Apathy not depression helps to predict dementia
July 13, 2020
Science Daily/University of Cambridge
Apathy offers an important early warning sign of dementia in individuals with cerebrovascular disease, but depression does not, new research led by the University of Cambridge suggests.
Depression is often thought to be a risk factor for dementia but this may be because some depression scales used by clinicians and researchers partially assess apathy, say scientists from the universities of Cambridge, King's College London, Radboud and Oxford.
The study, published on 11 July in the Journal of Neurology, Neurosurgery & Psychiatry is the first to examine the relationships between apathy, depression, and dementia in individuals with cerebral small vessel disease (SVD). SVD may occur in one out of three elderly individuals, causes about a quarter of all strokes, and is the most common cause of vascular dementia.
The team studied two independent cohorts of SVD patients, one from the UK and the other from the Netherlands.* Across both cohorts, they found that individuals with higher baseline apathy, as well as those with increasing apathy over time, had a greater risk of dementia. In contrast, neither baseline depression nor change in depression had any detectable influence on dementia risk.
These findings were consistent despite variation in the severity of participants' symptoms, suggesting that they could be generalised across a broad spectrum of SVD cases. The relationship between apathy and dementia remained after controlling for other well-established risk factors for dementia including age, education, and cognition.
Lead author, Jonathan Tay, from Cambridge's Department of Clinical Neurosciences said: "There has been a lot of conflicting research on the association between late-life depression and dementia. Our study suggests that may partially be due to common clinical depression scales not distinguishing between depression and apathy."
Apathy, defined as a reduction in 'goal-directed behaviour', is a common neuropsychiatric symptom in SVD, and is distinct from depression, which is another symptom in SVD. Although there is some symptomatic overlap between the two, previous MRI research linked apathy, but not depression, with white matter network damage in SVD.
Jonathan Tay said: "Continued monitoring of apathy may be used to assess changes in dementia risk and inform diagnosis. Individuals identified as having high apathy, or increasing apathy over time, could be sent for more detailed clinical examinations, or be recommended for treatment."
Over 450 participants -- all with MRI-confirmed SVD -- recruited from three hospitals in South London and Radboud University's Neurology Department in the Netherlands, were assessed for apathy, depression and dementia over several years.
In the UK cohort, nearly 20% of participants developed dementia, while 11% in the Netherlands cohort did, likely due to the more severe burden of SVD in the UK cohort. In both datasets, patients who later developed dementia showed higher apathy, but similar levels of depression at baseline, compared to patients who did not.
The study provides the basis for further research, including the mechanisms that link apathy, vascular cognitive impairment, and dementia. Recent MRI work suggests that similar white matter networks underlie motivation and cognitive function in SVD. Cerebrovascular disease, which can be caused by hypertension and diabetes, can lead to network damage, resulting in an early form of dementia, presenting with apathy and cognitive deficits. Over time, SVD-related pathology increases, which is paralleled by increasing cognitive and motivational impairment, eventually becoming severe enough to meet criteria for a dementia state.
Jonathan Tay says: "This implies that apathy is not a risk factor for dementia per se, but rather an early symptom of white matter network damage. Understanding these relationships better could have major implications for the diagnosis and treatment of patients in the future."
https://www.sciencedaily.com/releases/2020/07/200713120022.htm
A good blood supply is good for memory
February 14, 2020
Science Daily/DZNE - German Center for Neurodegenerative Diseases
Memory performance and other cognitive abilities benefit from a good blood supply to the brain. This applies in particular to people affected by a condition known as "sporadic cerebral small vessel disease." Researchers of the German Center for Neurodegenerative Diseases (DZNE) and the University Medicine Magdeburg report on this in the journal "BRAIN." Their study suggests that blood perfusion of the so-called hippocampus could play a key role in age- and disease-related memory problems.
Inside the human brain there is a small structure, just a few cubic centimeters in size, which is called the "hippocampus" because its shape resembles a seahorse. Strictly speaking, the hippocampus exists twice: once in each brain hemisphere. It is considered the control center of memory. Damage to the hippocampus, such as it occurs in Alzheimer's and other brain diseases, is known to impair memory. But what role does blood supply in particular play? A team of scientists headed by Prof. Stefanie Schreiber and Prof. Emrah Duezel, both affiliated to the DZNE and the University Medicine Magdeburg, investigated this question. The researchers used high-resolution magnetic resonance imaging (MRI) to examine the blood supply to the hippocampus of 47 women and men aged 45 to 89 years. The study participants also underwent a neuropsychological test battery, which assessed, in particular, memory performance, speech comprehension and the abilty to concentrate.
A double supply line
"It has been known for some time that the hippocampus is supplied by either one or two arteries. It also happens that only one of the two hippocampi, which occur in every brain, is supplied by two vessels. This varies between individuals. The reasons are unknown," explained Schreiber. "Maybe there is a genetic predisposition. However, it is also possible that the individual structure of the blood supply develops due to life circumstances. Then the personal lifestyle would influence the blood supply to the hippocampus." In the cognition tests, those study participants in whom at least one hippocampus was doubly supplied generally scored better. "The fact that the blood supply is fundamentally important for the brain is certainly trivial and has been extensively documented. We were therefore particularly focused on the hippocampus and the situation of a disease of the brain vessels. Little is actually known about this."
Patients benefited in particular
Of the study subjects, 27 did not manifest signs of brain diseases. The remaining twenty participants showed pathological alterations in brain blood vessels, which were associated with microbleeding. "In these individuals, sporadic cerebral small vessel disease had been diagnosed prior to our investigations," said Dr. Valentina Perosa, lead author of the current study, who is currently doing postdoctoral research in Boston, USA. These individuals exhibited a broad spectrum of neurological anomalies, including mild cognitive impairment. "The healthy subjects generally scored better on cognitive tests than the study participants with small vessel disease. Among the participants with disease, those with at least one hippocampus supplied by two arteries reached better scores in cognition. They particularly benefited from the double supply. This may be due to a better supply not only of blood but also of oxygen. However, this is just a guess," said Perosa.
Starting point for therapies?
"Our study shows a clear link between blood supply to the hippocampus and cognitive performance," Schreiber summarised the results. "This suggests that brain blood flow might play a key role in the declining of memory performance, whether caused by age or disease." Such findings help to understand disease mechanisms and can also be useful for the development of novel treatment options, she indicates: "At present we can only speculate, because we don't know, but it is possible that lifestyle has an influence on the formation of the blood vessels that supply the hippocampus. This would then be a factor that can be influenced and thus a potential approach for therapies and also for prevention. This is a topic we intend to investigate."
https://www.sciencedaily.com/releases/2020/02/200214134725.htm
Brain study paves way for therapy for common cause of dementia
July 4, 2018
Science Daily/University of Edinburgh
Scientists have uncovered a potential approach to treat one of the commonest causes of dementia and stroke in older people. Studies with rats found the treatment can reverse changes in blood vessels in the brain associated with the condition, called cerebral small vessel disease. Treatment also prevents damage to brain cells caused by these blood vessel changes, raising hope that it could offer a therapy for dementia.
Studies with rats found the treatment can reverse changes in blood vessels in the brain associated with the condition, called cerebral small vessel disease.
Treatment also prevents damage to brain cells caused by these blood vessel changes, raising hope that it could offer a therapy for dementia.
Small vessel disease, or SVD, is a major cause of dementia and can also worsen the symptoms of Alzheimer's disease. It is responsible for almost half of all dementia cases in the UK and is a major cause of stroke, accounting for around one in five cases.
Patients with SVD are diagnosed from brain scans, which detect damage to white matter -- a key component of the brain's wiring.
Until now, it was not known how changes in small blood vessels in the brain associated with SVD can cause damage to brain cells.
A team led by the University of Edinburgh found that SVD occurs when cells that line the small blood vessels in the brain become dysfunctional. This causes them to secrete a molecule into the brain.
The molecule stops production of the protective layer that surrounds brain cells -- called myelin -- which leads to brain damage.
Treating rats with drugs that stop blood vessel cells from becoming dysfunctional reversed the symptoms of SVD and prevented brain damage, tests found.
Researchers say that further studies will need to test whether the treatment also works when the disease is firmly established. They will also need to check if the treatment can reverse the symptoms of dementia.
Dementia is one of the biggest problems facing society, as people live longer and the population ages. Estimates indicate there are almost 47 million people living with dementia worldwide and the numbers affected are expected to double every 20 years, rising to more than 115 million by 2050.
The research, published in Science Translational Medicine, was carried out at the Medical Research Council Centre for Regenerative Medicine and the UK Dementia Research Institute at the University of Edinburgh. It was funded by the MRC, Alzheimer's Research UK and Fondation Leducq.
Professor Anna Williams, Group Leader at the University of Edinburgh's MRC Centre for Regenerative Medicine, said: "This important research helps us understand why small vessel disease happens, providing a direct link between small blood vessels and changes in the brain that are linked to dementia. It also shows that these changes may be reversible, which paves the way for potential treatments."
Dr Sara Imarisio, Head of Research at Alzheimer's Research UK said: "Changes to the blood supply in the brain play an important role in Alzheimer's disease as well as being a direct cause of vascular dementia. This pioneering research highlights a molecular link between changes to small blood vessels in the brain and damage to the insulating 'white matter' that helps nerve cells to send signals around the brain.
"The findings highlight a promising direction for research into treatments that could limit the damaging effects of blood vessel changes and help keep nerve cells functioning for longer. There are currently no drugs that slow down or stop Alzheimer's disease and no treatments to help people living with vascular dementia. Alzheimer's Research UK is very pleased to have helped fund this innovative research, which is only possible thanks to the work of our dedicated supporters."
Dr Nathan Richardson, the MRC's Head of Molecular and Cellular Medicine, commented: "This study is a great example of how innovative discovery science into regenerative mechanisms can be applied to improve our understanding of how vascular changes contribute to dementia. This research in rats opens up new possibilities for developing therapies for cerebral small vessel disease."
https://www.sciencedaily.com/releases/2018/07/180704161504.htm