Medical Bulletin 27/October/2025

Cholesterol contributes to brain and vascular health, but excessive levels can cause blockages that limit blood flow and increase dementia risk. Some people possess genetic variants that lower cholesterol by affecting the same proteins targeted by common drugs like statins and ezetimibe.

Using a method called Mendelian Randomization, which mimics natural randomized trials using genetic data, researchers compared individuals with and without these cholesterol-lowering variants. This technique minimizes confounding lifestyle factors and isolates the genetic influence on brain health.

The study revealed that a modest reduction—about one millimole per litre—was linked to up to an 80% lower dementia risk for certain cholesterol-related gene targets. Importantly, these findings suggest that long-term cholesterol control, beginning early in life, might be one of the most effective prevention strategies against dementia. However, the study cannot yet confirm whether cholesterol-lowering medications directly prevent the disease.

Lead author Dr. Liv Tybjærg Nordestgaard explained that high cholesterol likely contributes to atherosclerosis, a buildup of fatty deposits in blood vessels that can restrict brain blood flow. She emphasized the need for decades-long clinical trials to explore whether cholesterol-lowering treatments truly protect the brain—potentially opening new preventive approaches to one of the world’s fastest-growing health challenges.

Reference: Liv Tybjærg Nordestgaard, Aimee Hanson, Eleanor Sanderson, Emma Anderson, Venexia Walker, Anne Tybjærg‐Hansen, George Davey Smith, Børge G. Nordestgaard. Cholesterol‐lowering drug targets reduce risk of dementia: Mendelian randomization and meta‐analyses of 1 million individuals. Alzheimer\'s, 2025; 21 (10) DOI: 10.1002/alz.70638

Study uncovers link between brain activity, energy metabolism, and blood flow during sleep

Scientists from Mass General Brigham have discovered how the brain undergoes a perfectly synchronized shift in activity as it transitions from wakefulness to sleep. Published in Nature Communications, the study found that while the brain’s sensory and motor regions stay active during non-rapid eye movement (NREM) sleep, higher cognitive areas responsible for thinking and memory reduce activity and energy use. This dynamic balance helps the brain remain partly responsive to the external world, even while consciousness fades.

NREM sleep is a deep, restorative phase crucial for physical recovery, brain maintenance, and memory consolidation. It is also thought to help flush out metabolic waste from the brain. However, the interactions between energy use, brain activity, and blood flow during this stage have remained unclear. The study sought to reveal these hidden mechanisms that sustain both rest and responsiveness during sleep.

For this study, researchers recruited 23 healthy adult volunteers for short, afternoon nap sessions. Using an advanced tri-modal imaging method—EEG-PET-MRI—they simultaneously measured three aspects of the brain: electrical activity (EEG), blood flow (fMRI), and glucose metabolism (functional PET-FDG). This powerful approach allowed scientists to track how neuronal, vascular, and metabolic systems interacted in real time as participants entered and deepened into NREM sleep.

The results showed that overall brain metabolism decreased as sleep deepened, yet blood flow in sensory areas became more dynamic. In contrast, higher-order networks—linked to cognition and daydreaming—quieted down, and cerebrospinal fluid circulation increased. These patterns support the idea that the sleeping brain continues performing vital “housekeeping” functions while maintaining sensitivity to meaningful sensory triggers.

Lead author Dr. Jingyuan Chen noted that this research offers deeper insights into how brain activity and energy regulation during sleep may relate to neurodegenerative and sleep-related diseases. The team plans to expand this work with larger, more diverse samples and longer sleep recordings to refine their understanding of the brain’s complex choreography during rest.

Reference: Chen, J. E., et al. (2025). Simultaneous EEG-PET-MRI identifies temporally coupled and spatially structured brain dynamics across wakefulness and NREM sleep. Nature Communications. doi.org/10.1038/s41467-025-64414-x

Eye scans may offer new insights into aging and heart disease risk, Study finds

Researchers from McMaster University and the Population Health Research Institute (PHRI) have found that the tiny blood vessels in our eyes could hold vital clues to heart health and biological aging. Published in Science Advances, the large-scale study suggests that retinal scans could one day act as a simple, noninvasive screening tool to detect cardiovascular disease and gauge how quickly a person is aging biologically.

The retina’s intricate network of blood vessels provides a unique, noninvasive window into human health, reflecting the condition of the body’s microvascular system. Because the retinal vessels share structural and functional similarities with blood vessels in vital organs such as the heart and brain, any changes observed in the eye—like narrowing, reduced branching, or increased stiffness—can indicate early signs of systemic vascular damage. This makes the retina an ideal and highly sensitive tool for assessing overall circulatory health and biological aging.

For the study, scientists analyzed retinal imaging, genetic, and blood data from over 74,000 individuals across four major global cohorts — the Canadian Longitudinal Study on Aging (CLSA), the UK Biobank (UKBB), GoDARTS, and PURE. Advanced imaging analysis allowed the team to compare vessel structure to biological and cardiovascular markers. Further genetic and proteomic evaluations identified key molecules influencing aging and vascular integrity, notably MMP12 and IgG–Fc receptor IIb, both tied to inflammation and vascular degradation.

They found that people with simpler, less branched blood vessels were at increased risk of cardiovascular diseases and showed signs of biological aging, such as higher inflammation and shorter lifespan. Another important aspect of the study came from reviewing blood biomarkers and genetic data. Through this, researchers uncovered not just associations, but potential biological causes behind changes in the eye's blood vessels. This helped them identify specific proteins that may drive aging and disease.

Senior author Dr. Marie Pigeyre explained “These results open new avenues for preventive medicine. By pinpointing proteins and pathways that drive vascular aging, we can identify novel drug targets and reduce future cardiovascular burden.”

Reference: Ana Villaplana-Velasco et al. ,Mendelian randomization study implicates inflammaging biomarkers in retinal vasculature, cardiovascular diseases, and longevity.Sci. Adv.11,eadu1985(2025).DOI:10.1126/sciadv.adu1985