Blood Flow in the Parkinson’s Brain Stays Stable Over Two Years Even as Dopamine Markers Decline

Researchers using a single positron emission tomography imaging protocol have mapped how relative cerebral blood flow behaves in Parkinson’s disease, both at a single point in time and over two years, and compared it with the concurrent loss of dopamine transporter availability. The study, published in EJNMMI Research, reports that blood flow is reduced in the striatum and occipital cortex of people with Parkinson’s disease, tracks positively with dopamine transporter availability, and remains remarkably stable over a two-year follow-up period.

The team quantified relative cerebral blood flow, expressed as R1, together with dopamine transporter availability, using PET with the radioligand [18F]FE-PE2I. Measurements were made in the striatum, the substantia nigra, and cortical regions, allowing the investigators to examine both the dopaminergic basal ganglia circuitry and broader cortical perfusion in the same scans.

Three cohorts formed the basis of the analysis. A cross-sectional group included 38 subjects with Parkinson’s disease and 35 age- and gender-matched controls. A separate test-retest cohort of 9 Parkinson’s disease subjects allowed the reproducibility of the blood flow measurements to be assessed. A longitudinal cohort of 19 subjects was followed to estimate annual longitudinal changes in relative cerebral blood flow over a two-year interval.

In the cross-sectional comparison, Parkinson’s disease subjects showed significantly lower R1 in the striatum, at 0.94 ± 0.08 compared with 1.05 ± 0.11 in controls (p < 0.001), and in the occipital cortex, at 0.99 ± 0.07 versus 1.04 ± 0.07 (p = 0.006). These reductions indicate that perfusion is diminished not only in the deep nuclei central to the disease’s motor pathology but also in posterior cortical territory.

The relationship between blood flow and dopamine transporter availability was positive in both groups. In Parkinson’s disease subjects, low to moderate positive correlations were found in the striatum and substantia nigra, with r² values of 0.41 and 0.30 respectively (p < 0.001). Controls showed correlations of r² = 0.28 in the striatum and r² = 0.42 in the substantia nigra (p < 0.001). The authors interpret this as a positive association between the two measures rather than a causal relationship, since the analysis was cross-sectional.

Reproducibility of the R1 measurement was assessed in the test-retest cohort. Test-retest variability was 5.06% in the striatum, with a reported range of 4.06% to 6.82%, and 5.41% in the substantia nigra, ranging from 4.38% to 9.33%. Across cortical regions, variability was lower, ranging from 1.47% (range 0.85% to 3.72%) to 2.80% (range 1.23% to 4.42%). These figures indicate adequate test-retest reproducibility, with cortical measurements being the most stable.

Over the two-year follow-up, annual longitudinal changes in relative cerebral blood flow were modest. In the striatum the change was 1.95% per year (range 0.48% to 4.21%), while in the substantia nigra it was −0.47% (range −2.42% to 4.60%). Across cortical regions the annual change ranged from 0.92% (range −0.37% to 1.35%) to 1.17% (range 0.41% to 3.46%). Notably, these longitudinal changes were smaller than the test-retest variability itself, which the authors take to suggest relative stability of blood flow despite progressive dopamine transporter loss.

The study was prospectively registered in the EudraCT database under three registrations, dated 2011, 2017 and 2017. The authors conclude that relative cerebral blood flow is reduced in the striatum and occipital cortex in Parkinson’s disease, correlates positively with dopamine transporter availability, and shows adequate reproducibility, while remaining comparatively stable over a two-year interval. Because the longitudinal cohort comprised 19 subjects and the test-retest cohort only 9, the precision of the annual change estimates is limited, and the reported confidence ranges reflect that uncertainty. The findings characterise the behaviour of a perfusion marker measured alongside a dopaminergic marker in the same PET scans, rather than establishing a clinical outcome or treatment effect.

Subject of Research: Relative cerebral blood flow measured with [18F]FE-PE2I PET in Parkinson's disease, including cross-sectional differences, test-retest reproducibility and two-year longitudinal change.

Article Title: Cross sectional, test-retest and longitudinal changes of relative cerebral blood flow in Parkinson's disease

Article References: Oh, M., Jonasson, M., Kerstens, V., & Varrone, A. (2026). Cross sectional, test-retest and longitudinal changes of relative cerebral blood flow in Parkinson's disease. EJNMMI Research. https://doi.org/10.1186/s13550-026-01495-9

Image Credits: AI Generated

DOI: 10.1186/s13550-026-01495-9

Keywords: Parkinson's disease, relative cerebral blood flow, PET, [18F]FE-PE2I, dopamine transporter, striatum, substantia nigra, test-retest variability, longitudinal change, R1, occipital cortex, EJNMMI Research