Researchers from Nanyang Technological University, Singapore report that “enlarged perivascular spaces” — small fluid-filled channels around brain blood vessels that can be seen on routine MRI — were more common in people with mild cognitive impairment and were associated with several blood-based Alzheimer’s disease biomarkers in a multi-ethnic Singapore cohort of 979 participants.
Scientists from Nanyang Technological University, Singapore (NTU Singapore) report evidence that the brain’s waste-clearance pathways may become disrupted early in people at risk of Alzheimer’s disease.
The study focused on enlarged perivascular spaces — fluid-filled channels around blood vessels that are visible on standard MRI. Researchers say these channels are part of the brain’s “drainage” system that helps clear waste products, including beta amyloid and tau-related proteins, which are implicated in Alzheimer’s disease.
Led by Associate Professor Nagaendran Kandiah of NTU’s Lee Kong Chian School of Medicine, the team analyzed brain MRI markers and blood-based biomarkers in 979 participants recruited in Singapore. The cohort included nearly 350 cognitively normal participants, with the remainder showing early cognitive decline, including mild cognitive impairment (MCI) — a condition that can precede dementia.
After reviewing MRI scans, the researchers found that participants with MCI were more likely to have enlarged perivascular spaces than those without cognitive problems.
In blood testing, the team measured seven Alzheimer’s-related blood biomarkers and reported that enlarged perivascular spaces were associated with four of those measurements. In the published analysis, higher perivascular-space burden correlated with markers including p-tau181, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP), and was inversely associated with the Aβ42/40 ratio, a blood-based measure often used as an indicator of amyloid pathology.
The researchers also compared enlarged perivascular spaces with other MRI signs of cerebral small vessel disease, including white matter hyperintensities. While white matter changes were associated with a larger number of blood biomarkers overall, the study reported that, among participants with MCI, the association between Alzheimer’s-related blood markers and enlarged perivascular spaces was stronger than the association with white matter changes.
“Since these brain anomalies can be visually identified on routine magnetic resonance imaging (MRI) scans performed to evaluate cognitive decline, identifying them could complement existing methods to detect Alzheimer’s earlier, without having to do and pay for additional tests,” Kandiah said.
The researchers also highlighted why population-specific research may matter in dementia. Kandiah noted that the APOE ε4 risk variant is reported in less than 20% of Singapore dementia patients, compared with around 50% to 60% reported in past studies of Caucasian dementia populations.
External clinicians quoted in the research release said the findings could add a useful, readily available imaging clue when assessing people with cognitive symptoms. “These findings are significant because they suggest that brain scans showing enlarged perivascular spaces could potentially help identify people at higher risk of Alzheimer’s disease, even before symptoms appear,” said Dr. Rachel Cheong Chin Yee, a senior consultant and deputy head in geriatric medicine at Khoo Teck Puat Hospital, who was not involved in the research.
The NTU team said it plans to follow participants over time to test whether enlarged perivascular spaces can help predict who will progress to Alzheimer’s dementia, emphasizing that longitudinal confirmation and replication in other populations are needed before the marker could be used routinely for risk prediction.
