alzheimer’s disease


Cut Your Risk Of Alzheimer’s? Growing Evidence Says Maybe You Can — Modestly

Alexis McKenzie, right, executive director of The Methodist Home of the District of Columbia Forest Side, an Alzheimer’s assisted-living facility, puts her hand on the arm of resident Catherine Peake, in Washington, Feb. 6, 2012. (Charles Dharapak/AP)

Alexis McKenzie, right, executive director of The Methodist Home of the District of Columbia Forest Side, an Alzheimer’s assisted-living facility, puts her hand on the arm of resident Catherine Peake, in Washington, Feb. 6, 2012. (Charles Dharapak/AP)

It was the “two-thirds” in the press release headline that grabbed me: “Nine risk factors may contribute to two thirds of Alzheimer’s cases worldwide.”

So of course I read more about the new study:

Nine potentially modifiable risk factors may contribute to up to two thirds of Alzheimer’s disease cases worldwide, suggests an analysis of the available evidence, published online in the Journal of Neurology Neurosurgery & Psychiatry.

The analysis indicates the complexity of Alzheimer’s disease development and just how varied the risk factors for it are. But the researchers suggest that preventive strategies, targeting diet, drugs, body chemistry, mental health, pre-existing disease, and lifestyle may help to stave off dementia. This could be particularly important, given that, as yet, there is no cure, they say.

How I wish this meant that we can reduce our risk of Alzheimer’s by two-thirds. But no matter how I mangle the statistics, it doesn’t. Here’s what it does suggest, according to Dr. James Hendrix, director of global science initiatives for the Alzheimer’s Association: that for up to two-thirds of people who have Alzheimer’s, these modifiable risk factors may have contributed to it, and probably to when they got it.

“So,” he says, “if you were going to get Alzheimer’s, because maybe you had a genetic predisposition, and you take very good care of yourself, maybe you don’t get it until you’re 85 or 95. But if you smoke or you’re overweight or don’t exercise, maybe you get Alzheimer’s at 75. That’s really what this says — these could be contributing factors to if you get Alzheimer’s or when you get Alzheimer’s. It increases your risk.”

Of course, we’ve been hearing for years — at least since those smart Minnesota nuns got famous in 2001 — about how mental challenges like crossword puzzles could be linked to lower Alzheimer’s risk. But this latest paper seems part of a broad shift based on growing evidence about a far greater array of “modifiable risk factors.”

Exhibit No. 1: This summer, the Alzheimer’s Association ran a campaign on “10 Ways to Love Your Brain,” encouraging people to exercise, keep learning and quit smoking, among other advice. Exhibit No. 2: A round-up paper in the journal Alzheimer’s & Dementia laying out the levels of evidence on which lifestyle and health changes could protect people against Alzheimer’s.

The findings are relentlessly commonsensical: Many of the usual suspects that we already know are good for our health — exercise, heart-healthy diet, sleep, weight and blood pressure control — also appear to help fend off Alzheimer’s.

I asked Dr. Gad Marshall — a neurologist and associate medical director of clinical trials at the Center for Alzheimer Research and Treatment at Brigham and Women’s Hospital — how he’d respond to a neighbor who says, “Hey, I hear I can really move the needle on my risk of Alzheimer’s!” Continue reading


Study: New Antibody Therapy Can Reverse Traumatic Brain Injury Damage (In Mice)

Cleveland Browns QB Jason Campbell lies near midfield after suffering a concussion in a game on Nov. 24, 2013. Traumatic brain injuries, whether they occur on a sports field or in a war zone, are on the rise. (David Richard/AP)

Cleveland Browns QB Jason Campbell lies near midfield after suffering a concussion in a game on Nov. 24, 2013. Traumatic brain injuries, whether they occur on a sports field or in a war zone, are on the rise. (David Richard/AP)

Traumatic brain injuries, whether they occur on a sports field or in a war zone, are on the rise.

What’s worse, these head traumas have been linked to long-term neurodegenerative diseases, notably Alzheimer’s and a condition known as chronic traumatic encephalopathy, or CTE.

Now, a team of researchers report they’ve discovered the “missing link” between traumatic brain injuries and these degenerative brain diseases and developed a special antibody that may help prevent the conditions — at least in mice.

In a study published online in the journal Nature, researchers at Beth Israel Deaconess Medical Center identify the “missing link” culprit as “cis P-tau, a misshapen and toxic species of tau protein that has not been previously identified,” says Kun Ping Lu, MD, PhD, the study’s co-senior author and chief of the Division of Translational Therapeutics in the Department of Medicine at BIDMC and professor of medicine at Harvard Medical School.

Lu, in an interview, explains how these toxic proteins can build up in the brain and start causing serious damage after repeated head injuries:

A single concussion, a mild traumatic brain injury (TBI), results in moderate induction of cis P-tau, which returns to the baseline within 2 weeks. However, repetitive concussions, as might occur in contact sports, result in robust induction of cis P-tau that is persistent for months in mouse brains. This is similar to what is produced following a single severe TBI caused by a blast, as seen in military blast, or an impact, as seen in a severe car accident. Strikingly, cis P-tau is produced as soon as 12 hours after TBI, setting in motion the destructive course of events that leads to Alzheimer’s and CTE.

cis P-tau protein is extremely neurotoxic, disrupting neuron structure and function, progressively spreading to other neurons throughout the brain over time, leading to neuron death. Therefore, cis P-tau has the ability to kill one neuron after another in the brain over time, eventually leading to Alzheimer’s and CTE. These results in animal models are consistent with clinical observations that either repetitive concussions or single severe TBI can lead to Alzheimer’s or CTE.

Importantly, our cis antibody is not only able to spot only the toxic cis P-tau, but also to neutralize its toxicity to neurons. As a result, treating TBI mice with cis antibody can stop brain damage after TBI and prevent its debilitating long-term consequence of Alzheimer’s and CTE. Thus, cis P-tau is an early driver of TBI and its related Alzheimer’s disease and CTE, which can be effectively blocked by antibody therapy.

The immediate implications of these findings are to emphasize TBI prevention; however, if concussion occurs, it is critically important to allow the body defense system to remove the toxic tau protein completely before another concussion occurs. The most exciting development will be to humanize our current monoclonal antibody to develop early intervention to treat TBI and to prevent Alzheimer’s disease and CTE, which can be done within next a few years. In addition, because the same toxic tau protein also destroys brain cells in Alzheimer’s, this early intervention may be used to treat this most common form of dementia in older individuals.

The BIDMC release also states that “Lu and Zhou have interests in Pinteon Therapeutics, Inc., which has licensed Pin 1 technology from BIDMC.” Continue reading

Study: Do You Really Need Counseling On Your Alzheimer’s Gene Test?

Today on Radio Boston: A new Brigham and Women’s Hospital study finds that we may not need quite as much genetic counseling as we’d thought. Particularly on relatively cut-and-dried findings, like test results on a common gene that raises the risk of Alzheimer’s disease. Listen to host Anthony Brooks speak with Dr. Robert C. Green in the segment above.

From the Brigham’s press release:

A new study led by researchers at Brigham and Women’s Hospital (BWH) has found that people who received a written brochure instead of time-intensive genetic counseling about their genetic risk for Alzheimer’s disease did not experience greater anxiety or symptoms of depression than their counterparts a year later. The results of the randomized controlled study were published online in the journal Alzheimer’s and Dementia.

“As genetic testing of all kinds becomes commonplace, one of the primary challenges will be determining how to share this information with individuals seeking it in a way that limits the burden on health care providers but still puts the well-being of patients first,” said Robert C. Green, MD, MPH, a medical geneticist and researcher at BWH and Harvard Medical School and lead investigator of the study. “These new results show that for individuals seeking genetic risk information, we can use written material, rather than genetic counseling, to prepare them without causing greater long-term anxiety or distress.” Continue reading

Foggy Days, Sleepless Nights: When Alzheimer’s Care Goes Nocturnal

(Ronel Reyes/Flickr via Compfight)

(Ronel Reyes/Flickr via Compfight)

By Jessica Alpert

Marion Tripp was what you might call a quintessential “Yankee.” From impeccable pie crusts to crackshot deer hunting, she regularly impressed people with her wide range of skills. When her daughter and son-in-law started an organic farm in rural Maine, she’d bundle up in a snowmobile suit and sell their rutabagas at the local farmer’s market. I never knew Marion but her grandson — my husband — loves to remember her this way.

Not the way she was at the end.

Alzheimer’s ravaged Marion’s brain and left her confused, “mean,” paranoid, and violent. The last three years of her life, she had round-the-clock care since she rarely slept more than a few hours at a time. Her nocturnal habits were not unique. Indeed, in the world of Alzheimer’s, this tendency toward nighttime wakefulness is known as “sundowning.”

“Several things go awry with Alzheimer’s that affect the person’s brain chemistry and changes their circadian rhythm,” says Dr. Paul Raia, vice president of clinical services for the Massachusetts/New Hampshire chapter of the Alzheimer’s Association. He says there are various reasons for this nocturnal shift including lack of melatonin, diminished access to natural light and less rapid eye movement or REM sleep.

But it’s not just about being unable to sleep for long stretches of time. Like Marion Tripp, many Alzheimer’s patients are often agitated, angry, even violent. “During that period [of REM sleep], you are ridding the toxins from your brain and you’re stabilizing memory and you’re dreaming and essentially you are paralyzed with your body in a relaxing mode,” says Raia. “[The patients] may take a series of small naps throughout the day and when they wake up, they may not be fully awake. They can’t navigate well or negotiate well in their environment.” Continue reading

Pop Awake At Night? Researchers Blame ‘Sleep Switch’ In Your Aging Brain

(eflon via Compflight)

(eflon via Compflight)

If you’re on the older side and find yourself popping hideously awake in the middle of the night or far-too-early morn, here’s your line for the next time it happens: “Oh, that darned ventrolateral preoptic nucleus of mine! How I miss my old galanin!”

Researchers have just reported in the journal Brain that they’ve found a group of neurons — in the aforementioned nucleus — that function as a kind of “sleep switch,” and whose degeneration over the years is looking very much like the cause of age-related sleep loss. It’s also looking pivotal in the insomnia that often causes nocturnal wandering in people with Alzheimer’s disease.

“This is the first time that anyone has ever been able to show in humans that there is a distinct group of nerve cells in the brain that’s critical for allowing you to sleep,” said the paper’s senior author, Dr. Clifford Saper, chair of neurology at Beth Israel Deaconess Medical Center and professor of neurology at Harvard Medical School.

You may well be wondering exhaustedly how soon this insight — based on the post-mortem analysis of 45 human brains — will lead to better sleeping pills for older folks. I asked Dr. Saper that, too. No promises with timeframes at this point, but he does see the prospect for better-targeted sleeping pills for seniors, with fewer side effects like Ambien’s balance-related problems.

Our conversation, lightly edited:

Can this group of neurons actually explain the lion’s share of sleep problems that older people and people with Alzheimer’s disease have?

It really can. Let me give you a little background. We discovered this cell group in the brains of rats in 1996. We found that there’s a group of of nerve cells in a part of the brain called the hypothalamus that fire when animals are asleep. And we later found that if you eliminate those nerve cells, that animals lose up to 50 percent of all their sleep time, and the remaining sleep is fragmented. They can’t sleep for long bouts at a time; they keep waking up all the time.

At that time, we weren’t sure whether this would be the same in other species. So we looked at the brains of half a dozen other species — of mice and cats and monkeys — and we found that all of them have this cell group and that the cells were active during sleep in all of them. In every species we looked at, this same cell group had a particular neurotransmitter in it, called galanin.

I’ve never heard of that neurotransmitter before… Continue reading

Heroism At Home: An Intimate Look At Growing Ranks Of Caregivers

Screen shot 2014-01-31 at 10.38.03 AM

If you’re an adult living in the U.S., it’s a good bet that you (or your neighbor or close friend or colleague) are caring for an elderly family member. Indeed, more than 43 million Americans — about 18 percent of adults — care for a family member or friend 50 or older, according to the Family Caregiver Alliance; 15 million of these caregivers tend someone who has Alzheimer’s disease or some form of dementia.

Currently, family (read: unpaid) caregivers are the largest source of long-term care in the U.S. and health scholars expect that by 2050 the demand for such care will nearly double — and that family caregivers will have to continue meeting the greatest part of that need.

But the statistics don’t reveal the intimacy of such caregiving relationships: the terror of a mind slipping away, the humiliation and messiness of chronic illness, the often violent and shocking ways that bodies unravel. In her new book “The Caregivers: A Support Group’s Stories of Slow Loss, Courage And Love,” journalist Nell Lake details her two years observing a caregivers support group that includes a 50-year-old botanist who moved in with her aging mother to care for her, and a survivor of Nazi Germany who devotedly tends to his ailing wife, and others in the group (some of whom are dealing with serious health problems of their own). While documenting their lives, Lake offers views into the complexities of caregiving: the profound stress, the upheaval of family roles, the slow, often excruciating grief, as well as the graceful humanity of it all.

Here, lightly edited, is my Q & A with Lake, who lives with her family in Northampton, Mass.

RZ: You begin your book on a personal note, with a memory of your grandmother. Can you tell us a bit about her and how her story moved you to write about the larger issue of caregiving in America?

Journalist and author Nell Lake (photo: Sarah Prall)

Journalist and author Nell Lake (Courtesy Sarah Prall)

NL: My grandmother was a poised woman who lived her life with great energy. She had raised three children, kept a beautiful home, was active physically and also politically—involved in environmental causes and in the nuclear freeze movement in her community. She prized her independence and physical vitality, and, as she aged, she expressed a fear of ending up frail and in a nursing home. She kept materials from the Hemlock Society in a kitchen drawer.

In the summer of 1984, when I was 18, she found out from a doctor that she might have cancer. That night, she went to her garage, sat in her car, and turned it on. A neighbor found her the next day.

While my grandmother’s suicide didn’t directly spur me to pursue a story about long-term care and family caregiving, once I was sitting in on the caregivers support group, it was clear to me that I was immersing myself in the stage of life, an experience, that my grandmother had feared and successfully avoided. It became especially moving, then, for me to follow others who were making their way through the “shadow part of life,” as I put it in the book.

My memories of her shaped my lens: I wondered, Can we find ways to embrace this part of life, to meet it with less fear? Can we also try to make it better for everyone?

How did you connect with the hospital caregiver support group?

In late 2009, I went to a dinner party, a birthday celebration for a friend. I ended up seated next to a man whom I call Ben in the book. He told me that he was the lead behavioral health counselor at our local hospital, and that he also facilitated a weekly support group there for family caregivers. I told him I was a journalist interested in healthcare and mental health issues. He suggested I might want to sit in on the group, and later he asked the group members’ permissions. Before long I was listening to their stories.

Is there any particular quality you discovered about these caregivers that you didn’t expect?

It may sound surprising, but spending two years with the support group gave me a new and better sense for what constitutes heroism. I saw heroism in Penny, who had taken her forgetful mother, Mary, into her home. Caring for Mary was not easy, but Penny met Mary’s needs as best she could, sought to provide her mother with as much comfort, care, and happiness as seemed possible. I saw heroism, too, in Daniel, a caregiver who was himself quite frail, and whose wife was bipolar and in pain. Daniel also bravely did his best to meet his wife’s needs.

Their heroism, to me, was a willingness to keep returning to difficult circumstances, to persevere and act compassionately, to try to ease others’ suffering.

This idea of heroism is similar to the notion that bravery is not the quality of being free from fear; rather, bravery is a willingness to act in spite of fear.

Some (many?) caregivers are reluctant to take on so much responsibility, but feel they have no choice. Is this true for most informal caregivers these days and how does our modern notion of caregiving differ from past generations?

In the most important sense, there was less choice a century ago. The word “caregiver” didn’t exist; the words “daughter” or “wife” or “sister” sufficed to describe a caregiving role. Continue reading

Why To Exercise Today: Preserve Your Brain, Avoid Dementia

Shreyans Bhansali/flickr

Shreyans Bhansali/flickr

It’s raw and miserable out, with snow on the way: a perfect day for a long, sit-down lunch, or just hunkering down to work at home with a laptop, a warm cocoa and a soft couch. Right? No, no and absolutely no.

A new study that followed men in South Wales for 35 years puts numbers on what now should be obvious to us all: exercise is one of the most powerful tools you possess to help prevent dementia and cognitive decline in older age. So get up now and go sweat.

To me, the most eye-popping finding here is that by following a fairly simple health regimen, the chances of a “disease-free” life as you age increase dramatically:

Researchers report that people who consistently stuck to four or five “healthy behaviors” (regular exercise, no-smoking, a low bodyweight, a healthy diet and low alcohol intake) “experienced a 60 percent decline in dementia and cognitive decline – with exercise being the strongest mitigating factor – as well as 70 percent fewer instances of diabetes, heart disease and stroke, compared with people who followed none.”

More from the news release:

“The size of reduction in the instance of disease owing to these simple healthy steps has really amazed us and is of enormous importance in an aging population,” said Principle Investigator Professor Peter Elwood from Cardiff University’s School of Medicine. “What the research shows is that following a healthy lifestyle confers surprisingly large benefits to health – healthy behaviours have a far more beneficial effect than any medical treatment or preventative procedure.

“Taking up and following a healthy lifestyle is however the responsibility of the individual him or herself. Sadly, the evidence from this study shows that very few people follow a fully healthy lifestyle. Furthermore, our findings reveal that while the number of people who smoke has gone down since the study started, the number of people leading a fully healthy lifestyle has not changed,” he added.

Recent surveys indicate that less than one per cent of people in Wales follow a completely healthy lifestyle, based on the five recommended behaviours, and that five per cent of the population follow none of the healthy behaviours; roughly equating to a city with a population the size of Swansea (240,000).

Professor Elwood continued: “If the men had been urged to adopt just one additional healthy behaviour at the start of the study 35 years ago, and if only half of them complied, then during the ensuing 35 years there would have been a 13 per cent reduction in dementia, a 12 per cent drop in diabetes, six per cent less vascular disease and a five per cent reduction in deaths.” Continue reading

What Happens Early In The Brains Of People Who Get Alzheimer’s Late?

Alexis McKenzie, right, executive director of The Methodist Home of the District of Columbia Forest Side, an Alzheimer’s assisted-living facility, puts her hand on the arm of resident Catherine Peake, in Washington, Feb. 6, 2012. (Charles Dharapak/AP)

Alexis McKenzie, right, executive director of The Methodist Home of the District of Columbia Forest Side, an Alzheimer’s assisted-living facility, puts her hand on the arm of resident Catherine Peake, in Washington, Feb. 6, 2012. (Charles Dharapak/AP)

As we reported on Here & Now, this week brought news of a promising advance on Alzheimer’s disease: A study in the journal Nature that helps illuminate what goes wrong early on in the brains of people who get late-onset Alzheimer’s, the most common form. The researchers aimed to connect the dots between the gene APOE4, the strongest known genetic risk factor, and development of the actual disease.

Please read the Here & Now report for more detail, but for the bigger picture, here are some clear insights from Dr. Robert C. Green, a medical geneticist at Brigham and Women’s Hospital and Harvard Medical School. (To sum up in an adjective: Here & Now host Robin Young asked me if this was “great” news on Alzheimer’s; I only felt comfortable going as far as “promising.” Dr. Green takes it all the way to “exciting.”) His points:

It’s the kind of breakthrough we need to help us be smarter about the drugs that we take to multi-million-dollar clinical trials.

“What I think is the really exciting part of it is that, for nearly 20 years, we’ve known that APOE was a robust risk factor for Alzheimer’s disease, but we really didn’t  know why. And this paper is actually the first paper that begins to offer an answer as to why APOE4 is a risk factor at a molecular level. 

The way they did it is quite remarkable: They did it with gene expression profiles, a hot new area, and they found that certain genes were turned up or down by the APOE4,  and they were genes that appeared to regulate the production of the bad amyloid protein associated with Alzheimer’s disease. So the APOE4 didn’t directly influence the production of the amyloids; it seemed to regulate up or down these signaling genes, sort of like a cascade effect, to regulate some of the amyloid up and down. Continue reading

Study: Your Brain Makes Hundreds Of New Neurons A Day

(Digital Shotgun/flickr)

(Digital Shotgun/flickr)

This just in from the journal Cell: Your hippocampus, a key region for memory in your brain, makes a few hundred new neurons every day.

Does this mean you can now drink Tequila shots with impunity because you can more than make up for the brain cells you damage? Nope, no reason to think so. But the findings in Cell could have implications for future research in areas from antidepressants to Alzheimer’s disease.

Mainly, the new study helps cement the long-controversial claim that new neurons keep a-borning in the human brain all through life. And it does so in a creative new way, using carbon-14 left in humans by above-ground nuclear tests in the mid-20th century to measure the ages of brain cells.

I asked Prof. Joshua Sanes, director of Harvard University’s Center for Brain Science, to explain what the study could mean — why it matters whether our hippocampi keep making new neurons or not. His reply, lightly edited:

The basic dogma of neurobiology has been that you’re born with all the neurons you’re ever going to get, and then everything goes downhill from there.

But there was heated debate about this, and eventually, it was found in experimental animals that you do actually get new neurons throughout life — but weirdly, only in a few places. Where would depend on the species, but for mammals like us, it’s your olfactory bulb — what the heck that is about, nobody has any idea — and the other place is the hippocampus.

The hippocampus has proven to be critical to memory, and I’m not sure whether you’d say memories are stored there, but they certainly seem to be made there. You probably know about the famous patient HM: When he lost his hippocampus, he lost his ability to make memories.

So the idea arose that maybe if you’re making new neurons in the hippocampus, that’s to help you make new memories. In mice, there’s some evidence that favors that idea. I think nobody thinks it’s going to be as simple as that — that every time you need a new memory, you make a new neuron — but there are lots of experiments where they prevent the making of new neurons and somehow degrade memory in mice. And it seems that a lot of the things that a mouse does can affect how many new neurons are made, or at least how many of the new neurons that are made wire up.

One of those things is exercise: if you exercise more, you make, or keep, more new neurons. If you suffer a lot of stress, you make fewer neurons. Depression has been implicated; nobody knows how but there’s some idea that antidepressants can help you make new neurons, and if you’re depressed, you make fewer neurons.

So people have been interested in these new neurons, but nobody knew whether they were made in the human hippocampus, and this new study tells you that they are. Continue reading

Report: Alzheimer’s Cases Could Triple By 2050

In the not-too-distant future, Alzheimer’s will likely get very personal for many more of us as the nation confronts an “epidemic” of the progressive brain disease, according to a new report based on 2010 census data. Cases of Alzheimer’s could nearly triple over the next 40 years, researchers say.

Here’s USA Today on the study, just published online in the journal Neurology:

Numbers are projected to rise from about 5 million now to 13.8 million. The disease robs people of their memory, erases personality and makes even routine tasks like dressing and bathing impossible.

Ann Gordon/flickr

Ann Gordon/flickr

“We’re going to need coordinated efforts for this upcoming epidemic,” says lead author Jennifer Weuve, assistant professor of medicine at Rush Institute for Healthy Aging in Chicago. “People have trouble getting their heads around these numbers, but imagine if everyone in the state of Illinois (population 12.8 million) had Alzheimer’s. I look around Chicago and can’t imagine it…”

Researchers analyzed information from 10,802 black and white Chicago residents, ages 65 and older, from 1993 to 2011. Continue reading