Author Interviews, Cognitive Issues, Heart Disease / 26.10.2017
Dementia Incidence Lower For Atrial Fibrillation Patients Treated With Anticoagulation
MedicalResearch.com Interview with:
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Dr. Leif Friberg[/caption]
Dr. Leif Friberg MD, PhD
Associate professor in cardiology
Karolinska Institute
Friberg Resarch
Stockholm, Sweden
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: I have been doing research on atrial fibrillation and stroke risk for many years and knew that the very common heart arrhythmia is associated with a 40% increased risk of dementia. Considering that that 12-15% of 75 years olds have this arrhythmia, and even more at higher ages, the problem is significant to say the least.
The mechanism behind stroke in atrial fibrillation is that blood clots are formed in the heart. When these are dislodged they travel with the blood stream and may get stuck in the narrow vessels of the brain where they stop blood flow causing brain infarction or stroke. Oral anticoagulant drugs like warfarin or the newer so called NOAC (new oral anticoagulant) drugs are highly efficient in preventing formation of these large blood clots and offer at least 70% risk reduction. Now, blood clots come in different sizes. There are also microscopic clots that do not cause symptoms of stroke but all the same eat away at the brain at a slow but steady pace. Imaging studies shows this after only a few months or even weeks of atrial fibrillation. Our hypothesis was therefore: If anticoagulants are so effective in protecting against large clots, will they not help against the small ones too?
Dr. Leif Friberg[/caption]
Dr. Leif Friberg MD, PhD
Associate professor in cardiology
Karolinska Institute
Friberg Resarch
Stockholm, Sweden
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: I have been doing research on atrial fibrillation and stroke risk for many years and knew that the very common heart arrhythmia is associated with a 40% increased risk of dementia. Considering that that 12-15% of 75 years olds have this arrhythmia, and even more at higher ages, the problem is significant to say the least.
The mechanism behind stroke in atrial fibrillation is that blood clots are formed in the heart. When these are dislodged they travel with the blood stream and may get stuck in the narrow vessels of the brain where they stop blood flow causing brain infarction or stroke. Oral anticoagulant drugs like warfarin or the newer so called NOAC (new oral anticoagulant) drugs are highly efficient in preventing formation of these large blood clots and offer at least 70% risk reduction. Now, blood clots come in different sizes. There are also microscopic clots that do not cause symptoms of stroke but all the same eat away at the brain at a slow but steady pace. Imaging studies shows this after only a few months or even weeks of atrial fibrillation. Our hypothesis was therefore: If anticoagulants are so effective in protecting against large clots, will they not help against the small ones too?
Dr. Alessandro Biffi[/caption]
Alessandro Biffi, MD
Behavioral Neurology and Neuropsychiatry
Departments of Neurology and Psychiatry
Massachusetts General Hospital / Harvard Medical School
MedicalResearch.com: What is the background for this study?
Dr. Biffi: Intracerebral Hemorrhage (ICH) is the most severe form of stroke. It is a form of hemorrhagic (i.e. bleeding) stroke that accounts for ~ 15% of all acute cerebrovascular conditions, affecting ~ 70,000 Americans every year. However, because of its severity it is responsible for almost half of all stroke-related disability worldwide. Survivors of ICH are at very high risk for cognitive impairment (up to and including dementia) following the acute cerebral bleeding event. However, we possess very limited understanding of the time dynamics and risk factors for post-ICH dementia. In particular, prior to our study it was unclear whether the acute cerebral injury due to ICH would be the only mechanism potentially responsible for subsequent development of dementia.
This question is motivated by prior observations suggesting that Intracerebral Hemorrhage represents the acute manifestation of cerebral small vessel disease, a progressive degenerative disorder of small caliber arteries of the central nervous system.
There exist two major subtypes of small vessel disease:
1) cerebral amyloid angiopathy, caused by the deposition of a toxic protein product, beta-amyloid, in the blood vessels (in a process similar to the formation of beta-amyloid plaques that cause Alzheimer's disease);
2) arteriolosclerosis, caused by long-standing elevated blood pressure. ICH survivors have been previously shown to harbor very severe small vessel disease, which has been linked to dementia in patients without cerebral bleeding.
Our hypothesis was that early-onset dementia (occurring in the first 6 months after ICH) is a manifestation of the acute neurological damage associated with cerebral bleeding, whereas delayed onset dementia (developing beyond 6 months from the acute ICH event) is associated with known markers of small vessel disease, including imaging findings on CT/MRI and genetic markers (such as the APOE gene).
Dr. Kazem Rahimi[/caption]
Kazem Rahimi, DM, MSc
Oxford Martin School
University of Oxford
United Kingdom
MedicalResearch.com: What is the background for this study?
Dr. Rahimi: Vascular dementia is the second most common cause of dementia and is increasing in prevalence worldwide. Vascular dementia often occurs after stroke and can cause apathy, depression, and a decline in cognitive function, and can eventually result in death. High blood pressure (BP) has been identified as a potential risk factor for the development of vascular dementia. However, previous studies, which have been small in size, have reported conflicting results on the relationship between blood pressure and vascular dementia.
Dr. T. Jared Bunch[/caption]
T. Jared Bunch, MD
Director of Heart Rhythm Research
Medical Director for Heart Rhythm Services
Intermountain Healthcare System
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Bunch: Approximately 6 years ago we found that patients with atrial fibrillation experienced higher rates of all forms of dementia, including Alzheimers disease. At the time we started to ask the questions of why this association existed. We know that atrial fibrillation patients experience higher rates of stroke. These patients are placed on blood thinners, most commonly warfarin, to lower risk of stroke which at the same time expose that patient to a higher risk of intracranial bleeding. One possibility to explain the association was that perhaps dementia in the manifestation of many small clots or bleeds in the brain that in total lead to cognitive decline. If this is the case, then the efficacy and use of anticoagulation is very important in atrial fibrillation patients.
We conducted additional studies that showed this to be the case. In patients with no history of dementia, managed long-term with warfarin anticoagulation, those that had levels that were frequently too higher or too low that resulted in poor times in therapeutic range, experienced significantly higher rates of dementia. The risk was highest in younger atrial fibrillation patients that were less than 80 years of age. We then found that in atrial fibrillation patients that were frequently over anticoagulated and also use an antiplatelet agent, aspirin or plavix, the dementia rates nearly doubled. At this point we raised the question if atrial fibrillation increased the risk beyond anticoagulation, or does anticoagulation efficacy drive most of the risk. This question formed the background of the current study.
Dr. Saira Saeed Mirza[/caption]
Saira Saeed Mirza, MD, PhD
Department of Epidemiology
Erasmus MC, Rotterdam
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Mirza: Depressive symptoms appearing in late-life have been extensively studied for their relationship with dementia. They not only very frequently occur in demented patients, but also predict dementia. In this context, depressive symptoms have largely been assessed at a single time point only. However, depression is a disorder which remits and relapses, and symptoms do not remain same over the years. Given this pattern of disease progression, it is more important to study the course of depression over time in relation to long-term health outcomes such as dementia, rather than assessing it at a single time-point, which will neglect the course of depression. This is important as people follow different courses of depression, and different courses of depression might carry different risks of dementia.
When we studied the course of depressive symptoms over 11 years in community dwelling older adults in Rotterdam, and the subsequent risks of dementia, we observed that only those who had increasing or worsening depressive symptoms were at a higher risk of dementia. In this group of people, about one in five persons developed dementia. Interestingly, people suffering from high depressive symptoms at a single time point were not at a higher dementia risk than those without depressive symptoms.
Dr. Babak Hooshmand[/caption]
Babak Hooshmand, MD, PhD, MPH
Center for Alzheimer Research–Aging Research Center
Karolinska Institutet
Stockholm University, Stockholm, Sweden
Department of Neurology, Klinikum Augsburg
Augsburg, Germany
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Hooshmand: Low and subnormal levels of vitamin B12 as well as high levels of homocysteine (a vascular risk factor and neurotoxic amino-acid associated with B12 deficiency) are common conditions in the elderly and are associated with a variety of disorders, including cardiovascular and cerebrovascular
conditions. Our study showed that over 6-year of follow-up, both low vitamin B12 status and high homocysteine levels are associated with accelerated brain atrophy in older adults, which precedes clinical dementia.
