Multi-infarct dementia, sometimes called vascular dementia, is a form of progressive cognitive decline that results from accumulating lesions in the brain, usually as a result of a disruption in the blood supply.
Presentation
Multi-infarct dementia presents similarly to other forms of dementia. It is, nonetheless, distinguishable through its time course and progression. It tends to worsen progressively but in sudden, discrete steps with a worsening of intellectual performance followed by mild recovery. Some forms of multi-infarct dementia are associated with more gradual progression. This occurs particularly when subcortical structures are involved in lacunar infarctions and Binswanger dementia.
Focal neurologic findings become more apparent with disease progression. Patients tend to develop abnormalities in gait, muscular weakness in specific extremities, extrapyramidal dysfunction, Babinski reflex, increased deep tendon reflexes and hemiplegia.
Cognitive damage in multi-infarct dementia is usually more specific than generalized. Short-term memory may be more strongly present than other features of cognition. In addition, patients with multi-infarct dementia are at a higher risk of depression because they are more likely to be aware of their condition, especially in patients with partial aphasia.
Entire Body System
- Weakness
A 39-year-old man was admitted because of an abrupt onset of right-side weakness and dysarthria. During the 2 years before admission, he had suffered from insomnia, depressed mood and progressive memory disturbance. [ncbi.nlm.nih.gov]
Because weakness is a common symptom of many other disorders, the diagnosis is often missed in people who experience only mild weakness or in those whose weakness is restricted to only a few muscles. [brainfoundation.org.au]
The body continues to produce the harmful antibodies and weakness may recur. Plasma exchange is helpful before surgery or during times of extreme MG weakness. [healthline.com]
For example, you may have weakness in the muscles for eye movement, facial expressions, and swallowing. You can also have weakness in other muscles. This weakness gets worse with activity, and better with rest. [medlineplus.gov]
Weakness is more marked in proximal muscles and isolated weakness of limb muscles is the presenting feature in a minority of patients. Weakness of the following muscles may also be seen: Small muscles of the hands (finger extensors). [patient.info]
- Asymptomatic
CONCLUSION: The occurrence of "asymptomatic" emboli in the middle cerebral artery in patients with multi-infarct dementia is higher in the current study. [ncbi.nlm.nih.gov]
Brain MRI of elderly asymptomatic and paucisymptomatic individuals with a NOTCH3 mutation compared to MRI in classical cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). [raredr.com]
[…] weighted images, usually multiple confluent white matter lesions of various sizes, are characteristic - these lesions are concentrated around the basal ganglia, periventricular white matter, and the pons - these white matter lesions are also seen in asymptomatic [sites.google.com]
Many patients with SMM are asymptomatic, but some experience modest symptoms, such as mild anemia or a few small bone lesions. Many—but not all—patients with SMM progress to multiple myeloma. [themmrf.org]
[…] individual than the individual will likely develop symptoms eventually If a disease associated mutation is not found in an asymptomatic individual than we don't know if it is because they didn't inherit the mutation present in the family or if a mutation [en.wikibooks.org]
- Crying
Symptoms include confusion or problems with short-term memory; wandering, or getting lost in familiar places; walking with rapid, shuffling steps; losing bladder or bowel control; laughing or crying inappropriately; having difficulty following instructions [ninds.nih.gov]
Dementia symptoms include: Confusion and problems with recent memory Wandering or getting lost in familiar places Moving with rapid, shuffling steps Loss of bladder or bowel control Laughing or crying inappropriately Difficulty following instructions [alzheimers.emedtv.com]
Person having MID shows memory loss, confusion, judgment problem, agitation, wondering, fast walking, loss of bladder or bowel control, laughing or crying improperly. [depression-guide.com]
They may have mood swings, laugh or cry at inappropriate times and have a tendency to wander or get lost in familiar surroundings. There are no treatments that can restore brain cells. [understanding-dementia.com]
Symptoms of MID, which often develop in a stepwise manner, include: confusion, problems with recent memory, wandering or getting lost in familiar places, loss of bladder or bowel control (incontinence), emotional problems such as laughing or crying inappropriately [medicinenet.com]
- Antipsychotic Agent
London-Toronto, itd: Butterworth's [ CR ] [ PM ] [ EČ ][ 1 ][ GS ] Defilippi, J.L., Crismon, M.L. (2000) Antipsychotic agents in patients with dementia. [scindeks.ceon.rs]
Cardiovascular
- Heart Disease
People are living longer with chronic diseases, such as heart disease and diabetes. Causes of VaD VaD is caused by a lack of blood flow to the brain. [columbianeurology.org]
To prevent additional strokes, doctors may prescribe medicines to control high blood pressure, high cholesterol, heart disease, and diabetes. [mhanational.org]
To prevent more strokes, doctors may prescribe medicines to control high blood pressure, high cholesterol, heart disease, and diabetes. [nursinglink.monster.com]
Risk factors for stroke and vascular dementia include high blood pressure, high cholesterol, heart disease, smoking, and diabetes. For many people, risk can be reduced by adopting a healthy lifestyle. [alztennessee.org]
- Thrombosis
Abstract The primary antiphospholipid antibody syndrome (PAPS) has been described in patients with a history of fetal loss, thrombocytopenia and arterial or venous thrombosis. [ncbi.nlm.nih.gov]
Cerebral infarction due to embolism of cerebral arteries) I63.5 대뇌동맥의 상세불명 폐색 또는 협착에 의한 뇌경색(증)(Cerebral infarction due to unspecified occlusion or stenosis of cerebral arteries) I63.6 대뇌정맥 혈전증에 의한 비화농성 뇌경색(증)(Cerebral infarction due to cerebral venous thrombosis [dic.impact.pe.kr]
F01.1 Vascular Dementia Of Acute Onset Usually develops rapidly after a succession of strokes from cerebrovascular thrombosis, embolism, or haemorrhage. In rare cases, a single large infarction may be the cause. [azpsychiatry.info]
This may be explained in part by the fact that many different vascular pathologies may lead to cognitive impairment, including cerebral thrombosis, cardiac embolism, and hemorrhage. [web.archive.org]
Neurologic
- Cognitive Impairment
Narasimhalu K, et al: The prognostic effects of poststroke cognitive impairment no dementia and domain-specific cognitive impairments in nondisabled ischemic stroke patients. Stroke 2011;42:883-888. [karger.com]
Sachdev P (1999) Vascular cognitive disorder. Int J Geriatr Psychiatry 14:402–403 CrossRef PubMed Google Scholar 7. O’Brien JT, Erkinjuntti T, Reisberg B et al (2003) Vascular cognitive impairment. [oadoi.org]
- Agitation
This concise book identifies and diagnoses the multiple types of agitation in dementia patients. [books.google.com]
A patient with multi-infarct dementia and associated hypomanic features was treated effectively with clonazepam to control logorrhea, hyperactivity, agitation, intrusiveness, and impulsive violence and to promote cooperation and manageability. [ncbi.nlm.nih.gov]
agitated, or dangerous behaviors. [indiatoday.in]
Medications may be needed to control aggressive, agitated, or dangerous behaviors. The health care provider will usually prescribe these medicines in very low doses and adjust the dose as needed. [sites.magellanhealth.com]
- Apathy
Other symptoms of Binswanger's disease may include: Forgetfulness (but not as severe as Alzheimer's disease) Urinary incontinence Difficulty walking Clumsiness Changes in personality or mood (most likely in the form of apathy, irritability, and depression [alzheimers.emedtv.com]
CADASIL symptoms include recurrent stroke (with paralysis, loss of sensation, unsteady gait, slurred speech), migraine-like headaches, anxiety/mood disorders including depression and apathy, and loss of memory and executive function. [mscare.org]
Psychiatric disorders are also common and include depression, apathy and personality changes. [orpha.net]
Apathy: a major symptom in CADASIL. 2009;10:905-910. Dichgans M, Markus HS, Salloway S, et al. Donepezil in patients with subcortical vascular cognitive impairment: a randomized double-blind trial in CADASIL. Lancet Neurol. 2008;7:310-318. [rarediseases.org]
[…] to progress gradually or stepwise and comparatively slower than in multi-infarct dementia Generally associated with signs of subcortical pathology Early symptoms Impaired memory Reduced executive functioning Loss of visuospatial abilities Confusion Apathy [amboss.com]
- Personality Change
A variety of patterns of behavioral changes may be observed in MID, depression, psychosis, and personality change are common. [ncbi.nlm.nih.gov]
Psychiatric disorders are also common and include depression, apathy and personality changes. [orpha.net]
Personality is believed to be relatively well preserved, but personality changes may be evident in a proportion of cases with apathy, disinhibition, or accentuation of previous traits such as egocentricity, paranoid attitudes, or irritability. [azpsychiatry.info]
Memory can be seriously impaired in one person and only mildly impaired in another person. [healthline.com]
- Seizure
Plausible mechanisms discussed include the ability of clonazepam to stimulate serotonin synthesis, to bind highly and specifically to the active benzodiazepine binding site, and to raise the seizure threshold. [ncbi.nlm.nih.gov]
Other symptoms, like headache, seizures, or other neuropsychiatric manifestations should be appropriately treated. [seer.ufrgs.br]
Depression, psychosis, pseudobulbar palsy and focal neurological defects as well as seizures are also seen 2,3. [radiopaedia.org]
Although Chabriat et al did not report seizures in any of his patients, Dichgans et al in his series of 102 CADASIL patients noted seizures in 10 patients. [3] MRI findings in CADASIL include symmetrical and extensive hyperintense signal within the cerebral [neurologyindia.com]
Less common signs and symptoms may include: [5] Other psychiatric issues such as gambling, a seizure lasting 30 minutes or longer, or a cluster of shorter seizures for 30 minutes or more with little or no recovery between episodes (recurrent status epilecticus [rarediseases.info.nih.gov]
Urogenital
- Urinary Incontinence
Other symptoms of Binswanger's disease may include: Forgetfulness (but not as severe as Alzheimer's disease) Urinary incontinence Difficulty walking Clumsiness Changes in personality or mood (most likely in the form of apathy, irritability, and depression [alzheimers.emedtv.com]
incontinence DiffDx Repeating 'mini-infarcts' of HTN mimic the gradual deterioration typical of the more common Alzheimer's disease, which lacks prominent motor and reflex changes. [medical-dictionary.thefreedictionary.com]
incontinence) Later symptoms: Further cognitive decline: loss of judgement, disorientation Mood disorders (e.g., euphoria, depression) Behavioral changes (e.g., aggressiveness) Advanced stages: Further motor deterioration: dysphagia, dysarthria References [amboss.com]
Urinary incontinence is common, dysphagia and dysarthria may occur, and some patients develop emotionalism and/or depression. In the later stages, patients may become immobile, requiring 24-hour nursing care. [cambridge.org]
incontinence Withdrawal from social interaction Inability to interact in social or personal situations Inability to keep a job Diagnosis rules out other causes of dementia, including dementia due to metabolic causes. [lutheranaugustanacenter.com]
Workup
Workup of multi-infarct dementia generally consists of laboratory and imaging studies. Laboratory and blood tests are performed to exclude certain conditions that may also result in dementia. A range of blood tests are performed. These generally are a complete blood count, assessment of liver function tests, creatinine and urea for assessment of kidney function, thyroid hormones, vitamin B12, ESR to detect the presence of any infection, VDRL for syphilis and folate levels within the red blood cells. It may also be necessary to perform additional testing in certain patients such as HIV testing, ANA (antinuclear antibody), ANCA (antineutrophil cytoplasmic antibody), antiphospholipid antibody and lupus anticoagulants.
Imaging studies are necessary to diagnose the disease. Both CT and MRI can be very important diagnostic tools. Lesions that target blood vessels appear on both modalities. Characteristic features of CT and MRI scans in patients with multi-infarct generally are the presence of a number of bilateral infarcts in the limbic cortex, lesions in the white matter around the ventricles and lacunar strokes.
Multi-infarct dementia may also be differentiated from Alzheimer's disease with MRI. The prodromal phase of multi-infarct dementia will generally show lacunar infarcts within the white matter, in addition to leukoaraiosis. In contrast, the prodromal phase of Alzheimer's disease usually targets the limbic cortex, with frequent involvement of the hippocampus and the entorhinal cortex.
Positron emission tomography can also help in distinguishing multi-infarct dementia from Alzheimer's disease. Multi-infarct dementia is associated with hypoperfusion in the frontal lobes, especially in the superior frontal gyrus and the cingulate cortex. On the other hand, patients with Alzheimer's disease will exhibit decreased perfusion along a parietotemporal spread. CT accompanied by single-photon emission will generally show similar findings.
Cerebral angiography is not necessary to establish the diagnosis. Nonetheless, it may be performed prior to surgery of the carotid artery. In addition, it can help diagnosing cerebral vasculitis, in which vascular beading is prominent.
Additional tests are useful in assessing frequently associated disorders. These include Doppler scanning of the carotid arteries, Holter monitoring and echocardiography.
Serum
- Hypercholesterolemia
Symptomatic treatment can be offered to patients to treat migraines and potential concomitant vascular risk factors (hypertension, hypercholesterolemia and diabetes). [orpha.net]
Etiology VD may occur as a result of a prolonged and severe cerebral ischemia of any etiology; primarily Risk factors Advanced age History of stroke Underlying conditions associated with cardiovascular disease; : chronic hypertension;, hyperglycemia, hypercholesterolemia [amboss.com]
Examples of such risk factors include: Hypertension Diabetes Hypercholesterolemia Obesity Smoking Lack of exercise Insufficient fluid intake Unhealthy dietary choices These risk factors are controllable and can contribute significantly to prevention of [mapmygenome.in]
Hypercholesterolemia was defined as total serum cholesterol level > 240mg/dl. The final study population consisted of 51 patients. [journals.plos.org]
Some medication that have shown some efficacy in some studies, but have not being proven may include acetazolamide, and sodium valproate for the migraine, and acetylcholinesterase inhibitor for cognitive decline. [5] When hypertension, diabetes or hypercholesterolemia [rarediseases.info.nih.gov]
Treatment
Treatment of multi-infarct dementia is generally targeted to decrease future occurrences and lessen complications. Antiplatelet drugs are particularly important in preventing further cerebrovascular accidents. Evidence points out that the progression of multi-infarct dementia is significantly delayed by aspirin.
Furthermore, it is critically important to control risk factors that are directly associated with the occurrence and progression of the disease. Pharmacotherapy is targeted at chronic vascular and metabolic diseases such as diabetes mellitus, hypertension and hyperlipidemia. Other drugs act to increase cerebral blood flow. These include ergoloid mesylates, also known as hydergine, and pentoxifylline. The latter was shown to be beneficial in patients in a large multicentric, double blinded and placebo controlled European study, especially in regards to overall cognitive and intellectual ability.
Other potential drugs with neuroprotective effects include propentofylline, posatirelin and dihydropyridine calcium channel blockers such as nimodipine and nicardipine. The latter were found to delay cognitive and intellectual damage, not only in patients with multi-infarct dementia, but also those diagnosed with cerebrovascular conditions more generally.
Cholinergic neurotransmission may be of particular importance to multi-infarct dementia. Alzheimer's disease has been also linked to abnormalities in the cholinergic system. Clinical trials have already shown some benefit for cholinesterase inhibitors in multi-infarct dementia, although they are yet to be employed in the treatment of the disease.
Aside from pharmacotherapy, patients also require social and psychological support. All patients should be referred to community services. Their decision-making and rational judgment capacities should be adequately assessed, in addition to their ability to perform the basic functions of living such as driving and taking care for themselves.
In addition to cognitive deterioration, patients with dementia may frequently show irritability, agitation and even psychotic episodes. Selective serotonin inhibitors (SSRIs) seem to have a beneficial effect on agitation and psychosis, even though they have not been systematically studied in these patients. Patients also seem to tolerate SSRIs better than typical or atypical antipsychotics. It will be important to conduct large scientific studies to exactly assess their beneficial advantages.
Diet also plays an important role in the progression of the disease. Fish intake was correlated with decreased risk of dementia, in contrast to increased fat intake, which showed increased association. In addition, high homocysteine levels are also related to an increased risk of multi-infarct dementia. The latter usually results from decreased levels of vitamin B6, vitamin B12 and folic acid.
Prognosis
Decreases in life expectancy are associated with multi-infarct dementia in around half of all male patients. Individuals with a lower educational status as well as those who do not perform as well on neuropsychological tests also suffer from worse outcomes.
Multi-infarct dementia may also be complicated by death, but this generally results from associated conditions such as heart disease and malignancy.
Etiology
Multi-infarct dementia is associated with a multitude of factors such as smoking, diabetes mellitus, hypertension, as well as cerebrovascular and cardiovascular disease.
Smoking is one of the most important associated risk factors. One study on 21,123 individuals found that heavy smokers have more than double the risk compared to the general population to develop dementia after 2 decades. Heavy smokers were defined as those who smoke more than 2 packs per day and mean smoking period was around 23 years. The risk is not limited to multi-infarct dementia but also includes Alzheimer's disease and other forms of dementia. It is independent of gender and race [2].
Multi-infarct dementia may sometimes follow strokes. This scenario may more frequently be present in aged patients, those with a family history, and those who have a lower educational status. In addition, particular strokes may increase the risk, especially those that involve white matter around the ventricles, regions supplied by the thalamic artery, the hippocampus, the inferomedial temporal lobes and watershed areas between the parietal and superior frontal areas [3].
Epidemiology
Prevalence of dementia varies with age. In the United States, around 5% of all individuals between 71 and 79 years of age develop dementia with the risk increasing exponentially in patients older than 90. Among this population, around 40% of all individuals are ultimately diagnosed with this disease. Alzheimer's dementia is the most common form, affecting approximately 70% of all individuals with dementia. On the other hand, multi-infarct dementia is responsible for 17% of call cases although it is important to note that the two conditions may frequently overlap [4].
Incidence of multi-infarct dementia is estimated at 3.8 cases in every 1000 individuals per year, although this varies depending on the criteria employed. Incidence also increases greatly with age, from 0.3 to 2.2 cases in patients between 65 and 60 years of age and up to 15.9 in patients older than 90 [5]. The disease is more likely to affect men than women, in contrast to Alzheimer's dementia [6]. Multi-infarct dementia has greater predilection for particularly ethnic groups, especially individuals with Asian and African lineage [6] [7].
Pathophysiology
The pathophysiological mechanisms underlying multi-infarct dementia generally include infarcts, leukoaraiosis, hemorrhage and mixed forms.
Infarctions can lead to dementia when they are multiple and target a large number of brain regions, affecting the brain's ability to compensate for loss of localized function [8]. Nonetheless, small infarcts can be sufficient to lead to dementia, especially when they target the thalamus and the basal ganglia [4]. Small infarcts generally result from arteriosclerosis and are usually less than 1.5 cm in size. They are termed lacunar infarcts, and involve small arteries and arterioles. Lacunar infarcts have a predilection for the basal ganglia, the pons, the thalamus and the internal capsule [9].
Leukoaraiosis describes pallor of the white matter. It is the eventual result of accumulating loss of white matter constituents such as oligodendrocytes, axons and myelin sheath. Tissue around blood vessels is especially affected and there is concomitant damage to the blood-brain barrier [10]. Although ischemia is thought to underlie the development of leukoaraiosis, classical infarction may not be present. It has been hypothesized that excessive pulsation of the small vessels may ultimately lead to the pathophysiological manifestations [11].
Hemorrhage may also lead to brain damage. Hypertension is a principle causative factor, and results in a large number of small bleeding sites. They occur most commonly in the basal ganglia. On the other hand, amyloid deposition can lead to sites of limited hemorrhage in the white matter and the cortex [12]. Excessive accumulation of amyloid beta protein weakens the walls of the arteries and makes them particularly susceptible for rupture.
Mixed dementia consists of a combination between multi-infarct and Alzheimer's dementia. Patients suffering from both conditions are expected to be more strongly affected than those affected by one form only [13].
Prevention
Multi-infarct dementia can be prevented by controlling or eliminating risk factors such as hypertension, dyslipidemia, smoking and diabetes mellitus. Furthermore, physical activity may also be important in reducing the rate of cognitive decline among older women.
Summary
Multi-infarct dementia is a particular form of dementia associated with small lesions in the brain [1]. It tends to follow a progressive course with incremental deterioration. It is strongly associated with risk factors for cerebrovascular and cardiovascular disease, such as hypertension, diabetes mellitus, dyslipidemia and smoking. Smoking is a particularly important risk factor, with heavy smoking resulting in more than the doubling of the risk. Pathophysiological mechanisms underlying multi-infarct dementia include small infarcts, leukoaraiosis and small hemorrhages. Small infarcts generally result from arteriosclerosis and tend to have a predilection for subcortical structures. Hypertension is an important risk factor for limited bleeding in the basal ganglia. On the other hand, leukoaraiosis results from progressive loss of white matter, especially in perivascular spaces.
Workup of multi-infarct dementia is broad and is generally targeted at excluding other potential causes of dementia, such as hypothyroidism and B12 hypovitaminosis. Imaging studies with CT and MRI are necessary to diagnose multi-infarct dementia, and show distinctive findings. MRI and PET are particularly useful in differentiating multi-infarct dementia from Alzheimer's disease.
Treatment of multi-infarct dementia is principally with pharmacotherapy to decrease the occurrence of future strokes and slow the progression of the disease. Aspirin is particularly useful in preventing future cerebrovascular accidents and is associated with better intellectual functioning of patients with multi-infarct dementia.
Patient Information
Multi-infarct dementia is a form of dementia that targets older individuals and results from accumulating small lesions in the brain. These lesions are caused by a disruption of blood perfusion into specific areas of the brain. It is strongly associated with risk factors that affect the functioning of the heart and blood vessels, such as smoking, hypertension, diabetes and elevated lipid levels. Patients with vascular dementia progressively worsen, but unlike in Alzheimer's disease, deterioration is incremental and not continuous.
Workup is usually targeted at excluding other potential causes of dementia, such as deficiencies in folate and vitamin B12 and dysfunction in the thyroid gland. Imaging testing with MRI and CT are necessary to establish the diagnosis and can help distinguish multi-infarct dementia from Alzheimer's disease.
Treatment of multi-infarct dementia is aimed at decreasing future occurrences of cerebral lesions and delaying progression. Prevention and elimination of risk factors such as smoking, hypertension and diabetes is of paramount importance.
References
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- Rusanen M, Kivipelto M, Quesenberry CP Jr, Zhou J, Whitmer RA. Heavy Smoking in Midlife and Long-term Risk of Alzheimer Disease and Vascular Dementia. Arch Intern Med. 2011 Feb 28;171(4):333-9.
- Roman GC. The epidemiology of vascular dementia. Handbook of Clinical Neurology. 2008. vol. 89(3rd series):639-658.
- Plassman BL, Langa KM, Fisher GG, et al. Prevalence of dementia in the United States: the aging, demographics, and memory study. Neuroepidemiology. 2007;29:125-132.
- Bowler JV. Modern concept of vascular cognitive impairment. Br Med Bull. 2007;83:291-305.
- Hagnell O, Franck A, Grasbeck A, et al. Vascular dementia in the Lunby study: 1. a prospective, epidemiological study of incidence and risk from 1957-1972. Neuropsychobiology. 1992;26:43-49.
- Gorelick PB, Brody JA, Cohen DC, et al. Risk factors for dementia associated with multiple cerebral infarcts: a case-control analysis in predominantly African-American hospital-based patients. Arch Neurol. 1993;50:714-720.
- Wallin A, Milos V, Sjogren M, et al. Classification and subtypes of vascular dementia. International Psychogeriatrics. 2003;15:27-37.
- Horowitz DR, Tuhrim S, Weinberger JM, et al. Mechanisms in lacunar infarction. Stroke. 1992;23:325-327.
- Braffman BH, Zimmerman RA, Trojnowski JQ, et al. Brain MR: pathologic correlation with gross and histopathology. II. Hyperintense white matter foci in the elderly. AJR Am J Roentgenol. 1988;151:559-566.
- Bateman GA. Pulse-wave encephalopathy: a comparative study of the hydrodynamics of leukoaraiosis and normal pressure hydrocephalus. Neuroradiology. 2002;44:740-748.
- Lee SH, Kim SM, Kim N, et al. Cortico-subcortical distribution of microbleeds is different between hypertension and cerebral amyloid angiopathy. J Neurol Sci . 2007;258:111-114.
- Jellinger KA, Attems J. Neuropathological evaluation of mixed dementia. J Neurol Sci. 2007;257:80-87.