FDG PET dementia imaging

1. The Council noted that patient co-morbidities may impact on the clinical utility of FDGPET, for example people with poorly controlled diabetes may not be suitable for a glucose-based radiotracer. In these circumstances, SPECT is an appropriate alternative.
2.  Given that the current FDG-PET service is delivered from four centres in Scotland, the Council noted that some people may have to travel for PET scans and this has the potential to create inequalities in access. SPECT is widely available in Scotland.
3. Depending on how many people undergoing investigations for dementia would benefit from FDG-PET scanning, the Council acknowledged that the infrastructure and resource investment could be significant. The PET-CT service is already stretched in Scotland, with approximately 700 scans being done a month (mostly for people with cancer or suspected cancer). Based on the number of people with dementia, or suspected dementia, who are currently referred for a SPECT scan in Scotland, a clinical expert 
   estimated that approximately 20 people per month may be eligible for FDG-PET scanning. This number may change considerably depending on developments in the diagnosis and treatment of dementia, and whether these developments impact the demand for nuclear imaging.
4. The Council agreed that the clinical-effectiveness evidence published since 2018 is limited in quality and quantity. The studies identified focused on diagnostic accuracy, and it is not clear how the addition of FDG-PET to the diagnostic pathway impacts on clinical decision-making, the treatments that patients with dementia are offered, and the outcomes for patients. The heterogeneity between the studies means that robust conclusions are not possible. The Council also recognised the absence of cost-effectiveness evidence.
5. The Council noted that FDG-PET services for dementia are commissioned in NHS England, NHS Wales and NHS Northern Ireland. NHSScotland does not commission FDG-PET services for dementia even though the guidance in place in NHSScotland matches the guidance in the other UK nations. The Council also noted a lack of available information on the impact of FDG-PET for dementia diagnosis in other parts of the UK, either service delivery implications or patient outcomes.
6. The Council noted that the diagnosis and treatment landscape for dementia is evolving rapidly. In addition to the possible availability of disease-modifying dementia drugs in 
   the coming years, other areas of potential development include the application of precision medicine. Given this fast-changing landscape, it is difficult to predict exactly how the demand for nuclear imaging for dementia will change in the near future.
7. The Council recognised that the experience for patients undergoing an FDG-PET or SPECT scanning may differ, but that both scans are likely to create an additional stress for people who may already feel they are in a difficult and frightening place. The Council reiterated that scans should only be used when there is a likely impact on patient management decisions.
8. Following insight from a topic expert, the Council noted:
   • there is a need for good quality evidence, particularly evidence that directly compares perfusion SPECT with FDG-PET in this patient group
   • there is a need to consider why the service in NHSScotland differs from the other UK nations
   • FDG-PET scans generally take 10 minutes, whereas SPECT scans take approximately 30 to 45 minutes
   • FDG-PET scan images are generally easier to report on, compared with SPECT scan images
   • the images produced from SPECT scanning have improved over the years as the technology advances, but we cannot be confident how image quality compares with FDG-PET image quality. 

1. In 2023, the Scottish Intercollegiate Guidelines Network (SIGN) published a guideline on the assessment, diagnosis, care and support for people with dementia and their carers. The guideline included clinical effectiveness evidence on the use of FDG-PET and SPECT, based on an evidence review conducted by the National Institute for Health and Care Excellence (NICE) in 2018. This SHTG Recommendation updates the clinical effectiveness evidence on FDG-PET and SPECT presented by SIGN. Consideration has also been given to cost effectiveness, organisational issues and patient issues.

This SHTG Recommendation summarises studies on the use of FDG-PET and SPECT for predicting which people with MCI go on to develop dementia, and for differentiating between subtypes of dementia.

Predicting the progression from MCI to dementia
FDG-PET

2. For predicting progression from MCI to clinically diagnosed AD, a high-quality systematic review from 2018 (studies published between 1999 and 2017) reported that diagnostic accuracy results for FDG-PET varied across studies (sensitivity 25% to 100% and 
specificity 15% to 100%). A systematic review from 2024, which included more up-to-date studies, reported that sensitivities in predicting progression from MCI to clinically or neuropathologically diagnosed dementia (mainly AD) ranged from 43% to 100%, and 
specificities from 63% to 94%. The wide range of values was due to heterogeneity between studies in how images were assessed, how studies were conducted and differences in study populations.

SPECT
3. For predicting the progression from MCI to AD, one lower-quality systematic review with meta-analyses evaluated the accuracy of SPECT and FDG-PET (studies published between 1998 and 2006). Five of the included studies were on FDG-PET and four were on SPECT. The authors reported that the sensitivity (81%) and specificity (74%) values for SPECT imaging were lower than the sensitivity (87%) and specificity (89%) values for FDG-PET. Limitations with the review mean that the results of the meta-analyses should be treated with caution.

Differentiating subtypes of dementia
FDG-PET
4. For differentiating subtypes of dementia, a high-quality systematic review from 2020 (three cohort studies published between 2007 and 2011) evaluated the accuracy of FDG-PET for distinguishing neuropathologically confirmed AD from non-AD.In two studies (n=182), the median sensitivity and specificity of FDG-PET for distinguishing between AD and non-AD was 89% (range 84% to 94%) and 74% (range 73% to 74%), respectively. For distinguishing between AD and frontotemporal lobar degeneration (FTLD), one study (n=45) reported median sensitivity and specificity for FDG-PET of 97% (range 96% to 98%) and 66% (range 59% to 73%), respectively. Based on these findings, the authors concluded that FDG-PET was highly sensitive and moderately specific for diagnoses of neuropathologically confirmed AD. A systematic review from 2024 (14 studies published between 2007 and 2021) using clinically (rather than neuropathologically) diagnosed dementia subtype as the reference standard reported similar sensitivity and specificity results to the 2020 review for distinguishing between AD and non-AD or FTLD.
 
SPECT
5. For differentiating subtypes of dementia, a high-quality systematic review from 2020 (three studies published between 2007 and 2011, n=205), evaluated the use of SPECT to distinguish confirmed AD (based on postmortem examination) from various non-AD neuropathologic diagnoses.6 Median sensitivity was 63% (range 57% to 94%) and median specificity was 83% (range 76% to 92%).

Primary studies directly comparing FDG-PET and SPECT
6. We identified a 2020 retrospective observational study that directly compared FDG-PET with SPECT in diagnosing AD in people with MCI and dementia. The reference standard was an amyloid-PET scan.8 The sensitivity of FDG-PET and SPECT was 76% versus 43% (p<0.001), while specificity was 74% versus 83% (p=0.45). While these findings are broadly in concordance with the results from the systematic reviews, they must be treated with 
caution given the study limitations.

Economic evidence
7. We did not identify any economic evidence comparing FDG-PET with SPECT imaging for the diagnosis of dementia.

Patient issues
8. We identified one study which included a survey of 98 people (68 with dementia and 30 controls) who had an FDG-PET and SPECT scan.
9 Results suggested that both types of scan are generally acceptable to patients, and that perceived diagnostic accuracy tended to dictate preferences for one scan over the other.

Organisational issues
9. The PET-CT service in NHSScotland is in high demand and expansion of the service to include dementia imaging will require infrastructure and resource investment to ensure that scanning capacity for other patients (for example, people with cancer) is not 
negatively affected. Existing barriers to use of PET-CT for dementia imaging include a lack of spare capacity for scans as well as the production and supply of radioisotopes.
 

What were we asked to look at?
The Scottish Clinical Imaging Network (SCIN) asked us to assess the clinical and cost effectiveness of FDG-PET imaging, compared with HMPAO (99mTc labelled hexamethylpropyleneamine oxime)-SPECT imaging, in the diagnosis of dementia.

Why is this important?
A clinical diagnosis of dementia is based on information from different sources. An accurate diagnosis of the subtype of dementia is important, as patients with specific subtypes follow distinct clinical courses and responses to medication. Patients undergoing assessment for dementia may benefit from functional imaging to help clarify their diagnosis. In Scotland, the patients who may benefit from functional imaging are usually offered a perfusion SPECT scan, using the radiotracer HMPAO.
 
The SCIN considers FDG-PET a superior imaging tool, compared with perfusion SPECT, in this patient group. They also noted that while perfusion SPECT is widely available in Scotland, access to FDG-PET for people with dementia is extremely limited. A SCIN National PET-CT Review Group is considering which clinical indications would be relevant for potential PET-CT service expansion. This SHTG Recommendation will help inform a decision on whether dementia should be included within the list of indications.