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CADASIL

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Related Terms
  • Agnogenic medial arteriopathy, CASIL, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, chromosome 19, chronic familial vascular encephalopathy, dementia, familial Binswanger's disease, familial disorder with subcortical ischemic strokes, familial subcortical dementia (hereditary multi-infarct type), hereditary multi-infarct dementia, leukoaraiosis, NOTCH3, subcortical vascular dementia.

Background
  • Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, commonly known as CADASIL, is an inherited disease that affects small blood vessels, especially those leading to the brain. CADASIL affects the walls of the blood vessels, causing them to thicken to the extent that the flow of blood to the brain is diminished.
  • Most cases of CADASIL are inherited, or passed down from parents to children. CADASIL is the most common form of hereditary stroke disorder. It is caused by a mutation or defect in the NOTCH3 gene on chromosome 19, which affects the muscular walls of the small blood vessels in part of the brain. The NOTCH3 gene provides instructions for making the NOTCH3 receptor protein, which is essential to the normal functioning of smooth muscle cells in the blood vessels. Interestingly, the NOTCH3 gene is very similar to a mutated gene found in some forms of premature Alzheimer's disease.
  • When inherited, CADASIL follows an autosomal dominant pattern, meaning that only one copy of the defective gene is necessary for the disease to occur. There have been reports of CADASIL occurring in individuals with no family history of the disease. These cases may be the result of a spontaneous genetic mutation in the sperm or egg cells or in the developing embryo.
  • The most common symptoms associated with CADASIL include migraine headache and stroke, which are interruptions in the flow of blood to the brain. Over time, multiple strokes cause damage to the brain tissue and result in dementia, which affects cognitive function. Other symptoms may include problems with the brain tissue, decline in mental functioning, seizures, vision problems, and psychological problems such as depression. People with CADASIL may also have an increased risk of heart disease.
  • The exact prevalence of CADASIL is unknown. Because of the effects on mental status and cognitive functioning, some researchers question whether this disorder is underdiagnosed among psychiatric patients. Its prevalence was estimated to be about one in 50,000 adults by a Scottish study. Worldwide, about 400 families with CADASIL have been described in the scientific literature. CADASIL occurs in people from all racial and ethnic groups.
  • There is no cure for CADASIL, but there are many treatments to alleviate symptoms and prevent complications. Symptoms of CADASIL tend to begin at around age 30 and progress slowly. By age 65, most people with CADASIL have severe psychological problems. One study found that the mean age at death was about 65 for men and 71 for women.
  • The National Institute of Neurological Disorders and Stroke (NINDS) is currently conducting scientific studies to find drugs and other therapies that will reduce the cognitive problems caused by CADASIL.

Signs and symptoms
  • General: Symptoms may vary widely, even among members of the same family, in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Age of onset, disease severity, and disease progression cannot be predicted in individuals with the disease. In addition, it is possible that the symptoms and severity of CADASIL worsen with each successive generation. This is called anticipation.
  • Brain disease: Acute encephalopathy, which literally means "brain disease," has been reported in some patients with CADASIL. Symptoms of acute encephalopathy include confusion, headache, fever, seizures, and coma. Although this condition is reversible, it has been fatal in some patients. Encephalopathy may have many causes, including lack of oxygen to the brain, and reversal depends on the cause.
  • Cognitive problems: About 60% of people with CADASIL experience cognitive problems, including depression, dementia, and behavioral, language, and memory problems. Cognitive problems in CADASIL may begin as early as age 35 and tend to progress slowly. By age 65, most people with CADASIL have severe cognitive deficits and require assistance for activities of daily living and may eventually require long-term care.
  • Epilepsy: About 10% of people with CADASIL have epilepsy, which may be characterized by serious seizures. Epilepsy in CADASIL patients tends to appear in middle age.
  • Migraine headache: About 40% of people with CADASIL experience migraine headaches, most of which are accompanied by aura, the signs that precede onset of the headache. Visual aura may include seeing zigzag lines, flashing lights, or other hallucinations; temporary blind spots; sensitivity to light; blurred vision; or eye pain. Migraines may start at around age 26. Interestingly, the NOTCH3 gene is in the same location as the gene for a hereditary migraine disorder.
  • Psychiatric disorders: About 30% of people with CADASIL have some sort of psychiatric disorder. This may include depression, personality changes, or psychosis. Because of the effects on mental status and cognitive functioning, some researchers have questioned whether CADASIL is underdiagnosed in psychiatric patients.
  • Stroke: About 85% of people with CADASIL experience strokes or transient ischemic attacks (TIAs). A stroke or TIA is an interruption in the flow of blood to the brain. However, a stroke is more severe and may cause more damage, while a TIA, or ministroke, comes and goes more quickly. Symptoms include sudden weakness or numbness on one side of the body, confusion or trouble speaking or understanding speech, sudden onset of vision problems in one or both eyes, sudden loss of coordination with dizziness or inability to walk, and sudden severe headache. The average age of onset of strokes or TIAs in people with CADASIL is about 46 years of age. Incidence of TIA or stroke may increase during pregnancy.

Diagnosis
  • General: There are no generally accepted means of diagnosing cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). The specific symptoms, age of onset, and course of the disease help a clinician better understand the disorder in an individual patient. Key features that might cause a clinician to suspect CADASIL include stroke or TIA before age 60, changes in cognitive function, behavioral changes or problems, and migraine with aura, the signs that precede onset of the headache. In addition, a thorough family history should be obtained. Additional evaluations should include a focus on neurological and psychiatric issues.
  • Biopsy: In a biopsy, a small sample of tissue is removed from the body and analyzed in a laboratory. To diagnose CADASIL, a skin biopsy may be performed. Under an electron microscope, the walls of the blood vessels can be evaluated for changes associated with the disease. A biopsy can also detect destruction of the cells in the muscle tissue surrounding the small blood vessels.
  • Imaging: Magnetic resonance imaging (MRI) of the brain may reveal changes in electrical activity indicating epilepsy, changes in the blood vessels in certain parts of the brain, or evidence of past bleeding in the brain.
  • Genetic testing: If CADASIL is suspected, a genetic test may be performed to confirm a diagnosis. A sample of the patient's blood is taken and analyzed in a laboratory for the defect in the NOTCH3 gene. If this mutation is detected, a positive diagnosis is made.
  • Prenatal DNA testing: If there is a family history of CADASIL, prenatal testing may be performed to determine whether the fetus has the disorder. Amniocentesis and chorionic villus sampling (CVS) can diagnose CADASIL. However, because there are serious risks associated with these tests, patients should discuss the potential health benefits and risks with a medical professional.
  • During amniocentesis, a long, thin needle is inserted through the abdominal wall and into the uterus, and a small amount of amniotic fluid is removed from the sac surrounding the fetus. Cells in the fluid are then analyzed for normal and abnormal chromosomes. This test is performed after 15 weeks of pregnancy. The risk of miscarriage is about one in 200-400 patients. Some patients may experience minor complications, such as cramping, leaking fluid, or irritation where the needle was inserted.
  • During chorionic villus sampling (CVS), a small piece of tissue (chorionic villi) is removed from the placenta between the ninth and 14th weeks of pregnancy. CVS may be performed through the cervix or through the abdomen. The cells in the tissue sample are then analyzed for the mutation in the NOTCH3 gene. Miscarriage occurs in about 0.5%-1% of women who undergo this procedure.

Complications
  • Brain disease: Complications of acute encephalopathy may include confusion, headache, fever, seizures, and coma. Although this condition is reversible, it has been fatal in some patients. Encephalopathy may have many causes, including lack of oxygen to the brain, and reversal depends on the cause.
  • Cognitive decline: The main complication of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the steady decline in cognitive function. About 60% of people with CADASIL experience cognitive problems, including depression, dementia, and behavioral, language, and memory problems. While onset of strokes tends to occur at around age 35 and while symptoms progress slowly, most people with CADASIL have severe cognitive damage by age 65.
  • Heart disease: People with CADASIL may have increased risk of heart disease. People with CADASIL may not have the classic risk factors for heart attack, which include high blood pressure and high blood cholesterol levels. However, the damage to the blood vessels caused by the disease may predispose these individuals to heart attack.
  • Impaired mobility: Cognitive decline caused by recurrent strokes may cause enough damage to the brain to impair basic human functions, including walking, feeding, and speaking.

Treatment
  • General: There is no cure for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Treatment aims to reduce the incidence and severity of symptoms and prevent or manage complications. Certain medications may increase the risk of stroke and should be avoided. These may include anticoagulants, such as warfarin. In addition, angiography, or X-rays of the blood vessels, should be avoided, because of potential adverse effects.
  • Antidepressants: Because depression is a common symptom of CADASIL, antidepressant medications may be prescribed. There are several classes of antidepressant drugs. Tricyclic antidepressants include amitriptyline (Elavil®), imipramine (Tofranil®), and nortriptyline (Pamelor®). Selective serotonin reuptake inhibitors (SSRIs) include fluoxetine (Prozac®), paroxetine (Paxil®), and sertraline (Zoloft®). Monoamine oxidase inhibitors (MAOIs) include phenelzine (Nardil®) and tranylcypromine (Parnate®). Bupropion (Wellbutrin® or Zyban®) is in a unique class of antidepressants that may also help with smoking cessation. All of these medications may have side effects that can range from mild to severe and should be discussed in detail with a qualified healthcare provider.
  • Aspirin: Aspirin may be prescribed to reduce the risk of heart attack. Doses typically range from 80 to 325 milligrams daily as prevention against heart disease.
  • Migraine medications: Different drugs may be used to treat migraine headaches, which commonly occur in individuals with CADASIL. Common medications for migraine include nonsteroidal anti-inflammatory agents (NSAIDs) such as ibuprofen (Advil®, Motrin®, and others) and aspirin. Triptan medications may be used to treat severe migraine. These include sumatriptan (Imitrex®), rizatriptan (Maxalt®), naratriptan (Amerge®), zolmitriptan (Zomig®), almotriptan (Axert®), frovatriptan (Frova®), and eletriptan (Relpax®). Side effects of triptan medications may include nausea, dizziness, and muscular weakness. There have been rare reports of stroke or heart attack associated with triptan use. Ergot medications including ergotamine (Ergomar®) and dihydroergotamine were common migraine treatments before triptans became available. Because nausea may accompany migraine, antiemetic (antinausea) drugs such as metoclopramide or prochlorperazine may be useful. Opiates, particularly codeine, may be used for severe migraines that do not respond to other drugs. However, these drugs are habit forming and should be regarded as a last resort.
  • Psychiatric medications: Other medications may be prescribed to treat the variety of potential psychiatric symptoms, including psychosis, which may occur as CADASIL progresses.
  • Smoking cessation: Smoking is a major risk factor for stroke (a symptom of CADASIL) and other conditions, such as heart disease. Several options are available to help people quit smoking. These include behavioral modification programs, prescription drugs, and over-the-counter drugs such as the nicotine patch and nicotine gum.
  • Support groups: Support groups exist for people who have CADASIL and their family members. Although groups specific to CADASIL are limited, groups that focus on the needs of patients with Alzheimer's disease and Huntington's disease may be helpful. Such groups can provide emotional support and counseling, as well as practical help for navigating the challenges of daily life.
  • Investigational therapies: Scientific studies are evaluating the safety and efficacy of donepezil HCl (Aricept®), which is commonly used to treat symptoms of Alzheimer's disease. Use of this medication might help with the cognitive decline and dementia observed in CADASIL.
  • There is some evidence that people with high blood pressure tend to have faster progression of CADASIL. However, it is not clear if taking blood pressure-lowering medications can help slow down disease progression.

Integrative therapies
  • Note: Currently, there is a lack of scientific evidence on the use of integrative therapies for the treatment or prevention of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). The therapies listed below have been studied for related conditions, including cognitive function, dementia, and memory loss. The integrative therapies listed below should be used only under the supervision of a qualified healthcare provider and should not be used in replacement of other proven therapies.
  • Good scientific evidence:
  • Bacopa: Bacopa monnieri leaf extract is called brahmi in Ayurvedic medicine (medicine practiced in India) and is widely used in India for enhancing memory, relieving pain, and treating epilepsy. Although bacopa is traditionally used in Ayurvedic medicine to enhance cognition, high-quality clinical trials are lacking. Two methodologically weak studies found some evidence that bacopa improves cognition. However, more high-quality and independent research is needed before bacopa can be recommended for enhancing brain function in adults or children.
  • Bacopa may interact with medications such as calcium channel blockers (used for arrhythmias and high blood pressure), thyroid medications, phenytoin (Dilantin®), and drugs metabolized by the liver. Use cautiously with drugs or herbs that are metabolized by cytochrome P450 enzymes, thyroid drugs, calcium-blocking drugs, and sedatives. Avoid if allergic or hypersensitive to Bacopa monnieri, its constituents, or any member of the Scrophulariaceae (figwort) family. Avoid if pregnant or breastfeeding.
  • Ginkgo: Multiple clinical trials have evaluated ginkgo for a syndrome called cerebral insufficiency. This condition, more commonly diagnosed in Europe than the United States, may include poor concentration, confusion, absentmindedness, decreased physical performance, fatigue, headache, dizziness, depression, and anxiety. It is believed that cerebral insufficiency is caused by decreased blood flow to the brain due to clogged blood vessels. Some studies report benefits of ginkgo in patients with these symptoms, but most have been poorly designed and without reliable results. Better studies are needed before a conclusion can be made.
  • Avoid if allergic or hypersensitive to members of the Ginkgoaceaefamily. If allergic to mango rind, sumac, poison ivy, poison oak, or cashews, then allergy to ginkgo is possible. Avoid with blood thinners (like aspirin or warfarin (Coumadin®)), due to an increased risk of bleeding. Ginkgo should be stopped two weeks before surgical procedures. Ginkgo seeds are dangerous and should be avoided. Skin irritation and itching may also occur due to ginkgo allergies. Ginkgo should not be used in supplemental doses if pregnant or breastfeeding.
  • Music therapy: Music is used to influence physical, emotional, cognitive, and social well-being and improve quality of life for healthy people, as well as those who are disabled or ill. It may involve either listening to or performing music, with or without the presence of a music therapist. Music therapy may help maintain mental performance in elderly adults undergoing surgical procedures, reduce postoperative confusion and delirium, and increase energy levels.
  • Music therapy is generally known to be safe.
  • Unclear or conflicting scientific evidence:
  • Acupuncture: Acupuncture has been reported to help improve memory and cognitive performance in the elderly. However, there is currently insufficient available evidence for the use of acupuncture in cognitive disorders and communication disorders. More research is necessary.
  • Needles must be sterile in order to avoid disease transmission. Avoid with valvular heart disease, infections, or bleeding disorders, or with anticoagulants (drugs that increase the risk of bleeding), medical conditions of unknown origin, and neurological disorders. Avoid on areas that have received radiation therapy and during pregnancy. Use cautiously with pulmonary disease (like asthma or emphysema). Use cautiously in elderly or medically compromised patients, diabetics, or those with a history of seizures. Avoid electroacupuncture with arrhythmia (irregular heartbeat) or in patients with pacemakers.
  • Ayurveda: The herb brahmi (Bacopa monnieri) is used in many Ayurvedic preparations for a variety of ailments. There is evidence from well-designed studies that it may improve memory and cognitive function in adults. Another study suggests that the herbal preparation Maharishi Amrit Kalash (MAK)-4 may enhance attention capacity or alertness, and thus reverse some of the detrimental cognitive effects of aging. Further research is needed to confirm these results.
  • Ayurvedic herbs should be used cautiously, because they are potent, and some constituents can be potentially toxic if taken in large amounts or for a long period of time. Some herbs imported from India have been reported to contain high levels of toxic metals. Ayurvedic herbs may interact with other herbs, foods, and drugs. A qualified healthcare professional should be consulted before use. Use guggul cautiously with peptic ulcer disease. Patients should avoid sour food, alcohol, and heavy exercise with use of this herb. Mahayograj guggul should not be taken for long periods of time. Pippali (Piper longum) should be taken with milk and avoided with asthma. Avoid sweet flag, and avoid amlaki (Emblica officinalis) at bedtime. Avoid harda (Terminalia chebula) if pregnant. Avoid Ayurveda with traumatic injuries, acute pain, advanced disease stages, and medical conditions that require surgery.
  • Bacopa: Although bacopa is traditionally used in Ayurvedic medicine to enhance memory, additional study is needed before a firm conclusion can be drawn.
  • Bacopa may interact with medications, such as calcium channel blockers (used for arrhythmias and high blood pressure), thyroid medications, phenytoin (Dilantin®), and drugs metabolized by the liver. Use cautiously with drugs or herbs that are metabolized by cytochrome P450 enzymes, thyroid drugs, calcium-blocking drugs, and sedatives. Avoid if allergic or hypersensitive to Bacopa monnieri, its constituents, or any member of the Scrophulariaceae (figwort) family. Avoid if pregnant or breastfeeding.
  • Beta-carotene: Antioxidants such as beta-carotene may be helpful for increasing cognitive performance and memory. Long-term, but not short-term, beta-carotene supplementation appears to benefit cognition.
  • Avoid if sensitive to beta-carotene, vitamin A, or any other ingredients in beta-carotene products.
  • Black tea: Several preliminary studies have examined the effects of caffeine, tea, or coffee use on short- and long-term memory enhancement. It remains unclear if tea is beneficial for this use. Limited, low-quality research also reports that the use of black tea may improve mental performance or alertness and cognition.
  • Black tea contains caffeine, which is a stimulant. Avoid if allergic or hypersensitive to caffeine or tannins. Skin rash and hives have been reported with caffeine ingestion. Use caution in those with diabetes. Use caution if pregnant. Heavy caffeine intake during pregnancy may increase the risk of SIDS (sudden infant death syndrome). Very high doses of caffeine have been linked with birth defects. Caffeine is transferred into breast milk. Caffeine ingestion by infants can lead to sleep disturbances or insomnia. Infants nursing from mothers consuming greater than 500 milligrams of caffeine daily have been reported to experience tremors and heart rhythm abnormalities. Tea consumption by infants has been linked to anemia, decreased iron metabolism, and irritability.
  • Boron: Preliminary human studies report better performance on tasks of eye-hand coordination, attention, perception, short-term memory, and long-term memory with the use of boron. Although boron has not been studied in CADASIL, it may be beneficial in improving cognitive function.
  • Avoid if allergic or sensitive to boron, boric acid, borax, citrate, aspartate, or glycinate. Avoid with a history of diabetes, seizure disorder, kidney disease, liver disease, depression, anxiety, high blood pressure, skin rash, anemia, asthma, or chronic obstructive pulmonary disease (COPD). Avoid with hormone-sensitive conditions like breast cancer or prostate cancer. Avoid if pregnant or breastfeeding.
  • Chromium: Early research suggests that chromium picolinate may help improve cognitive function in the elderly. Further research is needed in this area.
  • Trivalent chromium appears to be safe, because side effects are rare or uncommon. However, hexavalent chromium may be toxic (poisonous). Avoid if allergic to chromium, chromate, or leather. Use cautiously with diabetes, liver problems, weakened immune systems (such as HIV/AIDS patients or organ transplant recipients), depression, Parkinson's disease, heart disease, and stroke, and in patients who are taking medications for these conditions. Use cautiously if driving or operating machinery. Use cautiously if pregnant or breastfeeding.
  • Cranberry: Preliminary study results show that cranberry juice may increase overall memory enhancement. Further well-designed clinical trials are needed to confirm these results.
  • It is best not to use sweetened cranberry juice or cranberry juice cocktail, due to the high sugar content. The use of 100% cranberry juice products is recommended by healthcare providers. Avoid if allergic to cranberries, blueberries, or other plants of the Vaccinium species. Sweetened cranberry juice may affect blood sugar levels. Use cautiously with a history of kidney stones. Avoid more than the amount usually found in foods if pregnant or breastfeeding.
  • Creatine: Early studies show that creatine may improve memory in certain populations, such as vegetarians and the elderly. Further research is required before conclusions can be made.
  • Avoid if allergic to creatine or with diuretics (like hydrochlorothiazide and furosemide (Lasix®)). Use caution in those with asthma, diabetes, gout, kidney, liver or muscle problems, or stroke, or those with a history of these conditions. Avoid dehydration. Avoid if pregnant or breastfeeding.
  • Gingko: There is preliminary research showing small improvements in memory and other brain functions with use of ginkgo in patients with age-associated memory impairment (AAMI), although some studies disagree. Overall, there is currently not enough clear evidence to recommend for or against ginkgo for this condition. It remains unclear if ginkgo is effective for memory enhancement in healthy patients. Further well-designed research is needed, as existing study results conflict.
  • Avoid if allergic or hypersensitive to members of the Ginkgoaceaefamily. If allergic to mango rind, sumac, poison ivy, poison oak, or cashews, then allergy to ginkgo is possible. Avoid with blood thinners (like aspirin or warfarin (Coumadin®)), due to an increased risk of bleeding. Ginkgo should be stopped two weeks before surgical procedures. Ginkgo seeds are dangerous and should be avoided. Skin irritation and itching may also occur due to ginkgo allergies. Ginkgo should not be used in supplemental doses if pregnant or breastfeeding.
  • Ginseng: The use of ginseng for mental performance has been assessed using standardized measurements of reaction time, concentration, learning, math, and logic. Benefits have been seen both in healthy young people and in older ill patients. Effects have also been reported for the combination use of ginseng with Ginkgo biloba. However, some negative results have also been reported. Therefore, although the sum total of available scientific evidence does suggest some effectiveness of short-term use of ginseng for mental performance, better research is necessary before a strong conclusion can be made.
  • Avoid ginseng with known allergy to plants in the Araliaceae family. There has been a report of a serious life-threatening skin reaction, possibly caused by contaminants in ginseng formulations.
  • Gotu kola: Ayurveda regards gotu kola (Centella asiatica) as an important rejuvenating herb for nerve and brain cells, believed to be capable of increasing intelligence, longevity, and memory. Limited available clinical research has investigated a combination product containing gotu kola on cognitive function in the elderly but did not find any benefit. Additional research is needed to confirm these findings.
  • Avoid if allergic to gotu kola, asiaticoside, asiatic acid, or madecassic acid. Avoid with a history of high cholesterol, cancer, or diabetes. Avoid if pregnant or breastfeeding.
  • Green tea: Several preliminary studies have examined the effects of caffeine, tea, or coffee use on short- and long-term memory and cognition. It remains unclear if tea is beneficial for this use. Limited, low-quality research reports that the use of green tea may improve cognition and mental performance or alertness.
  • Green tea contains caffeine, which is a stimulant. Avoid if allergic or hypersensitive to caffeine or tannins. Use cautiously with diabetes or liver disease.
  • Guarana: Guarana is a native species of South America and has stimulating properties when taken by mouth. Guarana is also used to enhance athletic performance and reduce fatigue. Guarana has not been shown to alter cognitive enhancement or arousal in preliminary studies. Caffeine found in guarana may improve simple reaction time, but may not improve immediate memory. Additional research is needed in this area.
  • Avoid if allergic or hypersensitive to guarana (Paullinia cupana), caffeine, tannins, or species of the Sapindaceae family. Avoid with hypertension, psychological or psychiatric disorders, liver impairment, or arrhythmias. Avoid with other stimulatory agents, especially ephedra. Use cautiously with breast disease, impaired kidney function, diabetes, preexisting mitral valve prolapse, iron deficiency, gastric or duodenal ulcers, bleeding disorders, or glaucoma, or if at risk for osteoporosis. Use cautiously if undergoing electroconvulsive therapy (ECT). Avoid if pregnant or breastfeeding.
  • Guided imagery: The term guided imagery may be used to refer to a number of techniques, including metaphor, story telling, fantasy, game playing, dream interpretation, drawing, visualization, active imagination, or direct suggestion using imagery. Early research suggests that guided imagery of short duration may improve working memory. Further research is needed before a firm conclusion can be drawn.
  • Guided imagery is usually intended to supplement medical care, not to replace it, and guided imagery should not be relied on as the sole therapy for a medical problem. Contact a qualified healthcare provider if mental or physical health is unstable. Never use guided imagery techniques while driving or doing any other activity that requires strict attention. Use cautiously with physical symptoms that can be brought about by stress, anxiety, or emotional upset, because imagery may trigger these symptoms. In patients feeling unusually anxious while practicing guided imagery, or in patients with a history of trauma or abuse, a qualified healthcare provider should be consulted before practicing guided imagery.
  • Jasmine: Odors and memory improvement are considered to be somehow linked in the brain. Two clinical trials using weakly jasmine-scented rooms found that subjects did not have improved recall of a physical environment without the jasmine odor trigger but could remember a word list better when exposed to a jasmine trigger. More research is needed in this area.
  • Use cautiously during pregnancy, according to traditional use. Use cautiously in patients allergic to jasmine, jasmine oil, or other fragrances. Use cautiously during lactation, as jasmine flowers applied to the breasts have been used as a lactifuge. Avoid oral consumption of essential oils, including jasmine essential oil, as they are extremely potent and can be poisonous.
  • Khat: Khat is a flowering evergreen plant that has been grown for use as a stimulant for centuries. Khat has been evaluated for its benefits for cognitive function. However, the results are mixed, with some studies showing benefit and others showing negative effects. Additional research is needed to clarify these findings.
  • When taken by mouth, it is unknown whether khat is physically addictive. However, it is linked to psychological dependence and is illegal in the United States. Avoid if allergic to the Celastraceae family (staff vine family). Use cautiously if taking amoxicillin, ampicillin, or stimulants. Use cautiously with a history of high blood pressure, tachycardia (fast heartbeat), depression, or motor tics (Tourette's syndrome). Avoid with glaucoma or mental illness. Avoid driving or operating heavy machinery after using khat. Avoid holding khat in the cheek for a long time. Avoid if pregnant or breastfeeding.
  • Kundalini yoga: Kundalini yoga is one of many traditions of yoga that share common roots in ancient Indian philosophy. It is comprehensive, in that it combines physical poses with breath control exercises, chanting (mantras), meditations, prayer, visualizations, and guided relaxation. Breathing exercises are an important part of Kundalini yoga. There is some evidence from studies with healthy volunteers that use of certain breathing techniques (such as breathing solely through one nostril or the other) may improve different aspects of cognitive function. More studies are needed to determine if these techniques can reliably be used to improve cognitive function and possibly aid in treating cognitive and nervous system disorders.
  • Avoid exercises that involve stoppage of breath, or with heart or lung problems, insomnia, poor memory, or concentration. Avoid certain inverted poses with disc disease of the spine, fragile or atherosclerotic neck arteries, risk for blood clots, extremely high or low blood pressure, glaucoma, detachment of the retina, ear problems, severe osteoporosis, or cervical spondylitis. Use cautiously with mental disorders, as some techniques may cause an altered state of consciousness. Kundalini yoga is considered safe and beneficial for use during pregnancy and lactation when practiced under the guidance of expert instruction. Lamaze techniques are based on yogic breathing. If started early in the pregnancy, it may be possible to master the ability of breathing to reduce stress and aid in labor. Teachers of yoga are generally not medically qualified and should not be regarded as sources of medical advice for management of clinical conditions.
  • Lavender: Although lavender is a sedative-type aroma, use during recess periods in a work environment after accumulation of fatigue seemed to prevent deterioration of cognitive performance in subsequent work sessions. Further well-designed studies are needed before a conclusion can be drawn.
  • Avoid if allergic or hypersensitive to lavender. Avoid with history of seizures, bleeding disorders, eating disorders (anorexia, bulimia), or anemia (low levels of iron). Avoid if pregnant or breastfeeding.
  • L-carnitine: There are a limited number of studies relevant to the use of carnitine for memory. According to available evidence, carnitine does not appear to have any effect on memory. Additional research is needed before a conclusion can be made.
  • Avoid with known allergy or hypersensitivity to carnitine. Use cautiously with peripheral vascular disease, hypertension (high blood pressure), alcohol-induced liver cirrhosis, and diabetes. Use cautiously in low-birthweight infants and individuals on hemodialysis. Use cautiously if taking anticoagulants (blood thinners), beta-blockers, or calcium channel blockers. Avoid if pregnant or breastfeeding.
  • Lemon balm: Clinical data suggest that the use of standardized lemon balm (Melissa officinalis) extract has some effect on particular self-reported measures of mood and cognitive performance. More rigorous studies need to be conducted using patient-relevant outcomes to better assess the validity of these results as they apply to patient care.
  • According to available research, lemon balm taken by mouth has been reported to be relatively well tolerated when taken for up to eight weeks. Evidence for topical administration of lemon balm cream suggested minimal side effects for up to 10 days of application. Avoid if allergic or hypersensitive to lemon balm. Avoid with Graves' disease or thyroid hormone replacement therapy. Use cautiously in glaucoma because lemon balm may increase eye pressure. Use caution when operating heavy machinery. Lemon balm preparations may contain trace amounts of lead. Avoid if pregnant or breastfeeding.
  • Macrobiotic diet: Macrobiotics is a predominantly vegetarian, whole-foods diet that emphasizes whole grains (especially brown rice), vegetables, fruits, legumes, and seaweeds. The evidence is mixed as to whether or not a macrobiotic diet helps, hinders, or has no effect on cognitive function in children.
  • There is a risk of nutritional deficiencies with use of an exclusive macrobiotic diet. However, this can be avoided with appropriate menu planning. Use cautiously with cancer or other medical conditions without expert planning or supplementation. Macrobiotic diets are not recommended in children or adolescents without professional guidance or appropriate supplementation, and they are also not recommended in pregnant or lactating women, due to potential deficiencies, unless properly supplemented.
  • Meditation: Some forms of meditation may have positive effects on cognitive function. However, there is not enough clear evidence that any specific form of meditation can support or enhance cognitive function.
  • Use cautiously with underlying mental illnesses. People with psychiatric disorders should consult with their primary mental healthcare professionals before starting a program of meditation, and they should explore how meditation may or may not fit in with their current treatment plan. Avoid with risk of seizures. The practice of meditation should not delay the time to diagnosis or treatment with more proven techniques or therapies and should not be used as the sole approach to illnesses.
  • Reiki: Early research suggests that reiki therapy may improve behavioral and memory problems in patients with mild cognitive disorders. However, additional studies are needed to confirm these findings.
  • Reiki is not recommended as the sole treatment approach for potentially serious medical conditions and should not delay the time it takes to consult with a healthcare professional or receive established therapies. Use cautiously with psychiatric illnesses.
  • Rhodiola: Early human study suggests that Rhodiola may benefit learning, memory, and mental performance. Well-designed studies are needed before a conclusion may be made.
  • Avoid if allergic or sensitive to Rhodiola. Use cautiously in people with diabetes, cardiovascular disease, or neurological or psychiatric disorders. Rhodiola is not recommended for use during pregnancy or breastfeeding.
  • Rhubarb: Preliminary research has investigated rhubarb along with other herbs in the treatment of age-associated memory impairment (AAMI). Studies of rhubarb alone are needed to discern rhubarb's effect on aging and memory.
  • Avoid if allergic or hypersensitive to rhubarb, its constituents, or related plants from the Polygonaceae family. Avoid using rhubarb for more than two weeks, because it may induce tolerance in the colon, melanosis coli, laxative dependence, pathological alterations to the colonic smooth muscles, and substantial loss of electrolytes. Avoid with atony, colitis, Crohn's disease, dehydration with electrolyte depletion, diarrhea, hemorrhoids, insufficient liver function, intestinal obstruction or ileus, irritable bowel syndrome, menstruation, pre-eclampsia, renal disorders, ulcerative colitis, or urinary problems. Avoid handling rhubarb leaves, as they may cause contact dermatitis. Avoid rhubarb in children under age 12, due to water depletion. Use cautiously with bleeding disorders, cardiac conditions, coagulation therapy, constipation, history of kidney stones, or thin or brittle bones. Use cautiously if taking antipsychotic drugs or oral drugs, herbs, or supplements (including calcium, iron, and zinc). Avoid if pregnant or breastfeeding.
  • Riboflavin: Adequate nutrient supplementation with riboflavin (vitamin B2) may be required for the maintenance of adequate cognitive function. Treatment with B-vitamins including riboflavin has been reported to improve scores of depression and cognitive function in patients taking tricyclic antidepressants. This may be related to tricyclic-caused depletion of riboflavin levels.
  • Avoid if allergic or hypersensitive to riboflavin. Since the amount of riboflavin a human can absorb is limited, riboflavin is generally considered safe. Riboflavin is generally regarded as safe during pregnancy and breastfeeding. The U.S. Recommended dietary allowance (RDA) for riboflavin in pregnant women is higher than for nonpregnant women and is 1.4 milligrams daily (1.6 milligrams for breastfeeding women).
  • Sage: Sage has long been suggested as a possible therapy for memory and cognitive improvement. High-quality research is needed to confirm available study findings and determine the best dose.
  • Avoid if allergic or hypersensitive to sage species, their constituents, or to members of the Lamiaceae (mint) family. Use cautiously with hypertension (high blood pressure). Use sage essential oil or tincture cautiously in patients with epilepsy. Avoid if pregnant or breastfeeding.
  • Soy: It is unclear if soy isoflavone supplementation in postmenopausal women may improve cognitive function. Results from studies are mixed.
  • Avoid if allergic to soy. Breathing problems and rash may occur in sensitive people. Soy, as a part of the regular diet, is traditionally considered to be safe during pregnancy and breastfeeding, but there are limited scientific data. The effects of high doses of soy or soy isoflavones in humans are not clear and therefore are not recommended. There has been a case report of vitamin D deficiency rickets in an infant nursed with soybean milk (not specifically designed for infants). People who experience colitis (intestinal irritation) from cow's milk may experience intestinal damage or diarrhea from soy. It is not known if soy or soy isoflavones share the same side effects as estrogens, such as increased risk of blood clots. The use of soy is often discouraged in patients with hormone-sensitive cancers such as breast, ovarian, or uterine cancer. Other hormone-sensitive conditions such as endometriosis may also be worsened. Patients taking blood-thinning drugs such as warfarin should check with a doctor and pharmacist before taking soy.
  • Turmeric: Curcumin has been shown to have antioxidant and anti-inflammatory properties and to reduce beta-amyloid and plaque burden in lab studies. However, there is currently not enough evidence to suggest the use of curcumin for cognitive function.
  • Avoid if allergic or hypersensitive to turmeric, curcumin, yellow food colorings, or plants belonging to the Zingiberaceae (ginger) family. Use cautiously with a history of bleeding disorders, immune system deficiencies, liver disease, diabetes, hypoglycemia, or gallstones. Use cautiously with blood thinners, such as warfarin (like Coumadin®), and blood sugar-altering medications. Avoid in medicinal amounts if pregnant or breastfeeding. Turmeric should be stopped prior to scheduled surgery.
  • Yoga: There is limited human research on yoga for memory improvement. Better studies are needed before a conclusion can be made.
  • Yoga is generally considered to be safe in healthy individuals when practiced appropriately. Avoid some inverted poses with disc disease of the spine, fragile or atherosclerotic neck arteries, risk for blood clots, extremely high or low blood pressure, glaucoma, detachment of the retina, ear problems, severe osteoporosis, or cervical spondylitis. Certain yoga breathing techniques should be avoided in people with heart or lung disease. Use cautiously with a history of psychotic disorders. Yoga techniques are believed to be safe during pregnancy and breastfeeding when practiced under the guidance of expert instruction (the popular Lamaze techniques are based on yogic breathing). However, poses that put pressure on the uterus, such as abdominal twists, should be avoided in pregnancy.

Prevention
  • General: Because cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited condition, there is currently no known way to prevent it. However, a number of options are available for prospective parents with a family history of CADASIL.
  • Genetic testing and counseling: Individuals who have CADASIL may meet with genetic counselors to discuss the risks of having children with the disease. Genetic counselors can explain the options and the associated risks of various tests, including preimplantation genetic diagnosis (PGD), amniocentesis, and chorionic villus sampling (CVS).
  • Preimplantation genetic diagnosis (PGD) may be used with in vitro (artificial) fertilization. In PGD, embryos are tested for the defective NOTCH3 gene, and only the embryos that are not affected may be selected for implantation. Because CADASIL can be detected in a developing fetus, parents may choose whether to continue the pregnancy. Genetic counselors may assist parents with these difficult decisions.

Author information
  • This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography
  1. Amberla K, Waljas M, Tuominen S, et al. Insidious cognitive decline in CADASIL. Stroke. 2004; 35:1598-602.
  2. Cumurciuc R, Henry P, Gobron C, et al. Electrocardiogram in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy patients without any clinical evidence of coronary artery disease: a case-control study. Stroke. 2006;37:1100-2.
  3. Cumurciuc R, Massin P, Paques M, et al. Retinal abnormalities in CADASIL: a retrospective study of 18 patients. J Neurol Neurosurg Psychiatry. 2004;75:1058-60.
  4. Dichgans M, Filippi M, Bruning R, et al. Quantitative MRI in CADASIL: correlation with disability and cognitive performance. Neurology. 1999;52:1361-7.
  5. Dichgans M, Mayer M, Uttner I, et al. The phenotypic spectrum of CADASIL: clinical findings in 102 cases. Ann Neurol. 1998;44:731-9.
  6. Federico A, Bianchi S, Dotti MT. The spectrum of mutations for CADASIL diagnosis. Neurol Sci. 2005;26:117-24.
  7. Haritoglou C, Rudolph G, Hoops JP, et al. Retinal vascular abnormalities in CADASIL. Neurology. 2004;62:1202-5.
  8. Joutel A, Dodick DD, Parisi JE, et al. De novo mutation in the Notch3 gene causing CADASIL. Ann Neurol. 2000;47:388-91.
  9. Kalaria RN, Viitanen M, Kalimo H, et al. The pathogenesis of CADASIL: an update. J Neurol Sci. 2004;226:35-9.
  10. Kumar SK, Mahr G. CADASIL presenting as bipolar disorder. [letter] Psychosomatics. 1997; 38:397-8.
  11. Lesnik Oberstein SA, van den Boom R, van Buchem MA, et al. Cerebral microbleeds in CADASIL. Neurology. 2001;57:1066-70.
  12. Leyhe T, Wiendl H, Buchkremer G, et al. CADASIL: underdiagnosed in psychiatric patients? Acta Psychiatr Scand. 2005;111:392-6.
  13. Markus HS, Martin RJ, Simpson MA, et al. Diagnostic strategies in CADASIL. Neurology. 2002;59:1134-8.
  14. Natural Standard: The Authority on Integrative Medicine. .
  15. Opherk C, Peters N, Herzog J, et al. Long-term prognosis and causes of death in CADASIL: a retrospective study in 411 patients. Brain. 2004;127:2533-9.
  16. Roine S, Poyhonen M, Timonen S, et al. Neurologic symptoms are common during gestation and puerperium in CADASIL. Neurology. 2005;64:1441-3.
  17. Schon F, Martin RJ, Prevett M, et al. "CADASIL coma": an underdiagnosed acute encephalopathy. J Neurol Neurosurg Psychiatry. 2003;74:249-52.
  18. Singhal S, Bevan S, Barrick T, et al. The influence of genetic and cardiovascular risk factors on the CADASIL phenotype. Brain. 2004;127:2031-8.
  19. Williamson EE, Chukwudelunzu FE, Meschia JF, et al. Distinguishing primary angiitis of the central nervous system from cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: the importance of family history. Arthritis Rheum. 1999;42:2243-8.
  20. United Leukodystrophy Foundation. .

Causes
  • General: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by a mutation or defect in the NOTCH3 gene. This gene provides instructions for making the NOTCH3 receptor protein, which is important to the normal development of the muscular walls of small blood vessels. When the NOTCH3 gene is defective, abnormal NOTCH3 receptor proteins build up in the smooth muscle cells that make up the blood vessels, gradually destroying them. This damage leads to strokes, which are interruptions in the flow of blood to the brain, and to other symptoms commonly seen in CADASIL.
  • Autosomal dominant inheritance: When CADASIL is inherited, or passed down among family members, it follows a dominant pattern. Individuals receive two copies of most genes, one from the mother and one from the father. For a dominant disorder to appear, only one defective copy of the NOTCH3 gene is necessary. If one parent has the disorder, there is a 50% chance that his or her child will have the disorder. If both parents have the disorder, there is a 75% chance that their child will have the disorder.
  • Random occurrence: In rare cases, a person with no family history of CADASIL will develop the disease. A spontaneous genetic mutation can occur in the sperm or egg cells or in the developing embryo in individuals with no family history of the disease.

Risk factors
  • Because cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is inherited, a family history is the only known risk factor for the disease.
  • CADASIL is inherited as an autosomal dominant trait, meaning that only one copy of the disease-causing gene is necessary for the disease to occur. If one parent has the disorder, there is a 50% chance that his or her child will have the disorder. If both parents have the disorder, there is a 75% chance that their child will have the disorder.
  • The exact prevalence of CADASIL is unknown. Because of the effects on mental status and cognitive functioning, some researchers question whether this disorder is underdiagnosed among psychiatric patients. Its prevalence was estimated to be about one in 50,000 adults by a Scottish study. Worldwide, about 400 families with CADASIL have been described in the scientific literature. CADASIL occurs in people from all racial and ethnic groups.

Copyright © 2011 Natural Standard (www.naturalstandard.com)


The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.

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