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Alzheimer's: Where Do We Go from Here?

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Alzheimer's clinical trials

Alzheimer’s disease is a progressive neurodegenerative disorder characterized by cognitive and behavioral impairment which interferes in day-to-day functioning of the affected. It is attributed to the formation of plaques and tangles in parts of the brain called the hippocampus and areas of the cerebral cortex that are involved in the process of thinking and decision making. As a result of these, the patients suffering from Alzheimer’s disease have impaired memory and decision-making capabilities.

10% of people worldwide over the age of 70 have significant memory loss; the underlying disease in half of those cases is Alzheimer’s disease.

What Causes Alzheimer's?

Though the exact mechanism of Alzheimer’s development is not known, it is thought to be caused by abnormal deposition of proteins around the parts of the brain involved in memory and decision making. One such protein is Amyloid, the aggregation of which forms plaques. Deposits of another protein called the Tau protein form neurofibrillary tangles. These aggregates of protein deposit over the brain cells and result in the pathogenesis of Alzheimer’s disease.

Factors that are thought to increase the risk of Alzheimer’s development include:
  • Increasing Age
  • Family history of the disease
  • History of Down’s syndrome
  • Untreated Depression
  • Head Injury
 

Clinical Features of Alzheimer's

The clinical features of Alzheimer’s disease develop years after abnormal protein deposition in the brain cells and have a different rate of progression in different individuals. It begins with memory lapses in the early phase of the disease to significant functional loss and loss of quality of life in the latter stages.  

People with Alzheimer’s have difficulty carrying out daily tasks like cooking and driving. As a result of impaired memory, they may ask the same questions over and over and find it difficult to comprehend even the simplest of things. They easily misplace things and get lost when out of the house. As the disease worsens, some people may develop depression and violent tendencies. In severe cases, people may find difficulty swallowing food and gradually lose speech.

Diagnosing Alzheimer's

To reach the diagnosis of Alzheimer’s disease your doctor will take a thorough clinical history and assess your memory and thinking skills.

An Alzheimer’s can be diagnosed with certainty only after death by microscopic examination of the brain- which shows abnormal protein deposits. In addition to clinical history and memory assessment the following tests can help in ruling out other disorders that may cause cognitive impairment in suspected cases:
  • Blood test: Blood tests can help rule out other body conditions leading to memory loss- including vitamin deficiency and thyroid abnormalities.
  • Imaging: MRI and CT scan of the brain can help detect visible abnormalities in the brain that lead to cognitive impairment-like trauma or tumors.
 

Managing Alzheimer's

Treatment for Alzheimer’s is aimed at providing symptomatic relief to improve cognition and memory. Drugs used for Alzheimer’s treatment include:
  • Cholinesterase inhibitors: These drugs are currently the first-line drugs used in Alzheimer’s treatment. This group of drugs prevents depletion of the Acetylcholine-a chemical messenger required for the cell to cell communication in the brain. The level of Acetylcholine is found to be low in people suffering from Alzheimer’s disease. These drugs also improve depression symptoms in these people.
  • Memantadine: Memantadine helps slow the progression of the disease and may improve memory in patients with Alzheimer’s disease. It acts by blocking the effects of an excitatory brain chemical called Glutamate.
  • Antidepressants and psychotherapy may help people with Alzheimer’s disease suffering from depression.
  • Cognitive Stimulation Therapy: This therapy aims at improving memory and problem-solving skills in people with AD by engaging them in group activities and exercises.
 

Recent Alzheimer's Advances and Clinical Trials

Mesenchymal stem cell: A clinical trial to assess the safety, efficacy and potential side effects of mesenchymal stem cell infusion in the treatment of patients with Mild to moderate cognitive impairment caused by Alzheimer’s disease is being conducted. Stem cells can grow in the brain and potentially repair brain damages caused by abnormal protein deposition and improve memory. It is currently in Phase-1 of its clinical trial.

Memantine: A study to assess the effects of the drug Memantine in brain function and symptom improvement in patients with Alzheimer’s disease is currently undergoing. Memantine is thought to improve memory in patients with Alzheimer’s disease and it acts by blocking Glutamate receptors in the brain. It is currently in Phase 4 of its clinical trial.

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Daratumumab: Daratumumab is currently in phase 2 of its clinical trial to explore if it can have a meaningful clinical effect in people suffering from mild to moderate cases of Alzheimer’s disease. Daratumumab is an FDA approved treatment of Multiple myeloma, cancer of the blood plasma. There is a significant rise in levels of CD38+ T cell expression in patients with early Alzheimer’s disease. Daratumumab acts by targeting these CD38 cells. So the drug is being studied for its potential benefits in the management of the early stages of the disease.

Sodium Oligomannate: A study to assess the safety, efficacy, and tolerability of Sodium Oligomannate in the treatment of mild to moderate Alzheimer’s disease is being conducted. Recent studies have shown evidence to associate gut microbial disturbance with Alzheimer’s disease progression. Sodium Oligomannate is thought to remodel gut microbiota and prevent the progression of Alzheimer’s disease. It is in phase 2 of its clinical trial.

Transcranial Magnetic Stimulation and Constraint-Induced Language Therapy: Loss of speech is a cardinal symptom of Alzheimer’s disease associated with distress and impaired quality of life in these patients. Studies have shown TMS to be effective in improving cognition in patients with Alzheimer’s disease. A study to assess the benefits of combining TMS and Constraint-Induced Language Therapy in improving verbal communication in people with Alzheimer’s disease. The combined therapy is currently in phase-1 of its clinical trial.

Lifestyle changes: A clinical trial is currently underway that aims at assessing the benefits of comprehensive lifestyle modification in slowing, stopping, or reversing disease progression in the early stages of Alzheimer’s disease. Lifestyle interventions in the study include taking a balanced diet, activities to reduce stress, exercise, and group support sessions. It is in Phase-2 of its clinical trial.  

 
References:
  1. Jason Weller et al. Current understanding of Alzheimer’s disease diagnosis and treatment. F1000Res. 2018; 7: F1000 Faculty Rev-1161.Alzheimer's disease


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