The use of PET using FDG for the evaluation of dementia or Alzheimer's does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.

 

For contracts without primary coverage criteria, the use of PET for the evaluation of dementia or Alzheimer's is considered investigational.  Investigational services are an exclusion in the member certificate of coverage.

 

PET Scans (Positron Emission Tomography) for any diagnosis other than those that are addressed through specific policy are not covered based on benefit certificate primary coverage criteria for effectiveness.

 

For contracts without primary coverage criteria, PET Scans (Positron Emission Tomography) for any diagnosis other than those that are addressed through specific policy are considered investigational and are not covered.    Investigational services are exclusion in the member certificate of coverage.

 

Specific coverage policies are listed individually.

This Policy references four Blue Cross Blue Shield Association Technology Evaluation Center Assessments on miscellaneous applications of PET.

 

An updated literature search was performed in 2003 using MEDLINE (via PubMed) and the Medical Subject Heading® (MeSH®) term “emission-controlled tomography” as a major heading but excluding studies focused on neoplasms or cardiology applications as well as studies using single photon emission computed tomography. Review was limited to 1998 through 2003, English-language journals, and studies on humans.

 

Recent review articles discuss the potential applications for PET in various neurological and psychological conditions.

 

The role of PET in dementia is an active area for research but is not yet clear.  The Centers for Medicare and Medicaid Services (CMS) issued a decision memorandum on April 16, 2003, that would not support coverage of FDG PET in Alzheimer’s disease (AD) because the evidence did not demonstrate its use improved patient outcomes. This decision was based, in part, on a technology assessment conducted at Duke University through the Agency for Healthcare Research and Quality (AHRQ) Evidence-based Practice Center. This assessment used decision analysis modeling to examine whether the use of FDG PET would improve health outcomes when used for diagnosis of AD in 3 clinical populations:

 

PET was considered to have an 88% sensitivity (79% to 94% = 95% confidence interval [CI]]) and 87% specificity (77% to 93% = 95% CI) for diagnosing AD. The report concludes that outcomes for all 3 groups of patients were better if all patients were treated with agents such as cholinesterase inhibitors rather than using FDG PET to select patients for treatment based on PET results since the complications of treatment were relatively mild and treatment was considered to have some degree of efficacy in delaying the progression of AD. Thus, the adverse effect of not treating subjects with AD who had false-negative PET results was influential in this analysis. However, this conclusion was sensitive to the toxicity associated with treatment.

 

More recently, on October 7, 2003, CMS accepted a petition from University of California at Los Angeles (UCLA), School of Medicine, to reconsider its policy for “use of FDG PET to distinguish patients with AD from those with other causes of symptoms confounding the diagnosis of dementia or to assist with the diagnosis of early dementia in beneficiaries for whom the differential diagnosis includes one or more kinds of neurodegenerative disease, in cases where specific criteria have been met.”  CMS issued a draft of a  decision memo 15 Jun 04 indicating they would cover PET for patients meeting very specific criteria in spite of the following statement from the Duke Evidence Based Center report on FDG-PET for Alzheimer's, requested by CMS and published 30 Apr 04.  "Publications since the prior TA (tech assessment, 2001) do not provide evidence supporting revised estimates of the operating characteristics of PET for discriminating AD from other competing diagnoses…  Three studies suggest FDG-PET could be valuable for distinguishing patients with MIC (mild cognitive impairment) who rapidly convert to frank AD.  Two were relatively small studies that require validation and assessment of incremental value above conventional clinical measures.  A third, larger study of FDG PET for prediction of progression for patients with MCA also suggests a potential role for PET in predicting clinical course for patients with dementia.  However, this study did not comment on findings for patients with AD only, and results for PET, while suggestive of higher sensitivity and specificity, did not differ in a statistically significant manner from clinical findings."  "CMS will continue to work with the National Institute on Aging (NIA), Agency for Healthcare Research and Quality (AHRQ), Alzheimer's Association (AA), device manufacturers, and experts in AD and imaging to develop a large practical clinical trial to address" PET for patients with mild cognitive impairment or early dementia who do not meet their specific coverage criteria.

 

 

 

 

 

 

 

Definitive diagnosis of Alzheimer dementia (AD) requires histopathologic examination of brain tissue obtained by biopsy or autopsy. In practice clinical criteria based on clinical examination, neurological and neuropsychological examinations and interviews with informants are used to diagnose AD by excluding other diseases that can cause similar symptoms and to distinguish AD from other forms of dementia. There are currently no cures or preventive therapies for AD. Early diagnosis might facilitate early\ treatment of cognitive, behavioral and psychiatric symptoms which could perhaps delay functional deficits and improve quality of life. Early diagnosis may be crucial in the future if other therapies become available to treat or slow progression of disease. FDG-PET can demonstrate reduction in glucose metabolism associated with dementia. These changes in metabolism have been shown to be detectable years before the onset of clinical symptoms.6 The changes typically have a characteristic pattern of hypometabolism that could be useful not only in distinguishing AD from normal aging but also from other dementias, psychiatric disorders and cerebrovascular diseases (Mosconi, 2008; Szelies, 1994; Dolan, 1992).

 

A 2015 Cochrane Review intended to determine the diagnostic accuracy of FDG PET for detecting people with mild cognitive impairment (MCI) at baseline who would clinically convert to Alzheimer disease dementia or other forms of dementia at follow-up (Smailagic, 2015). Database searches were performed to January 2013. Included studies evaluated the diagnostic accuracy of FDG PET to determine the conversion from MCI to Alzheimer disease dementia or to other forms of dementia. Sixteen studies (total N=697 participants) were included in the qualitative review and 14 studies (n=421 participants) were included in the analysis. Since there are no accepted thresholds to define PET positivity and studies used mixed thresholds for diagnosis, the authors used a hierarchical summary ROC to derived pooled estimates of performance characteristics at fixed values. 5 studies evaluated the accuracy of FDG PET for all types of dementia.  The sensitivities were between 46% and 95% while the specificities were between 29% and 100%; however, a meta-analysis was precluded because of too few studies with small numbers of participants. The report indicates most studies were poorly reported, and the majority of included studies had an unclear risk of bias, mainly for the reference standard and participant selection domains.

 

In a 2014 systematic review (quality assessment of included studies was not reported), Davison and colleagues (Davison, 2014) included studies reporting diagnostic performance of FDG-PET and SPECT identified through a MEDLINE search of studies published up to Feb 2013. 3 studies (total N=197 patients) used histopathology as reference standard. In patients with or without a clinical diagnosis of Alzheimer disease, sensitivity was 84%, and specificity was 74%; in patients with memory loss or dementia, sensitivity was 94%, and specificity was approximately 70%; in patients undergoing evaluation for dementia sensitivity was 94% and specificity was 73%. Precision estimates were not given. In 3 different studies (271 participants), the sensitivities and specificities of FDG-PET for distinguishing AD and Lewy body dementia ranged from 83% to 99% and from 71% to 93% respectively. And in 2 studies (183 participants), for predicting conversion from MCI to Alzheimer disease, sensitivity versus specificity of PET were 82% and 8957% versus 78% and 8567%, respectively.

 

A 2009 meta-analysis compared the ability of FDG-PET, A 2009 meta-analysis compared the ability of FDG-PET, single-photon emission computed tomography (SPECT), and structural MRI to predict patients’ conversion from MCI to Alzheimer disease (Yuan, 2009). Using 24 articles including 1112 patients identified among studies published between 1990 to April 2008 (6 studies with 280 patients on FDG-PET, published 2001-2005), the authors found no statistically significant difference among the 3 modalities in pooled sensitivity, pooled specificity, or negative likelihood ratio; Results are shown in table 4. There was strong evidence of between-study heterogeneity and marked asymmetry in the funnel plot (with studies missing from the bottom left quadrant), results indicating possible publication bias of studies with null results. Efforts to identify sources of heterogeneity (eg, publication year, age, male-female ratio, follow-up interval, years of education, mean Mini-Mental State Examination [MMSE] score at baseline) yielded no significant results

 

A 2001 technology assessment conducted at Duke University through the Agency for Healthcare Research and Quality (AHRQ) Evidence-based Practice Center used decision-analysis modeling to examine whether the use of FDG-PET would improve health outcomes when used for diagnosis of Alzheimer disease in 3 clinical populations: patients with dementia, patients with MCI, or subjects with no symptoms but with a first-degree relative with Alzheimer disease (Matchar, 2001). For the review, a search was performed using MEDLINE, CINAHL and the HealthSTAR databases from January 1995 to January 2001. 18 articles (1018 participants) were included. Reference standard used in the studies was either histopathology or clinical diagnosis. Studies reported various cutoffs for PET positivity so an un-weighted SROC method was used to calculate the pooled area under the curve. Results are summarized in table 4. The report concluded that outcomes for all 3 groups of patients were better if all patients were treated with agents such as cholinesterase inhibitors rather than using FDG-PET to select patients for treatment based on PET results, because the complications of treatment were relatively mild, and treatment was considered to have some degree of efficacy in delaying the progression of Alzheimer disease.

 

 

Annual policy review completed with a literature search using the MEDLINE database through February 2018. No new literature was identified that would prompt a change in the coverage statement.