Optimizing 2-[18F]-FDG-PET in the diagnosis of dementia disorders.

The studies in this PhD project aimed at optimizing the clinical value of 2-[18F]FDG-PET in the diagnosis of dementia disorders by proposing three disease-specific 2-[18F]FDG-PET biomarkers and evaluating the clinical value of 2-[18F]FDG-PET against commonly used biomarkers. 

Early and accurate diagnosis of dementia is essential to establish proper treatment, support, and care. However, the clinical diagnosis may be complicated by a clinicopathological heterogeneity in Alzheimer's dis¬ease and other dementias together with a considerable overlap between the dementia diseases. 

2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (2-[18F]FDG-PET) has achieved an emerging supportive role in dementia diagnostic as distinctive metabolic patterns are specific for both Alzheimer's disease, dementia with Lewy bodies and frontotemporal dementia. 

The addition of biomarkers such as 2-[18F]FDG-PET and cerebrospinal fluid biomarkers are recommended, if clinical diagnosis is uncertain after standard diagnostic assessment. However, there is limited knowledge on how to weigh, combine and interpret the biomarkers across the spectrum of dementia diseases. Another challenge is the growing amount of extensive and complex patient data, which potentially result in underutilization of important diagnostic information. 

The studies in this PhD project aimed at optimizing the clinical value of 2-[18F]FDG-PET in the diagnosis of dementia disorders by proposing three disease-specific 2-[18F]FDG-PET biomarkers an evaluating the clinical value of 2-[18F]FDG-PET against commonly used biomarkers. 

In study I, the objective was to compare the added clinical value of cerebrospinal fluid biomarkers and 2-[18F]FDG-PET to a standard diagnostic program in a routine clinical setting. The study population consisted of 81 subjects suspected of having Alzheimer's disease, who were examined with a standard diagnostic program, 2-[18F]FDG-PET and cerebrospinal fluid biomarkers as part of the clinical work-up. The clinical value on diagnosis, prognosis and patient management was comparable for the two biomarkers across all diagnoses when added individually to the standard diagnostic program. However, the clinical value for correctly classified Alzheimer's disease patients was higher for cerebrospinal fluid biomarkers than for 2-[18F]FDG-PET. 

In study II, the objective was to develop and evaluate a visual rating scale for cingulate island sign on 2-[18F]FDG-PET to support the diagnosis of dementia with Lewy bodies and differentiating from Alzheimer's disease. The study population consisted of 35 patients with dementia with Lewy bodies, 36 patients with Alzheimer's disease and 23 controls. The visual rating scale for cingulate island sign was able to significantly differentiate patients with dementia with Lewy bodies from patients with Alzheimer's disease and controls. 

In study III, the objective was to evaluate the value of 2-[18F]FDG-PET biomarkers to commonly used diagnostic tests in the differential diagnosis of dementia using a data-driven decision model. In addition, two automated disease-specific 2-[18F]FDG-PET biomarkers were proposed, i.e. API-PET and occipital vs. temporal index, to improve the diagnostic accuracy for frontotemporal dementia and dementia with Lewy bodies, respectively. 

The study population consisted of 259 subjects diagnosed with either Alzheimer's dis¬ease, dementia with Lewy bodies, frontotemporal dementia, vascular dementia, or subjective cogn tive decline. The addition of 2-[18F]FDG-PET biomarkers to the other diagnostic tests improved the classification accuracy for both frontotemporal dementia and dementia with Lewy bodies. Moreover, API-PET and occipital vs. temporal index improved the accuracy for frontotemporal dementia and dementia with Lewy bodies. 

In conclusion, the addition of 2-[18F]FDG-PET was valuable in the clinical decision-making. Particularly, the proposed visual rating scale for cingulate island sign showed promising results for distinguishing dementia with Lewy bodies from Alzheimer's dis¬ease. In addition, the two automated disease-specific 2-[18F]FDG-PET biomarkers for identifying dementia with Lewy bodies and frontotemporal dementia had potential for improving the differentiation from Alzheimer's dis-ease. Future prospective studies are needed to validate the proposed visual rating scale for cingulate island sign and the automated disease-specific 2-[18F]FDG-PET biomarkers.