https://www.theguardian.com/science/2016/aug/31/tantalising-signs-that-new-alzheimers-drug-could-benefit-early-stage-patients-aducanumab

Trial shows tantalising signs that new Alzheimer's drug could benefit early-stage patients

Injections of the antibody aducanumab appear to slow condition in patients at earliest stages of disease, raising hopes for treatment

Ian SampleScience editor

 @iansample

Wed 31 Aug 2016 18.00 BSTLast modified on Tue 28 Nov 2017 15.34 GMT

 The red in the brain scan on the left represents amyloid-beta plaques. At the highest dosage of the treatment being trialled, the brain on the right shows the clearance of plaques. Photograph: Ayres, Michael/Sevigny et al/Nature

A trial of a new Alzheimer’s drug has shown it could benefit patients in the earliest stages of the disease, raising hopes that a treatment for the devastating condition may finally be on the horizon.

While the trial was designed to assess the safety of the treatment and not whether patients fared better on the drug, an “exploratory analysis” of the data revealed that the treatment appeared to slow the mental decline of patients who responded to the therapy.

The small study of only 165 people with mild symptoms of the disorder found that a dozen monthly injections of the antibody aducanumab removed clumps of protein that build up in the Alzheimer’s brain.

A leading theory of the disease holds that the steady accumulation of a protein called amyloid-beta in the ageing brain kills off healthy neurons and brings about the memory and cognitive impairments experienced by Alzheimer’s patients.

In the trial, the strongest glimpse of mental improvement was seen in patients who had the highest dose of drug and who showed the greatest reduction in amyloid plaque proteins in follow-up brain scans. These patients did not worsen at all after six months of treatment. But the small number of patients enrolled in the study means that two much larger trials, which are now recruiting 2,700 patients in 20 countries, are needed to confirm whether the tantalising signs of benefit are real.

Alzheimer’s experts welcomed the results, but cautioned that it is too early to know whether the drug will be a help for patients. Other antibody treatments have looked impressive in early studies only to fail later on in larger trials.

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John Hardy, a neuroscientist at UCL who first proposed that amyloid was a driver of Alzheimer’s disease, said: “It’s very interesting and nice to see all these positive data, and it has caused genuine excitement in the field, but it’s a very small number of patients and too small to draw any definitive conclusions from.”

The results from the trial led by the US biotech firm, Biogen, and a Swiss company called Neurimmune, are reported in the journal Nature. The data were first released at a scientific conference in March last year.

Aducanumab was hailed as a potential treatment for Alzheimer’s when scientists found the antibody in people who aged without suffering the sort of mental decline that goes hand in hand with old age. It appeared that the antibody prevented the build-up of amyloid plaques and staved off dementia.

When injected into Alzheimer’s patients, one or two in every thousand of the antibodies enter the brain where they latch on to wayward amyloid-beta proteins. Researchers at Biogen believe that other cells called microglia then arrive and clear the aberrant proteins from the brain. The drug appears to be most effective if the accumulation of amyloid protein is blocked before it causes too much damage. The process may start 15 years before people show symptoms.

A neuroscientist explains: the need for ‘empathetic citizens’ - podcast

In the latest trial, some patients experienced side effects. MRI scans showed a shift in the brain fluid that was more common at high doses and in people who carry the APOE type-4 gene, which is a major risk factor for Alzheimer’s disease. The scientists are now working on ways to avoid the side effect or diminish the problems by reducing the doses patients receive.

David Allsop, professor of neuroscience at Lancaster University, said the side effects will have to be overcome if the therapy is to find widespread clinical use. “Nevertheless, these findings could be a gamechanger if the effects on memory decline can be confirmed in more extensive follow-on studies.”

There are 850,000 people with dementia in Britain, a number that is expected to reach one million by 2025. Alzheimer’s is the most common form of the condition. “If this drug works, we’ll have a treatment for patients suffering from this devastating disease,” said Biogen’s Alfred Sandrock.

“These results provide tantalising evidence that a new class of drug to treat the disease may be on the horizon, said David Reynolds at Alzheimer’s Research UK.

James Pickett at the Alzheimer’s Society was similarly optimistic: “These results are the most detailed and promising that we’ve seen for a drug that aims to modify the underlying causes of Alzheimer’s disease.”

https://www.theguardian.com/science/2016/aug/31/tantalising-signs-that-new-alzheimers-drug-could-benefit-early-stage-patients-aducanumab

https://www.theguardian.com/society/2016/nov/02/a-decade-of-deadlock-over-alzheimers-treatment-may-be-drawing-to-a-close

A decade of deadlock over Alzheimer's treatment may be drawing to a close

The next phase of trials for a new Alzheimer’s drug will answer the real question: are brain plaques the root cause of the disease, or just a symptom?

Hannah DevlinScience correspondent

 @hannahdev

Wed 2 Nov 2016 18.57 GMTLast modified on Tue 28 Nov 2017 12.07 GMT

 “I haven’t heard of anyone who’s got better from Alzheimer’s,” wrote the late Terry Pratchett of his diagnosis in 2008. Nearly a decade on not much has changed for patients. Photograph: Adrian Sherratt/REX

When Terry Pratchett was diagnosed with Alzheimer’s he recalled his wife’s relief that he hadn’t got a brain tumour. “All I could think then was, ‘I know three people who have got better after having a brain tumour. I haven’t heard of anyone who’s got better from Alzheimer’s,’” the late author wrote in 2008.

Nearly a decade on, not much has changed for people facing a new diagnosis of Alzheimer’s. Unlike patients with heart disease, cancer or diabetes, there is no well-trodden medical track to follow and no treatments that can slow the disease’s devastating progress.

Between 2002 and 2012, 99.6% of drugs studies aimed at preventing, curing or improving Alzheimer’s symptoms were either halted or discontinued. The consistent failure of trials, at vast financial cost to drugs companies, caused many to shut down dementia programmes as a result.

The latest trial results from Merck, together with other drugs in the final stage of development, provide hope that the years of deadlock may be drawing to a close.

The Merck trial may be preliminary, in the clinical sense, but it represents an entire career’s work for some of the scientists involved. “We’re 16 years into the program,” said Matt Kennedy, the neuroscience director at Merck who led the research. “It’s a good example of how long it takes.”

The first challenge scientists faced was creating a compound that would get through the blood-brain barrier, without also causing toxic side-effects or damaging healthy structures in the brain. Simply optimising the structure of the compound to do this took a decade, Kennedy said.

The latest results appear to show that the scientists got this bit right - the drug appeared to have few side-effects and it substantially lowered levels of toxic amyloid compounds.

The real question, which the next phase of the trial should answer, is whether the formation of plaques are a root cause of the disease or simply a visible symptom. Previous drugs aimed at clearing abnormal tangles of proteins from the brain have not been successful, and some argue that by the time the plaques are present irreparable brain damage may have already occurred.

It is possible that previous drugs based on the so-called amyloid hypothesis, were given to patients whose disease was too far advanced for them to benefit. Merck hopes that its drug, which acts at an earlier stage in the disease process by shutting down the production of the misshapen proteins rather than clearing them once they appear, will fare better.

There is no guarantee that the drug will ultimately make it to market, but in a field that has seen such scant progress, the fact that a major clinical trial is underway is welcome news.

Professor John Hardy, a neuroscientist at University College London and pioneer in the study of Alzheimer’s disease, said: “Conveying some excitement isn’t the wrong thing to do in this case.”

https://www.theguardian.com/society/2016/nov/02/a-decade-of-deadlock-over-alzheimers-treatment-may-be-drawing-to-a-close

https://www.theguardian.com/society/2017/jul/16/stressful-experiences-can-age-brain-by-years-alzheimers-experts-hear

Stressful experiences can age brain 'by years', Alzheimer's experts hear

Child’s death, divorce or job loss linked to poorer cognition in later life, study finds, with African Americans more susceptible

Press Association

Sun 16 Jul 2017 20.56 BSTLast modified on Wed 14 Feb 2018 21.10 GMT

 The researchers found that African Americans may be even more affected because they experienced far more stressful events than white people during their lifetimes. Photograph: Design Pics/Rex

Stressful life experiences can age the brain by several years, new research suggests. Experts led by a team from Wisconsin University’s school of medicine and public health in the US found that even one major stressful event early in life may have an impact on later brain health.

The team examined data for 1,320 people who reported stressful experiences over their lifetime and underwent tests in areas such as thinking and memory. The subjects’ average age was 58 and included 1,232 white Americans and 82 African Americans. A series of neuropsychological tests examined several areas, including four memory scores (immediate memory, verbal learning and memory, visual learning and memory, and story recall).

Stressful life experiences included things such as losing a job, the death of a child, divorce or growing up with a parent who abused alcohol or drugs. The results showed that a larger number of stressful events was linked to poorer cognitive function in later life.

Poor quality sleep could increase Alzheimer's risk, research suggests

When looking specifically at African Americans, the team found they experienced 60% more stressful events than white people during their lifetimes. Researchers said that, in African Americans, each stressful experience was equivalent to approximately four years of cognitive ageing.

The study, which has not been published in a peer-reviewed journal, was presented at the Alzheimer’s Association international conference in London.

Dr Maria Carrillo, the chief science officer for the Alzheimer’s Association, said: “The stressful events that the researchers were focusing on were a large variety ... the death of a parent, abuse, loss of a job, loss of a home ... poverty, living in a disadvantaged neighbourhood, divorce.” She said that even a change of school could be regarded as a stressful life event for some children.

Dr Doug Brown, the director of research at the Alzheimer’s Society, said: “We know that prolonged stress can have an impact on our health, so it’s no surprise that this study indicates stressful life events may also affect our memory and thinking abilities later in life. However, it remains to be established whether these stressful life events can lead to an increased risk of dementia.

“Studying the role of stress is complex. It is hard to separate from other conditions such as anxiety and depression, which are also thought to contribute towards dementia risk.

Dementia and Alzheimer's leading cause of death in England and Wales

“However, the findings do indicate that more should be done to support people from disadvantaged communities that are more likely to experience stressful life events. As we improve our understanding of risk factors for dementia, it is increasingly important to establish the role that stress and stressful life events play.”

Other research has suggested there are plausible links between stress and chronic inflammation, which in turn may accelerate the development of dementia. But experts believe that a health lifestyle and a healthy diet can help mitigate this risk, even for those people going through stressful events.

https://www.theguardian.com/society/2017/jul/16/stressful-experiences-can-age-brain-by-years-alzheimers-experts-hear

https://www.theguardian.com/society/2018/jun/21/alzheimers-link-to-herpes-virus-in-brain-say-scientists

Alzheimer's link to herpes virus in brain, say scientists

Research reveals strains of virus more abundant in brains with early stage of disease, though uncertainly whether virus is a trigger or a symptom

Hannah DevlinScience correspondent

 @hannahdev

Thu 21 Jun 2018 16.00 BSTLast modified on Thu 21 Jun 2018 18.50 BST

 Brain scan of a patient with Alzheimer’s disease. Photograph: BSIP/UIG via Getty Images

The presence of viruses in the brain has been linked to Alzheimer’s disease in research that challenges conventional theories about the onset of dementia.

The results, based on tests of brain tissue from nearly 1,000 people, found that two strains of herpes virus were far more abundant in the brains of those with early-stage Alzheimer’s than in healthy controls. However, scientists are divided on whether viruses are likely to be an active trigger, or whether the brains of people already on the path towards Alzheimer’s are simply more vulnerable to infection.

“The viral genomes were detectable in about 30% of Alzheimer’s brains and virtually undetectable in the control group,” said Sam Gandy, professor of neurology at the Icahn School of Medicine at Mount Sinai, New York and a co-author of the study.

The study also suggested that the presence of the herpes viruses in the brain could influence or control the activity of various genes linked to an increased risk of Alzheimer’s.

The scientists did not set out to look for a link between viruses and dementia. Instead they were hoping to pinpoint genes that were unusually active in the brains of people with the earliest stage of Alzheimer’s. But when they studied brain tissue, comparing people with early-stage Alzheimer’s and healthy controls, the most striking differences in gene activity were not found in human genes, but in genes belonging to two herpes virus strains, HHV6A and HHV7. And the abundance of the viruses correlated with clinical dementia scores of the donors.

“We didn’t go looking for viruses, but viruses sort of screamed out at us,” said Ben Readhead, assistant professor at Arizona State University-Banner Neurodegenerative Disease Research Center and lead author.

Gandy said the team were initially “surprised and sceptical” about the results, based on brain tissue from the Mount Sinai Brain bank, and so repeated the study using two further brain banks – in total 622 brains with signs of Alzheimer’s and 322 healthy control brains – and detected the very same genes. “We’ve tried to be conservative in our interpretation and replicated the results in three different brain banks, but we have to at least recognise that these diseased brains are carrying these viral genomes,” he added.

Strobe lighting provides a flicker of hope in the fight against Alzheimer’s

The scientists could not prove whether viruses actively contribute to the onset of disease, but they discovered a plausible mechanism for how this could happen. Some of the herpes genes were found to be boosting the activity of several known Alzheimer’s genes.

David Reynolds, chief scientific officer of Alzheimer’s Research UK, said this element was significant. “Previous studies have suggested that viruses might be linked with Alzheimer’s, but this detailed analysis of human brain tissue takes this research further, indicating a relationship between the viruses and the activity of genes involved in Alzheimer’s, as well as brain changes, molecular signals, and symptoms associated with the disease,” he said.

However, others were more sceptical. Prof John Hardy, a geneticist at University College London, said: “There are some families with mutations in specific genes who always get this disease. It’s difficult to square that with a viral aetiology. I’d urge an extremely cautious interpretation of these results.”

The viruses highlighted are not the same as those that cause cold sores, but much more common forms of herpes that nearly everyone carries and which don’t typically cause any problems. The study in no way suggests that Alzheimer’s disease is contagious or can be passed from person to person like a virus – or that having cold sores increases a person’s risk of dementia.

Poor quality sleep could increase Alzheimer's risk, research suggests

There are currently 850,000 people living with dementia in Britain, and the number is projected to rise to a million by 2025 and 2 million by 2050. But despite hundreds of drug trials during the past decade, an effective treatment has not yet emerged.

“While these findings do potentially open the door for new treatment options to explore in a disease where we’ve had hundreds of failed trials, they don’t change anything that we know about the risk and susceptibility of Alzheimer’s disease or our ability to treat it today,” said Gandy.

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• https://www.theguardian.com/society/2018/jun/21/alzheimers-link-to-herpes-virus-in-brain-say-scientists

https://www.theguardian.com/society/2015/oct/20/the-deviousness-of-dementia

The deviousness of dementia

When memory disappears, something more than memory gets lost. This is how a world begins to unravel – and how caregivers unwittingly become part of the chaos

by Dasha Kiper

Tue 20 Oct 2015 05.59 BSTLast modified on Wed 29 Nov 2017 08.57 GMT

 In November 2010, when I was 25 years old, I moved in with a man who was 98. This man, whom I’ll call Mr Schecter, wasn’t a friend or relation or anyone I knew. He was a Holocaust survivor in the first stages of dementia, and I’d been hired to look after him. Although my background was in clinical psychology, I was by no means a professional caregiver. I was employed because Mr Schecter’s son – I’ll call him Sam – had seriously underestimated his father’s condition. Sam’s mistake was understandable. The most obvious paradox of dementia is the victim’s frequent inability to recognise it, and Mr Schecter went about his life as though burdened by the normal aches and pains of aging rather than by an irrevocable and debilitating illness. If he put the laundry detergent in the oven or forgot which floor he lived on, he’d shake his head and sigh, Mayn kop arbet nisht (“my head doesn’t work”). But it was a lament, not a diagnosis. And this denial, both clinical and profoundly human, led Sam to misjudge the illness as well.

The deviousness of dementia - Podcast

Mr Schecter lived in a two-bedroom apartment on a pleasant, tree-lined street in the Bronx. For a man nearing 100, he was amazingly spry. Short, solidly built, with a firm handshake, Mr Schecter exhibited at our first meeting all the hallmarks of dementia. He repeated himself, his mind wandered, and he asked the same questions over and over. He also insisted that he didn’t need help, that he still went to work (he had, of course, stopped), and that if I rented a room from him, it would be on a month-by-month basis. More than anything else, he wanted me to understand that he had agreed to the arrangement only as a concession to his son.

As for me, any doubts about taking up Sam’s offer disappeared when I stepped into Mr Schecter’s apartment. The unimaginative furniture, framed pictures of grey city streets and sombre landscapes, and hundreds and hundreds of jacketless books, as many in Yiddish as English, seemed to contain the world of my grandparents. It was an apartment out of time, and perhaps unconsciously I felt that Mr Schecter’s past offered a way out of my present. I had grown alienated from my studies and had recently ended a relationship that had both consumed and confined me. I felt adrift, unsure of what to do. So when I learned that Mr Schecter, like my maternal grandfather, had been interned in a Soviet labour camp during the second world war, I naively thought I could protect him, that I could somehow compensate for the resilience that had sustained him in the past.

But I had another reason as well. Having studied pathology primarily through the dispassionate lens of quantitative analysis, I saw Mr Schecter as an opportunity to observe how a person fights to preserve his sense of self, even as a neurological disease is eroding it. Although empirical research – brain scans and blood analyses – approaches dementia like any other physiological illness, it can inadvertently distance us from what Oliver Sacks referred to as “the inner state, ‘the situation’” of the person. For unlike diseases that attack the body, dementia, by degrading the physiology of the brain, induces an altered state of consciousness, a consciousness both like and unlike our own, both a mirror and a mask.

Dementia, of course, has been identified, classified, and even anatomically annotated. And because we’ve labelled the anomaly, describing it as something carved out in the brain, a swerve from the norm, a deterioration of cognitive ability, we believe we understand it. Having lived with a dementia patient for more than a year, I am not sure I agree. I believe that something remains hidden, something we’re not inclined to see, precisely because dementia steers us away from it.

When someone loses an arm or a leg, we know exactly what’s missing; but with the loss of memory, something greater than memory is at stake. Memory isn’t just about remembering, and memory loss isn’t just about forgetting. Memory is responsible for creating continuity, meaning, and coherence both for ourselves and for those around us. Its integration into every function of life, from speaking and learning to the forming of relationships, actually makes its loss all the more difficult to comprehend, since the visible repercussions – repetition, confusion, anxiety, and mood swings – distract us from the deeper, more intangible privation. 

About 5.3 million people in the US experience some form of dementia, ranging from mild cognitive impairment to Alzheimer’s disease. By 2050 the affected population is projected to triple. In the UK, dementia affects about 850,000 people. In September, George McNamara, head of policy at Alzheimer’s Society, stated that “Dementia is already the biggest health challenge this country faces. It costs the UK in excess of £26bn, which equates to £30,000 a person with dementia – more than the cost of either cancer or heart disease.”

Dementia not only affects the minds of its victims; it also creates a world so fragmented, so skewed and redundant – so indifferent to normal rules of behaviour – that caregivers unwittingly become part of the madness. And this, unfortunately, is what the doctors and the guidebooks offering counsel to caregivers often fail to notice. Because we automatically posit a clear distinction between caregiver and patient, between the normal and the abnormal, we don’t see that the true burden for caregivers is, in fact, the absence of such a divide. When a loved one loses cognitive purchase, it’s not only his or her world that begins to unravel, but the caregiver’s as well.

“So where are you from?” Mr Schecter asked as soon as I put down my bags. “Where did you go to school? Where do your parents live?”

“Russia,” I told him, adding that my family had moved to San Francisco in 1992 and that I’d gone to the University of California at Davis, then Columbia for graduate school.

He digested this for about 30 seconds and then looked me in the eye. “So where were you born? Where did you go to school? Where do your parents live?” He didn’t ask these questions every day for a year. He asked them five or six times a day, every day, for a year. Other questions soon flew at me – which food in the fridge was mine, what time was his son coming, where were his keys, had the morning newspaper arrived – questions that came with such mind-numbing regularity that I began to think we were performing shtick for an invisible audience.

The more Mr Schecter tried to fill in the gaps of his memory, the more automatic his behaviour became. Every time I heard him wind his mechanical wristwatch, check his pockets for keys, or relentlessly pace the hallway at night, my body would tense up, unnerved by his anxiety and my own helplessness. His desperation to remain intact enveloped me. It became an assault on my senses, an assault on possibility and hope, and it made me feel that nothing could ever change.

But I knew I had to endure it. Because for those stricken by dementia, repetition is not merely a symptom but also a refuge, a coping mechanism that attempts to counter memory loss. Such loss, after all, is frightening, and people with dementia vainly attempt to impose order on their surroundings. What mattered to Mr Schecter was not my answers to his questions, but the act of communication, of following a familiar script, of engaging in normal behaviour. That was what kept the chaos at bay. And because it was my job to ground him, I became a co-conspirator in normality, or at least the pretence of normality. I wasn’t just an ear that Mr Schecter could talk into; I was a presence that reassured him of his own existence.

One of the strangest outcomes of living with a dementia patient is that only one of you becomes used to having company. While I quickly became accustomed to Mr Schecter’s accented English, his dark, mottled skin, and his curious shuffling gait, which pitched him forward even as he remained upright, he would often be startled on seeing me in the mornings or finding me in the kitchen at night. He’d forgotten that I was in the house and what I looked like. After a while, he began to sense that he wasn’t living alone: someonewas around who could tell him the day of the week or what time Sam was coming. But that someone was less a roommate than a vaguely familiar guest, a short, dark-haired woman whom he would graciously invite to join him for lunch or dinner, usually offering her her own food.

For the most part, I was a comforting presence, someone who made him tea and the occasional dinner, someone he could talk to – and how the man liked to talk! There were stories about Warsaw, his imprisonment in a Siberian labour camp, his eventual release and relocation in Sweden, and his emigration to America. No matter how many times I heard the same stories (and the loops got shorter by the week), I could not, as Sam kindly suggested, ask him to stop. How could I eject Mr Schecter from the world that reassured him of who he was? Indeed, there came a time when I knew every intonation, every chuckle, every syntactic turn. I knew when he might lapse into Yiddish or say a word or two in Polish. I knew when he would pause and struggle with a name or date – at which point I’d chime in with the answer and he’d open his eyes in amazement and unfailingly exclaim: “You know?” And I would say resignedly, “I do.”

This incessant repetition became the basis of our relationship. He relied on me to assure him of the status quo, and I, in turn, relied on his dependence, taking it as proof of our closeness. Sadly, as the synaptic connections of his memory weakened, mine only grew stronger. I didn’t just listen to him, I felt that I stood to inherit his world. I knew a moment would come when he’d forget for ever the names and faces of his parents, the hoyf on Geisha Street where he played, and the Medem sanitarium, outside Warsaw, which he helped run. He would forget the joy and disbelief of miraculously running into his brother in the Siberian forest while both were being forced to work in neighbouring labour camps, just as he would forget the tragedy of losing his brother to pneumonia six months after they were reunited. So his memories seeped into me, until I felt that his world and mine formed a collective reality.

Although dementia often makes its victims uncharacteristically open, I couldn’t help but feel that he was confiding in me because of me, and not because of his illness. Why else did we sit every day in his living room, not two feet apart, as he spoke in the emotional register one reserves for a dear friend? And when his mind invariably turned to his first wife’s death and he confided with tears in his eyes that as hard as it was on him, it was even harder on Sam, he would grip my hand so hard that I felt his despair course through my body. So I would inch towards him as he began to lean towards me, and pressed together, we sat with grief in our arms, in silence.

But only as long as nothing distracted him. For when the phone rang, jarring us apart, it broke more than just the silence. Mr Schecter would trundle off to the desk in the hall while I went to my room to give him some privacy. After a minute of conversation, I could almost hear Sam say over the wire, “How is Dasha?” To which Mr Schecter invariably replied, “How should I know? She’s sleeping, the door to her room is closed, the light is off.” (The door was never fully closed, and the light was always on.)

These disruptions, when I abruptly disappeared from his consciousness, never failed to shock me. Each time he hugged me or visibly relaxed when I found his keys, I felt recharged by his sincerity and affection. But each time he forgot our conversations or what I had done for him, the same hurt and disbelief welled up inside me. I couldn’t seem to harden myself, despite everything that I read about dementia. Only gradually did I begin to comprehend that my own healthy brain was as incapable of adjusting to him as his brain was to me.

An insidious paradox works against understanding dementia. The rules that guide a normal memory make it nearly impossible to accept memory loss in others. Apparently, the healthy brain needs to believe that memory is reciprocal and communal, which makes sense, since without such expectation we couldn’t form bonds of affection or trust or, conversely, feelings of antipathy or fear, all of which are necessary for survival.

The very idea of memory loss is counterintuitive. Even when we know that dementia is mercilessly erasing experiences, we still feel that its victims are capable of keeping emotional tabs on their relationships, since those bonds were formed gradually over time. Memory isn’t just a mechanism that records events; it’s an internal clock responsible for the impression of moving forward in time. Because Mr Schecter’s clock had stopped while mine continued to tick, he and I were perpetually out of sync. Because I remembered, I derived meaning from our encounters, while he, who soon forgot everything, could not. Although I spent a great deal of time with Mr Schecter, he (in his reality) did not spend time with me – which is why each of us, in a very different way, ended up living alone in his apartment in the Bronx.

Like many refugees, Mr Schecter held fast to his European heritage, making few accommodations to his new home. The Beatles, Michael Jackson, Marilyn Monroe, OJ Simpson might as well have never existed. Instead, Mr Schecter read the Yiddish Forward, helped put out a Yiddish newsletter, and joined the board of the YIVO Institute for Jewish Research, where he also worked as a volunteer archivist, collating various materials in Polish, Yiddish, and Russian. But now that he had stopped going to work, he began to fixate on things he could control. Aside from repeatedly calling his son, he channelled his energy into rearranging the food in the fridge or fiddling with the electric fixtures and lamps.

To Sam, his father’s behaviour was consistent with his usual inability to acknowledge or adapt to change.

One of the cruellest aspects of dementia – one that guidebooks are loth to mention – is that its symptoms often recapitulate a laundry list of aggravating behaviours that have always marked a familial relationship. For Sam, the behaviours that had nettled him when his father was 60 irritated him no less now that his father was almost 100. Dementia was simply another reason to find his father deficient. To help Sam over this hurdle, I showed him pictures of the dementia brain, with the hippocampus pitifully shrunken to half its normal size. Staring at the coloured images of the healthy versus the diseased brain, Sam looked appropriately sombre. Here was visual evidence that his father was no longer the person that Sam had been fighting for decades, no longer someone responsible for his emotional outbursts. Yet only an hour after Sam had viewed these photographs, he and his father were shouting at each other again.

Sam’s inability to make the shift surprised me. And I was reminded that the line between a healthy yet fallible memory and one compromised by dementia isn’t always apparent, since both give rise to similar denials and distortions. So it’s often difficult to differentiate personal idiosyncrasies from natural cognitive decline. Before dementia erases who we are, it shows us what we are – and who can say for certain where a person’s defences end and his dementia begins? On some level the distinction doesn’t exist; we create it.

Sadly, it is only when dementia truly overwhelms people, when they can no longer function and protect themselves, that we finally see the condition for what it is. One night, when Sam slept over, he looked up to find his father reaching for the phone.

“Who are you calling?” Sam asked.

“My son,” Mr Schecter replied.

“Oh?” said Sam. “Who am I?”

“You’re Sam,” his father said, impervious to the contradiction and chuckling at the silliness of the question.

For a moment, Sam seemed stunned. Then he walked over to his father and gently hung up the phone. At last, he realised that something was happening that had nothing to do with the dramas of family life. His father had travelled someplace where Sam could not follow, a departure that Sam had to accept if he was going to help his father (and himself) deal with the disease. From Sam’s expression, it was clear that he now acknowledged the chasm that had opened up between them. But the next day, when Mr Schecter went to the kitchen to rearrange the food in the fridge for the 100th time, the father-and-son skirmishing started up again.

As with most victims, Mr Schecter’s condition worsened in the evening (“sundowners syndrome”), and often he confused Sam with his uncle or with the doctor who had treated him in Siberia. During the day, however, his illness was more capable of deceiving people. I’m thinking of a Sunday afternoon in May when the three of us took a stroll around the neighbourhood. Since Mr Schecter had lived in the same building for some 45 years, many people greeted him warmly. “Everybody knows Mr Schecter,” Sam exclaimed cheerfully. On hearing this, his father stopped and said with a wistful smile, “Except Mr Schecter.” This rare, self-deprecating remark did more than just amuse Sam, it comforted him: he looked over at his father and smiled as if they were sharing a joke, as if they were sharing the same reality.

Such moments are seductive precisely because they make us think that dementia is just a phase, that its victims may one day be capable of commiserating with us about their affliction. So whenever I saw that Sam was being lulled by one of his father’s lucid events, I would tell him gently, “Hope is the enemy.”

Because of such moments, caregivers teeter between hope and despair. Unsure about the depth of the disease, they can’t gauge what their patients know or don’t know. Guidebooks use the term “ambiguous loss” when referring to the terrible day when the patient’s mind is truly gone, when he is physically present but psychologically absent. Yet the real ambiguity, it seems to me, precedes the final stage, when we don’t know how much is gone and consequently how much we’re supposed to grieve. These are the months, or more often the years, when caregivers live in perpetual crisis. Phones never stop ringing (because patients often feel abandoned) and questions are repeated (because answers can’t be retained) and no lost item is ever found (because moments after it’s located, loved ones start looking for it again). At this point, desperate caregivers are told, “Be patient, it gets better” – which is less a rallying cry than the bleak acknowledgment that one day the patient will no longer have the wherewithal to cause trouble.

Such is the deviousness of dementia: its ability to keep hope alive while its symptoms signify only futility. As long as his father seemed like himself, Sam could continue to argue with him. As long as they kept fighting and as long as Sam clung to that familiar futility, it felt as though nothing had changed.

Dementia itself is partially responsible for this. Although the disease clearly affects explicit memory (the ability to learn or recall events), it doesn’t completely expunge implicit memory (which is connected to the emotions). Though Mr Schecter’s explicit memory made him deny our frequent interactions, his implicit memory couldn’t entirely get rid of me. Indeed, he would obsess over my safety and practically cover me with kisses when I returned home after an outing.

What’s confusing to caregivers is not the absence of a memory system, but rather its fragmentation. It was the constant back-and-forth of his knowing and not knowing me, of resenting and appreciating me, that prompted my own oscillation between hope and hopelessness. After all, I was in a relationship with a human being, not a pile of broken memory circuits. So the contradictions I witnessed began to seem more and more like the normal defences of an old man who simply wanted it both ways: he wanted complete independence yet demanded constant attention.

One evening, perhaps seven or eight months into my stay, Mr Schecter decided to change the battery in the smoke detector, which was in the hall, near the ceiling. Ignoring my warnings, he retrieved a chair from the kitchen and put it under the alarm. When I tried to stop him, he retorted that he was “the boss” and knew what he was doing. Usually, when he tried to fix things, I would distract him. But on this occasion, I refused to pretend that he knew better. For just one minute, I needed him to understand that there was such a thing as objective reality. “Forget about the alarm,” I said firmly. “It’s too dangerous to stand on the chair.”

He waved me away and put a foot on the chair. Aggravated by his condescension, I felt an uncharacteristic urge to strip him of his delusions.

“You don’t know what you’re doing!” I shouted. “You haven’t been to work in over a year! You don’t do a damn thing alone!”

He paused, and I continued to berate him. My words both startled and amused him. “You are crazy,” he told me with the superior air one reserves for spoiled children. Perhaps I was crazy for a moment. His forgetfulness, along with his inconsistent and contradictory behaviour, were sapping my sense of reality. And now this 99-year-old man was about to climb on a chair and perhaps kill himself in the bargain – all because I didn’t matter. My self-righteousness meant nothing to him. It was too much, and I accused him of being impossibly stubborn, of being both needy and domineering, and finally, shamefully, I called him “a burden”. That stopped him. For a moment he glared at me and then shuffled off to his bedroom.

Appalled by what I’d done, I carried the chair back to the kitchen and collapsed on the linoleum floor. I was angry at him for the perpetual stress, the perverse logic, the incapacity to understand who I was and what I was doing for him. But mostly I was angry at myself for being cruel. As I sat sulking and reprimanding myself, he returned to the kitchen. He wanted a snack, but finding me on the floor, he stopped and broke into his wide, sweet smile. Then he noticed my tearful face and was dumbfounded and genuinely moved.

“Are you alright?” he asked. “Who should I punish for upsetting you?”

Why do we try so hard to keep people intact when we know they’re broken beyond repair? Human nature, it seems, also abhors a vacuum, even if it’s someone else’s. Apparently, I needed Mr Schecter’s memory more than he did. I needed him to know that I had acted reprehensibly, not necessarily because I deserved chastisement but because without his memory I was not accountable to him, and without such accountability I risked losing both empathy and purpose.

Memory and language are bundled together. So when memory disappears, the victims are not only diminished but also yanked out of the only context they have ever known. All they can do is fall back on language, and since language implicitly posits an intact memory, we’re fooled into thinking that people remember the words we utter. Even those who ought to know better – the caregivers who deal with dementia on a daily basis – often fail to remember that their patients forget. In this way, language instils hope and makes fools of us all.

Unable to sleep one night, I wondered how long Mr Schecter had before he lost his ability to speak. He was already struggling with English. Would Yiddish be next? What would happen when he could no longer coherently articulate his annoyance or anger? My mind turned to Samuel Beckett. In Waiting for Godot, language both protects us from absurdity and makes the absurdity possible. The play ripples with nonsensical dialogue, silly misunderstandings, pointless quibbles, inconsequential mutterings, illogical arguments, empty promises, and the occasional nod toward suicide. No other work of literature possesses the dark comedy, the misery, and the peculiar ratio of hope to hopelessness so characteristic of dementia. No wonder we resist the disease’s implications and perverse logic, for that way leads to nihilism and despair.

Our perseverance in the face of absurdity (where memory and language no longer serve us) keeps us from getting at the core of dementia. But since any sort of communication is by its very nature hopeful, we are brought up short by a paradox: language nullifies the very bleakness and meaninglessness it means to express. This, too, Beckett understood. Stick around dementia patients long enough, and his language begins to sound eerily familiar:

And we do go on, because decency requires it, because we cannot abandon those we love, and because the momentum of language, with its implicit hopes and promises, continues to carry us along.

Illustrations by Damien Cuypers

• This is an edited version of an article that first appeared in the autumn edition of The American Scholar.

• Follow the Long Read on Twitter at @gdnlongread, or sign up to the long read weekly email here.

https://www.theguardian.com/society/2015/oct/20/the-deviousness-of-dementia

https://www.theguardian.com/society/2018/feb/13/a-third-of-people-with-dementia-in-england-not-receiving-full-care

A third of people with dementia in England 'not receiving full care'

Age UK says many people do not have individual care package to which they are entitled

Haroon Siddique

Tue 13 Feb 2018 00.01 GMT

 The NHS says people with dementia should have an individual care plan reviewed at least once a year. Photograph: Matt Cardy/Getty Images

More than one in three people in England diagnosed with dementia are not getting the follow-up care they are entitled to, a charity has said.

The NHS specifies that everyone diagnosed with the condition should have an individual care plan that is reviewed at least once a year.

But Age UK found that as of November, out of the 458,461 people with a recorded diagnosis of dementia, only 282,573 had a new care plan or at least one care plan review on record in the previous 12 months.

The charity describes the plans, which set out the tailored support someone should receive and should be updated in line with the progression of the disease in the individual, as “the gateway to follow-up support from the NHS”.

With the number of people with dementia in the UK forecast to rise from 850,000 in 2015 to 1 million by 2025, Age UK warned a failure to provide the plans will hamper the ability of the growing number of people with the disease to live in the community.

Caroline Abrahams, Age UK’s charity director, said: “Our analysis suggests that many people with dementia are losing out on the NHS follow-up support they need and are supposed always to be offered, once they have received their diagnosis.

“As a result, they and their loved ones are missing precious opportunities to get help with living as well as possible with the disease. The absence of a care plan also means that people with dementia are not being signposted to services that really could improve their physical and mental health, and sense of wellbeing.”

She reminded the government of its commitment under the prime minister’s challenge on dementia 2020 to improving the “quality of post-diagnosis treatment and support for people with dementia and their carers”.

Age UK said there are not enough good local support services for people with dementia but, in its Promising Approaches to Dementia report, published on Tuesday, it highlighted a number of “evidence[-based], cost-effective and scalable” interventions that could form part of care plans.

They include counselling, specialist nurses providing advice and support, horticultural therapy and dance-based therapy.

Kate Jopling, a policy and strategy consultant and the author of the report, said: “What we’ve produced is a practical resource for individuals, organisations and communities who want a better deal for people with dementia. It sets out what people with dementia want, what’s been tried elsewhere, what evidence there is that it works.”

A Department of Health and Social Care spokeswoman said: “We want to make this the best country in the world for dementia care and we therefore expect everyone with dementia to have a personalised care plan.

“NHS England data shows that over the last two years, more people with dementia are getting better access to support.”

Age UK’s analysis was based on data from 7,185 GP practices in England, published by NHS Digital. NHS England guidance says: “There is an urgent need to ensure every person who has dementia has an individual care plan.”

https://www.theguardian.com/society/2018/feb/13/a-third-of-people-with-dementia-in-england-not-receiving-full-care

https://www.theguardian.com/news/2018/aug/10/my-death-is-not-my-own-the-limits-of-legal-euthanasia

The long read

‘My death is not my own’: the limits of legal euthanasia

Henk Blanken knows Parkinson’s disease might one day take him past the point at which he wants to carry on. Dutch law says it is legal for a doctor to help him die when the time comes – but there’s no guarantee that will happen

Fri 10 Aug 2018 06.00 BST

 I’m half the man I used to be. One half of my body twitches. I drool when I’m peeing, and I tear up at the sight of tiny broken birch branches in the snow. Sometimes my left hand jerks up, leading to slapstick scenes in which I involuntarily chuck a glass of water over my shoulder. In 2011, at the age of 51, I was diagnosed with Parkinson’s. After 10 or maybe 15 years, the doctor said, I would start needing help. But it was also possibile that I would grow old with Parkinson’s. “It won’t kill you,” he said.

It will end crappily though, I thought.

The typical patient with Parkinson’s becomes disabled after eight to 10 years, but this typical patient does not exist. Everyone is different. Six years after being diagnosed, I was still on the tennis court. Then everything went wrong. Within a few months I became a wavering wreck. Walking turned into stumbling and I was forced to shuffle along behind a frame.

The time had come for brain surgery, my neurologist declared, and I was admitted to a clinic in the north of the Netherlands “for observation”. It took me several days to get used to the other patients. There were seven of them: three men and four women. I watched their nonsensical tremors and how they moved, step by petty step, as they tried desperately to swerve the wheels of their walking frames in the right direction. They ate in silence. One of them, a grumpy farmer from the countryside, sat quietly urinating on the worn-out lift chair.

One patient, a man in his 70s with a sturdy head and a weathered gaze, sat opposite me during dinner. Crouched like a frightened bird, he ate his sauerkraut mash while keeping his mouth close to the plate and drooling. From time to time some of the food fell back from his fork or from his raw, red swollen lower lip. When his plate was half empty, a nurse mercifully fed him a few more bites. His chin sagged on to the plate, his gray beard dipping in the cold sauerkraut mash.

My God. I had pictured hallucinations. I had read that Parkinson’s patients have a much greater risk of dementia. I had accepted that one day my wife would have to cut up my food and tie my shoelaces. I had scoured eBay for a reasonably-priced mobility scooter. I had more or less come to terms with all that, but after spending time at the clinic, my neurologist’s remark – “It won’t kill you” – took on an entirely new meaning. If everything goes wrong, I thought, this is what lies ahead of me. And it won’t even kill me.

What was worse? The looming oblivion of dementia or the cruel physical failures that come with Parkinson’s disease? Was it better to be trapped in a confused mind, or have a lucid mind while being trapped in a rebellious body?

Over recent years, I had discussed these kinds of questions with a friend of mine named Joop. We met occasionally and talked about dying, as if we were discussing a long-term weather forecast. Joop suffered from Alzheimer’s and had started to forget the basics of daily life. What he did know was that he didn’t want to die the way his father did, in a nursing home. “I don’t want to end up chasing after the nurses,” he told me.

Even as we replace old hips or knees or organs with new ones, and even as average life expectancy continues to increase, our brains keep on ageing. Neurodegeneration is the price we pay for the intense human drive to deny that existence is finite. Sooner or later our brains start to falter, nerve cells break down, and we end up in a nursing home, chasing nurses, chasing shadows, chasing ourselves.

I understood Joop’s deepest fear only too well. Nico, my father-in-law, was 91 when, in the middle of the night, he mistook his wife for an intruder and attacked her with a kitchen knife. Shortly after the incident, he was placed in the closed ward of a geriatric facility. That image never left my mind: the helplessness of the confused man we left behind when the lock of the glass door clicked, his bewildered eyes staring at us in an unstoppable kind of loneliness. Weeks later, when we were visiting Nico, he reproached his wife for neglecting him. She never came to visit him, he grumbled, even though less than an hour beforehand she had fed him pieces of bread, with tears in her eyes.

On our way home, it hit me that I would rather die than end up like that. For the first time, I seriously considered the possibility of one day voluntarily ending my life. After all, I thought, the Netherlands has the best-regulated voluntary euthanasia system in the world.

Until the 1950s, the historian James Kennedy has argued, the Netherlands was more conservative, more religious and less prosperous than most other European countries. Then everything changed, and this fearful nation turned into a pioneer. We became an open, liberal society that led the way on ethical issues. We tolerated drugs, legalised abortion, and our prostitutes paid taxes.

Where we had once been devout and Calvinist, in the 60s we entered a godforsaken era. Churches were turned into shops or apartments. By the end of the century, Christian political parties had lost their grip on power, and their dogmas no longer dictated matters of life and death. The nation had long debated the question of whether assisted death should, in certain cases, be legalised. And in 2001, the Dutch parliament voted to make the Netherlands the first nation in the world to legalise euthanasia. Central to the argument in favour of the new law was the right to self-determination. “My death is my own,” as the Dutch say.

Today, nine out of 10 Dutch citizens support the euthanasia law, which went into effect in April 2002. This law allows physicians to honour requests to assist a patient who wants to end their life, if there is “unbearable and hopeless suffering” with no hope of improvement. This means that a physician could, for example, prevent someone with lung cancer from dying choking in their own blood.

The debate did not cease once the law was passed. New groups of patients demanded an even more liberal interpretation of the same law. And after every verdict that broadened the criteria for euthanasia, another group of citizens campaigned for even more progressive legislation. With every new demand, the debate would fire up once again. Supporters see the expansion of the law as moral progress, while opponents predict that we are moving towards a society reminiscent of Nazi Germany, where we get rid of those deemed “useless”, such as the very elderly or those with severe mental illness.

Nevertheless, the euthanasia debate seems to have entered a faltering phase. A very un-Dutch thing has happened. We appear to be tongue-tied. The Netherlands – the country that, more than any other, wants to believe in every person’s right to voluntary death, the country that talks lightly about painless death as it were a money-back guarantee – is struggling with the dilemma surrounding dementia and death.

Ifirst met Joop on a cold and rainy September day in 2012. He was in his 70s. A year after he was diagnosed with Alzheimer’s, Joop was still remarkably fit. But when he started telling me the story of his choir and their performances in nursing homes for the third time in 20 minutes, I realised dementia had already disrupted his short-term memory.

Even though Joop was unaware, in that moment at least, of how much his illness had already begun to eat away at his mind, he knew what was in store for him. He could not let go of the images he had seen in those nursing homes. He had decided that when the day eventually came that he could no longer live with Janny, the love of his life, he would rather die.

“How do you think that day will go?” I asked him. He imagined that it would almost be an ordinary day. His children and grandchildren would come to say goodbye. “And then the doctor will walk in and give me an injection,” he said.

That might have been somewhat naive. For some time, Janny and Joop had been looking for a doctor who would be willing to help him die at the time he had chosen: the day when Joop was no longer capable of living at home. The doctors they had spoken to had explained that until Joop’s suffering was unbearable, they could not perform euthanasia. But when Joop asked, “What will you do when my dementia is more severe and I’m incompetent?” the doctors explained that, at that stage, they could not perform euthanasia.

I don’t think Joop ever completely understood this catch-22. Dementia poses special problems for euthanasia cases. Under Dutch law, a doctor is allowed to help a person with severe dementia to die, if that patient had prepared an advance euthanasia directive back when they were still mentally competent. Joop had one of those. He assumed everything had been arranged. But it hadn’t.

Of the 10,000 Dutch patients with dementia who die each year, roughly half of them will have had an advance euthanasia directive. They believed a doctor would “help” them. After all, this was permitted by law, and it was their express wish. Their naive confidence is shared by four out of 10 Dutch adults, who are convinced that a doctor is bound by an advance directive. In fact, doctors are not obliged to do anything. Euthanasia may be legal, but it is not a right.

As doctors have a monopoly on merciful killing, their ethical standard, and not the law, ultimately determines whether a man like Joop can die. An advance directive is just one factor, among many, that a doctor will consider when deciding on a euthanasia case. And even though the law says it’s legal, almost no doctors are willing to perform euthanasia on patients with severe dementia, since such patients are no longer mentally capable of making a “well-considered request” to die.