Impact of 'Silent' Small Strokes on Brain Function and Alzheimer's Development

Saima Hilal, PhD
National University of Singapore (Tahir, Singapore)


Meike W. Vernooij, MD, PhD
Erasmus Medical Center (Rotterdam, Netherlands)
M. Arfan Ikram, MD, PhD
Erasmus Medical Center (Rotterdam, Netherlands)


M. Kamran Ikram, MD, PhD
Erasmus Medical Center (Rotterdam, Netherlands)
Wiro J. Niessen, PhD
Erasmus Medical Center (Rotterdam, Netherlands)
Marius de Groot, PhD
Erasmus Medical Center (Rotterdam, Netherlands)
Christopher Chen, FRCP
National University of Singapore (Singapore)
Vincent Mok, FRCP
Chinese University of Hong Kong (Hong Kong, China)
Year Awarded:
Grant Duration:
July 1, 2018 to June 30, 2021
Alzheimer's Disease
Award Amount:
Grant Reference ID:
Award Type:
Postdoctoral Fellowship
Award Region:
Saima Hilal, PhD

The Clinical Relevance of Cortical Cerebral Microinfarcts in Degenerative Brain Pathology such as Alzheimer’s Disease


Damage to the small vessels in the brain is one of the major causes of Alzheimer’s disease (AD). Adequate treatment is currently not available because the exact process behind this disease is still unknown. With this proposal, we aim to find the cause for AD by finding small strokes in the brain. This will help us understand why AD is so common in people with small strokes and will help create means to cure and prevent this disease.



Alzheimer’s disease (AD) is the most common type of dementia which involves not only the accumulation of abnormal protein in the brain, but also damage to the blood vessels. In this disease, both large as well as small vessels are affected. These vessels, particularly the smaller ones, undergo detrimental changes leading to a type of vascular disease in the brain known as cerebral small vessel disease. There are several markers of small vessel disease in the brain, and the ones which remain understudied are cortical cerebral microinfarcts. These are tiny strokes that involves the outer layer of the brain, an important functioning layer. It is thought that these tiny strokes play a major role by producing cognitive problems and development of dementia. This project aims to examine why AD is so common in people with small strokes and will help create means to cure and prevent this disease.


The main goal of the project is to identify small strokes (cortical microinfarcts) on brain MRI scans and understand how these strokes contribute to brain changes and development of Alzheimer’s disease (AD), and what can be done to prevent it.

In order to achieve this, we will first aim to determine the association between cortical microinfarcts and MRI markers which reflect brain atrophy. In the second sub-aim, we will also examine how these microinfarcts damage brain wiring as well as its connections. Following this we will examine how these microinfarcts, through disruption of brain connections, contribute to cognitive problems and development of dementia. Finally, we aim to determine the differences in the impact of microinfarcts on brain changes that may exist among Asians compared to Caucasians. Latter aim will be achieved in collaboration with researchers in Hong Kong and Singapore.

This project is a unique investigation in identifying and determining the impact of microinfarcts on brain changes and their independent contribution to Alzheimer’s dementia (AD), which has not been examined previously, especially in living persons. We anticipate that this research will uncover many novel associations and mechanisms that have not been examined before. The main portion of our analysis will be conducted among three large population-based studies, which enhances the generalizability and clinical relevance of our work. Moreover, the main strength of our study is the use of big data and their integration within this project using a harmonized method.

The results of the study will shed new light on how microinfarcts contribute to brain atrophy and disrupt the brain’s “connecting wires,” which leads to development of AD. These effects may be different in different ethnicities, which is of benefit to research fields around the world, as we can use this knowledge to better target vulnerable groups. It will also provide new targets of interest that may aid in development of new therapies directly influencing the specific mechanism to slow the progression of AD.

About the Researcher

I am a post-doctoral scientific researcher with one and a half years’ of experience researching vascular and neurodegenerative pathologies underlying Alzheimer’s disease and related disorders. Upon completion of my medical degree and training in neurology from Dow Medical College, Karachi, Pakistan, I went on to pursue a master’s degree in public health, with a specialization in clinical epidemiology, from the  National University of Singapore. From the same school, I undertook a PhD programme, where my research was focused on identifying novel markers of vascular and neurodegenerative pathologies in cognitive impairment and dementia using MRI and retinal imaging. Over the last three years, I was one of the pioneers in identifying a new marker of cardiovascular and cerebrovascular diseases, eg, cortical cerebral microinfarcts (CMIs) on three Tesla MRI scans. Following completion of my PhD in 2016, I was offered a post-doctoral fellowship at Erasmus University Medical Center, Rotterdam, the  Netherlands. Here, I am studying plasma amyloid-beta levels as biomarkers for cerebrovascular disease, dementia and stroke. My research uses molecular, imaging, cognitive, and clinical information to further comprehend the pathophysiological mechanism behind brain vascular changes and cognitive dysfunction from normal to diseased individuals. 

Personal Story

I always had a strong passion for neurology when I followed a premedical career path in my high school. When I entered medical school, topics in neuroanatomy, and being posted in the Neurology ward would always excite me. Though I was fascinated by the complexity of brain, I also used to wonder how devastating it is for patients with neurological disorders to lose function and independence. When I shifted to Singapore and joined the memory and cognition group, the first couple of years were challenging, as I was exposed to dementia patients for the first time. Under the guidance of my supervisor, I was able to push myself to learn more about dementia especially the vascular pathology behind this disease. This is also when I discovered that diseases like dementia are underdiagnosed in Pakistan, as it is commonly mistaken as part of “aging.” Through both research and clinical work, I was able to learn more about dementia and how to manage this disease. From this experience, I have decided to further my career in scientific research dedicated to Alzheimer’s disease and other neurodegenerative disorders.

During my research, I have incorporated several methods of neuroimaging, retinal imaging, bioinformatics, cardiovascular diseases, and cognition, which added nicely to my growing interest in dementia. My training and experiences have led me to firmly believe that research in today’s era involves widespread collaboration, where research findings need to be validated across studies, which increases the impact of dementia research. My proposal will open new pathways for solving the complex neurological diseases posed by Alzheimer’s disease and related disorders. I am very grateful to BrightFocus grantors for giving me this opportunity to pursue my passion in dementia research.


Wong LCK, Wong MYZ, Tan CS, Vrooman H, Venketasubramanian N, Cheng CY, Chen C, Hilal S. Interethnic differences in neuroimaging markers and cognition in Asians, a population-based study. Sci Rep. 2020 Feb 14;10(1):2655. doi: 10.1038/s41598-020-59618-8. PubMed PMID: 32060376. PubMed Icon Google Scholar Icon

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