Associations of MRI-visible perivascular spaces with longitudinal cognitive decline across the Alzheimer’s disease spectrum

Abstract

Objective To investigate the characteristics and associations of MRI-visible perivascular spaces (PVS) with clinical progression and longitudinal cognitive decline across the Alzheimer’s disease spectrum. Methods We included 1429 participants (641 [44.86%] female) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. PVS number and grade in the centrum semiovale (CSO-PVS), basal ganglia (BG-PVS), and hippocampus (HP-PVS) were compared among the control (CN), mild cognitive impairment (MCI), and Alzheimer’s disease (AD) groups. PVS were tested as predictors of diagnostic progression (i.e., CN to MCI/AD or MCI to AD) and longitudinal changes in the 13-item Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-Cog 13), Mini-Mental State Examination (MMSE), memory (ADNI-MEM), and executive function (ADNI-EF) using multiple linear regression, linear mixed-effects, and Cox proportional hazards modeling. Results Compared with CN subjects, MCI and AD subjects had more CSO-PVS, both in number (p < 0.001) and grade (p < 0.001). However, there was no significant difference in BG-PVS and HP-PVS across the AD spectrum (p > 0.05). Individuals with moderate and frequent/severe CSO-PVS had a higher diagnostic conversion risk than individuals with no/mild CSO-PVS (log-rank p < 0.001 for all) in the combined CN and MCI group. Further Cox regression analyses revealed that moderate and frequent/severe CSO-PVS were associated with a higher risk of diagnostic conversion (HR = 2.007, 95% CI = 1.382–2.914, p < 0.001; HR = 2.676, 95% CI = 1.830–3.911, p < 0.001, respectively). A higher CSO-PVS number was associated with baseline cognitive performance and longitudinal cognitive decline in all cognitive tests (p < 0.05 for all). Conclusions CSO-PVS were more common in MCI and AD and were associated with cognitive decline across the AD spectrum.

Association between enlarged perivascular spaces and cerebrospinal fluid aquaporin-4 and tau levels: report from a memory clinic

“…Several studies have described an association between MRI-visible PVS and neurodegenerative diseases, particularly in CSO white matter ( Boespflug et al, 2018 ; Vilor-Tejedor et al, 2021 ; Perosa et al, 2022 ; Wang et al, 2022 ). Moreover, AQP4 is known to undergo over-expression and loss of perivascular localization in response to aging and AD pathologic changes ( Zeppenfeld et al, 2017 ; Boespflug et al, 2018 ).…”

The Alzheimer's Disease Neuroimaging Initiative in the era of Alzheimer's disease treatment: A review of ADNI studies from 2021 to 2022

“…Changes in these measures in MCI and AD participants were significantly associated with CSF Aβ42, FDG PET, and cognition. 164 Enlargement of the perivascular space in the centrum semiovale was associated with WMH volume, 166 glucose hypometabolism in A+ participants, 167 brain tau, 168 diagnostic conversion and longitudinal cognitive decline, 169 and sTREM2. 166 sTREM2, in turn, mediated the association between enlarged perivascular space in the centrum semiovale and CSF p‐tau181.…”

Blood–Brain Barrier Disruption and Perivascular Spaces in Small Vessel Disease and Neurodegenerative Diseases: A Review on MRI Methods and Insights

“…18 A higher PVS score in the CSO has also been related to lower cognitive performance as well as longitudinal cognitive decline in AD dementia patients. 50 Furthermore, a lower DTI-ALPS index has been related to a lower cognitive function in AD patients. 22 Several studies have investigated the association between PVS and typical AD biomarkers.…”

“…However, it is not yet clear if MRI‐visible PVS are the outcome or the driver of protein accumulation. Patients with AD dementia have a higher degree of PVS in comparison with controls, especially in the CSO 41,50 and hippocampus 51 . Furthermore, a lower DTI‐ALPS index has been related to AD dementia diagnosis, 52 and FW in the hippocampus has been shown to be elevated in patients with mild cognitive impairment (MCI) 53 .…”

“…Additionally, stronger diffusion attributed to ISF in the normal‐appearing white matter, as assessed by 3C‐IVIM, has been associated with lower hippocampal volume, a classical marker of AD neurodegeneration 18 . A higher PVS score in the CSO has also been related to lower cognitive performance as well as longitudinal cognitive decline in AD dementia patients 50 . Furthermore, a lower DTI‐ALPS index has been related to a lower cognitive function in AD patients 22 …”