main limitations of the review were poor reporting, variability of study design and a lack of standardisation of image interpretation between centres. Due to small study numbers and large variation in how the studies were carried out, we are unable at present to recommend the routine use of rCBF SPECT for diagnosing FTD in clinical practice.