One night several years ago, I checked out of a hotel in Cairo and hailed a cab to the airport. It was just after 1am. I had been in Egypt for a week, researching a story on the Muslim Brotherhood, and I had come down with a nasty bug. A blood vessel in my right eye burst, but the doctor said it would probably go away in a few days. I had with me my laptop, a duffel bag crammed with T-shirts, a crushed-velvet blazer, a toothbrush, a razor, medications, an exceptionally tattered copy of Herzog, and an empty, oversized suitcase, which I had been dragging around the world for several weeks and was starting to feel like a vestigial organ. That evening, when my flight landed in Hamburg and I checked into a hotel across the street from the terminal, the woman at the front desk said: “This arrived for you.”
She produced a box that had been shipped from Brussels and loaded it on to a luggage cart. I took it to my room and ripped it open. It was filled with miniature bottles of a yoghurt-like drink that was supposed to cure dementia. I put the bottles in my suitcase, and the next morning I caught my connecting flight to New York.
At any given moment, thousands of trials are taking place all around the globe, geared toward eradicating Alzheimer’s disease, Lewy body dementia, frontotemporal dementia, vascular dementia and all the other dementias, disorders and syndromes that gradually, inexorably turn once-intact brains into hollowed-out husks. Each trial usually includes scores of patients, who researchers call enrollees, and each enrollee has at least one caregiver, and sometimes two or three. Before the enrolment, and before the caregiver signs the paperwork and commits to monthly visits, there are all the conversations between the caregiver and other concerned parties (the enrollee’s children, for example) – the strategy sessions. The thinking is: we can only take part in so many studies; if we pick the right study, we get first dibs on the magic potion, before anyone else, at a reduced rate. So you do your due diligence. You follow developments.
You can track ongoing trials on a website provided by the US National Library of Medicine. In the first few months after my father was diagnosed with mild cognitive impairment – it did not feel mild at the time – I scoured, frantically, ClinicalTrials.gov in search of an elixir. Initially, the maths looked promising. There are, as I write, 508 active Alzheimer’s trials. Since not all cases of mild cognitive impairment (MCI) convert to full-blown Alzheimer’s, and since it takes about a year for those that do, and since it takes another six to eight years to die from Alzheimer’s – some patients live as long as 15 or even 20 years – you can convince yourself that some neuroscientist or clinical biologist will unearth the magic bullet or bullets, the hoped-for “cocktail”, just in time, and we will be able to rectify this madness.
Madness is the nub of it. In the beginning, everyone – the patient and the people who love the patient – goes a little crazy. It’s only later, after you begin to see things better – not through the prism of denial or hope, but through statistics – that you realise none of those pills are likely to accomplish anything; that garden therapy and watercolour therapy cannot, in fact, heal damaged tissue; that the numbers cannot be spun. You are in a darkened room without doors or windows.
* * *
It takes a long time to see things clearly. First, you must convince yourself that nothing can be done. So you scour, hunt, email, call and text doctors and PhDs in New York, Washington, Baltimore, Phoenix, Los Angeles, Tel Aviv, Stockholm and Paris. You Google “Alzheimer’s groundbreaking research”. You persist with a crazy lust for answers. Everyone you speak to is exceedingly kind. They have had this conversation many times. You start by saying, almost apologetically, that you want to know what the most promising trials are, where they are taking place, who is in charge. A few years ago, there was a lot of buzz surrounding solanezumab. You ask questions about timeframes, conventional wisdoms, odds and percentages. You lapse, unwittingly, into descriptions of your father, which are really synopses of his curriculum vitae (“then there was his PhD, then med school, then his residency at Mass General”), which are fuelled by a deeply irrational subtext: certainly, you can’t let him fade away.
At the time, all this is reassuring. You believe the logic you spout, because what else is there to do? Your mother does, too, because she’s dying inside, every day, over and over, and your sister tries to, although she’s more tethered to reality, less convinced by the casting about for a cure that feels so intangible. The casting-about is shot through with hope, hopelessness and fear. You have conversations you wish you never had (“I’d make sure your parents’ finances are in order”) and conversations that offer false hope (“Hang in there – we’re working 24/7”) and conversations that leave you in a weird purgatory. “We’ve cured Alzheimer’s a thousand times in mice,” a neurologist at Johns Hopkins told me. “Is that cause for hope?” I asked. “I don’t know,” he said. It’s the not-knowing that propels you – not so much the hope that you’re going to unearth something as a fear that you’ll give up before you do. You realise, slowly, that the researchers, the people running the trials, are your friend and foe. They give you hope, and they want you to feel hopeful: if they make you feel hopeful, maybe you’ll enrol your father in their trial. Everyone is looking for brains in various states of decline.
The associations and the umbrella organisations – the prescribers of support groups and bullet points and frequently asked questions – exacerbate this tension, this not knowing where you stand. They are part of a self-perpetuating complex. They create a membership of pain, and they codify it with corporatised websites, messageboards, hashtags, drives, walks, runs, celebrities who are Alzheimer’s-aware, glossy magazines, newsletters, social media feeds and officially designated months. November is Alzheimer’s Disease Awareness & Family Caregivers Month. September is World Alzheimer’s Month. June is Alzheimer’s & Brain Awareness Month. One wonders what will happen to all the people and money when they find a cure. One wonders what will happen to November. When a new therapy comes along, the newsletters light up: Vitamin B! Optogenetic stimulation! Optogenetic stimulation?
All of the posts come with the same caveats: mice, preliminary tests, Food and Drug Adminstration (FDA) approval. “Many experts believe there will be significant breakthroughs in Alzheimer’s research in the near future,” reads the Alzheimer’s Association site, “but this cannot be accomplished without volunteers.” We’re almost there – and your father might put us over the top. Many experts believe as much.
At a certain, indefinable point, you discover the system cannot be gamed. You become a little desperate.
This is how I ended up in Hamburg with a 39C fever and a scary-looking eye on a rainy night in October – because a gentleman in Brussels with an impressive title and a confident, almost stentorian voice told me he was about to go to market with a strawberry-flavoured concoction that “has been shown” – always the passive voice! – to ameliorate cognitive ability, memory function, etc etc. Alas, you can’t buy something in the US that hasn’t been approved by the FDA, and you can’t ship large quantities of anything liquid into the country, so I found someone in Brussels who could buy it for me wholesale, asked her to ship it to the hotel in Hamburg, and hoped it would arrive before I did.
A few months later, my father drank the last miniature bottle from the oversized suitcase. Soon after, we had a conversation during which he forgot my wife’s name. “Kate,” I said. “You were at the wedding, in Seattle.” It was one of many awful things I said at that time.
* * *
In early 2012, my mother found one of the best neurologists in the country, at Columbia. Her credentials didn’t really matter. What mattered was that she was a nice person. This was the best thing you could say about the doctors, since none of them could actually cure my father. All they could do was be nice. She called my father Dr Savodnik, and she laughed at his jokes, which, by then, were no longer funny. They ran tests. I was living in Sri Lanka, with Kate, who was a US foreign service officer in Colombo, when I learned that my father’s MCI had converted to Alzheimer’s.
A few months later, Kate and I were married in a converted warehouse in Seattle. There were a lot of candles. My mother-in-law, who is a pious Catholic, knitted a beautiful chuppah. My father-in-law made a point of spending a lot of time with my father, to talk with him, to nod earnestly at everything he said, to introduce him to his mother and brothers and sisters, and to ignore my father’s occasional lapses. My father held it together for most of the evening, but had to go back to his hotel early. By then, he had to expend enormous amounts of energy to shake hands and not lose his train of thought, to be calm, to stay sane, to preserve whatever glint of hope was still flickering inside. He knew he was slipping, and he was filled with anger and grief and, mostly, fear. But at the wedding, he was OK, distracted briefly from the oncoming tsunami. I remember posing for a photograph with Kate and our parents, standing against an exposed brick wall. We had just signed our ketubah. Kate looked beautiful; I felt like I didn’t deserve her, which was how all men ought to feel on their wedding day. My mother, for the first time in years, seemed happy. My father’s head was smaller than I remembered it. His smile was a little wan, unfocused.
When I try to remember the way my father was, I don’t remember particular moments. There are no specific memories that crystallise his personality. There is nothing I can recall that perfectly embodies or symbolises the totality of his life, our relationship, my childhood.
When I think about the way things were, I hear his voice, I smell his aftershave, I remember him through a series of disparate images, sounds and associations – an arm around my shoulder, a melody, a chord, a peal of laughter, a joke that someone told in the Catskills 50 years ago. He was a giver of unexpected gifts: a recording of Vladimir Horowitz, a computer, a tie, a copy of War and Peace, a car, a conversation on a highway in the middle of America that has coloured everything I’ve thought ever since. The experience of remembering is kaleidoscopic, moving, frenetic. I tend not to dwell for long on any place or time, because that feels inadequate, almost disrespectful; and, really, because when I am forced to sift through all the crevices of the past, the colours and textures and rhythms and fast-receding incantations of yesterday, last year, 15, 20, 40 years ago – a birthday, a reprimand, the emergency room, my bar mitzvah, a few words that reminded me who I was – the pain is searing and exquisite.
He was born in the Bronx. He started playing the piano when he was 10. When he was 14, he built his own telescope. (We still have it.) His mother died a few months after he started graduate school. His father sold sewing machines. There is a picture of him saying a prayer at my parents’ wedding. He died the next year. His name was Philip, and, to honour him, my parents gave me his first initial. I was born in 1972, and there is a photograph I especially enjoy of my mother, father and grandmother, who is cradling me, outside our house, in the late afternoon sun. I am one month old. My grandmother is wearing a dress with race cars on it, my mother looks like the lead vocalist from a Peter, Paul and Mary cover band, and my father, with his burgundy, wide-collared shirt and three-inch belt buckle, is leaning in just so. When he takes the picture, he sets the camera on auto-shoot, pushes the button and hurries back to us. He looks a little winded. He is smiling widely, in a way his father never smiles in any of his pictures. There is anticipation, joy, hope.
In the beginning, he taught. After a year in California and two years in Massachusetts, we moved to Pittsburgh. My sister was born. We had a backyard. My father had a dual appointment, in philosophy and psychiatry, at the University of Pittsburgh. He wrote articles. He co-wrote a book. He went to conferences. It began to feel stifling. He resented that there was a vernacular, a politicking. He could see where this would lead: a better appointment, in New York or Boston; a timeshare on the Cape; a Volvo station wagon; dinner parties; stimulating conversation; tenure. It didn’t feel like enough. A friend made an introduction, and a psychiatrist who had recently opened a hospital in California offered him a job. My mother had almost finished her dissertation, and we moved to Palos Verdes. My sister was nearly one. I was almost five.
He straddled two identities. He loved the wide openness of California – private practice, a beautiful house, a pool, a view, a lemon tree, a modicum of independence – but he feared that he had deserted himself back east. He tried to bridge that gap by building the world he craved in the world he inhabited: walls of books, two pianos, travel, art, short-term teaching gigs. There was always an echo of discontent. He would say: “California has been good to us.” It sounded almost like an apology. It made home feel temporary. As if it was not home, but a place where we lived, accidentally, for now.
Later, when he and my mother made more money, it became easier to wade in and out of these two worlds. The money allowed for ease of movement. It didn’t erase the old chasm, but it made it much easier to paper over it. This was the subject of one of the last conversations I remember having with my father before he started to become someone else. We were in Berlin. He and my mother had rented an apartment near the Tiergarten for a month. I was living in Moscow, and I visited for a week. We saw The Magic Flute, and then we had dinner on Friedrichstrasse. This was in July 2007. My mother mentioned a novel she had just read. My father said he was thinking of writing a novel. My mother asked when he planned to do that. He hadn’t thought about the logistics. “It’s going to be about a character who wants to be three people at one time,” he said. Then he ordered another glass of wine. “It will be set in New York in the not-too-distant future.”
* * *
By early summer 2017, my sister and I had given up on finding an Alzheimer’s cure. We never talked about this. The calls, the emails, the late-night surfing and the frenzied tracking-down of researchers simply tapered off. By then, Kate and I had moved to Los Angeles, just north of downtown. We had a two-year-old, and Kate was pregnant. I tried to visit my parents a few miles away in Manhattan Beach at least once a week. I usually brought our daughter, Josephine. Kate came most weekends. My father was mostly confined to a hospital bed, at home, and eating only pureed foods. He spoke rarely; usually, the things that came out were more half-words or word particles. It had been two years since I’d heard him say my name. He slept a lot, but he didn’t seem to be in pain, and he could make eye contact.
My mother had refused to put him in a home. Instead, she had hired several part-time aides to change, feed, dress and undress him. They brushed his teeth, gave him a daily shave, clipped his nails, administered his nightly dose of oxygen, changed the bandages on his bed sores. Every night, Noley, who came from Manila and was a fan of the new Filipino president, much to my mother’s chagrin, slept in a bed next to my father’s. Noley’s job was to get up every two hours to move my father from one side to the other so he didn’t develop more bedsores. My mother, who slept down the hall in a guest bedroom, insisted he text her photos. “You know,” she said, “with the timestamp.”
Then, in late July, I received a Google alert about an anti-Alzheimer’s treatment under development called optogenetic stimulation. The alert linked to a post at the tech-news site Futurism, headlined “New evidence suggests Alzheimer’s doesn’t destroy memories, it only blocks them”. The post had been prompted by an article in the scientific journal Hippocampus, and it strongly supported the findings of another study, conducted in 2016 by a team of MIT neurobiologists and published in the journal Nature.
I had stopped reading my Alzheimer’s-related notifications in mid-2013, because there were too many of them, and they were always about incremental advances that were not going to save my father’s life. But I could never bring myself to turn them off, and once in a while I would glance at whatever turned up in my inbox. That was how I learned about what the neuroscientists call opto. “The research could possibly revolutionise Alzheimer’s research and treatment, helping the 5 million Americans who are suffering from the disease,” the Futurism post declared. The next day, the Washington Post published a similarly enthusiastic piece: “‘The finding could be revolutionary,’ says Ralph Martins at Edith Cowan University in Australia. ‘It has the potential to lead to novel drug development to help with regaining memories.’”
It is important to make clear that opto will not cure Alzheimer’s any time soon. What makes it remarkable is that, unlike most anti-Alzheimer’s treatments, which seek only to retard or stop the progression of the disease, opto holds out the hope that a memory – a piece of a former self – can be retrieved. Until recently, Alzheimer’s was believed to erase whole categories of memories. Opto is premised on the theory that the problem is not with the memory that has supposedly been lost, but with the mechanism needed to recall that memory. “It’s really a disruption of the neurocircuitry necessary for memory retrieval,” Li-Huei Tsai, a neuroscientist and the head of the Picower Institute for Learning and Memory at MIT, told me. “This is extremely important.”
Christine Denny, a neurobiologist at Columbia and the lead author of the Hippocampus article, was cautious. “There is a lot of controversy in this field,” Denny said in an interview. “Are memories gone? It’s possible to get the memory back online, but I don’t want to oversell it.” For one thing, Denny doesn’t know how opto will affect human beings. Her subjects were mice. Just as importantly, Denny’s study dealt with relatively simple memories. (In the study, mice were exposed to a lemon scent and then subjected to an electric shock. Healthy mice remembered that the one led to the other. Mice with dementia did not. Mice that had been sick and were subsequently treated with opto tended to remember much more often.)
“A complex memory,” Denny explained, “would be your grandmother” – meaning all the thoughts, feelings and associations that fill out not simply a moment or place, but an entire person and a relationship. Jennifer Perusini, a former postgraduate researcher at Columbia who co-wrote the Hippocampus article, said: “It is definitely possible that, in the near future, techniques like deep-brain stimulation or drugs that improve memory retrieval may help to treat complex and widespread memory loss in Alzheimer’s patients.”
Dheeraj Roy, a postdoctoral fellow who was the lead author of the 2016 MIT study, said: “We already have very good reason to believe that it doesn’t just work in simple memories. We’re getting fairly sophisticated – things we love, things we hate.” Opto has raised many questions, Roy said – for example, can we resurrect the memories of people with moderate or severe Alzheimer’s? And can we extract old and not just recently formed memories? So far, researchers have focused on the hippocampus, where new memories reside. They have yet to explore fully the cortex, where old memories are stored. Old memories, as everyone who knows someone with Alzheimer’s knows, stick around much longer than more recently formed ones, but not for ever. Eventually, they go away, too.
The idea that, one day, we’ll be able to extract simple memories, and sometime after that, more complex ones – involving thoughts, feelings, complicated or tangential associations – is, of course, tantalising. It suggests that, however far-fetched it might sound right now, eventually we might be able to resurrect whole personalities. It is hard to overstate how exciting this is – or will be – to the families of people suffering from Alzheimer’s and other dementias, to say nothing of the patients themselves. Loved ones of people dying from Alzheimer’s suffer through two deaths – the gradual death of the mind, the personality, and then, many years later, the more gradual death of the body. It is a protracted and ghastly expiration – one that feels, to those on the inside, as if they are being suffocated by a cosmic force that will not relent until it has extracted all the rage, tears, nightmares, absurd, upside-down conversations, fights and blowups that a single human being can muster.
* * *
After the Google alert, I thought about what it would be like for my father to come back. I had thought about this before, in the beginning, but back then I didn’t allow my fantasising to go too far. I knew that we were losing irreplaceable parts of him every day, and I did not think they could be salvaged. I thought that, at best, we might be able to slow the march of death, and we would adjust to the new reality – this sickly, slapstick version of my father – and we would be overjoyed. Because there were limits to what we could expect to do, I forced myself not to think about things I assumed we could not do – such as returning him to his original self. But now we knew that we couldn’t do anything; that, in fact, we had been deluding ourselves all along, and that the window of delusion was being eclipsed by an overpowering darkness. My father had been ill for at least seven years, probably eight or nine, and the inevitable was coming into sharper relief every day.
A few months back, in January, I had gone to a movie one night with Kate in Manhattan Beach. We had left Josie with my mother, at her house, and when we came back, around 11pm, we discovered my mother leaning over my father’s hospital bed, crying. My father had been battling a cough, and the cough had turned into a bad wheezing noise that sounded like an infection. The hospice nurse arrived. Then an ambulance. Then we were in the emergency room. The nurses asked my father questions in loud voices. Someone said “sweetie”. My mother became angry. I became angry. The emergency-room doctor told us this was how they usually go. There was a waft of human waste. Another doctor, younger, bespectacled, told us we should be aware of our options. She was vague; my mother yelled: “What do you mean?” They administered antibiotics. A nurse came in and said: “He’s doing much better.” I went back to Manhattan Beach. It was 4am. I stared at my daughter, in her crib, sleeping. Kate, in bed, whispered that she loved me. I dreamed I was on a chaise lounge on a crowded beach in Tel Aviv, next to Saul Bellow, whom I had never met, and he was saying how much he had enjoyed dinner at my parents’ house in Edgartown. “That telescope is really something.”
I woke up early and went back to the hospital. I learned that the infection had become worse, and my father was, in fact, going to die. I called Kate, and then my sister, and listened to a social worker tell my mother this was probably for the best. Another doctor arrived. I started to compile a list of people I should text or email. The doctor told us my father would be OK. I called Kate again. She made me feel better. I heard Josie laughing. I went into a stall in the men’s room and cried.
Later, in the shower, when I replayed the whole cavalcade of events, it felt as if time had been compressed, as if all the things that had just happened should have been stretched out across three or four or even six months, but that they had been squeezed into 12 hours.
Seven or eight years ago, on the other side of the invisible doldrums separating our lives before and after Alzheimer’s, I’m not sure we would have known how to navigate these straits. Now it felt almost natural – no less awful, but manageable. Instead of getting mired in any one development or hurt, we floated through the many hurts. We were numb, raw, stripped down. We had become inured to loss, but more importantly, we had figured out how to fit the remaining, non-Alzheimer’s parts of our lives into an Alzheimer’s shell, or abode, and there was a tension that held everything together, enabling us to slide not quite seamlessly from one mindset to another. We never forgot that my father was slowly disappearing – this was true, most of all, of my mother – but we became better at accommodating that awareness.
What would it be like if opto turned out to be the miracle we had been waiting for, if my father were returned to his previous self and we could resume the trajectory we had been on eight or nine years ago? When I imagined this, I could remember my father in his pre-Alzheimer’s state. I missed that person so much. I had wanted him there so many times: at my book party, when my daughter was born, when I needed advice. But I could not really remember myself. I had distinct memories of my life before my father became sick, but the person I was seemed like a rose-coloured adumbration of my present self. That person did not seem like a credible character. He seemed porous and one-dimensional, and there were things about him I regretted. Science might be able to return my father (or, more to the point, future Alzheimer’s patients) to his pre-Alzheimer’s state, but it could not undo the sea change that had taken place in the people who loved him. For that to happen, we would have to forget everything that had happened in the past decade – and our memory, for better and worse, is perfectly intact.
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