- Parkinson's Disease
- HIV
- Multiple Sclerosis
- Binswanger's and Wilson Diseases
- Creutzfeldt-Jakob Disease
- Diffuse Lewy-Body Disease
- Huntington’s Disease
- Pick’s Disease
- Frontotemporal Dementia
- Vascular Dementia
James Parkinson discovered the disease that now bears his name in 1817. Parkinson’s disease is the fourth most common neurodegenerative disorder seen in older adults (Berkow and Fletcher 1992). It involves a progressive deterioration of the nigrostriatal dopaminergic system (motor system) and is associated with the depletion of dopamine (neurotransmitter involved with motor functions) in the basal ganglia (part of the brain associated with the control and coordination of movement). The disease also involves the erosion of the limbic system, cortical projections, and midbrain. It is believed that Parkinson’s disease may be partially the result of environmental toxins. It is estimated that around .02 percent of the general population develops this disease with as high as 25 percent for those over the age of seventy-five (Lezak 1995). It affects more men than women, rarely sets in before the age of thirty, and is more prevalent in minority groups (Lezak 1995).A gene has been linked to the disease. This gene is believed to be responsible for the regulation of a protein called “synuclein.” This protein is also found in the plaques of patients with Alzheimer’s disease.
Symptoms of Parkinson’s Disease:
Symptoms of the disease may initially be lateralized (on one side of the body) and include: hand tremors that resemble pill rolling movements, drooling, lack of facial expression, rapid onset of a resting tremor (tremor involving several muscle groups that is apparent during rest but tends to disappear during purposeful movement), and cogwheel rigidity (continual rhythmical interruption of passive movement that presents as a slight catch with each movement). Other symptoms include: akinesia (partial loss of voluntary muscle movement, or slowed initiation of motor movement), poor handwriting, bradykinesia (loss of voluntary muscle movement), absence of arm swing when walking, postural abnormalities (stooped posture or stiffness), joint pain, gait disturbances (disturbances in the ability to walk, often using small shuffling steps), and retropulsion (tendency to fall backwards) (Ayd 1995). The presence of dementia is estimated to occur in 20 to 40 percent of Parkinson’s patients (Snyder and Nussbaum 1998).
Cognitive Deficits Often Mimic Frontal Symptoms:
Cognitive deficits associated with Parkinson’s tend to mimic frontal lobe damage. This is in part due to the wiring of the frontal lobe. Our brains have five separate circuits or “loops” that run subcortically between the frontal lobes and other major cortical structures. In subcortical diseases such as Parkinson’s, the frontal lobes and other cortical structures are damaged at the subcortical level via these five circuits. As the disease progresses, frontal symptoms such as poor executive planning and mental flexibility begin to be more prevalent. The degeneration of these circuits would impair the person’s ability to form a preparatory set or concentrate and would result in rigid thinking. Attentional deficits are common, as are deficits in working memory and verbal fluency. Immediate verbal memory tends to diminish but can usually be triggered through association. Visual memory, vocabulary, syntax, reasoning, and grammar tend to remain intact (Cooper et al. 1991).
Depression Is Common in Parkinson’s Disease:
Depression is common in Parkinson’s patients, with a higher incidence in patients suffering symptoms of pain associated with the disease (Lezak 1995). Dopamine replacement therapy is almost the universal treatment of the disease and patients are now surviving ten to fifteen years with proper treatment (Lezak 1995). This still brings to the forefront the realization of one’s mortality. A Parkinson’s patient and many other patients suffering neurological disease must negotiate thoughts of death on a daily basis. Existential therapy or a strong spiritual faith can greatly assist the person suffering from Parkinson’s disease in finding meaning in their lives and in the disease process.
Parkinson-Plus Syndrome:
Parkinson-plus syndromes are difficult to distinguish from Parkinson’s disease. This is a class of disorders that tend to mimic some of the symptoms of Parkinson’s disease with a few minor distinctions. These symptoms include: progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome), the multiple system atrophies (olivopontocerebellar atrophy), striatonigral degeneration, Shy-Drager syndrome, and possibly corticobasal ganglionic degeneration. The prevalence rates for these disorders are low and are usually initially marked by disturbances in motor functions. Most are not responsive to dopamine therapies, which helps distinguish Parkinson-plus syndrome from Parkinson’s disease.
Progressive Supranuclear Palsy Symptoms:
This rare disorder is a subtype of a Parkinson-plus syndrome. Symptoms often begin around the age of sixty and are usually symmetrical at onset. Resting tremor usually occurs later in the disease process (Snyder and Nussbaum 1989). Symptoms are similar to other symptoms that characterize subcortical dementias but begin to mimic cortical dementias as symptoms progress. Symptoms include motor dysfunction, emotional disturbances, cognitive slowing, memory impairment, and executive dysfunction. Dysarthria (difficulty in articulation) is often present earlier than normally seen in Parkinson’s disease. Gait disturbance is also prevalent early in the disease and negotiating stairs becomes difficult (Berkow and Fletcher 1992). Other symptoms that are characteristics of the disease include: difficulty looking straight up or down, facial spasticity, and difficulty maintaining posture (Johnson et al. 1992). Dementia usually occurs later in the disease. Although drastic drops in dopamine levels mark the disease, symptoms usually respond poorly to dopaminergic medications (medications that replace dopamine) and usually progress faster than seen in Parkinson’s disease.There is significant slowing in all mental processing, although accuracy usually remains relatively intact early in the disease (Campbell 1989). Therefore it has been postulated that memory is not as impaired as the timing mechanism of memory (Lezak 1995). Deficits can also be noted in visual-spatial abilities, visual tracking and scanning, hand-eye coordination, word finding, and visual field discrimination. Falls are common, and there is usually trouble in writing and eating. Blurring and double vision are also common.Short-term memory difficulties are common but not to the degree seen in dementia of the Alzheimer’s type. Apathy is often present and irritability and depression are common (Lezak 1995).As the disease progresses, movement rigidity, defective control of mouth and neck muscles, drooling, and impassive facial expression become prevalent. Treatment is limited to medications to ease the symptoms and discomfort.
Parkinsonism:
Parkinsonism is not the same as Parkinson’s disease. Parkinson’s disease refers to a specific disease entity, whereas parkinsonism refers to a syndrome that consists of four motor signs. These four motor signs are rigidity, tremor, postural abnormalities, and bradykinesia (slowing in the execution of movements) (Snyder and Nussbaum 1998). Parkinsonism is seen in Parkinson’s disease but is also seen in several other disease processes.
Acquired Immunodeficiency Syndrome Dementia Complex:
AIDS dementia complex is progressive, with symptoms that mimic a subcortical dementia. Initial signs usually center around memory problems, neuromotor deficits such as tremor and ataxia, poor concentration, and impairment in psychomotor speed. As the disease progresses, behavioral and mood problems become prevalent and psychosis may set in (Ayd 1995). Symptoms of aphasia, agnosia, and apraxia are usually absent during the first stages of the disease (Welsh-Bohmer and Ogrocki 1998). This disorder is easily diagnosed, but treatments are limited.
Multiple sclerosis or MS (disseminated sclerosis) is a common neurologic disorder that affects over 300,000 Americans (sixty to three hundred per 100,000 individuals). It usually affects people between the ages of fifteen and fifty, and the average life expectancy after onset is twenty to twenty-five years (Campbell 1989). It affects more women than men, occurs more in temperate zones, and is more common in people of Northern European heritage.
Relapsing Subtypes:
There are several subtypes of the disorder. These include: Balo’s sclerosis, Schilder’s disease, Devic’s disease, central pontine myelinolysis, and Marchiafava-Bignami disease. Multiple sclerosis is a relapsing disease (Campbell 1989). Symptoms often occur, clear up, and then reoccur. Symptoms may clear up for months or years before recurring. There is also a progressive pattern in which symptoms never completely clear up, but gradually or rapidly become worse.Changes within the Brain:
Swelling of the brain and central nervous system followed by demyelination marks multiple sclerosis. Demyelination is the loss of the protective coating (myelin) on nerve fibers that act to speed up nerve impulses. This results in scattering of well-demarcated sclerotic plaques throughout the brain and spinal cord (Campbell 1989).Symptoms:The cause of the disease is unknown. Initial symptoms usually include loss of control of motor movements, weakness or numbness in one or more limbs, and visual deficits. Other symptoms include: sensory deficits, gait and balance difficulties, weakness, and cognitive changes. Only 20 to 30 percent of patients develop cognitive deficits sufficient to label them as demented (Snyder and Nussbaum 1998).
When dementia is present, patterns mimic those seen in subcortical dementias (movement disorders, cognitive slowing, executive dysfunction, memory impairment, and mood and personality changes). Treatment options include medications designed to treat the symptoms as they occur and medications designed to modify the disease activity.
Let’s begin examining the subcortical diseases with a brief overview of Binswanger’s disease is also called subcortical atherosclerotic encephalopathy. Otto Binswanger first described the disease in 1894, and it is the result of decreased blood flow to the brain, usually occurring between the ages of fifty and sixty. It is associated with hypertension and arterial wall thickening. The disease is associated with axonal loss, lacunar infarcts, dilation of perivascular spaces and loss of myelin (Welsh-Bohmer and Ogrocki 1998).Symptoms of the Disease: Multiple symptoms associated with the disease include: amnesia, cognitive deficits, episodes of stroke or seizure, apathy, changes in personality and mood, language deficits, and gait and motor difficulties (Ayd 1995). Symptoms are usually gradually progressive.
Wilson’s disease (hepatolenticular degeneration) is a rare, inherited disorder. It affects the body’s ability to metabolize copper. Wilson’s disease manifests itself as toxic levels of copper are deposited in the brain tissue, liver, and other organs. Prevalence rates are estimated at three in 100,000 individuals (Ayd 1995, 676). The disease is transferred to offspring through a recessive gene on chromosome 13 and usually becomes symptomatic between the ages of five and fifty, although it’s more common between the ages of ten and twenty-five (Snyder and Nussbaum 1998).
Symptoms:
Definitive symptoms of Wilson’s disease are the Kayser-Fleischer ring (a greenish-brown pigmentation around the cornea of the eye) and cirrhosis of the liver (Ayd 1995). Other symptoms include a mix of psychiatric and neurological abnormalities including: emotional and personality changes, parkinsonian symptoms, tremors, rigidity, postural instability, cognitive deterioration, and dysarthria (slowness or incoordination of speech-related muscles). Treatment focuses on limiting the intake of copper and in taking measures to eliminate copper from the system (Snyder and Nussbaum 1998).
Creutzfeldt-Jakob disease (spastic pseudosclerosis; cortico-striato-spinal degeneration) is an extremely rare, progressive dementia (occurs in one individual per one million per year worldwide) that is caused by the transmission of a prion (Tabrizi et al. 1996). Prions are infectious proteins that seem to lack DNA. In 1997 Dr. Stanley Prusiner won the Nobel Prize for his discovery of prions. Creutzfeldt-Jakob disease occurs two to three times more often in males and typically occurs in the mid fifties (Campbell 1989). In this extremely rapidly progressing disease, death usually occurs within a year after the onset of symptoms.
Symptoms:
Symptoms include memory impairment, motor problems, hemiparesis (paralysis of one side of the body), hemianopia (visual-field deficits mimicking blind spots), dysarthria (speech impairment marked by weakness or slowness of speech musculature), myoclonus (brief repetitive muscle contractions stemming from the central nervous system), depression, seizures, and behavioral and emotional problems (Ayd 1995). Welsh-Bohmer and Ogrocki (1998) identify a triad of symptoms that aid in the diagnosis of the disorder. These include: myoclonus, acute onset of dementia, and electroencephalogram results showing general slowing of brain activity with occasional sharp spikes. The slowly progressive form of the disease can be distinguished from AD by noted changes in reflex and motor abnormalities (Tabrizi et al. 1996). The disease is highly contagious, especially with direct contact with infected brain tissue. There is no known treatment for this disease, and it usually first affects the cerebellum, or lower areas of the brain.
Diffuse lewy body disease is marked by lewy body degeneration throughout the neocortex, limbic system, hypothalamus, and brainstem. Lewy bodies are found in nerve cells and are more prevalent in pigmented brain stem neurons. Lewy bodies are found in 5 to 10 percent of normal brains of people over the age of sixty and in 10 percent of brains of people diagnosed with Alzheimer’s disease (Ayd 1995). They are also found in the brains of virtually all cases of people diagnosed with Parkinsonism and lewy body dementia. The presence of lewy bodies does not indicate the presence of the disease and the number present in the brain does not correlate with the severity or duration of the disease (Ayd 1995).Symptoms of dementia with lewy bodies include progressive dementia coupled with severe rigidity and moderate Parkinson’s symptoms. It has been postulated that the neurological findings may be associated with degeneration in the areas where lewy bodies form. Diffuse lewy body disease should be suspected if a rapidly progressive dementia is present followed by rigidity, visual hallucinations, and other features of Parkinson’s (Burkhardt et al. 1988).Diagnosis of the DisorderDiffuse lewy body dementia affects both outer-brain (cortical) and inner-brain (subcortical) structures. There seems to be pathology within the brain that is similar to Alzheimer’s disease in some cases (Katzman et al. 1995). Therefore, there are currently two subtypes of the disorder identified. The first is called lewy body variant of AD and the second is diffuse lewy body disease (Welsh-Bohmer and Ogrocki 1998). Both types are marked by progressive cognitive decline that interferes with normal social or occupational functioning. Memory impairment may not be evident in the early stages of the disease but becomes more apparent as the disease progresses. There is often impairment in attention, visuospatial abilities, and other skills that are dependent upon frontal-subcortical structures (Kaye 1998).
Symptoms Associated With The Disease:
Symptoms associated with diffuse lewy body disease include:
- Fluctuating cognition with pronounced variations in attention and alertness
- Spontaneous motor features of parkinsonism Recurrent detailed and elaborate visual hallucinations (Kaye 1998; Perry et al. 1996).
- Frontal lobe impairments
- Slowing of motor functionsForgetfulness (Wagner and Bachman 1996).
- Syncope (fainting)
- Repeated falls
- Transient loss of consciousness
- Systematic delusions
- Sensitivity to neuroleptic medications
- Hallucinations (Kaye 1998).
Kaye also notes that the diagnosis of dementia with lewy bodies is less likely if there is history of strokes, focal neurologic signs on imaging, or evidence that another physical illness or brain disorder may be attributable to the symptom cluster.
Huntington’s disease is an inherited disease that begins in middle adulthood. Erratic, involuntary muscle movements and progressive memory and emotional deterioration mark the disease. It was originally called Huntington’s chorea for the Greek word “chorea,” meaning dance. This is a reference to the twisting, spastic movements associated with the disease. This progressive disorder has been localized to a genetic deficit on chromosome 4 (Huntington’s Disease Collaborative Research Group 1993).
Areas of the Brain Affected:
The basal ganglia is usually the first structure affected by the disease. Later the disease progresses to the frontal lobes where symptoms of inattention and lack of motivation appear. Huntington’s disease is classified as a frontal-subcortical disease (Joynt and Shoulson in Heilman and Valenstein, eds. 1985). The disease goes largely untreatable except for measures taken to ease the symptoms and discomfort.
Diagnosis:
The disease is easily diagnosed and even predictable with blood tests, given its genetic etiology. It is believed that the malformed Huntington’s protein is formed into fibrils that represent the beta-amyloid plaques seen in Alzheimer’s disease. Huntington’s disease affects an estimated four to eight people in 100,000 and 50 percent of the children of a parent with the disease will inherit it (Harper 1992). Symptoms usually manifest themselves in adults between the ages of forty and fifty and can last as long as twenty to thirty years. If the disease is inherited from the mother, it tends to progress more slowly and appear later in life than when it is inherited from the father.
Symptoms:
Symptoms are variable but often mimic the progression of Parkinson’s disease in their initial motor effects and eventual effects on frontal lobe functioning. Cognitive deficits implicate the caudate nucleus in its mental rather than its motor functions. Eye movements slow down and become jerky (nystagmus). Other manifestations include slowed mental processing, shortened attention span, poor concentration, inflexibility in thinking, and slowed motor performance with the nondominant hand. Motor learning is impaired and working memory becomes especially susceptible to interference. Retrieval deteriorates as the disease progresses and visuospatial functions remain impaired throughout the disease process. Verbal functions (like speech comprehension, language processing) tend to remain preserved until the later stages of the disease with the exception of speech production (Welsh-Bohmer and Ogrocki 1998). Depression is likely to accompany Huntington’s disease. Some initial presentations initially involve psychiatric symptoms such as depression or symptoms that mimic schizophrenia (Folstein et al. 1979).
Pick’s disease (also known as circumscribed cortical atrophy) is named after the psychiatrist Arnold Pick (1851-1924) (Campbell 1989). This disease is the most widely known subtype of frontotemporal dementia. Its presentation is unique in that the first symptoms usually center on strange behaviors, lack of judgment, and impulsiveness rather than the memory problems seen in many other forms of dementia. Pick’s disease is relatively rare, comprising only about 2 percent of dementia patients, or less than one tenth of 1 percent of the general population (Lezak 1995). Because cognitive functions are usually preserved early in the illness, psychosis usually needs to be ruled out as a differential diagnosis (Kaye 1998). The duration of the disease is usually between two to seventeen years (Lezak 1995, 220).In this progressive dementia involving the temporal and frontal lobes, symptoms are similar to other disease processes involving the same anatomy. Early symptoms may involve difficulties with attention, significant changes in personality and emotion, and lack of motivation. Language disturbances usually involve impaired verbal fluency and reduced conversational speech (Moss et al. 1992). Personality and emotional changes are usually more pronounced than seen in Alzheimer’s disease, although the severity of dementia is usually not as prevalent.
Who Does It Affect and What Can We Do?
The average age of onset for Pick’s disease is fifty-five years old (Campbell 1989). It affects more women than men, and there is a strong correlation between developing Pick’s disease and having a blood relative with the disease. Up to 60 percent of patients with a frontotemporal dementia have a family history of the disease (Kaye 1998). Frontotemporal dementia has been linked to chromosome 17 and is usually revealed in neuroimaging by atrophy (wasting) in the frontal and anterior temporal lobes. SPECT scanning may reveal decreased cerebral blood flow over the frontal lobes, which is a distinct finding for this type of dementia (Kaye 1998). Treatment options are limited but include cholinesterase inhibitors coupled with behavior modulating medications, such as benzodiazepines, antidepressants, and/or neuroleptics.
This type of dementia occurs at about one-fourth the rate of Alzheimer’s disease (Lezak 1995). It is referred to by this name because the frontal and anterior temporal lobes show localized atrophy (wasting) and upon autopsy reveal a loss of neurons, astrocytosis (small tumors) with intraneuronal inclusions (Pick bodies), and inflated neurons. Mutations in the tau gene on chromosome 17 have been associated with a frontotemporal dementia with parkinsonism (Poorkaj et al. 1998).
Key Features of Frontotemporal Dementia:
The frontal lobe (forehead region of the brain) is responsible for the control of a number of behaviors that are referred to as “executive functioning.” Ogrocki and Welsh-Bohmer identify several features of executive functioning that can be affected in disorders involving the frontal lobes. These include: attention, planning, self-awareness, abstraction, flexibility in thinking, self-regulation, behavior execution and inhibition, decision making, changes in personality, and creativity (2000, 23). In frontal-lobe dementias these functions are severe enough to impair daily functioning.
Characteristics Unique to Frontotemporal Dementia (Kaye 1998):
- Insidious onset with slow progression
- Conduct and behavioral deficits appearing early in the disease process
- Neglect of hygiene (Loss of personal awareness)
- Inappropriate social behavior
- Disinhibition, impulsivity, and distractibility Excessive eating, smoking, or alcohol consumption
- Pica (compulsive eating of items that are not considered eatable)
- Changes in speech patterns Social withdrawal
- Perseverative (repetitious) or ritualistic behaviors
- Changes in speech output Echolalia (repeating what they have recently heard)
- Stereotyped speech (constant repetition of phrases)
- Late mutism (progressive reduction of speech)
- Physical changesIncontinence
- Early or prominent primitive “frontal” reflexes
- Late akinesia, rigidity, tremor
Vascular dementia can affect either the cortical or subcortical areas of the brain. Its progression is fluctuating (step-like) rather than steady (hill-like) like some of the more progressive dementias. It was formerly referred to as “multi-infarct dementia” and is often associated with cerebral arteriosclerosis (thickening or hardening of the arterial wall). It is the result of a series of strokes, which have produced enough brain tissue damage to cause the onset of cognitive impairment. Infarct refers to an area of dead or dying brain tissue resulting from obstruction or destruction of the blood vessels that normally supply blood to that area. Vascular dementia accounts for about one fourth of progressive dementias (Tomlinson et al. 1970). Vascular findings are frequently seen with Alzheimer’s disease related cortical pathology (Welsh et al. 1996). There has been a correlation found between some forms of vascular dementia, AD, and the ApoE gene, which suggests possible shared physiology (Saunders et al. 1993).
Types of Vessel Disease:
Symptoms of Vascular Dementia:
- There are two types of strokes (also called cerebral vascular accidents or CVAs).
- An embolism is a clot or other obstruction that is carried from a larger vessel into a smaller one. It obstructs the circulation of blood and results in damaged tissue. A thrombosis is a formed clot that remains at the point at which it formed. A thrombosis typically involves a much slower progression than an embolism. Damage can also be in the form of softening of the brain tissue (encephalomalacia).
- Cerebral hemorrhage is a massive bleeding into the brain. This bleeding results in abrupt tissue damage and is often fatal. It is often the result of hypertension (high blood pressure). An aneurysm is a vascular dilation or swelling of blood vessels, which results from defects in the elasticity of the vessel wall (Kolb and Whishaw 1995).
- Single strokes usually result in much more localized or specific deficits than the more global vascular dementia, although a single stroke placed in the right area, such as the angular gyrus or anterior or paramedian thalamus, can mimic a multi-infarct’s dementing process (Kaye 1998). Strokes can also be transient and fleeting in nature. These small strokes are referred to as transient ischemic attacks (“mini-strokes”). Lateralized motor dysfunction (weakness, lack of coordination, or paralysis on one side of the body) and acute speech impairments are cardinal symptoms of vascular involvement. If this occurs to you or someone you know, seek medical help immediately.
- Symptoms are variable but can include: memory impairment, lateralized motor impairment, difficulties in walking, urinary incontinence, deficits in judgment, personality changes, and changes in impulse control (Campbell 1989). A common pattern seen in subcortical vascular dementias is language impairments marked by broken fluency in speech (Barr et al. 1992). In this type of symptom presentation, comprehension usually remains intact, as does the ability to name objects (Villardita 1993). Inefficient information processing and motor slowing are also common hallmarks of the disorder (Welsh-Bohmer and Ogrocki 1998). For a diagnosis of vascular dementia to be given, there is usually a noted deficit in memory and a deficit in one or two other cognitive domains.
- Researchers at the University of Kentucky are currently following over 600 nuns from the School Sisters of Notre Dame. The nuns undergo annual evaluations and have agreed to donate their brains for investigation upon death. Studies have shown a correlation between brain infarcts and the number of plaques and tangles within the brain (Snowdon et al. 1997). Heyman and associates (1998) demonstrated that patients with both a history of infarcts and AD showed more severe dementia than those patients with AD alone.