Evaluation of glymphatic system activity using diffusion tensor image analysis along the perivascular space and amyloid PET in older adults with objectively normal cognition: a preliminary study

Abstract

ObjectivesDiffusion tensor image analysis along the perivascular space (DTI-ALPS) is a recently introduced method for the assessment of the glymphatic system without the need for contrast injection. The purpose of our study was to assess the glymphatic system in cognitively normal older adults with or without subjective cognitive decline (SCD) using DTI-ALPS, and correlating with amyloid PET.Design and participantsTo evaluate the glymphatic system in cognitively normal older adults using DTI-ALPS, we built a prospective cohort including a total of 123 objectively cognitively normal older adults with or without SCD. The ALPS index was calculated from DTI MRI and was assessed by correlating it with standardized uptake value ratios (SUVRs) from amyloid PET and clinically relevant variables. The study subjects were also divided into amyloid “positive” and “negative” groups based on the result of amyloid PET, and the ALPS indices between those two groups were compared.ResultsThe ALPS index was not significantly different between the normal and SCD groups (P = 0.897). The mean ALPS index from the amyloid positive and amyloid negative group was 1.31 and 1.35, respectively, which showed no significant difference (P = 0.308). Among the SUVRs from variable cortices, that of the paracentral cortex was negatively correlated with the ALPS index (r = −0.218, P = 0.016). Multivariate linear regression revealed that older age (coefficient, −0.007) and higher SUVR from the paracentral cortex (coefficient, −0.101) were two independent variables with a significant association with a lower ALPS index (P = 0.015 and 0.045, respectively).ConclusionDTI-ALPS may not be useful for evaluation of the glymphatic system in subjects with SCD. Older age was significantly associated with lower ALPS index. Greater amyloid deposition in the paracentral cortex was significantly associated with lower glymphatic activity in cognitively normal older adults. These results should be validated in future studies on the relationships between ALPS index and other fundamental compartments in glymphatic system, such as perivenous space and the meningeal lymphatic vessels.

PET/MRI multimodality imaging to evaluate changes in glymphatic system function and biomarkers of Alzheimer’s disease

“…These studies showed that ALPS-index correlated with SUVR in specific cerebral regions in AD patients and CN subjects. Park, et al found a significant linear correlation between DTI-ALPS and [ 18 F]flutemetamol SUVR in the paracentral region of 123 elderly subjects (r = 0.218, P = 0.016), but not in other brain regions 9 . Hsu, et al examined the relationship between ALPS-index and [ 18 F]AV-45 SUVR across various brain regions in 50 participants, finding significant correlations except in the parahippocampal region, though the correlation coefficients were modest 10 .…”

“…DTI data were acquired using two b-values of 1000 and 2000. In the previous studies, standardized uptake value (SUV) and its ratio to reference tissue (SUVR) were used at several brain regions for their analysis 9 , 10 . However, our study implements the centiloid scale as a measure for amyloid deposition in amyloid PET imaging 11 .…”

“…It is based on the principle that minimal perivascular water diffusion corresponds to an index close to one, with the index increasing as perivascular diffusivity increases. This approach has been utilized in various studies to investigate the relationship between glymphatic system activity and cognitive function, as well as tracer uptake of amyloid imaging in AD patients and cognitively normal (CN) participants [8][9][10] .…”

Diffusion Tensor Image Analysis ALong the Perivascular Space (DTI-ALPS): Revisiting the Meaning and Significance of the Method

“…17 Also, a comparative study with amyloid PET for subjective cognitive decline by Park et al showed no significant difference between the mean ALPS-index of the amyloid-positive group and the mean ALPS-index of the amyloid-negative group. 22 Kamagata et al examined changes in the following noninvasive MRI metrics related to the perivascular network in patients with MCI and AD: PVS volume fraction (PVSVF), fractional volume of free water in white matter (FW-WM) and ALPS-index. Their results showed that AD patients had significantly higher total PVSVF, WM, basal ganglia PVSVF, and FW-WM and lower ALPS-index than healthy controls.…”

Interplay between the Glymphatic System and the Endocannabinoid System: Implications for Brain Health and Disease

“…With the DTI-ALPS technique, the diffusion capacity within the perivascular space in the white matter on the outer aspect of the lateral ventricle's body is assessed as a ratio concerning the diffusion capacity within the perivascular space and that in a direction perpendicular to the principal flow direction of the white matter fibers (referred to as the ALPS index) [5,[10][11][12][13][14][15][16][17][18][19][20].…”