(Focus - India)
September 21st is observed as World Alzheimer's Day, which aims to raise awareness about the disease and also helps highlight the issues faced by Alzheimer's patients. It gives people and organizations an opportunity to demonstrate how we can overcome these issues and help affected people live well.
Dr. Surendra Khosya, an eminent neurologist from India, also supports that it is essential to create awareness among individuals, which can be achieved through International Alzheimer's society and local society.
Dr. Surendra Khosya is an MBBS, MD, DM in Neurology, currently serving as a Senior Consultant, Neurology Department at EHCC Hospital, Jaipur, Rajasthan, India.
In a rural setup, we can detect Alzheimer's or dementia in 60% to 70% of patients coming to OPD or the healthcare facility. In India, where less than 8% of the population is over 65 years, the total number of Alzheimer's or dementia-affected populations is lesser as compared to developed countries.
Alzheimer's is a disease commonly associated with older age [1]. Are there any ways to predict its risk of occurrence at an early age?
Dr. Surendra - Yes, Alzheimer's Disease is a disease of older age, and most patients are affected after 60. But suppose the patient has a positive family history of AD or any mutation regarding AD, like the presenilin 1, or presenilin 2, and APOE4 mutation; in that case, the patient has a risk of getting AD at an early age.
Suppose the patient has a history of diabetes, hypertension, dyslipidemia, obesity, a history of a head injury, a poor lifestyle, or an unhealthy diet. In that case, they also have risk of developing AD at an early age.
Many biomarkers are in the developing phase for detecting AD at an early age, like cerebrospinal fluid (CSF), beta-amyloid level, tau protein level, etc. We conduct blood tests and several imaging techniques, like FDG-PET Scan, amyloid PET, and tau imaging, to detect the total beta-amyloid level.
We refer to some theories like amyloid cascade theory, neurodegeneration theory, phosphorylated tau theory, neurovascular theory, and the mitochondrial theory. If beta-amyloid is present only in the brain and we detect it in cerebrospinal fluid, then we say this is the cellular phase of Alzheimer's disease. If the patient has beta-amyloid, phosphorylated tau protein, and evidence of neurodegeneration or neuroinflammation, then we say the patient is in the preclinical stage of Alzheimer's disease.
By using several imaging techniques, based on the history and beta-amyloid level, we can detect AD at the preclinical stage before 15 to 20 years of development of AD. Most of our patients develop the cellular phase 15 years before the development of dementia. Minimum cognitive impairment runs almost 10 to 15 years; 30% to 60% of neuropsychiatric patients develop dementia within 10 to 15 years.
In the context of India having less than 10% of its population above 65 years [2], how common is Alzheimer's Disease in India?
Dr. Surendra - The elderly population is less in developing countries or low-income countries because the life expectancy in India is almost between 65 to 70 years. We see that the patients have an economic background, literacy level, and socio-cultural status variations. Currently, we do mini-mental state examination (MMSE) or detailed neuropsychological assessment for English-speaking or literate people.
But in rural areas of India, most of the population is illiterate. They can only come to the hospital or meet a neurologist for neuropsychological assessment. When a patient develops dementia, many reflect on the disease of aging.
In a rural setup, we can detect Alzheimer's or dementia in 60% to 70% of patients coming to OPD or the healthcare facility. In India, where less than 8% of the population is over 65 years, the total number of Alzheimer's or dementia-affected populations is lesser as compared to developed countries.
It is a positive sign. Alzheimer's disease was first identified by Alois Alzheimer in the year 1918, but till 2022, no drugs could cure AD. Monoclonal antibodies are a hope that some newer drug in the future or some new trials can prove that they can reverse AD. We may have some new drugs in the market in the next four or five years.
How do you treat your Alzheimer's Disease patients?
Dr. Surendra -
Most OPD patients have a history of forgetfulness. They often forget what they ate, what they are doing, and where they are going. Patients find it difficult to remember their bank balance and manage their daily activities. In that case, we diagnose them to see if it is reversible or not, like hyperthyroid, Vitamin B-12 deficiency, brain tumour, or any impact of haemorrhage.
Suppose the imaging tests suggest that a patient has Alzheimer's or dementia, we inform their family about the disease course and management, which help them to maintain daily activity, plan their future, and guide them to use their medication box.
We suggest the family members take over patients' financial and routine management.
Currently, no medication can reverse the symptoms; instead, we can only manage the symptoms using anticholinergic drugs and acetylcholinesterase inhibitors like rivastigmine and donepezil.
Suppose the patient has other Alzheimer's or dementia symptoms, like depression, anxiety, psychosis, or agitation. In that case, we treat the symptoms to improve the quality of life and living.
How does treatment vary by the stage of the disease?
Dr. Surendra -
Early stage or preclinical stage: In this case, we help patients in reducing the risk factor for the progression of dementia by using anti-hypertensive, anti-diabetic drugs, and histamines to maintain a healthy routine, which also involves a high protein diet and multivitamins.
Later stage or advanced stage: We explain the disease course and management. If the patient had psychosis or depression, we would add newer drugs.
FDA has approved newer biologicals, monoclonal antibodies. However, aducanumab has not yet been administered because of the scarcity of data. This drug is approved forcefully due to its biochemical availability. But until now, in trials, there is no clinically significant improvement data with aducanumab.
We have other monoclonal antibodies like solanezumab and donanemab, which are in the pipelines but are still ineffective. Some beta and gamma secretin inhibitors, like BACE1 and BACE2, came in trial form. Still, they are not approved because of the side effects and lack of significant data on cognitive functions.
Do you think the approval of aducanumab is a positive sign for future drug development?
Dr. Surendra - It is a positive sign. Alzheimer's disease was first identified by Alois Alzheimer in the year 1918, but till 2022, no drugs could cure AD. Monoclonal antibodies are a hope that some newer drug in the future or some new trials can prove that they can reverse AD. We may have some new drugs in the market in the next four or five years.
Deep Brain Stimulation (DBS) is an effective approach for treating neurologic and psychiatric disorders. Do you see any role of DBS in treating Alzheimer's Disease [3]?
Dr. Surendra - DBS is effective in many psychiatric disorders and neurodegenerative disorders like Parkinson's disease.
In Alzheimer's, there are two hypotheses:
an increase in the beta-amyloid level and
a decrease in norepinephrine level from a locus coeruleus
The challenge in DBS is to find a compelling target. In the future, we can go with a target or stimulation site which can reverse the progression of the disease. Obese patients who undergo DBS show improvement in their memory function. After the DBS in the fornix area, the condition of Alzheimer's patients can also improve.
Are there any other neuromodulation techniques that effectively reduce the severity of Alzheimer’s disease?
Dr. Surendra - In some trials, vagus nerve stimulation showed positive results. Other than that, we can increase the collateral flow in the brain by using sphenopalatine ganglion stimulation. The neurovascular theory says that decreased circulation or chronic cerebral hypoperfusion leads to vascular dementia or AD.
In the future, we hope that sphenopalatine ganglion stimulation can reduce the severity of AD, reverse the symptoms, or prevent mild cognitive impairment (MCI) patients from dementia.
What would be your takeaway message for elderly people and Alzheimer's Disease patients?
Dr. Surendra - AD is not only related to age; there are many other risk factors. Controlling hypertension, diabetes, obesity, and cholesterol and exercising regularly are some preventive measures for AD.
If any patient develops AD, they can also live happily by managing their routine activity, making notes, making the schedule, and even working on their financial services for the next five to ten years.
If any newer medicine comes in the market, that can reverse the symptom, reduce the severity, and improve the quality of life then it will be very helpful for patients suffering from Alzheimer’s.
Before we conclude, would you like to share anything else regarding the treatment and management pathway of Alzheimer’s disease?
Dr. Surendra - At present, in India or other developing countries, there is no awareness of AD or dementia, especially in rural setup. It is essential to create awareness among individuals, which can be achieved through International Alzheimer's Society and local societies. We can even make a support group for Alzheimer's disease patients at the local, state, and country levels.
Thank you very much for your valuable insights.
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