The US Food and Drug Administration’s recent approval for Biogen's aducanumab is the first treatment to be approved for Alzheimer's disease in almost 20 years. While some have hailed the nod as a “milestone moment” in the battle against an incurable and debilitating disease, many have spoken, written and protested against the use of the drug.
Alzheimer’s is the most common cause of dementia, a broad-based term used to describe different brain disorders that affect memory, thinking, behaviour and emotions. According to the 2020 World Alzheimer’s Report, more than 50 million people in the world are living with dementia. The number is expected to rise to 152 million by 2050, with the greatest increases in low and middle-income countries.
The coronvairus in some cases has been shown to cause neurological problems as well. A recent study shows an overlap between COVID-19 and brain changes common in Alzheimer's.
Ranchi’s Rajendra Institute of Medical Sciences director Dr Kameshwar Prasad, also a former head of the department of neurology at AIIMS in New Delhi, talks about the importance of recognising the early signs of Alzheimer’s, steps to check its onset and Covid’s effect on neurological problems. Edited excerpts of an interview:
Biogen’s aducanumab is the first medication for Alzheimer’s to get FDA approval in almost two decades. Considering its cost, it cannot be afforded by most. What do you have to say about this drug? How does it work?
Frequently Asked Questions
A vaccine works by mimicking a natural infection. A vaccine not only induces immune response to protect people from any future COVID-19 infection, but also helps quickly build herd immunity to put an end to the pandemic. Herd immunity occurs when a sufficient percentage of a population becomes immune to a disease, making the spread of disease from person to person unlikely. The good news is that SARS-CoV-2 virus has been fairly stable, which increases the viability of a vaccine.
There are broadly four types of vaccine — one, a vaccine based on the whole virus (this could be either inactivated, or an attenuated [weakened] virus vaccine); two, a non-replicating viral vector vaccine that uses a benign virus as vector that carries the antigen of SARS-CoV; three, nucleic-acid vaccines that have genetic material like DNA and RNA of antigens like spike protein given to a person, helping human cells decode genetic material and produce the vaccine; and four, protein subunit vaccine wherein the recombinant proteins of SARS-COV-2 along with an adjuvant (booster) is given as a vaccine.
Vaccine development is a long, complex process. Unlike drugs that are given to people with a diseased, vaccines are given to healthy people and also vulnerable sections such as children, pregnant women and the elderly. So rigorous tests are compulsory. History says that the fastest time it took to develop a vaccine is five years, but it usually takes double or sometimes triple that time.
This drug has been approved by US FDA's accelerated approval process on the basis of demonstrated effects on a surrogate endpoint, which may predict clinical benefit but there remains residual uncertainty of its clinical benefit. The drug works by reducing the clumps of protein deposits, called amyloid plaques, in a time-dependent and dose-dependent manner. The deposits are hypothesized to cause brain-cell degeneration and hence their reduction has the potential to show benefit but the company has been asked to do confirmatory Phase 4 trials, the failure of which will lead to withdrawal of the approval.
Given the costs, it may be prudent to wait with cautious optimism for the results of the confirmatory trial because Phase 3 trials were not unequivocally in favour of the drug.
Why did it take so long for an Alzheimer’s drug to come out?
The main reason is that we do not know the exact cause of this disease. There are multiple hypotheses, but no clear cause. Hence, the effects of potential therapies are either clinically meaningless or require large sized, long-term trials.
The findings of a recent Cleveland Clinic-led study identified mechanisms by which Covid-19 can be associated with Alzheimer's disease-like dementia. The research published in Alzheimer's Research and Therapy indicates an overlap between Covid-19 and brain changes common in Alzheimer's. What do you have to say about this finding?
Yes, this is correct. The ApoE4 genotype is also associated with both severe Covid, post-Covid cognitive impairment as well as Alzheimer's disease. This means there may be a greater risk of developing memory and other cognitive problems in those with ApoE4 allele. Whether this will result in a progressive disease like Alzheimer's disease is yet to be investigated but this is a matter of intense current research. While there is no clear evidence that the virus attacks the brain, there have been establishments of a relationship between the virus and genes/proteins that are linked with neurological diseases like Alzheimer's. As a member of a WHO group and a University of Texas, San Antonio group, I am also investigating this topic.
What happens to the brain cells in Alzheimer’s?
The brain has main cells called neurons and supporting cells called glia. In Alzheimer's, neurons progressively decrease in number, probably because of the toxic effects of an accumulating protein called beta-amyloid.
How serious is the Alzheimer’s problem in India? At what age can a person be affected? What are the initial symptoms to look out for? Can a young person also have memory loss?
In India, it is estimated that there were 4.1 million cases of dementia in 2015, will be 7.4 million by 2030, and 14 million by 2050. Around 50 percent of these will be due to Alzheimer's disease. This is age-related, prevalence is 2 to 3 percent above age 60 years, 5 to 10 percent above 65; 15 to 20 percent above 75 and 25 to 50 percent above 85.
Initial symptoms are memory loss but all those complaining of memory problems are not early Alzheimer's. There are many causes of memory problem, some reversible, some not. Only if the problem is progressive and interferes with activities of daily living that one should suspect dementia. Young persons can also have memory loss but unless there is a positive history of Alzheimer's, it is due to some (other) cause.
Is there a way one can prevent the disease? Once affected, how can it be reversed?We are conducting a study to find the risk factors for Alzheimer’s, a first of its kind of study in India. This study looks at cardiovascular, endocrine, hepatic, neurological, ophthalmic, psychiatric, dermatological, oncological, and respiratory diseases in a cohort of 8,000 people aged 45 or over. To prevent the onset of this disease one should keep using the brain, remain connected to family and friends, manage stress, exercise regularly, have a good sleep and imbibe a healthy lifestyle. Once affected, Alzheimer's can't be reversed but can be treated to keep one as active as possible but there are many causes of dementia which can be treated and reversed.