Stroke is the brain equivalent of a heart attack. It occurs if either the blood supply to the brain is blocked (called an ischemic stroke, for instance by a blood clot), or if a blood vessel in the brain is ruptured (hemorrhagic stroke). When either of these things happen, brain cells begin to die or are at risk of damage.
Stroke can affect anyone at anytime. Every year around 17 million people suffer a stroke worldwide. It is estimated that 1 in 4 persons will have a stroke during their lifetime. Although stroke can affect anyone at anytime, two-thirds of all strokes occur in people aged over 65 years.
Many people are not aware of the symptoms of stroke or transient ischemic attack (TIA) and often do not go to hospital if either of these events happen. Symptoms of stroke are sudden. Common symptoms are:
- numbness or weakness of face, arm or leg – especially on one side of the body
- vision problems
- loss of coordination
- confusion or trouble speaking or understanding
- severe headache.
Symptoms of a TIA are similar to stroke, but are transient and can last only minutes or hours.
If you, or someone you know has symptoms, seek emergency medical help immediately.
Direct risk factor for stroke are:
- High blood pressure
- Smoking
- Heart disease
- Diabetes
- Excess alcohol intake
- High blood cholesterol
Dementia is a general term for memory loss and other cognitive abilities serious enough to interfere with daily life. Alzheimer's disease accounts for 60-80% of dementia cases.
Dementia is not a normal part of aging.
Alzheimer's and other dementias worsen over time. They are progressive diseases, where dementia symptoms gradually worsen over a number of years. In its early stages, memory loss is mild, but with late-stage dementia, individuals lose the ability to carry on a conversation and respond to their environment.
As of 2015, there were over 46 million people worldwide with dementia, 58% of them live in low- and middle-income countries. This figure is set to increase to more than 131 million people by 2050. Much of this increase will be in rapidly developing and heavily populated regions such as China, India and Latin America.
Dementia primarily affects older people. Up to the age of 65, dementia develops in only about 1 person in 1000. The chance of having the condition rises sharply with age to 1 person in 20 over the age of 65. Over the age of 80, this figure increases to 1 person in 5.
We do not yet fully understand what causes Alzheimer's disease in most people. In early-onset Alzheimer's, which occurs between a person's 30s and mid-60s, there is strong evidence of a genetic component.
Late-onset Alzheimer's, which usually develops in a person's mid-60s, arises from a complex series of age-related brain changes that occur over decades. The causes probably include a mix of these changes, along with genetic, environmental, and lifestyle factors. These factors affect each person differently.
Many factors can eventually contribute to dementia. Some factors, such as age or family history, can't be changed. Others can be addressed to reduce your risk.
- Diet and exercise
- Vitamin and nutritional deficiencies
- Heavy alcohol use
- Cardiovascular risk factors
- Depression
- Diabetes
- Smoking
Dementia affects people differently. No two people will have symptoms that develop in exactly the same way.
Symptoms vary between Alzheimer's disease and other types of dementia, but there are broad similarities between them all. The most common signs are memory loss and the loss of practical abilities, which can lead to withdrawal from work or social activities. If you think that these problems are affecting your daily life, or the life of someone you know, you should talk to a doctor.
There is no way to predict whether a particular person will develop the disease. It is possible to test for the ApoE4 gene, but such a test does not predict whether a particular person will develop Alzheimer's disease or not. It merely indicates that they are at greater risk. There are in fact people who have had the ApoE4 gene, lived well into old age and never developed Alzheimer's dementia, just as there are people who did not have ApoE4, who did develop it.
Although there are no drugs that can cure dementia, there are several drug treatments that can help some people.
The currently available treatments can slow down the progression of the disease in some cases for periods between 6 and 18 months. The main class of such compounds is the cholinesterase inhibitors.
Non-drug treatments, including practical and emotional support, are important and effective in helping people with dementia and carers.
Currently, there is no definitive evidence about what can prevent Alzheimer's disease or age-related cognitive decline. Although there are no specific preventative measures to recommend, what can be recommended is minimizing risk factors by maintaining a healthy lifestyle (balanced diet, staying physically, mentally and socially active, not smoking and not drinking too much alcohol).
Roughly one in four stroke patients develop some form of dementia, most commonly Alzheimer’s disease, within ten years. The frequency of this co-occurrence is such that there is an urgent need to better understand the common cause of these two diseases, and how they are linked.
There are major gaps in our understanding of underlying causes of each disease and the relationship between vascular risk factors. Current model systems are focused on each disease separately, and the interplay between these two diseases has remained unexplored. Basically, we do not know the cause and consequence in the cascade, or what the genetic drivers, or intermediate steps are.
We also need a better understanding of how the molecular signatures, genetic or metabolic, relate to lesions in the brain, and to discover the earliest changes in the brain using magnetic resonance imaging (MRI) or positron emission tomography (PET) imaging techniques.
CoSTREAM aims to improve our understanding of the co-occurrence of stroke and Alzheimer’s disease. The project builds upon large data sets on both diseases and combines genetics, metabolomics, brain imaging and biotechnology to identify and investigate these common mechanisms.
More specifically, we aim to:
- Understand and identify common genetic and molecular signatures
- Identify biomarkers
- Identify evidence-based targets for the development of innovative treatment
- Link and validate biomarkers and signatures to advanced MRI and PET imaging
- Discover compensatory mechanisms that enable innovative treatment and prevention
- Translate these findings into a validated organ-on-chip model of the neurovascular unit for future therapeutic research
CoSTREAM has access to a combined dataset spanning more than 11,500 cases of stroke, nearly 20,000 cases of Alzheimer’s disease (including mild cognitive impairment) and over 74,000 healthy controls with up to 25 years of follow-up, including multiple repeat assessments. It includes two large, ongoing follow-up studies.
We have been able to pinpoint specific genomic regions that mediate risk to stroke or Alzheimer’s disease, and found the common genetic pathogenesis of the disorders and created a polygenic risk score based on genes implicated in stroke that predicts AD.
Using metabolomics, we have found promising metabolic markers and pathways for stroke as well as Alzheimer’s disease, as well as common pathways for both. Metabolic changes have also been shown to be associated with neurodegeneration and vascular brain pathology.
CoSTREAM has successfully analysed MRI data from multiple sites using automated tractography and found consistent relationships between tract measures, age, and memory ability across sites.
Multiple risk factors, including demographic factors, vascular risk factors and cardiovascular diseases have been related to Alzheimer’s disease and stroke. Evidence that loneliness is associated with increased risk of cognitive decline and dementia rather than a result of dementia or depression was found.
Multiple protective factors, including lifestyle factors, social network, leisure time activity have been identified for AD and incident stroke. In addition, it was also found that leisure time activity can compensate the harmful effect of diabetes on cognitive decline and improves the protective effect of Nordic prudent Dietary Pattern on cognitive function. Higher education is associated with a lower risk of dementia after stroke or TIA, particularly in men, which might be explained by a higher cognitive reserve.
For Alzheimer’s disease, we found evidence that a specific pathway risk score interacts with smoking history.
Furthermore, we provided evidence that antihypertensives and statins might reduce the incidence of dementia. Using Mendelian Randomization, we benchmarked the protective effect of education on AD and found suggestive evidence confirming the association of smoking, 25-hydroxyvitamin D concentrations and coffee consumption. Higher hom*ocysteine levels and lower folate levels are associated with increased risk of small vessel stroke. We also found evidence that a genetic variant in PDE3A influences endothelial function in early life and leads to subsequent increased risk of ischaemic stroke. We have been able to develop a cutting-edge prototype of a neurovascular unit on a chip that can be used for translational research.
So far, the project has published more than 80 major scientific publication and gave over 50 oral and poster presentations.
