Does Small Vessel Disease Cause Dementia

Cerebral Small Vessel Disease Clinical Neuropsychological And Radiological Phenotypes Histopathological Correlates And Described Genotypes: A Review

Sadandavalli Retnaswami Chandra

1Clinical Neurosciences, National Institute of Mental Health and Neurosciences, Bangalore 560029, India

2Department of Neurology, National Institute of Mental Health and Neurosciences , Bangalore 560029, India

3Department of Neurochemistry, National Institute of Mental Health and Neurosciences , Bangalore 560029, India

4Department of Clinical Psychology, National Institute of Mental Health and Neurosciences , Bangalore 560029, India

5Department of Biostatistics, National Institute of Mental Health and Neurosciences , Bangalore 560029, India

Academic Editor:

Abstract

1. Introduction

Type 1. Arteriolosclerosis .

Type 2. Cerebral amyloid angiopathy .

What Are The Symptoms Of Vascular Dementia

The symptoms of vascular dementia depend on the location and amount of brain tissue involved. Vascular dementia symptoms may appear suddenly after a stroke, or gradually over time. Symptoms may get worse after another stroke, a heart attack, or major surgery. These are signs and symptoms of vascular dementia

• Increased trouble carrying out normal daily activities because of problems with concentration, communication, or inability to carry out instructions
• Memory problems, although short-term memory may not be affected
• Confusion, which may increase at night
• Stroke symptoms, such as sudden weakness and trouble with speech
• Personality changes
• Mood changes, such as depression or irritability
• Stride changes when walking too fast, shuffling steps
• Problems with movement and/or balance
• Urinary problems, such as urgency or incontinence
• Tremors

How Does Vascular Dementia Progress

Vascular dementia usually progresses gradually in a step-wise fashion in which a person’s abilities deteriorate after a stroke, and then stabilise until the next stroke. If further strokes do not occur, the abilities of people with Vascular dementia may not continue to decline, or in some cases, may improve. However, these improvements may not last. Sometimes the steps are so small that the decline appears gradual. On average though, people with Vascular dementia decline more rapidly than people with Alzheimer’s disease. Often they die from a heart attack or major stroke.

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Can A Regular Mri Show Chronic Microvascular Ischemic Disease

Most of the time, the condition is undiagnosed. It is only when a person undergoes a scam that microvascular ischemic disease is accidentally discovered. Usually, brain MRI showed mild chronic microvascular disease. A regular MRI will reveal a homogenous appearance of the brain.

What does this mean: Prominent sulci and CSF spaces are consistent with cerebral atrophy. Hypodensity within the white matter is non-specific, read more Have mild atrophy and nonspecific signal within the matter. Have mild atrophy and nonspecific signal within the white matter. Also chronic small vessel ischemic change in the brain.

Svd And The Risk For Dementia

The powerful message in all of this is that we need to explore the premise that individuals and societies may succeed in lowering their risk for dementia by reducing vascular risk factors and changing potentially harmful lifestyles. A review of advances in stroke research accomplished during 2018 confirms the impact of adverse lifestyle exposures on brain health and on cognition . Decades ago the lesson was established that a successful cure is dwarfed in its societal impact by a reduction in risk, and books intended for the public are now available with advice on how to achieve the goal of reducing the risk for dementia .

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Csvd As A Dynamic Disease

There is increasing evidence showing that CSVD is more dynamic than originally thought. Lesions progress over time and the long-term outcome and impact on brain damage vary. Cavitation is not the only fate of acute lacunar ischaemic stroke. An acute lacunar ischaemic stroke can also disappear or resemble a WMH . In a prospective study , definite cavitation was only present in 20% of patients, and was marginally associated with increasing time from stroke onset to follow-up scans. A large proportion of lacunar lesions remained looking like WMH. Thus, only calculating cavitated lacunes could lead to a large underestimation of lacunar ischaemic stroke burden. Similarly, WMH burden is likely to be overestimated without previous scans of index stroke lesions.

Cerebral Small Vessel Disease And Blood Pressure Management

Collecting evidence suggests associations between traditional vascular risk factors, such as hypertension, diabetes, hypercholesterolemia, atherosclerosis, cardiovascular and cerebrovascular involvement, and cognitive disorders and dementia. These associations are complex and sometimes differ depending on when in life the risk factors are assessed.

Diabetes is a well-established risk factor for cognitive impairment, the mechanism of this process, however, is not fully understand. The effect of insulin acting directly on the brain is thought to increase the deposition and reduce the degradation of amyloid-protein. Interestingly, Okereke et al showed that women without clinical diabetes but with higher levels of C-peptide, representing insulin secretion, had increased risk of cognitive impairment. Furthermore, Luchsinger et al showed that individuals with higher levels of fasting insulin, with or without clinical diabetes, exhibited a 70% higher risk of developing AD.

Hypertension has historically been considered as one of the most critical risk factors for vascular dementia development, as one of the many causative co-factor for neurodegenerative dementia, and for white matter lesions. Chronic hypertension has been shown to accelerate amyloid deposition, blood-brain barrier dysfunction, microglial cells activation, and subsequent neuronal loss and cognitive impairment in animal models.

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Ideal Response To Svd At The Clinical Level

The patient with SVD keeps many subspecialists occupied. He or she sees the neurologist for failing memory function and for other consequences of lacunar infarcts, the ophthalmologist for failing vision, the nephrologist for failing kidney function, the cardiologist for heart failure, and the family physician and geriatrician for control of vascular risk factors. Each specialist is focused on how to protect his or her subspecialty organ from damage. As a result, there is enormous duplication of effort, when a centralized Vascular Clinic that focusses on optimizing the function of the small blood vessels may be effective. In addition to monitoring and treating the vascular risk factors, such a clinic would also help patients with the lifestyle changes they need to bring about to reduce further SVD and provide support to accomplish these goals.

Relationship Between Ad Biomarkers And Cerebral Svd

As cognitive function can be substantially affected by several factors, including AD pathology, contribution to cognitive impairment by cerebral SVD could be under- or overestimated depending on the cognitive reserve of each individual . For this reason, there is no linear correlation between AD pathology and cognitive impairment . It seems that cerebral SVD independently induces cognitive impairment with concurrent, synergistic exacerbation by AD pathology, resulting in MCI to dementia . Thus, the utilization of biological AD markers in place of its syndromal definition would be beneficial for evaluating the effect of cerebral SVD on AD development. The biomarkers that can be detected and quantified in AD are cerebral A plaques, pathologic tau, and neurodegeneration . The biomarkers of cerebral A plaques are low CSF A42 and cortical amyloid positron emission tomography ligand binding . Biomarkers of pathologic tau are elevated CSF phosphorylated tau and cortical tau PET ligand binding . Biomarkers of neurodegeneration are cerebral hypometabolism on 18F-fluorodeoxyglucose PET, and atrophy on MRI . The results of studies regarding relationships between AD biomarkers, including cerebral A plaques, pathologic tau, and neurodegeneration, and cerebral SVD, are summarized in Table 1.

Table 1. Relationship between AD biomarkers and cerebral SVD.

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Signs Of Vascular Dementia

If you or the people around you notice any of the signs below, you should visit your GP:

• Not being able to understand or respond to things very quickly.
• Not being able to remember things.
• Finding it difficult to concentrate.
• Not being able to find the right word when youre speaking.
• Struggling to plan ahead for everyday tasks.
• Difficulty in learning new tasks
• Seeming down or depressed.

At a later stage, signs may include:

• Becoming confused.
• Behaving differently, especially if youre being aggressive or behaving inappropriately.
• Lacking motivation.
• Not being able to control your emotions.
• Finding it difficult to walk and keep your balance.
• Having problems controlling your bladder.

How Common Is Small Vessel Disease Of The Brain

Small vessel disease accounts for up to 25% of all ischemic strokes3 but also put patients at twice the risk for these conditions4. In addition, CSVD is a leading cause of functional loss, disability and cognitive decline in the elderly. Neuroimaging development allows increased understanding of CSVD.

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Causes And Risk Factors

The cause of microvascular ischemic disease isnt completely understood. It can be the result of plaque buildup and hardening that damages the small blood vessels nourishing the brain. This is the same process that narrows and damages blood vessels to the heart and can lead to heart attacks.

Damage can block blood flow through the blood vessels in the brain, depriving brain cells of oxygen. Or, it can cause blood vessels in the brain to leak and bleed, which can damage neighboring neurons.

Risk factors for microvascular ischemic disease include:

• high blood pressure

Association With Arterial Stiffness

Arterial stiffness is independently associated with cerebral SVD including WMH , SLI , and MB . The mechanism of cerebral SVD is considered to involve vascular endothelial dysfunction, which may be associated with arterial stiffness . Further, blood-brain barrier failure or progression of arteriosclerotic changes may lead to cerebral parenchymal damage . As there are vessel similarities between the kidney and the brain, the presence of chronic kidney disease may also be associated with cerebral SVD based on similar mechanisms .

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Is There Treatment Available

While no treatment can reverse damage that has already been done, treatment to prevent additional strokes is very important. To prevent strokes, medicines to control high blood pressure, high cholesterol, heart disease and diabetes can be prescribed. A healthy diet, exercise and avoidance of smoking and excessive alcohol also lessen the risk of further strokes. Sometimes aspirin or other drugs are prescribed to prevent clots from forming in the small blood vessels.

Drugs can also be prescribed to relieve restlessness or depression or to help the person with dementia to sleep better. In some cases surgery known as carotid endarterectomy may be recommended to remove blockage in the carotid artery, the main blood vessel to the brain. Recent research suggests that cholinesterase inhibitor medications such as Donepezil and Galantamine , which are helpful for some people with Alzheimer’s disease, may also be of some benefit to some people with Vascular dementia. However, the evidence is not yet as clear or compelling as that for the use of these medications with Alzheimer’s disease.

Support is available for the person with Vascular dementia, their families and carers. This support can make a positive difference to managing the condition. Dementia Australia provides support, information, education and counselling for people affected by dementia. Up-to-date information about drug treatments is also available from Dementia Australia.

How Is Vascular Dementia Treated

Vascular dementia can’t be cured. The main goal is to treat the underlying conditions that affect the blood flow to the brain. This can help cut the risk of further damage to brain tissue.

Such treatments may include:

• Medicines to manage blood pressure, cholesterol, triglycerides, diabetes, and problems with blood clotting
• Lifestyle changes, such as following a healthy diet, getting physical activity, quitting smoking, and quitting or decreasing alcohol consumption
• Procedures to improve blood flow to the brain, such as carotid endarterectomy, angioplasty, and stenting the carotid arteries are located in the neck and provide blood flow from the heart to the brain
• Medicines, such as cholinesterase inhibitors to treat the symptoms of dementia or antidepressants to help with depression or other symptoms

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Small Vessel Disease And Vascular Cognitive Impairment

Vascular dementia can also be caused by small vessel disease. This is when the small blood vessels deep within your brain become narrow and clogged up. The damage stops blood from getting to parts of your brain. The damage can build up over time and may cause signs of vascular cognitive impairment. This can eventually lead to vascular dementia.

Many of the things that increase your risk of small vessel disease, such as high blood pressure and diabetes, also increase your risk of stroke.

You can read more about how to reduce your risk of stroke and small vessel disease.

How Is Vascular Dementia Diagnosed

If youre noticing signs of vascular dementia, then you need to go and see your GP as soon as possible.

Your GP will talk to you and do a number of tests to see what may be causing your symptoms. Its probably a good idea to take a friend or family member with you to help you answer your GPs questions. They may have noticed symptoms that you are not aware of, or may be able to say how long youve had them.

To help them rule out any other causes your GP is likely to:

• Talk to you about your symptoms.
• Go through your medical history to see if you have any conditions that are linked to vascular dementia, like heart problems, high blood pressure or diabetes.
• Perform a brief memory test.
• Ask you some questions about your mood.
• Speak to your friend or relative about any changes they may have noticed.
• Take some blood or ask for a urine sample, so that they can check for other problems that could be causing your symptoms such as an infection, thyroid problems or low levels of vitamins or hormones.
• Look at the medication youre taking to see if that could be causing any of your symptoms. It is a good idea to bring a list of all the medications, vitamins and supplements you take including those prescribed by your doctor and the ones you buy yourself.

Your GP may refer you to a dementia specialist. This could be:

• An old-age psychiatrist .
• A geriatrician .
• A neurologist .
• A psychologist .
• A specialist dementia nurse.

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Risk Factors And Causes Of Lacunar Infarcts

Four possible main aetiologies for lacunar ischaemic stroke have been proposed : atheroma of parent arteries or perforating arterioles, embolism from the heart or carotid arteries, and intrinsic small vessel disease . Atheroma in MCA appears to cause < 20% of lacunar ischaemic stroke. In the Warfarin Aspirin Symptomatic Intracranial Disease trial, only 11% of all patients with stroke were lacunar type, which is surprising if MCA stenosis is supposed to be a common cause of lacunar stroke. A recent study also did not find any association between lacunar stroke and MCA stenosis. A systematic review of Asian studies showed that parent artery atherosclerosis accounted for 20% of single lacunar infarcts in anterior circulation territory however, these hospital-based studies were rather small and some were even retrospective. Larger and tubular lacunar infarcts might be more likely to be caused by proximal artery diseases. However, the results of both our study and the Secondary Prevention of Small Subcortical Stokes Trial suggest that it is not possible to identify the cause of a particular recent lacunar ischaemic stroke based on its size, shape or location.,

Key Points About Vascular Dementia

• Vascular dementia is a disorder characterized by damaged brain tissue due to a lack of blood flow. Causes can include blood clots, ruptured blood vessels, or narrowing or hardening of blood vessels that supply the brain.
• Symptoms can include problems with memory and concentration, confusion, changes in personality and behavior, loss of speech and language skills, and sometimes physical symptoms such as weakness or tremors.
• Vascular dementia tends to progress over time. Treatments can’t cure the disease, but lifestyle changes and medicines to treat underlying causes might help slow its progress.
• Surgical procedures to improve blood flow to the brain can also be helpful. Other medicines might slow the progression of dementia or help with some of the symptoms it can cause.
• A person with vascular dementia may eventually need full-time nursing care or to stay in a long-term care facility.

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Which Is The Best Treatment For Small Vessel Disease

The treatment for small vessel disease involves medications to control the narrowing of your small blood vessels that could lead to a heart attack and to relieve pain. Your doctor could prescribe: Nitroglycerin. Nitroglycerin tablets, sprays and patches can ease chest pain by relaxing your coronary arteries and improving blood flow. Beta blockers.

New Drug Shows Promise For Preventing And Even Reversing Damage From Age

Cerebral small vessel disease is one of the most commonly associated causes of age-related dementia and stroke. New research, led by the University of Edinburgh, may have finally uncovered the mechanism by which SVD causes brain cell damage, as well as a potential treatment to prevent the damage, and possibly even reverse it.

SVD is thought to be responsible for up to 45 percent of dementia cases, and the vast majority of senior citizens are suspected of displaying some sign of the condition. One study strikingly found up to 95 percent of subjects between the ages of 60 and 90 displayed some sign of SVD when examined through MRI scans.

The new research set out to examine early pathological features of SVD and found that dysfunction in endothelial cells are some of the first signs of the disease’s degenerative progression. These are cells that line small blood vessels in the brain and, in early stages of SVD, they secrete a protein that impairs production of myelin, a compound essential for the protection of brain cells.

The hypothesis was that if this endothelial cell dysfunction could be repaired then subsequent brain damage from SVD could be prevented. The study did successfully treat rats engineered with SVD using drugs that stabilize this endothelial cell dysfunction. Not only did symptoms of SVD disappear but, in early-stages of the disease, the treatment was found to reverse the associated brain damage.

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