+ diffuse lesions dementia. + classification & characteristics dementia is defined as an...

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Diffuse Lesions

Dementia

+Classification & CharacteristicsDementia is defined as an acquired neurological

syndrome associated with deterioration in intellectual and communicative function and general behavior.

Irreversible forms of dementia are most commonly associated with neurological diseases such as Alzheimer’s disease (AD), Huntington’s disease (HD), Parkinson’s disease (PD), Lewy Body disease (LBD), and Pick’s disease.

Dementia can also result from chronic cerebrovascular disease that produces multiple cerebral infarcts (multi-infarct dementia), as well as from acquired immunodeficiency associated with the HIV virus.

+Classification & CharacteristicsNeuropathology varies somewhat with

specific forms of dementia.

Generally, there are brain atrophy and neurochemical deficiencies with all dementias, but variations in the localization of the atrophy is dependant on the specific form of dementia.

Dementia can be broadly classified as cortical, subcortical, or mixed.

+Cortical vs. Subcortical DementiaCortical dementias describe a process of

degeneration primarily of the neocortical association areas.

Individuals affected by cortical dementias usually have better preserved motor speech skills.

Subcortical dementias describe a process of degeneration in the basal ganglia, thalamus, and brainstem.

Individuals affected by subcortical dementias usually have better preserved language skills.

Lewy body disease affects mixed areas in brainstem structures, such as the substantia nigra and the locus ceruleus, as well as the neocortex.

+Progressive Dementia

Dementias may be classified as primary progressive (degenerative), vascular, specific infection, and other.

Cortical progressive dementias include Alzheimer’s disease, Pick’s disease, and frontotemporal lobar dementia.

Subcortical progressive dementias include Parkinson’s disease (PD), Huntington’s disease (HD), Wilson’s disease, and progressive supranuclear palsy.

+Alzheimer’s Disease

Alzheimer’s disease is a degenerative neurological disorder characterized by deterioration in behavior, cognition, memory, language, communication, and personality.

AD is responsible for 60% of dementias. It is more common in women than in men. It is associated with a family history of Down

syndrome, and individuals with Down syndrome are more likely than those without it to develop AD in later life.

AD was first described in 1906 by the German neurologist Alois Alzheimer.

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Alzheimer’s Disease

Histopathologically, neurofibrillary tangles, neuritic plaques, and granulovacuolar degeneration, affect the hippocampus and amygdaloid nucleus, first, and then move to affect cortical association areas.

Neuronal loss, especially of large neurons in the in the frontal and temporal lobe regions result in a10% loss of brain weight (atrophy).

The motor strip and basal ganglia are spared until late into the disease process.


Early symptoms/onset of AD is usually gradual.

Memory problems are the earliest and most frequently noted symptoms, affecting both recent and remote memory.

Difficulty in learning and retaining new material is common, resulting in work-related problems.

Behavior and personality changes include irritability, hostility, apathy, suspiciousness, and frustration.

Communicatively, speech becomes more vague and empty with naming problems.


Inferential ability is impaired.

Visual-spatial orientation and construction abilities decline.

As the disease progresses, memory problems are more serious and obvious.

More serious behavioral changes include indifference, poor social judgment, and lack of emotional responses.

Communication problems worsen, with further deterioration in the content of speech, and some structural (grammar) problems.

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Alzheimer’s disease

There is further deterioration in problem-solving skills, visual-spatial skills, leading to misperception, spatial disorientation, and poor construction.

Restlessness and agitation are noticeable, leading to disorganized behavior and wandering.

Global deterioration in intellectual functioning and language skills may result in mutism, echolalia, palilalia, and perseveration.

Rigidity and spasticity appear with motor movements.

Additional disturbances may be noted with incontinence, sleep-wake cycle, delusions/hallucinations, and violence/emotional lability.

Alzheimer’s Disease: Summary

Profile Insidious progressive course of cognitive disability, often many years duration; onset before or after age 65

Diagnosis Proliferation of neural plaques and tangles on autopsy

Subtypes • Sporadic (most cases)• Familial 5-10% of cases)

Communication Language impairment is common, with the semantic system most affected; progression to mutism

Behavior Depression, insomnia, incontinence, delusions, and agitation

+Pick’ Disease

Pick’s disease was first described in 1892 by Arnold Pick, a German neurologist.

His patient had presented in life with progressive loss of language.

After death, the patient’s brain was shown to have asymmetric atrophy as opposed to the more general atrophy associated with Alzheimer’s disease.

Pick’s disease produces severe atrophy of the frontal and temporal lobes.

http://www.youtube.com/watch?v=8L7EseDwYxQ




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Pick’s Disease

There is the presence of neuronal cytoplasmic inclusions, called Pick bodies, in the cerebral cortex.

There is a relative absence of neurofibrillary tangles or neuritic plaques.

Similar to AD in its effects (but not its histopathology), Pick’s disease results in cortical dementia.

Individuals with Pick’s disease often present with progressive aphasia initially, and then cognitive memory problems arise.

+Pick’s Disease

Anybody can develop Pick’s disease.

Although it does exist as a familial disease [autosomal dominant] in some families, the majority of cases are sporadic.

It affects men and women alike, usually in their 50s and 60s, but it has been diagnosed in people varying in age from 20 to 80 years.

The rate of progression varies enormously ranging from a duration of less than 2 years to well over 10 years.

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Pick’s Disease

Pick’s disease varies in the way it affects individuals.

The more common symptoms include: personality change; loss of inhibitions; rudeness/impatience; inappropriate social behavior; repetitive, meaningless behavior routines (e.g.,

repeatedly folding napkins and putting them away); failure to recognize objects;

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Pick’s Disease

using objects incorrectly; speech problems, such as echolalia; overeating, changes in dietary preference, and/or

obsessional cravings for certain types of food; attention problems; and changes in sexual behavior.

Muteness, because of severe frontal lobe atrophy, is more common in Pick’s disease than AD.

Fronto-temporal Lobar Dementia: Summary

Profile Insidious onset more likely before age 65; progressive course, often slow

Diagnosis Focal cortical atrophy

Subtypes • frontal variant (executive dysfunction)

• temporal variant (semantic deficits)

• nonfluent aphasia variant

Communication Varies with subtype

Behavior Wide range, especially frontal lobe variant

+Parkinson’s Disease (PD)

Parkinson’s disease is a progressive neurological syndrome associated with depigmentation of the substantia nigra, a midbrain structure functionally related to the basal ganglia.

The clinical syndrome reflects striatal dopamine deficiency, of both storage and production.

7-15% of individuals with PD develop dementia (Lees, 1985).

Onset is typically in the 50s and 60s with early motor problems of tremor, rigidity, and bradykinesia.

With disease progression, the majority of PD patients will evidence intellectual deficits, such as deterioration in memory skills, deterioration in problem-solving skills, and deterioration in reasoning skills.

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Dementia with Lewy Bodies

Dementia with Lewy bodies (DLB) is a progressive dementia, the hallmarks of which are hallucinations and fluctuating levels of attention.

DLB is thought to be the second most common degenerative dementia after AD.

DLB is associated with protein deposits called Lewy bodies that occur subcortically, and in the parahippocampal gyrus, frontal, and temporal and insular cortices.

Neurofibrillary tangles may be present in the cortex and subcortex.

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Lewy bodies were first described by F. H. Lewy in 1912.

They were initially linked to idiopathic Parkinson’s disease, but more recently, they have been identified as a distinct disease entity.

Like other neuronal inclusions, Lewy bodies maybe found in the brain’s of those with AD, and PD as well.

Symptoms of DLB can range from traditional Parkinsonian effects, such as loss of spontaneous movement (bradykinesia), rigidity (muscles feel stiff and resist movement), tremor, and shuffling gait, to effects similar to those of Alzheimer's disease, such as acute confusion, loss of memory, and loss of, or fluctuating, cognition.

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Visual hallucinations may be one of the first symptoms noted, and patients may suffer from other psychiatric disturbances such as delusions and depression.

Onset of the disorder usually occurs in older adults, although younger people can be affected as well.

Classic early symptom is fluctuating confusion.

DLB may be a fairly rapid illness, lasting approximately 5-7 years, although it may be progress more quickly or slowly.

Consensus guidelines for the clinical diagnosis of DLB were developed by McKeith et al. (1966).

http://www.youtube.com/watch?v=43XWaIlx3Zc&feature=related

+Dementia with Lewy Bodies

The central feature is progressive cognitive decline amounting to dementia;

Deficits on tests of attention--fronto-cortical skills and visuospatial ability--may be especially significant.

Two of the following are required for a probable, and one for a possible, diagnosis of DLB: Fluctuating cognition with pronounced variations in

attention and alertness.Recurrent visual hallucinations that are typically

well formed and detailed.Spontaneous motor features of Parkinsonism.

+Dementia with Lewy Bodies

Features supportive of the diagnosis are• Repeated falls;• Syncope or transient loss of consciousness; • Neuroleptic hypersensitivity; • Systematized delusions; and • Hallucinations in other modalities.

DLB is less likely if there is evidence of cerebrovascular disease, revealed by focal neurological signs or brain imaging or of any other physical or brain illness that may account for the clinical picture.

Lewy Body Dementia: Summary

Profile periods of normal cognition alternate with abnormal cognition; progressive course, often rapid

Diagnosis Lewy bodies at autopsy

Subtypes attentional impairmentvisual hallucinationsParkinsonism

Communication

motor speech disorder with hypophonia

Behavior Periods of delirium; daytime drowsiness

+Huntington’s Disease

Huntington’s disease (HD) is another degenerative neurological disease resulting in a variety of subcortical dementia.

Named for Dr. George Huntington, who first described this hereditary disorder in 1872, HD is now recognized as one of the more common genetic disorders.

More than a quarter of a million Americans have HD or are "at risk" of inheriting the disease from an affected parent.

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Huntington’s Disease

HD is transmitted by an autosomal dominant gene on the short arm of chromosome 4.

It has a 50% transmission rate to the offspring.

Onset is usually in the early 30s to 40s, affecting men and women equally, but late onset has been seen in the 80s.

There is a juvenile form that has onset as early as age 4 years, and these children rarely live into their adult years.

The disease contributes to neuronal loss in the caudate nucleus, the putamen, and the cortex.


Early symptoms include gradual change in behavior and personality, depression, irritability, and anxiety, leading to emotional outbursts.

Some individuals may become suspicious, or nagging/complaining.

With beginning cognitive decline in memory, judgment, and executive function, a false sense of superiority—grandiosity may be observed.

Abnormalities of movement, resembling fidgeting, are early signs of chorea, resulting in disorganized speech.


With progression, generalized chorea, characterized by irregular, spasmodic, jerky, complex, rapid, and involuntary movements of the limb and facial muscles, are observed.

Intellectual deterioration is noted, with aggravation of memory, judgment, and executive disturbances.

Other symptoms include attention deficits, dysarthric speech, confusion and disorientation, language impairment, hostility, physical and verbal abuse.

Death is usually within 10 to 20 years of onset from complications such as choking, infection, or heart failure.

+Vascular Dementia (VD)

In the past, the gradual loss of mental faculties in the elderly as commonly ascribed to “hardening of the arteries.”

Multi-infarct (MID) or vascular dementia results from multiple strokes.

It is the second most frequent form of dementia and account for approximately 17% of dementia cases.

It is a mixed dementia as there may be both cortical and subcortical involvement.

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Vascular Dementia

The characteristics of MID are influenced by the location and total amount of infarcted tissue.

Clinical features of MID include history of hypertension and history of arteriosclerosis.

MID patients are typically younger than AD patients, with onset beginning in the 60s.

The incidence among men is almost twice than that of women.

+Vascular Dementia

MID can result from large vessel strokes in major cerebral arteries, such as the anterior middle, and posterior cerebral arteries, and produce focal damage.

MID can also result from lacunar states, arising from ruptures of small arterial branches, causing damage to the basal ganglia, thalamus, midbrain, and brainstem.

MID is characterized abrupt onset, stepwise deterioration, and fluctuating course.

The patient may appear confused and not be able to recall and event, and then appear to make a sudden, total recovery.

+Vascular Dementia

Some skills within a certain domain, such as cognition, may be impaired while others remain intact.

Focal neurological signs and symptoms include pseudobulbar palsy, gait abnormalities, and weakness of an extremity.

Emotional lability, somatic complaints, and depression, but with better preservation of personality and behavior than in other forms of dementia.

Vascular Dementia: Summary

Profile abrupt deterioration; course may be stable, improving or worsening (stair-step decline)

Diagnosis varied, including multiple-infarcts, small vessel disease, multiple lacunes, hypoperfusion or hemorrhage

Subtypes • predominantly cortical clinical signs• predominantly subcortical clinical

signs• extent of brain lesions

Communication

motor speech disorder prominent; may have simplified grammar and writing; slowness and reduced initiation

Behavior depression and mood changes

+Subcortical Vascular Dementia

Binswanger’s disease, sometimes referred to as subcortical dementia, is a rare form of dementia characterized by cerebrovascular lesions in the deep white-matter of the brain.

It produces memory loss and changes in cognition, and mood.

Patients usually show signs of abnormal blood pressure, stroke, blood abnormalities, disease of the large blood vessels in the neck, and disease of the heart valves.

Other prominent features of the disease include urinary incontinence, difficulty walking, clumsiness, slowness of conduct, lack of facial expression, and speech difficulty.

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Subcortical Vascular Dementia

These symptoms, which tend to begin after the age of 60, are not always present in all patients and may sometimes appear only as a passing phase.

It is a slowly progressive condition for which there is no cure.

Patients with this disorder usually die within 5 years after its onset.

+Dementia From Specific Infection

A number of infectious disease processes give rise to dementia components and symptoms.

For the purpose of our discussion, we will focus on Creutzfeldt-Jakob disease (CJD) and acquired immunodeficiency syndrome. (AIDS).

Creutzfeldt-Jakob Disease (CJD) is a rare, fatal brain disorder, which causes a rapid, progressive dementia and associated neuromuscular disturbances.

+Dementia From Specific Infection

The disease is often referred to as a subacute spongiform encephalopathy because it usually produces microscopic vacuoles, or holes, in neurons that appear "sponge-like".

The disease is named after Drs. Hans Gerhard Creutzfeldt and Alfons Jakob, who documented the first cases of this illness in the 1920s.

Although there are several variants of CJD, the most common is called sporadic CJD.

Reports indicate that CJD is not confined to the United Kingdom but has been found worldwide.

+Dementia from Specific Infection In general, disease affects both men and women

of diverse ethnic backgrounds, usually between the ages of 50 to 75 years, resulting in a prevalence rate of about one person per million of the population.

Within the 60 to 74 year age group, however, sporadic CJF occurs in almost 5 cases per million people.

Therefore, there are some 50-60 deaths due to sporadic CJD in the United Kingdom, Australia, Canada, and the USA each year.

+ Dementia from Specific Infection

The cause of sporadic CJD remains uncertain although the most popular current theory suggests that a normal protein in the brain undergoes a spontaneous change to an abnormal form.

This theory holds that neither a virus nor other previously known infectious agent triggers the protein change.

Instead, a pathogen called a "prion," short for “proteinaceous infectious particle,” is thought to transform normal, benign protein molecules into infectious, deadly ones.

This transformation then induces a chain reaction to alter the shape of the other benign protein molecules into the deadly form.

+Dementia from Specific Infection

The average duration of CJD from the onset of symptoms to the inevitable death is four to six months.

Most patients die within one year; however, longer duration periods of two or more years have been noted, usually in the familial form and with an earlier age of onset.

The initial stage of the disease can be subtle with ambiguous symptoms of insomnia, depression, confusion, personality and behavioral changes, strange physical sensations, and problems with memory, coordination and sight.

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Dementia from Specific Infection

As the disease advances, the patient experiences a rapidly, progressive dementia and in most cases, involuntary and irregular jerking movements known as myoclonus.

Problems with language, sight, muscular weakness, and coordination worsen.

The patient may appear startled and become rigid.

In the final stage of the disease, the patient loses all mental and physical functions.

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Dementia from Specific InfectionThe patient may lapse into a coma and usually dies

from an infection like pneumonia precipitated by the bedridden, unconscious state.

A diagnosis of CJD should be considered when an adult patient develops a rapid dementia and myoclonus.

If CJD is suspected, the first step is usually to exclude the possibility that other treatable illnesses are causing the troubling symptoms.

Presently, there is no single test for diagnosing CJD.

+Dementia from Specific InfectionThe most helpful test traditionally has been the

EEG which often shows a characteristic abnormal brain wave activity pattern.

A computed tomography (CT) brain scan is usually normal, initially, but may evidence atrophy as the disease progresses.

Recently, scientists have developed a test to detect the 14-3-3 protein in the cerebrospinal fluid.

Magnetic resonance imaging (MRI) brain scans provide another form of assistance in diagnosing CJD when they reveal hyperintense signals in the basal ganglia on T2-weighted images.

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Blood tests for the genetic mutations associated with familial prion diseases provide further means for diagnosing CJD.

A definitive diagnosis of CJD has traditionally required a brain biopsy or autopsy to detect the characteristic changes in the brain tissue caused by the disease.

The difficulties involved in diagnosing CJD may prevent identification of the disease in some cases.

Since the disease progresses rapidly, the patient may die before a diagnosis can be made.


Consequently, CJD may be mistaken for a variety of psychological illnesses and other neurological disorders like Alzheimer's Disease, Pick's Disease, Huntington's Disease, cerebral hematomas and vascular irregularities.

At the present time, there is no known effective treatment for CJD and the disease is fatal.

The only treatments available for CJD patients focus on easing their symptoms and discomfort, and helping with urinary incontinence and feeding issues.


AIDS Dementia Complex (ADC) is one of the most common and clinically important CNS complications of late HIV-1 infection.

It is a source of great morbidity and, when severe, is associated with limited survival.

ADC is generally thought to be caused by HIV-1 itself, rather than by another opportunistic infection.

ADC was first identified early in the AIDS epidemic as a common and novel CNS syndrome.


The three components of the term AIDS Dementia Complex embody central features of the condition.

AIDS emphasizes its morbidity and poor prognosis, particularly when its severity is at stage 2 or greater.

Dementia designates the acquired and persistent cognitive decline with preserved alertness that usually dominates the clinical presentation and determines its principal disability.

Complex emphasizes that this disease not only impairs the intellect, but also concomitantly alters motor performance and, at times, behavior.


This involvement of the nervous system beyond cognition is evidence of a wider involvement of the CNS than occurs in some other types of dementia such as Alzheimer's disease.

Additionally, myelopathy may be an important and predominating aspect of ADC, as well as organic psychosis.

By contrast, neither neuropathy nor functional psychiatric disturbance are included in ADC.

ADC develops principally in the context of late HIV-1 infection and associated severe immunosuppression.

Its prevalence accordingly varies depending on the characteristics of the population sampled.


Investigators have hypothesized that macrophage and microglial infection drives a chain of pathologic processes that eventuate in neuronal dysfunction.

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Some of these infectious effects are exerted directly on neurons while others involve intermediary cells, eventually resulting in neurotoxicity.

Although the severity and relative prominence of some symptoms and signs compared to others may vary among individual patients, the general character of ADC involves three functional categories: cognition, motor performance, and behavior.

Of the three categories, cognitive and motor dysfunction are the most helpful in characterizing patients and in defining diagnosis.


Stage 0.5 and 1 ADC: Cognitive impairment usually underlies patients' earliest symptoms.

Patients most often have difficulty attending to more complex tasks at work or at home:•They need to make lists, sometimes very detailed, of the day's activities.•They lose track of actions (e.g., leave the water boiling, get up to go to another room and then forget why they did so) or of conversations in mid-sentence ("What was I saying?").


Processing unrelated or complex thoughts becomes slower and less facile.

While similar lapses can trouble many normal people especially in the face of fatigue or generalized illness, lapses in ADC patients intrude on daily function to a greater degree.

Multi-staged tasks become difficult, e.g., the waiter can no longer keep verbal orders straight when he arrives at the kitchen or the avid reader needs to reread paragraphs or pages.


When such dysfunction is mild, it may be difficult to substantiate the basis for these complaints by bedside examination, and it is important to apply tests that are sensitive to these abnormalities, including particularly tests requiring concentration, change of sets, and timed performance.

Because it was constructed for other conditions, the standard Mini-Mental Status may not be sufficiently sensitive at this point.


However, when ADC patients do perform abnormally, it is usually on reversals (reversing a five-letter word like "world," or subtracting from 100 by 7's), complex sequential tasks (placing the right thumb on the left ear and sticking out the tongue), or remembering three objects.

Although motor symptoms are far less common during this early phase, individuals relying on rapid or fine coordination may note a change.

For example, the guitarist may no longer be able to keep up with a difficult piece or the athlete may be slowed to below a competitive level.

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An inquiring history may discover a change in handwriting or, less commonly, clumsiness in tying shoes or buttoning a shirt.

The time course and onset of milder ADC is variable. It may begin insidiously or abruptly and progress

more rapidly to a higher stage, or it may continue to evolve slowly or even remain static for some period.

Particularly important is the distinction of ADC from clinical depression, which can produce similar complaints but carries distinct therapeutic implications.

Hypochondriasis and anxiety in those understandably worried about body function may also lead to similar complaints.


Stage 2-4 ADC: Cognitive function in these subjects is clearly abnormal and obviously impairs functional status.

Nonetheless, patients with stage 2 or 3 ADC can maintain the civilities of casual conversation and personal interaction so it too can be missed by a cursory history and examination.

With more careful questioning of both the patient and associates, however, it is clear that stage 2 patients are too slow or forgetful to work, manage the household or, importantly, even maintain their own medications.


They may get lost walking or driving and cannot be relied on to prepare meals, much less to balance the checkbook.

On examination, the Mini-Mental Status is now often abnormal.

Assessments of attention and concentration are frequently impaired, and patients have trouble recalling three objects after 5 or 10 minutes.

Timed activities are further slowed and attempts to draw complex objects may produce only simplified representations.


With increased severity, there is frank disorientation to time and place.

Motor abnormalities may also become more clearly symptomatic and obvious to the patient's family and associates.

Walking may be sufficiently unsteady to require a cane or someone alongside to prevent falling.

Hyperreflexia and pathologic reflexes are now almost always present, and gait instability and slowness is more clearly evident not just on turning, but even on the straightaway.


With further progression, ambulation constantly requires someone to balance and support the patient or is entirely precluded (stage 3 or 4).

Thinking and speaking also becomes slower and the content more impoverished.

Concomitant behavioral changes may become more evident.

Patients appear duller and less vivacious. If left alone, they may sit still without

spontaneously offering conversation, but only answering briefly in response to questions.


This poverty of output and apathy may be mistaken for depression, but in most of these patients, disinterest and lack of initiative are the predominating aspects of behavior without sadness.

A similar syndrome complicates pediatric AIDS.

The disorder in children may be proportionally more important in the sense that it both occurs more commonly than in adults and results in even greater morbidity.


It can manifest as a progressive encephalopathy with reversal of pediatric developmental milestones and subsequent microcephaly or can be static with developmental delay.

Clinical presentation combines cognitive and motor dysfunction.

Its etiology and pathogenesis are likely similar to the adult condition, although altered somewhat by involvement of the developing brain.

+ diffuse lesions dementia. + classification & characteristics dementia is defined as an...

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