Longitudinal FDG-PET Metabolic Change Along the Lewy Body Continuum
Authors: Ferreira Daniel , Przybelski Scott A. , Lesnick Timothy G. , Diaz-Galvan Patricia , Schwarz Christopher G. , Murray Melissa M. , Dickson Dennis W. , Nguyen Aivi , Reichard Ross R. , Senjem Matthew L. , Gunter Jeffrey L. , Jack Clifford R. , Min Paul H. , Jain Manoj K. , Miyagawa Toji , Forsberg Leah K. , Fields Julie A. , Savica Rodolfo , Graff-Radford Jonathan , Ramanan Vijay K. , Jones David T. , Botha Hugo , St. Louis Erik K. , Knopman David S. , Graff-Radford Neill R. , Day Gregory S. , Ferman Tanis J. , Kremers Walter K. , Petersen Ronald C. , Boeve Bradley F. , Lowe Val J. , Kantarci Kejal 
Published: January 2025

Importance

Although 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a well-established cross-sectional biomarker of brain metabolism in dementia with Lewy bodies (DLB), the longitudinal change in FDG-PET has not been characterized.

Objective

To investigate longitudinal FDG-PET in prodromal DLB and DLB, including a subsample with autopsy data, and report estimated sample sizes for a hypothetical clinical trial in DLB.

Design, Setting, and Participants

Longitudinal case-control study with mean (SD) follow-up of 3.8 (2.3) years. Cases were recruited consecutively between 2007 and 2022 at a referral center and among the population. Patients with probable DLB or mild cognitive impairment with Lewy bodies (MCI-LB) were included. Individuals without cognitive impairment were included from a population-based cohort balanced on age and sex for comparison. All participants completed at least 1 follow-up assessment by design.

Exposure

Patients with MCI-LB and DLB.

Main Outcomes and Measures

Rate of change in FDG-PET was assessed as standardized uptake value ratios (SUVr). Clinical progression was assessed with the Clinical Dementia Rating Sum of Boxes (CDR-SB) score.

Results

Thirty-five patients with probable DLB, 37 patients with MCI-LB, and 100 individuals without cognitive impairment were included. The mean (SD) age of the DLB and MCI-LB groups combined (n = 72) was 69.6 (8.2) years; 66 patients (92%) were men and 6 (8%) were women. At follow-up, 18 participants (49%) with MCI-LB had progressed to probable DLB. Patients with MCI-LB had a faster decline in FDG-SUVr, compared with that of participants without cognitive impairment, in the posterior cingulate, occipital, parietal, temporal, and lateral frontal cortices. The same regions showed greater metabolic decline in patients with DLB than in participants without cognitive impairment, with the addition of anterior-middle cingulate, insula, and medial frontal orbital cortices. Rates of change in FDG-PET in these brain regions were combined into a region of interest (ROI) labeled longitudinal FDG-PET LB meta-ROI. The rate of change in FDG-SUVr in the meta-ROI correlated with the rate of change in CDR-SB, and sample size estimates were reported for potential clinical trials in DLB. Findings were confirmed in the subsample with neuropathologic confirmation (n = 20).

Conclusions and Relevance

This study found that brain hypometabolism begins to evolve during the prodromal stages of DLB with changes paralleling symptomatic progression. These data may inform clinical practice and trials planning to use FDG-PET for biologic staging, monitoring disease progression, and potentially assessing treatment response.