In Pursuit of Memory

by Joseph Jebelli

  ‘Why not?’ asked Danie.

  ‘Well… I don’t really know.’

  The contrast between Arnold’s awareness of the past, of memories far away in space and time, and his ability to make sense of the present was staggering. Danie had coaxed him several times into trying to answer some of my questions more accurately, offering gentle help here and there. But there was no denying it: Arnold was fading. The disease had taken its first casualty, a brain region right next to the hippocampus known as the parahippocampal gyrus. This is where new memories are stored and retrieved. It’s why short-term memory loss is the first symptom of Alzheimer’s. It provides a kind of memory pit stop, so that memories can be processed and then eventually transferred to the frontal cortex for long-term storage. We don’t know why this region is targeted first. Plaques and tangles will ultimately invade other parts of Arnold’s brain, including the frontal cortex, but for now, those appear mercifully intact.

  ‘Shall I give you the tour?’ Arnold asked me. We’d been talking in his sitting room for about half an hour, during which I’d also noticed his mirthful, tongue-in-cheek sense of humour. He’d often playfully reproach Danie for not remembering something, or if he suspected Danie was being mischievous behind his back. ‘Don’t play that game with me, young man!’ he’d admonish.

  Arnold then took us to see his attic. According to Danie, this is where he spends most of his time. It looked much like the sitting room, only with more books and bigger paintings. Danie was particularly keen to see it today, to assess the recent water damage in the roof–patches of damp had slowly been creeping their way along the ceiling’s coving, causing it to bow precariously above Arnold’s photograph-laden dressers. In the adjacent bathroom, parts of the ceiling had collapsed altogether.

  ‘Arnold! I’m gonna chase up that builder again!’ Danie called from the bathroom. ‘We really need to get this sorted!’

  Arnold had weekly visits from NHS carers. I asked him what he thought of them.

  ‘Carers?’ he said, puzzled. ‘Oh no… I don’t know anything about that.’

  ‘What about Tom?’ reminded Danie, who was now busily inspecting the cornices above us. ‘You know, that guy who comes round.’

  ‘Tom? Tom… Oh yes… he’s a pleasant man… probably at least twenty years younger than me though.’

  While Danie continued to examine the ceiling, Arnold and I walked out on to a small balcony that overlooked a row of modest square gardens lining the street. The sky was still overcast. He pointed out a tall ash tree. ‘That’s my favourite tree on this road,’ he said. ‘It’s beautiful. Do you see how it’s actually two trees?’ A second, darker tree was growing alongside it. And then, eyes still fixed on it, he said something unexpected: ‘I have a lot of memories that mean a great deal to me… It worries me… But what can I do?’ Then he looked at me with a shrug of resignation and added, ‘Not a lot.’

  I wondered what to make of Arnold’s comments. Until that moment I’d only been able to talk to friends and carers about the condition; my granddad had already lost awareness of his memory problems when he visited us again from Iran. Perhaps the cruellest irony of Alzheimer’s, for the family above all else, is that the more advanced it gets, the less cognisant a patient becomes of their plight. Arnold’s moment of clarity was therefore all the more important, and a part of me wanted to press him for further insight.

  But as we headed back downstairs, he quickly forgot what he’d said and asked me to remind him who I was. I told him I was a friend of Danie, and that I was writing a book on memory.

  ‘Oh! Wonderful!’ he exclaimed. ‘But… I have to say, I don’t think Danie will be much help for that.’

  Arnold is in the early, mild stage of the disease, Dr Foell told me during our conversation in his office. Foell is a plain-speaking, eccentric physician. He immigrated to England shortly after the collapse of the Berlin Wall and has been a general practitioner for the past thirteen years. A shade under six foot, he’s an astonishingly fit man who sits on an inflatable exercise ball during consultations and adopts a no-nonsense, almost predatory approach to solving his patients’ problems. I liked him immediately.

  It had been several weeks since I visited Arnold, and I wanted to learn more about how someone with Alzheimer’s is diagnosed.

  ‘Good question,’ Foell admitted. ‘I often say that the best way to find out would be to kill you, and then slice your brain to look for plaques and tangles. But that doesn’t really help you!’ The reality, Foell explained, is that diagnosis is not a single act; it’s a process.

  First, Arnold must be excluded from the range of other maladies causing memory loss–such as depression, infection, stroke and cancer. This is done by gathering a medical history, performing an examination and arranging blood tests. Then Foell needs to know that Arnold is safe. He needs to make sure nothing can happen to Arnold before their next meeting. He asks questions like ‘Where have you been?’, ‘What did you do?’, ‘How do you look after yourself?’, ‘Can you talk me through a normal day?’, ‘Do you lock yourself out of the house?’, ‘Do you leave the cooking hob on?’

  ‘I found it very disturbing that Arnold lived on his own,’ Foell solemnly confessed. ‘Without his friend’s son, organising his safety wouldn’t be possible.’

  Globally, there’s a new diagnosis every four seconds, and even that’s a conservative estimate.1 In England, for example, it’s thought that only 48 per cent of people with dementia receive a diagnosis.2 The remaining 52 per cent may be people whose symptoms are mistaken for something else–like stress, the side effects of medication, normal ageing–or elderly people who live alone. Isolated patients can go for years without a diagnosis because no one flags up that there’s a problem. One has to wonder how many souls in total go undiagnosed; a recent estimate put the figure at 28 million.3 This is clearly an enormous problem, but as we shall see in chapter eight, it’s slowly being solved.

  After Foell was satisfied that Arnold’s circumstances presented no looming danger, he sent him to a remarkable modern creation known as a memory clinic.

  ‘Lemon. Key. Ball.’ Lemon, key, ball. Lemon, key, ball. I repeated the words over and over in my head, as if trying to put a paperweight on the memory. I’m doing the Addenbrooke’s Cognitive Examination, or ACE, in the office of Karen Magorrian, a senior nurse at the Charing Cross Hospital Memory Clinic in west London. It was here–with her–that Arnold began his journey into Alzheimer’s in earnest, and I wanted to retrace his steps as best I could.

  ‘If I gave you a hundred, could you take away seven?’ Karen had a distinctly soothing quality to her voice–an effect born out of twenty years’ experience with dementia patients.

  ‘Yes,’ I replied.

  ‘And what would your answer be?’

  ‘Ninety-three.’

  ‘Carry on please.’

  ‘Eighty-six. Seventy-nine. Seventy-two. Sixty-five—’

  ‘Lovely. Thank you. And what were those three words I asked you to remember?’

  ‘Lemon, key, ball.’

  ‘Good. Now I’m going to give you a name and address to remember: Harry Barnes, 73 Orchard Close, Kingsbridge, Devon.’

  Bloody hell! ‘Okay.’

  ‘Can you repeat it?’

  ‘Harry Barnes, 73, Orchard… Devon.’

  ‘Try again.’

  ‘Harry Barnes, 73, Orchard Close, Kings… bridge? Devon.’

  ‘Lovely. Excellent.’

  ‘Can you tell me the name of our current Prime Minister?’

  ‘David Cameron.’

  ‘And who was the female Prime Minister we once had?’

  ‘Margaret Thatcher.’ She must have had this kind of test, I thought, having suffered dementia in her final years.

  Karen continued in this vein, going on to test areas of attention and visual-spatial cognition. She asked me to draw a clock, and identify pictures of animals and partially concealed letters. I scored ninety-three out of a hundred.

  E
mbarrassingly, I fell short on the vocabulary section of the test. Karen asked me to name as many words as I could–no names or places–beginning with the letter P. After ‘pen’, ‘pencil’, ‘paper’ and ‘pigeon’, I threw in some fancy ones–‘palpable’, ‘polymath’, ‘perspicacious’. I managed a few more and then went completely blank. I was so nervous about the high expectations (I am writing a book, after all) that my brain just froze. Worse still, I started thinking about names and places–Peter, Peru, Patagonia–as if getting those out of the way would somehow help me find what was actually being asked of me. This section represented a tiny fraction of the test. I wondered what it would feel like to brain-freeze on every section, as many patients did. But unthinking my thoughts, unwinding my reason, reversing it all into a foggy, unreachable abstraction, was unimaginable. By definition, no clear-headed individual could understand what it felt like.

  The purpose of a test like this isn’t to provide a diagnosis, but rather to get some sense of a person’s memory and thinking abilities. Memorising three words or an address, for example, are good ways of assessing working memory: a type of short-term memory that we use to carry out tasks. Recalling historical facts or animal names measures declarative memory: the form of long-term memory for knowledge and ideas gathered over a lifetime (discussed in chapter three). The more active parts of the test–drawing a clock, summoning maths and vocabulary skills–determine what’s known as executive function: the cognitive processes we use to achieve a certain goal.

  Karen then explained what happens to a decidedly poor scorer. A group of neurologists, psychiatrists and nurses will meet for a House-style brainstorming session about what the diagnosis could be. The demands of the test can give an idea of what brain region is damaged, and if the patient seems depressed, stressed, or anxious, psychiatric problems are also considered. But if–like Arnold–the patient is elderly and displays a global failure of memory and cognition, Alzheimer’s becomes the prime suspect. When brain scans corroborate that suspicion–showing cell loss beyond normal ageing, especially in the hippocampus–and further memory tests confirm it, ‘probable Alzheimer’s’ is diagnosed, care is arranged, and acetylcholinesterase inhibitors are prescribed. And that’s that. Treatment-wise, we’re still where we were in the 1980s. ‘We use Aricept [donepezil] a lot, and I’d say that in about 60 per cent of patients we get two or three years of stability. Their relatives will come back and tell us they are less agitated, and sleeping better. But some people just don’t respond to it.’

  Arnold was one of those people. By early 2016, just over two years since Danie first noticed his symptoms, Arnold continued to decline. His confusion was now verging on distress. He seemed frailer, less steady on his feet, almost ‘shrunken’, as Danie put it. He was also forgetting to feed himself, and increasingly relied on carers to prepare meals and deal with household affairs.

  To a neurologist, this timeline is unsurprising: upon diagnosis, the average life expectancy is eight years, with most of that time spent in the moderate stage of the disease–what Arnold was now experiencing. To a neuroscientist, it suggests that plaques and tangles have finally infiltrated other parts of Arnold’s brain, including the frontal lobes, destroying his ability to process logical thoughts, and the temporal and parietal lobes, giving rise to fear and anxiety. Because the temporal and parietal lobes process sensory information, damage can also result in paranoid delusions. A familiar person might seem like a stranger with bad intent, and relatives often recall moments when their loved one greets them with suspicious stares or hostility.

  Lacking traditional family support, Arnold was beginning to become a danger to himself. One day, the carers arrived to discover that he had left all the cooker hobs on, filling the house with gas. On another, they found bruises running up his arm; it turned out he’d fallen down the stairs in the middle of the night. Determined to make life as comfortable as possible, Danie arranged private care for Arnold and juggled his own work–life commitments by requesting daily reports from the new carers.

  Danie’s father flew over from South Africa, and used the time with his old friend to recount stories from their childhood in Johannesburg. Arnold listened with a mixture of mirth and bewilderment. For Danie’s father, the friend he knew was still there, despite everything.

  But it wasn’t long before what Arnold’s adopted family feared most happened. When Danie met Arnold at the memory clinic for a follow-up appointment, he was greeted as a complete stranger. ‘I could have been anybody, a passer-by in the street,’ Danie said in a lugubrious voice when I met him for coffee. We were sitting in a small café in Mayfair, where he works, on a clear spring morning. ‘I told him my name to help jog his memory, and he did sort of recognise me. He knows he knows me, but he can’t remember how he knows me.’

  I asked Danie how things were at home. ‘Oh God. It’s like dealing with a child,’ he confessed. ‘We had this whole saga about the kettle, because I took away his stove-top kettle and bought him an electric kettle. Well, that just blew his mind! He didn’t want to use it. So it eventually disappeared and I had to buy another one–we’ve been through several kettles now. I bought him a new bedside lamp, and a few weeks later that disappeared. It’s like they’re intruders into his world.

  ‘I bought him a toaster at the weekend and just put it on the counter and started using it, because if I have a conversation with him about it, I’m gonna want to strangle myself and him. I’ve got to think about my sanity, too.’

  Danie had no burning desire to put Arnold in a nursing home, but things were falling apart. To test the waters, he took Arnold to visit one that had been recommended by a friend. It was privately run, and was also near Arnold’s house. The facility had two dementia wings, catering for both moderate- and late-stage Alzheimer’s. ‘This is fascinating,’ Arnold said as the pair were shown around. In the moderate wing, he was his usual cheerful self. He shook hands and exchanged pleasantries with the residents, gazing in astonishment like a tourist visiting a zoo, said Danie, who, in stark contrast, was horrified by what he saw. ‘I hated it,’ he admitted. ‘The people running it were really nice, but the residents, mostly women, all looked completely zonked out. I thought, Well, you’re definitely not at this stage. I can’t put you here.’

  The pair then walked into the late-stage wing. The rooms were spacious and well decorated, and it had a calming, serene atmosphere. Nevertheless, the residents’ state of mind couldn’t be ignored. Hearing Danie recall this part of their trip, an image of my grandfather flashed into my mind. Towards the end, he remained slouched in a chair, silent but for the occasional wail for his long-deceased wife–a shell of his former self. Late-stage Alzheimer’s has been described as ‘death before death’. By this point, the disease has systematically wiped out huge chunks of brain tissue, effectively erasing the ability to speak, eat, swallow and even smile. A late-stage patient needs care twenty-four hours a day, with everything, from getting dressed to walking to the bathroom. They are utterly dependent on others; left alone, they will spend the entire day staring into space before dying of starvation or an infection.

  The tragedy wasn’t lost on Arnold. In this wing, he was much less sanguine. ‘Oh dear,’ he groaned, disturbed by what he was seeing. ‘I certainly don’t want this to happen to me.’ Danie thanked the staff for their time, and promptly took his old companion home.

  Though he had thought that moving Arnold was the right approach, after the visit to the care home he vowed to rededicate himself to Arnold’s care. He was going to keep Arnold at home for as long as the illness permitted. ‘It’s hard. It’s really hard. You’re expected to have all the answers, and I don’t have all the answers. There are nights when I work until eight o’clock and then rush over to make sure he’s all right. I’ll end up getting home and eating dinner at ten. But these are my weak moments; otherwise I’m really happy to do it.’

  I had long wondered what patients do when they have no family. Apart from emotional support, family
members take care of the minutiae of everyday life. Although hired carers can do this to an extent, they were certainly no substitute for my grandfather’s three daughters, who had stayed in Iran after my father and uncle left to learn English and get a decent education. In his final years, my aunts fed and washed him, did his shopping, managed his estate, and spent countless hours–however futile–exploring photograph albums with him, explaining each picture of the family and life he had once had. This is the power of family. They thread everything together; they keep things on an even keel.

  Arnold may not have the same level of support, but in Danie he has one astonishingly loyal friend. I made a point of visiting Arnold again a few months later. Despite not responding to current treatment, this charming octogenarian has helped make physicians, memory specialists and scientists alike more aware of how dementia manifests in the real world. While much attention in novels and popular film is given to early-onset Alzheimer’s, the reality is that most patients are elderly people like Arnold. His story is one of millions whose ending we must change. To do that, scientists know that an effective treatment can only come from a better understanding of the disease. And this will only come from the burgeoning field of medical genetics.

  5

  The Alzheimer’s Gene

  I can’t think. But I still feel. And most of the time I feel scared. Scared because it’s too soon. I haven’t finished yet.

  Nicola Wilson, Plaques and Tangles

  THREE AUNTS, ONE uncle and now her father. With that, Carol Jennings, a thirty-year-old teacher from Nottingham, had made up her mind. On 11 April 1986 she walked to her desk, took out a sheet of Basildon Bond paper, and began.

  ‘Dear Sir,’ she penned in dark blue ink. ‘I was very interested to read of your research in the Alzheimer’s Disease Society News and think my family could be of use.’ On a separate sheet Carol jotted down a family tree depicting relatives from both her father’s generation and grandfather’s generation. ‘Actually, I am the daughter of Walter,’ she continued, ‘who you will see from the family tree is sixty-three years old and has Alzheimer’s, as does his sister, Audrey. His brother, Arthur, may also have the disease… please contact me at the above address if you think we could be of help.’