Researchers at Nanyang Technological University, Singapore (NTU Singapore) have identified a potential early indicator of Alzheimer’s disease in routine brain scans. The team found that the brain’s natural “drains,” which remove toxic waste, are more likely to become blocked in individuals showing early signs of the disease.
These blockages, known as enlarged perivascular spaces, could serve as an important early warning signal for Alzheimer’s, one of the most common forms of dementia.
“Since these brain anomalies can be seen on routine MRI scans conducted for cognitive assessments, identifying them could help detect Alzheimer’s earlier without additional tests,” said Associate Professor Nagaendran Kandiah of NTU’s Lee Kong Chian School of Medicine (LKCMedicine), who led the study.
Justin Ong, a fifth-year LKCMedicine student and first author, noted that early detection allows doctors to intervene sooner, potentially slowing symptoms such as memory loss, reduced processing speed, and mood changes. The study was part of LKCMedicine’s Scholarly Project module in its Bachelor of Medicine and Bachelor of Surgery program.
Focus on Asian Populations
The study is notable for focusing on Asian populations, rather than predominantly Caucasian participants as in most prior research. Nearly 1,000 people from various ethnic groups in Singapore were studied, including individuals with no cognitive issues and those with mild cognitive impairment.
Asian-focused research is crucial because dementia risk factors vary across ethnicities. “Among Caucasians with dementia, about 50–60% carry the APOE4 gene, a major Alzheimer’s risk factor. In Singapore dementia patients, it’s less than 20%,” said Assoc Prof Kandiah, also Director of the Dementia Research Centre at LKCMedicine.
Brain Drainage and Alzheimer’s Indicators
Perivascular spaces surround the brain’s blood vessels and help clear harmful waste, including beta amyloid and tau proteins, which accumulate in Alzheimer’s. When this drainage is inefficient, these spaces expand and become visible on MRI scans.
The NTU team analyzed participants’ MRI scans alongside Alzheimer’s biomarkers, including beta amyloid and tau proteins. Among nearly 1,000 participants, close to 350 had no cognitive impairment, while the remainder showed early signs of cognitive decline.
MRI Scans Show Strong Links
The study found that individuals with mild cognitive impairment were more likely to have enlarged perivascular spaces. These brain “clogs” correlated with four of seven Alzheimer’s-related blood measurements, indicating higher levels of amyloid plaques, tau tangles, and brain cell damage.
The researchers also compared these findings to white matter damage, a known Alzheimer’s indicator. Surprisingly, the link between biochemical markers and enlarged perivascular spaces was stronger than the link with white matter damage, suggesting that clogged brain drains may appear earlier in the disease process.
Clinical Implications
“These findings have substantial clinical significance,” said Assoc Prof Kandiah. “While white matter damage is widely used to evaluate dementia, enlarged perivascular spaces may provide unique value for detecting early Alzheimer’s.”
Independent experts highlighted the study’s importance. Dr Rachel Cheong Chin Yee, Senior Consultant at Khoo Teck Puat Hospital, said MRI-detected enlarged perivascular spaces could help identify individuals at risk even before symptoms appear. Dr Chong Yao Feng, Consultant at the National University Hospital, noted that cerebrovascular disease and Alzheimer’s, traditionally considered separate, may interact in ways previously underappreciated.
Next Steps
Clinicians observing enlarged perivascular spaces on MRI scans should consider Alzheimer’s risk alongside other vascular issues. NTU researchers plan to follow study participants to track progression to dementia and validate the predictive value of these brain drain blockages.
If confirmed across populations, routine MRI scans could one day include enlarged perivascular space detection as a tool for earlier Alzheimer’s diagnosis, potentially allowing interventions before permanent brain damage occurs.
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