'Having accurate diagnosis for dementia is the first step': Dr Ramanan, Mayo Clinic

He talks about how recent research will help shape treatment and diagnosis

Dr Vijay K. Ramanan

Dementia breeds dread, according to a 2014 survey in the UK. When around 500 adults aged over 50 were asked which condition they feared the most, 68 per cent said dementia, followed by cancer (9.44 per cent) and heart disease (3.88 per cent). It is not the fear of the unknown, for there are no surprises on how it will end―doctors and caregivers of patients with dementia fight a losing battle and are aware of it. It is the fear of losing the very essence that makes you a person, long before death shows up. But there is hope, according to Dr Vijay K. Ramanan, neurologist, Mayo Clinic in the US.

“As a field, we have come a long way in our understanding of the disease, but there is more work yet to be done,” he tells THE WEEK. “I think there are many reasons to be optimistic about having better options for diagnosis and treatment over the years ahead.” Ramanan, whose focus includes diagnosis of and research into screening mechanisms and novel treatment targets for Alzheimer’s, Lewy body dementia and related disorders, talks about how recent research will help shape treatment and diagnosis of the disease, and whether a lack of cure frustrates him as a doctor. Excerpts:

The US Food and Drug Administration recently approved the use of lecanemab for the treatment of Alzheimer’s disease. How does it help in slowing down the progression of the disease?

Amyloid-beta plaque buildup in the brain (between neurons that disrupts cell function) is one factor in the development of Alzheimer’s disease. The aim of lecanemab is to reduce the burden of amyloid plaques in the brain. A recent placebo-controlled clinical trial showed that lecanemab treatment modestly slowed the progression of cognitive decline in patients diagnosed with early symptomatic stages of Alzheimer’s disease who had evidence of elevated amyloid plaque burden. Treatment also included potential side effects, which will require thoughtful selection of patients appropriate for the drug, as well as intensive safety monitoring.

A recent report said that Alzheimer’s could be caused by an infection. What makes specific viruses and bacteria like HSV-1 (herpes) and Chlamydia pneumoniae capable of triggering Alzheimer’s? And, can an antiviral really help against dementia?

There is no high-quality evidence for antiviral or other anti-infectious drugs as treatments for Alzheimer’s disease. Research suggests that immune system function in the brain may play a role in the disease, but additional study is needed to understand this better and any impact on treatment.

For years, beta-amyloid was seen as the villain, but it has been found that amyloids have antimicrobial properties and actually protect the brain from infections. Will that in any way change the current treatment’s focus?

It’s hard to ignore amyloid as a factor in Alzheimer’s disease, particularly given what is known about some of the rare genetic causes of the disease, which involve mutations in genes central to amyloid protein processing. However, Alzheimer’s is a complex disease that likely has multiple underlying roots, and this may in the future require combination treatment approaches in some patients to address those different mechanisms.

How has recent research and breakthrough helped in our understanding of dementia and Alzheimer’s in particular?

The clinical trial results for lecanemab and donanemab (an antibody drug said to slow down cognitive decline in Alzheimer’s patients) represent a step forward in treatment options, and good news for patients overall. Because of how complex those drugs are, neurology practices will be challenged to adapt their infrastructure and workflows, and those adaptations may have other downstream benefits for the future when hopefully additional treatment strategies are possibilities. There is also ongoing research on biomarkers, which may in the coming years help with efficient and early screening through blood tests paired with imaging and other assessments.

Is there anything specific that a person in early stages of dementia can do to slow down its progression?

Having an accurate diagnosis is the first step. This is particularly important as some of the medications that can modestly help with cognitive symptoms in certain diseases may yield no help or even some harm if a different diagnosis is present. Healthy lifestyle habits are also important, including regular physical exercise, remaining socially and mentally active, getting quality sleep, eating a healthy and balanced diet, and managing other medical conditions that can impact the brain’s health, such as hypertension and diabetes.

Can a person with a family history of dementia lower the risk of getting it?

A person’s family history influences risk, but typically this influence is modest and mixed with other factors. Regardless, maintaining healthy lifestyle habits on a consistent basis can help to minimise the risk of cognitive decline later in life.

Dementia, especially Alzheimer’s, is usually associated with ageing. But there are cases where the onset is much earlier. Is it down to the genes in those cases?

Most cases of Alzheimer’s and related diseases are due to a mixture of genetic, lifestyle and environmental factors. We know some, but not all, of these risk factors. In some patients―more likely when onset is very early―the disease is caused by a gene mutation. However, this is relatively rare overall, and many patients can develop Alzheimer’s dementia and have no specific genetic cause implicated. In those cases, it may be that other genes (including some we don’t yet know about) are involved along with non-genetic factors.

While genes do play a role, does gender?

There is a rapidly growing literature on sex and gender differences in Alzheimer’s and related diseases (women are at a greater risk). More work is needed to understand the drivers of these differences, including the impacts of social, cultural and economic factors.

The elderly are advised to stay active and be social to delay or ward off the onset of dementia. In that sense, do you think the pandemic-induced lockdown could have led to an increase in cases?

Social and physical engagement are clearly important pieces of supporting brain health, but as with other factors their effects are likely nuanced. There may be some instances where life rhythm changes, such as diminished social and physical activity, contribute to unmasking of cognitive symptoms, which were either previously present in milder form or which would have revealed themselves slightly later.

While there is a lot of research happening, a cure seems far away. Is our understanding of Alzheimer’s still limited?

Alzheimer’s disease is at the same time extremely common, very devastating and exceptionally complex. As a field, we have come a long way in our understanding of the disease, but there is more work yet to be done. I think there are many reasons to be optimistic about having better options for diagnosis and treatment over the years ahead.

Does it frustrate you at times that there is no cure yet?

The goal is to help patients with neurological disease, using all available and appropriate tools to optimise their care. For our patients, additional treatment options cannot come too soon. However, in the interim, management does not have to be an “all or nothing” endeavour.

What is the one advice for patients and caregivers that you swear by?

When diagnosed with a progressive disease, it is natural to think about the future or look towards experiences of others. However, sometimes fears and stigma about Alzheimer’s disease outpace reality, particularly for a disease that is highly individualised. I encourage my patients not to let a diagnosis own their day-to-day lives in the present. Once a management plan is in place, returning the focus to where it would otherwise be―leading a high-quality life and making adaptations where needed―can be helpful.