Neurodegenerative diseases

Neurodegenerative diseases is an umbrella term for a range of conditions which primarily affect cells (neurons) in the brain. These cells degenerate, which result in the development of dementias and/or movement disorders. Parkinson’s disease and Alzheimer’s disease are the two most common neurodegenerative disorders. At present much knowledge is being accumulated concerning the disease mechanisms, but the causative factors of these conditions are still largely unknown.
Besides Parkinson’s disease, there are also other movement disorders which look like Parkinson’s disease. Examples of these disorders are multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). To some extent these disorders present with the same symptoms as Parkinson’s disease: tremor, hypokinesia, rigidity and postural instability. However, other parts of the brain are affected in these Parkinson-like syndromes. For this reason medication used for Parkinson’s disease is usually not effective in those other conditions.

Parkinson’s disease (PD)
Parkinson’s disease (PD), also known as idiopathic parkinsonism, is characterized by a slowly progressive disturbance of posture and movements, with symptoms like tremor, rigidity, hypokinesia (decreased movement of body parts), and (in the long run) postural instability. Tremor is the most apparent and well-known symptom. Even though around 30% of individuals with PD do not have tremor at disease onset, most develop it as the disease progresses. It is usually a rest tremor, which means that the tremor is maximal when the limb is at rest and briefly disappearing with voluntary movement and during sleep. Rigidity is stiffness and resistance to limb movement caused by increased muscle tone: an excessive and continuous abnormal contraction of muscles. Besides these motor problems PD can also cause cognitive symptoms like dementia, apathy and depression and other non-motor symptoms.
The causes of idiopathic PD are unknown. Probably it is a combination of genetic and environmental pathological influences.
Treatment of PD is aimed at reducing symptoms. Unfortunately no treatments are yet known to cure PD or to slow its progression.

Multiple system atrophy (MSA)
Multiple system atrophy (MSA) is classified by two types: parkinsonian and cerebellar, depending on which types of symptoms predominate at the time evaluation. The parkinsonian type of MSA looks a lot like PD. Usually the hypokinesia is more prominent than the tremor. Predominant signs of the cerebellar type of MSA are lack of muscle coordination. In both types of MSA severe autonomic symptoms like orthostatic hypotension may develop. Orthostatic hypotension is a form of low blood pressure which makes a person feel dizzy or lightheaded, or even faint, when he/she stands up from sitting or lying down.
Treatment is aimed at reducing symptoms. Usually there is almost no positive effect to antiparkinsonian medication.

Progressive supranuclear palsy (PSP)
Progressive supranuclear palsy (PSP) is a rare brain disorder that causes serious and progressive problems with control of gait and balance, along with complex eye movement and thinking problems. PSP is sometimes referred to as Steele-Richardson-Olszewski syndrome, reflecting the combined names of the scientists who defined the disorder. PSP usually starts between the age of 50 and 80 years. One of the classic signs of the disease is an inability to aim the eyes properly, which occurs because of lesions in the area of the brain that coordinates eye movements. Affected individuals often show alterations of mood and behavior, including depression and apathy as well as progressive mild dementia. The most frequent first symptom of PSP is a loss of balance while walking. Individuals may have unexplained falls or a stiffness and awkwardness in gait.
At this time there is no effective treatment for PSP. In some individuals the slowness, stiffness, and balance problems of PSP may respond to antiparkinsonian agents such as levodopa, but the effect is usually temporary.

Corticobasal degeneration (CBD)
Corticobasal degeneration (CBD) is a progressive neurological disorder, which typically occurs in patients aged between 45–70. Patients with CBD usually present with either a movement disorder or cognitive deficits. As the disease progresses, most patients will develop both types of symptoms, often with a delay of 2-3 years. Movement symptoms are similar to those found in Parkinson’s disease, such as poor coordination, akinesia (an absence of movements), rigidity (a resistance to imposed movement), impaired balance, and limb dystonia (abnormal muscle postures). Other possible symptoms include visual-spatial impairments, apraxia (loss of the ability to make familiar, purposeful movements), hesitant and halting speech, myoclonus (muscular jerks) and dysphagia (difficulty swallowing).
There is currently no specific treatment for CBD. Instead individual symptoms are targeted with specific medications. For example, rigidity and difficulty walking may partially respond to treatments for Parkinson’s disease.

Alzheimer’s disease (AD)
Alzheimer’s disease is the most common form of dementia. Dementia is the loss of cognitive functioning (thinking, remembering, and reasoning) and behavioral abilities, to such an extent that it interferes with a person’s daily life and activities. Dementia ranges in severity from the mildest stage, when it is just beginning to affect a person’s functioning, to the most severe stage, when the person must depend completely on others for basic activities of daily living. Although not all memory loss indicates Alzheimer’s disease, one in ten people over 65 years of age, and over half of those over 85 have Alzheimer’s disease. Eight cognitive domains are most commonly impaired in AD: memory, perceptual skills, attention, constructive abilities, orientation, problem solving and functional abilities.
Currently there is no cure for Alzheimer’s disease. Treatments are aimed at reducing the symptoms of AD and improve quality of life for those with AD and their caregivers.

Frontotemporal dementia (FTD)
Frontotemporal dementia (FTD) is the cause of dementia in 12-20% of the cases. FTD usually begins between the age of 45 en 60 years. First symptoms are behavioural symptoms like disinhibition and compulsive behaviour, and changes in personality like apathy. FTD progresses to immobility and loss of speech and expression. Motor symptoms as in Parkinson’s disease can occur, usually when FTD has already progressed. There is a strong genetic component to the disease; FTD often runs in families. There is no treatment to slow the progression of FTD, and treatment is aimed to help control symptoms like unacceptable or dangerous behaviours. Anti-depressants have shown to improve some symptoms.

Dementia with Lewy Bodies (DLB)
Dementia with Lewy Bodies (DLB) is the second most common cause of dementia, after Alzheimer’s Disease. It usually occurs in older adults between 50-85 years old, and affects slightly more men than women. It shares symptoms—and sometimes overlaps—with several diseases, especially AD and PD. Core features of DLB are: fluctuating cognition with great variations in attention and alertness from day to day and hour to hour, recurrent visual hallucinations (in 75% of people with DLB), and motor features of Parkinson’s Disease like muscle stiffness, mild tremor and movement problems. Movement and motor problems occur in later stages for 70% of persons with DLB. But for 30% of DLB patients, and more commonly those that are older, Parkinson’s symptoms occur first, before dementia symptoms. In these individuals, cognitive decline tends to start with depression or mild forgetfulness.
As with other neurodegenerative brain diseases, there are no treatments that can slow or stop the brain cell damage caused by DLB. Current strategies focus on relieving symptoms.

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