In the UK, dementia affects 5% of the population aged over 65 years and 25% of those over 85 years. Frontotemporal dementia (FTD) represents one subtype and is thought to account for up to 16% of all degenerative dementias. Although the core of the diagnostic process in dementia rests firmly on clinical and cognitive assessments, a wide range of investigations are available to aid diagnosis.

Regional cerebral blood flow (rCBF) single-photon emission computed tomography (SPECT) is an established clinical tool that uses an intravenously injected radiolabelled tracer to map blood flow in the brain. In FTD the characteristic pattern seen is hypoperfusion of the frontal and anterior temporal lobes. This pattern of blood flow is different to patterns seen in other subtypes of dementia and so can be used to differentiate FTD.

It has been proposed that a diagnosis of FTD, (particularly early stage), should be made not only on the basis of clinical criteria but using a combination of other diagnostic findings, including rCBF SPECT. However, more extensive testing comes at a financial cost, and with a potential risk to patient safety and comfort.

To determine the diagnostic accuracy of rCBF SPECT for diagnosing FTD in populations with suspected dementia in secondary/tertiary healthcare settings and in the differential diagnosis of FTD from other dementia subtypes.

Our search strategy used two concepts: (a) the index test and (b) the condition of interest. We searched citation databases, including MEDLINE (Ovid SP), EMBASE (Ovid SP), BIOSIS (Ovid SP), Web of Science Core Collection (ISI Web of Science), PsycINFO (Ovid SP), CINAHL (EBSCOhost) and LILACS (Bireme), using structured search strategies appropriate for each database. In addition we searched specialised sources of diagnostic test accuracy studies and reviews including: MEDION (Universities of Maastricht and Leuven), DARE (Database of Abstracts of Reviews of Effects) and HTA (Health Technology Assessment) database.

We requested a search of the Cochrane Register of Diagnostic Test Accuracy Studies and used the related articles feature in PubMed to search for additional studies. We tracked key studies in citation databases such as Science Citation Index and Scopus to ascertain any further relevant studies. We identified ‘grey’ literature, mainly in the form of conference abstracts, through the Web of Science Core Collection, including Conference Proceedings Citation Index and Embase. The most recent search for this review was run on the 1 June 2013.

Following title and abstract screening of the search results, full-text papers were obtained for each potentially eligible study. These papers were then independently evaluated for inclusion or exclusion.

We included both case-control and cohort (delayed verification of diagnosis) studies. Where studies used a case-control design we included all participants who had a clinical diagnosis of FTD or other dementia subtype using standard clinical diagnostic criteria. For cohort studies, we included studies where all participants with suspected dementia were administered rCBF SPECT at baseline. We excluded studies of participants from selected populations (e.g. post-stroke) and studies of participants with a secondary cause of cognitive impairment.

Two review authors extracted information on study characteristics and data for the assessment of methodological quality and the investigation of heterogeneity. We assessed the methodological quality of each study using the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) tool. We produced a narrative summary describing numbers of studies that were found to have high/low/unclear risk of bias as well as concerns regarding applicability. To produce 2 x 2 tables, we dichotomised the rCBF SPECT results (scan positive or negative for FTD) and cross-tabulated them against the results for the reference standard. These tables were then used to calculate the sensitivity and specificity of the index test. Meta-analysis was not performed due to the considerable between-study variation in clinical and methodological characteristics.

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.

Background

This review focused on one type of dementia, frontotemporal dementia (FTD). This neurodegenerative disease affects the frontal and temporal lobes of the brain and accounts for up to 16% of all degenerative dementias. People who have this disease may develop changes in their behaviour, speech or ability to plan. It is important to identify people with FTD correctly as the disease course and response to treatment differs from other dementias such as Alzheimer’s disease.

One test used by healthcare professionals to help make a diagnosis of FTD, is regional cerebral blood flow single photon emission computed tomography (rCBF SPECT). This investigation allows visualisation of blood flow within the brain. In FTD it is thought that the pattern of blood flow to the brain can be used to tell the difference between FTD and other dementias. However, it is not clear whether using rCBF SPECT in this way improves our ability to make an accurate diagnosis of FTD. As all investigations come with a financial cost, it is important that their benefit is known.

Aim: This review assessed the evidence regarding the accuracy of rCBF SPECT in detecting FTD in people with suspected dementia.

Study characteristics

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.

Quality of the evidence

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.

Key findings

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.