As paati lost her memory and identity, we would sit by her side and recollect fond memories from the past, in the hope that our narration would magically revive her brain. With artificial intelligence and targeted therapies, perhaps there’s hope for millions like paati.
Winner of the Nature India Essay Competition 2020.
My paati (Tamil for grandmother) once showed me her diary, in which she had written down names of some people in our family. I sensed a certain degree of disquiet, as she explained that she had trouble recollecting names now and then. At the time, paati was entering her 70s. Apart from forgetting names, she was in perfect health. Her subtle memory lapses indicated mild cognitive impairment (MCI), a condition that can be an early sign of Alzheimer’s Disease (AD). However, not all those who have MCI develop AD, and in people with MCI, the cognitive impairment does not interfere with day-to-day functioning and does not alter their behavior.
However, with time, paati’s memory lapses became more frequent. In addition, behavioral changes such as mood swings, irritability, and poor spatial navigation became apparent. A visit to the neurologist and a brain scan confirmed her diagnosis as moderate stage AD. As the years passed, paati’s condition worsened. Hallucinations, disturbed sleep patterns, anger, tantrums, fear, and confusion became frequent. At this stage, she could not identify others around her, and one could say that she lost her own identity as well. She was unable to perform basic tasks, and we had to appoint a nurse to care for her. During her last days, paati lost her ability to communicate, was bedridden, and her brain and body effectively shut down.
Around 50 million people have dementia worldwide, and AD is the most common cause of dementia in the elderly. The number of people with dementia is expected to reach ~75–80 million by 2030. The global annual cost of dementia, including social and economic costs, is about a trillion USD. The costs are predicted to increase and will likely present a grave social problem, given the greater proportion of older people in the world today due to improvements in health care.
AD is devastating not just for the sufferer, but also caregivers, health-care systems, and society. Paati‘s memory loss, confusion, and inability to perform basic tasks lead to isolation, depression, and withdrawal from society. From a caregiver’s perspective, I recall moments when my family and I would empathise with paati’s anger and confused state of mind, but there were also times when her mood swings and irritability took a toll on us. I remember a time when paati left the house thinking she lived elsewhere, and we found it quite challenging to convince her to return home.
During my doctoral pursuit in neuroscience, I was able to reflect on paati’s predicament through a scientific lens. When we see a familiar face, watch a scene from a movie, or visit a childhood haunt, these stimuli evoke certain memories, emotions, or responses that are unique to each of us. The human brain is an intricate network of neurons, the functional units in our brain. Different neuronal networks in our brain process various sensory stimuli from the world around us and consequently evoke responses that shape our personality and define who we are. In AD, neurons in the brain die and are unable to communicate with one another. The loss of neurons commences in the limbic network in the brain, which is critical for learning, memory, and emotions. As the disease progresses, the neuronal loss spreads to other regions in the brain that send commands to the body to perform basic tasks. At this stage, entire neuronal networks are disrupted and cease to function. In the final stages, widespread neuronal death occurs, with significant shrinkage of brain tissue.
Currently, there is no cure for AD. Although medications alleviate some behavioral symptoms, they do not halt the progression of AD. The treatment landscape has been riddled with failures in clinical trials due to several challenges. Firstly, a ‘single-target’ approach, in which a drug works to correct one aspect of the AD-afflicted brain, has not been effective, given the multiple ways in which the disease affects the brain. To address this challenge, scientists have been working to develop a better understanding of the biology of AD in animal models. This preclinical research has led to the discovery of several targeted therapies that, when administered together, could correct multiple aspects of this complicated disease simultaneously.
Another key challenge lies in the late diagnosis of AD. Often, a definitive diagnosis is made only when people begin to show overt symptoms beyond just memory impairment. At this stage, therapies often fail, since the disease has already progressed significantly and irreversibly. A glimmer of hope for addressing this challenge is emanating from the fascinating world of Artificial Intelligence (AI). In a study conducted in California, researchers successfully trained an AI learning algorithm to detect subtle changes in brain metabolism from brain scans of people referred to a memory clinic. The algorithm demonstrated 100% sensitivity for predicting AD in these people six years before the definitive diagnosis was made. Perhaps we might bear witness to a time in the near future when such learning algorithms could be used in neurologists’ clinics to predict AD in people who show memory impairments, thus providing excellent opportunities for early interventions.
In her active days, one could often find paati sitting on the kitchen floor with a large plate in front of her. The aroma of cocoa powder would waft through the air. I would rush into the kitchen, to find her busy mixing the special ingredients that went into making her homemade chocolates, using a recipe that she had committed to memory. As paati lost her memory and identity, we would sit by her side and recollect such fond nuggets from the past, in the hope that our narration would magically revive her brain. I imagine that countless others around the world must also be attempting such methods to rejuvenate the memories of their loved ones afflicted with AD.
With scientific advancements in the field of AI and targeted therapies, perhaps their hopes would become a reality some day.
[Gowri Natarajan is a neuroscientist based in Hyberabad.]