A closer look at neurodegenerative diseases

Although there are many forms and causes of dementia, Alzheimer’s disease (AD) is the most common in older adults. The exact mechanisms of how and why various forms of dementia develop are still being investigated.
In Alzheimer’s disease, changes in the brain may begin a decade or more before cognitive decline is noticed. Abnormal deposits of proteins – amyloid plaques and tau tangles – form throughout the brain and prevent nerve cells (neurons) from communicating with each other. Healthy neurons stop functioning, lose connections with other neurons, and die. The damage initially appears to take place in the parts of the brain that are essential to forming memories. As more neurons die, other parts of the brain are affected and begin to shrink.

The various forms of dementia are difficult to differentiate diagnostically. Physicians may

• ask the patient and caregiver about overall health, use of medicines, diet, past medical problems, ability to carry out daily activities, and changes in behavior and personality;
• conduct memory, problem solving, attention, counting, and language tests;
• order standard medical tests, such as blood and urine samples, to identify other possible causes of the symptoms;
• use magnetic resonance imaging (MRI) to visualize changes in the brain, such as white and grey matter atrophy;
• order positron emission tomography (PET) to visualize amyloid and/or tau deposits;
• perform lumbar puncture, in which a small sample of cerebrospinal fluid – which surrounds the brain and spinal cord – is removed from the spinal canal for laboratory analysis for amyloid and tau molecules.

Physicians might repeat these tests to gain information about how the patient’s disease is developing over time.

Unfortunately, there is currently no cure for Alzheimer's disease. However, certain treatments like behavioral therapy and medication can help ease the symptoms of the disease, and starting treatment early may help preserve daily functioning for some time. In addition, early diagnosis will allow families to take care of financial and legal matters, address potential safety issues in the patient’s surroundings, adapt the person’s home, and develop support networks.

Two pathological changes are regarded as hallmark signs of Parkinson’s disease. The first is the breakdown and death of dopamine-producing cells in the substantia nigra. The substantia nigra is one of several structures in the brainstem that make up the basal ganglia, which is extremely important for movement. Scientists still do not know what causes these cells to die, but when dopamine levels decrease, it causes abnormal brain activity that leads to impaired movement and other symptoms of Parkinson’s. By the time a Parkinson’s disease patient dies, they may have lost up to 70 percent of the dopamine neurons in this region. As the disease progresses, neurons in other areas of the brain and brainstem begin to die as well.

Researchers have also noted the presence of Lewy bodies, which are clumps of specific substances within brain cells. Among the substances contained in Lewy bodies, scientists focus on a protein called alpha-synuclein (a-synuclein). It is found in all Lewy bodies in a clumped form that cells cannot break down.

Normal (left), Parkinson's disease (right): Computer illustration showing healthy substantia nigra and degenerated substantia nigra in the human brain. The substantia nigra plays an important role in reward, addiction, and movement.

No specific laboratory or imaging test can conclusively diagnose Parkinson’s disease. However, because several other disorders can cause similar symptoms, it is important to arrive at a diagnosis as soon as possible. The diagnosis is based on a patient’s medical history, a review of their signs and symptoms, and a physical and neurological examination. The physician may also order laboratory or imaging tests to rule out other conditions.

A single-photon emission computed tomography (SPECT) examination – called a dopamine transporter (DaT scan) – can support the suspicion of Parkinson’s disease. However, it is often only possible to confirm a Parkinson’s disease diagnosis once Parkinson’s disease medication has been initiated and the patient has significantly improved. Frequently, it takes time to diagnose Parkinson’s disease. Physicians may recommend regular follow-up appointments to evaluate the patient’s condition and symptoms over time.

At present, there is no cure for Parkinson’s disease, but a variety of medications provide considerable relief from the symptoms. Treatment for each patient is based on their individual symptoms. Medications can help control and often significantly improve symptoms, but they cannot reverse the effects of the disease. The medications include

• drugs that increase dopamine levels in the brain;
• drugs that affect other brain chemicals;
• drugs that help control symptoms that are not movement-related.

Over time, however, the benefits of the drugs frequently diminish or become less consistent.
Additional treatments involve physical, occupational, and speech therapies that help with movement and balance disorders, tremors and rigidity, decline in mental function, and speech problems. Other supportive measures include a healthy diet and getting more rest.

In some more advanced patients with unstable medication responses, deep brain stimulation (DBS) surgery may be advised. This involves implanting electrodes into a specific part of the patient’s brain and connecting them to a small generator implanted in the chest. The device and electrodes painlessly stimulate the brain to block signals that cause many of the movement-related symptoms of Parkinson's – such as tremor, slowness of movement, and rigidity. Although DBS may provide sustained relief from symptoms, it doesn't keep Parkinson's disease from progressing and some symptoms may gradually return.

Multiple sclerosis (MS) is an autoimmune disease. The body’s own immune system attacks the myelin sheaths that cover and protect the axons. These nerve fibers connect nerve cells within the central nervous system (i.e., the brain and spinal cord). Axons are like cables, and the fatty myelin sheaths insulate them. 

When this insulation is destroyed, the nerves’ ability to conduct electrical and chemical signals becomes slower, uncoordinated, or entirely nonexistent, depending on the severity of the damage. Over time, the uninsulated nerve fibers themselves, and even whole nerve cells, die. This leads to brain atrophy. Damage to specific brain regions can make it hard to perform specific skills located in that region. There are two forms of multiple sclerosis : in relapsing-remitting multiple sclerosis, patients have periods when symptoms flare up, and periods when they calm down; in progressive multiple sclerosis, the symptoms get steadily worse.

There is no single test for multiple sclerosis; a combination of tests is used to rule out other diseases that may cause similar symptoms and to diagnose multiple sclerosis. After taking the patient’s medical history and physical examination, a physician might order the following tests:

• Blood tests are currently mainly used to rule out other diseases with similar symptoms, although research is under way to also detect MS-related biomarkers in the blood.
• Magnetic resonance imaging(MRI) is used to detect damage or scarring of the myelin sheaths in the brain and spinal cord.
• Lumbar puncture involves removing a small sample of cerebrospinal fluid – which surrounds the brain and spinal cord – from the spinal canal for laboratory analysis. This sample can show abnormalities in immune cells and antibodies that are associated with MS.
• Evoked potential tests measure the minute electrical signals that occur in certain areas of the brain in response to stimulation, such as from sound, touch, or sight. They can be measured by electrodes placed on the scalp.

Physicians can repeat these tests to gain information about how the patient’s disease is developing over time.

Biomedical research has revealed many similarities between neurodegenerative diseases, including atypical protein accumulations and induced cell death. These similarities suggest that therapeutic advances against one neurodegenerative disease might improve therapies for others as well. Most of today’s medications only treat the symptoms, which provides some relief to patients, but does not prevent the disease from progressing. Disease-modifying therapies (DMTs), which can create a lasting effect on the trajectory of clinical and cognitive decline, are needed to address the underlying causes of these diseases. But progress has proven challenging.

Scientific complexities in neurodegenerative diseases include getting medicines across the blood-brain barrier, finding appropriate animal models that can inform human efficacy, a lack of validated molecular targets for drug development, and a lack of well-defined biomarkers that can help measure consistency of treatment effect in clinical trials.[11] Additionally, many neurodegenerative diseases are heterogenous conditions with multiple root causes that make it difficult to diagnose patients, identify treatments, and predict how individual patients will respond to it.