The Tangled Neuron

Lewy Body Dementia: Hard to Diagnose

Harry Lewis was diagnosed with Alzheimer’s when he was 59.  Along with his problems with memory and thinking, he began to have hallucinations.  “Other people’s hallucinations are about small children, or maybe money,” his wife Sue says, laughing.  “My husband kept seeing a naked blond in the living room.” 

Harry’s doctor prescribed Zyprexa, an antipsychotic medicine, to control the hallucinations.  It seemed to work, but then Harry had two grand mal seizures in four days.  This kind of extreme sensitivity to antipsychotic medications is a symptom of dementia with Lewy bodies (DLB), and is one of the criteria doctors use to diagnose the disease.  On Harry's 60th birthday, his diagnosis was changed from Alzheimer’s to DLB.

Joseph Friedman, MD

It’s not unusual for people to be diagnosed with another dementia before getting a diagnosis of dementia with Lewy bodies.  In Part 2 of the Tangled Neuron series on Lewy bodies, Joseph Friedman M.D., Director of the NeuroHealth Parkinson's Disease and Movement Disorders Center in Warwick, Rhode Island and member of the Lewy Body Dementia Association Scientific Advisory Council, talks about why it’s so hard to diagnose this disease. 

Lewy Body Dementia: One Couple's Story

Twenty-some years ago, Sue Lewis gritted her teeth and walked into the VFW (Veterans of Foreign Wars) bar in her rural West Virginia town. It wasn’t her kind of place, but she had to pick up a girlfriend there because they were going to the movies.

Harry Lewis spotted her from across the room, and decided he wanted to get to know her. He bought her a drink. Not long after, they were married.

Harry and Sue Lewis

“On the surface, we were opposites,” Sue says. “He quit high school to go into the Navy, and he has very traditional values. I have a master’s degree in social work and am an old hippie. I grew up in Michigan in a house with six bathrooms; he grew up in West Virginia and had an outhouse. But I figured out, hey, this guy is intelligent – he stretched my thinking. We fed each other intellectually. We were so interesting to each other.”

Beyond Drugs: Other Ways to Treat Alzheimer's and Dementia (Part 4 - Pyschosocial Risk Factors in African-Americans)

Summary:  The level and effect of psychosocial risk factors for Alzheimer's may not be the same for African-Americans and Whites.  This could mean we need different methods to prevent, diagnose and treat cognitive problems in African-American and White populations.  Large-scale studies are needed to confirm this finding.

Alzheimer's is equal opportunity and color blind, right?  Well, not exactly.  We already know that some risk factors, such as diabetes, are more common among African-Americans.  And we know that other risk factors, such as the APOE4 gene variation, may affect African-Americans differently than Whites.  But what about psychosocial factors such as emotional states or the strength of social networks? 

Lisa Barnes, Ph.D.

Dr. Lisa Barnes gave a presentation on "Psychosocial Factors and Cognition in African-Americans and Whites" during the "Psychosocial Issues and Neuropsychology" session at ICAD 2008.  Dr. Barnes, who is Associate Professor of Neurological Sciences and Behavioral Sciences at the Rush Alzheimer's Disease Center, sent me some additional information via email to round out my understanding of her work.

The data she presented at ICAD was from participants in three large, ongoing studies at Rush:  the Chicago Health and Aging Project, the Memory and Aging Project and the Minority Aging Research Study.  In these populations, she and her colleagues (including Dr. Robert Wilson) have found the following differences in the level of psychosocial risk factors between the two races:

• African-Americans are more likely to experience negative emotions or distress than Whites
• African-Americans tend to experience more depression than Whites
• African-Americans report lower levels of social engagement than Whites. 

A Quick and Easy Biomarker for Alzheimer's?

Summary:  A new method of visually assessing shrinkage of certain areas of the brain using standard MRIs may improve the diagnosis and treatment of Alzheimer's.

ICAD was all about biomarkers.  Biomarkers are physical or biochemical characteristics that are signs of an ongoing disease process in a living person.  They include genetic variations, molecules in blood or spinal fluid, and patterns seen on imaging tests.  To be useful in screening for a disease or monitoring the progress of a disease, they should be easy to obtain.  This typically involves collecting blood, urine, stool or saliva samples, or performing a radiological test. The use of biomarkers for certain diseases is well-accepted - for example, blood tests are used to indicate the presence of certain cancers or the risk of heart disease.

But for Alzheimer's, diagnosis is currently based on neuropsychological tests and medical histories showing cognitive impairment.  Brain scans (MRI and CT scans) are not typically used to diagnose Alzheimer's, but instead are used to exclude other conditions that can cause cognitive problems.

Speaker after speaker at ICAD explained that we need biomarkers to:

• diagnose [and eventually treat] Alzheimer's in early stages, perhaps even before symptoms appear

• diagnose Alzheimer's more accurately, at any stage

• measure the effect of drugs on disease progression in clinical trials.

This concept sounds good, but there are practical problems:

• studies have not yet confirmed the accuracy of many of the biomarkers proposed; a high percentage of false positive results seems possible

• new technologies to measure potential biomarkers like amyloid protein in the brain are expensive and not yet available outside of research facilities

• some studies have shown that the levels of certain proteins in spinal fluid may be an accurate biomarker, but the required spinal tap is unappealing to many patients.

Ranjan Duara, MD

Dr. Ranjan Duara, Medical Director of the Wien Center for Alzheimer's Disease and Memory Disorders in Miami Beach, Florida and Associate Professor of Medicine, Neurology and Psychiatry at the University of Miami, thinks we already have a biomarker that is accurate, inexpensive and doesn't require drawing spinal fluid.  He has developed a system for visually measuring and rating the atrophy, or shrinkage, of three areas within the medial temporal lobe of the brain.  He and his colleagues recently completed a study showing that this method can help differentiate among people who are cognitively normal, those with Mild Cognitive Impairment and those with Alzheimer's.  The study also showed that this assessment can help predict which patients will progress from Mild Cognitive Impairment to Alzheimer's.

My Brain Age is 80: Cognitive Testing

Summary:  Cognitive Drug Research Ltd. plans to offer web-based cognitive testing to individuals.  A poor result on this test might encourage someone to seek further testing, or try to improve his overall health.  But I'm not sure what my own score means in terms of everyday life, or whether the commercially available brain fitness programs would improve my score.

My brain age is 80, at least according to the test posted on Portfolio.com.  To find out why I scored thirty years older than my actual age, and what it might mean, I contacted Cognitive Drug Research Ltd. (CDR), the company that developed the test.

"This is the attentional subset of our cognitive test system," said Professor Keith Wesnes, CEO of CDR.  "The attention tests measure your ability to focus, process information and sustain attention.  While memory loss is the classical symptom of the dementias, our research has shown that poor attention is an important deficit in Alzheimer's disease as well as memory loss, and that in other types of dementia, for example Lewy Body Dementia and Parkinson's dementia, it is one of the central deficits."

Imaging with Pittsburgh Compound-B (PIB) – An Amyloid Surprise?

New imaging techniques have shown that many cognitively normal elders have as much amyloid protein (thought by some to cause Alzheimer’s) in their brains as do people diagnosed with Alzheimer’s. Does this mean that these cognitively normal elders are on the brink of developing Alzheimer’s, or does it mean that the amount of amyloid in the brain doesn’t always correlate to the amount of memory loss?

The Alzheimer Research Forum has now posted three parts of a four-part report from the Human Amyloid Imaging Conference. Their report covers the mixed results from studies using evidence Pittsburgh Compound-B (PIB) imaging of amyloid, and the potential effect on early diagnosis and clinical trials.

CADASIL: Young Onset Dementia Caused by a Stroke Disorder

Summary: CADASIL is a type of stroke disorder that can cause young onset dementia. Two web sites have been developed by women whose families are affected by the disease.

Billie Duncan-Smith’s husband Steve’s first symptom came when he was 38. He woke up with an excruciating headache, and started vomiting because the pain was so bad. Over the next few years, he would suffer many such migraines, some lasting for several weeks. An MRI of his brain showed a high number of white matter lesions, but Steve’s doctors weren’t sure what was causing his headaches.

Billie and Steve in 2004

While Steve suffered, Billie searched the internet and contacted medical experts all over the world. She sent his records and test results to those who offered to help. Finally, someone at the U.S. National Institutes of Health called her to suggest Steve might have CADASIL (Cerebral Autosomal Dominant Arteriopathy with Sub-cortical Infarcts and Leukoencephalopathy), a type of stroke disorder.

The Myth of Alzheimer's?

We seem to be rethinking everything right now - the energy we use, the pollution we create, the foods we eat. Peter Whitehouse, a prominent Alzheimer’s researcher and doctor, is also rethinking the disease we call late onset Alzheimer’s.

In his new book, The Myth of Alzheimer's: What You Aren't Being Told About Today's Most Dreaded Diagnosis, written with Danny George, Dr. Whitehouse questions just about everything we think we know about Alzheimer’s and memory loss. Their book comes at a time when I’ve started to rethink my late father’s dementia after two years of blogging about Alzheimer’s research.

Detecting Alzheimer’s and Other Memory Disorders Before Symptoms Appear: The FDDNP-PET Scan

Summary: PET scans using a compound called FDDNP show promise for detecting Alzheimer’s and other neurodegenerative diseases before symptoms are apparent. If follow-up studies confirm the accuracy of this imaging technique, researchers will be a step closer to the vision of early detection and treatment to delay progression.

When my father complained about memory problems, his family doctor told him there was nothing wrong.

Dreaming About A Cure, Talking About Care: Part 4 of 4 - New Ideas for Care and Cure

Whether we view Alzheimer’s as a disease, or as part of aging, most of us know from personal experience that the way we deal with it is terribly inadequate. In the past three posts, I’ve written about the growing recognition that Alzheimer’s isn’t a single disease, and the controversy about whether we should spend our limited resources on trying to find a “cure.”

Maybe if we give up our fantasies of a single “cure” for Alzheimer’s, we can start talking about better ways to view and treat dementia. These discussions have already begun in labs, at conferences, on email lists, and in homes around the world. While preliminary, they provide us with a glimpse of how Alzheimer’s care might look in the future.

Dr. Peter Whitehouse’s work is an example. Earlier in his career, he focused on drug development. Now he’s more interested in prevention and in intervention studies aimed at improving quality of life for dementia sufferers.

“We need to re-evaluate what’s important,” he says. “Regardless of cure, care needs more attention. Trying to find a cure is part of caring, but there’s an imbalance. We have a great obligation to think clearly about the condition, then do things to improve it. We need to think about ethical considerations – for example, there are still children whose brains are being damaged by lead. Addressing this problem is important for future generations. And instead of focusing on degeneration, we should be focusing on renaissance and legacy.”

Dr. Whitehouse’s recent work includes research on using electronic aids for reminiscence therapies (LifeBook) and archiving individual stories of people’s experiences with disease (including dementia) and medical treatment (StoryBank). His main intervention studies will be at The Intergenerational School, a Cleveland public school serving learners of all ages. He founded the school with his wife Catherine. “The IG school represents one way of pulling it all together,” he says. “Purpose, a sense of community, remaining cognitively active, leaving a legacy, being engaged and valued - these things are much more important to quality of life.”

In labs and at conferences, other scientists are discussing new approaches to Alzheimer’s research, such as more accurate “sub-typing” for identifying different types of dementia, and focusing on investigating potential causes of dementia other than beta amyloid. I’ll write more about this in another post.

And within DASN, members are talking about how to improve care:

- “I think the 'person-centered' model is the ideal for both the care partner and the person with dementia. Each of us has different needs, so no care plan would suit even the majority of folks touched by this disease.” (Shirl Garnett, western Australia, diagnosed with early onset dementia at 59)

Shirl Garnett

- “The mind-body-spirit approaches developed by new age physicians to address those other diseases must be brought to bear on AD. Further, I believe that new era medicine - consciousness and healing - could inform the research being done in the AD research centers and private laboratories.” (Jay Smith, California, diagnosed with early onset Alzheimer’s)

- “Services in the form of support for caregivers and those of us with dementia can often be provided in part by volunteers. I am convinced that there are many more volunteers who are qualified and would contribute if given the opportunity.” (Charley Schneider, Missouri, diagnosed with early onset Alzheimer’s)

- “I think that the key to finding a better medication for treatment and possibly a cure lies in the minds (no pun intended)of those that ARE diagnosed in their 30's, 40's and 50's. If they were open to allowing us to be a part of research in clinical trials I personally think that this would speed up the process for their goal of a cure. So, so many of us work so diligently with great urgency to make this happen as we don’t have the time that the associations and researchers do to plan this all out as our time is running out. Why not focus on those under 50? They might be surprised how much money is saved in research if they would just broaden their horizons so to speak.” (Tracy Mobley, Missouri, diagnosed with early onset Alzheimer’s disease at the age of 38)

Tracy Mobley

- “What makes the best sense of all is empowering people with dementia to care for themselves as much as possible and for as long as possible. People with dementia absolutely can learn some things far into the disease. I truly believe that people with early dementia can be taught to better understand and manage their own disease and behaviors. I further believe that a society which allows people with dementia to stay involved in their chosen activities also prolongs life and emotional health.” (Carole Mulliken, Missouri, diagnosed with vascular dementia)

Dr. Whitehouse sees hope in this kind of open-minded discussion. “If we can think through Alzheimer’s in a deeper way, will have insights into how the brain works. Underneath Alzheimer’s is a re-thinking about what it means to be human, and science’s role in society.”

Dreaming About A Cure, Talking About Care: Part 2 of 4 - More Care, Less "Cure"?

In my last post, I wrote about how researchers are beginning to question whether Alzheimer’s is really one disease. A different view of the definition of Alzheimer’s naturally leads to a different view of what we should do about it:

1. If Alzheimer’s is a disease, we need to continue to try to find the cure for it.

2. If Alzheimer’s is cognitive dysfunction caused by multiple aging-related conditions, we should shift our focus to steps we can take to prevent those conditions.

Dr. Peter Whitehouse, Professor of Neurology at Case Western Reserve University, is one of those who holds the second view. Because he doesn’t think Alzheimer’s is a single disease, he believes it’s unlikely that researchers will find a “cure.” He’s concluded we should focus resources on care and services for people with cognitive impairment, and on prevention, rather than searching for a “magic bullet” cure. “Care needs to be dominant over cure,” he says.

Richard Taylor, a retired psychologist, DASN member and author of the book Alzheimer's from the Inside Out, was diagnosed three years ago with dementia. He agrees there should be a shift in funding.

Richard Taylor, Ph.D

“This disease creates turmoil in 99.9% of the families who are dealing with it,” he says. “While ‘bench’ researchers run around chasing their molecular tails, people who are living with the disease as carers and carriers battle with themselves and each other.

When will more attention be paid to this real problem and less to the conditions of nude mice? I realize both areas need research, lots of research. In the mean time millions of people are struggling with the psycho-social consequences of the disease.

The vision of a world without Alzheimer's is compelling. Shouldn't the cries for help from people confronting it be just as compelling? There needs to be a more equitable split in research dollars between tomorrow's and today's issues.”

As I think through the care versus cure question, I wonder what a decision to shift resources away from research would have meant for my dad, whose cerebral amyloid angiopathy (CAA) caused microbleeds in his brain that led to his dementia and death. I don’t think the preventative measures we talk about now (healthy diets, exercise, staying engaged, etc.) would have made a difference for him. Basic research into the causes of and treatments for CAA and Alzheimer’s would have helped him more.

But in the last few years, research facilities have been forced to delay Alzheimer’s-related experiments and lay off scientists because they can’t get funding. With money already scarce for Alzheimer’s research, do we really want to shift resources from cure to care?

Lisa Genova, the neuroscientist and author mentioned in my earlier post, doesn’t think so. “As a neuroscientist who understands the biology of this disease and as someone who knows the researchers who are driven and dedicated to finding a cure, I honestly believe that a cure for this disease is within grasp, and to take funding away would be a crazy, horrific mistake,” she says.

Jeanne Lee, a DASN member living in Hawaii, and author of the book Just Love Me: A Life Turned Upside-down by Alzheimer’s, doesn’t want research funding reduced, but would like to see it redirected. “I do agree too much money is spent on the later stages of Alzheimer's or dementia,” she says. “The research monies need to go towards the other end of the disease when WE are still capable of knowing what is happening in our lives. We have medicines for early stages of cancer, diabetes and other diseases, and sometimes they’re caught early enough to be cured. This is what we need for Alzheimer’s and dementia, so why would you say research is not necessary?” Jeanne was diagnosed with dementia of the Alzheimer’s type in 1995.

Jeanne Lee

Many scientists agree with Jeanne that research must focus on stopping dementia long before onset. Dr. Whitehouse has specific ideas of how we should address research on early medical interventions. “I’d prefer to see research on healthy aging, and understanding the value of basic preventative measures, such as physical exercise,” he says. “Many of these measures are good for a lot of things besides Alzheimer’s, so the money would be better spent.”

On this aspect, Jay Smith, another DASN member mentioned in my last post, agrees with Dr. Whitehouse. “More research should be done to identify and isolate the various environmental and lifestyle causes of the disease - diet, nutrition, life style, stress, genetics, environmental toxins, etc. - as has been done in diabetes, heart disease and cancer over the past twenty years,” he says.

Wrong Question?

Other DASN members don’t like the care versus cure question. Carole Mulliken, a former teacher and school counselor diagnosed with vascular dementia at 59, says that, “…in most cases, framing a question in ‘either or’ format guarantees a false conclusion. To tie ourselves up in deciding which of the two is more important eliminates the possibility of putting energy in to multi-faceted responses.”

Carole Mulliken

Chuck Jackson another DASN member who has been diagnosed with early onset dementia agrees. “If we have a medical cure,” he says, “or medical treatment that stops progress of the disease in early stages, then we won’t need expensive care facilities after a certain amount of time. The bottom line is how to facilitate both care research and medical research.”

Richard Taylor feels the same way. “It's the wrong question to ask. The crucial question is why are there so few dollars that a choice has to be made. It's tragic, it's irresponsible, and everyone should be ashamed and angry we all aren't doing more to address the consequences of this plague.”

But if the current trend of reduced government spending for Alzheimer’s research continues, and private donors don’t step up with more donations, we’ll have to make a choice between cure and care.

Dreaming About A Cure, Talking About Care: Part 1 of 4 - Is Alzheimer's Really A Disease?

Last night, I dreamed Dad was getting better. He called to say he was back home, and sounded upbeat. He was finding words more easily than when we last had talked. I immediately started thinking about things we could do to speed his recovery: green tea, meditation, maybe even a little red wine. More than a year after Dad died, I'm still dreaming about a cure.

I'm not alone in my dreams. "I really thought that we would have a cure before I had to worry about onset. I was terribly wrong," says Chuck Jackson, a former employment counselor whose mother and nine of her siblings had early onset Alzheimer's. Four of his cousins have died of the disease, and how he, his brother and three of his cousins have been diagnosed with it.

This talk of a cure is echoed around the world in hundreds of labs and millions of homes. But I don't think we're anywhere close.

If you are diagnosed with Alzheimer's today, your doctor may prescribe Aricept, Namenda or other medicines. The most these drugs will do is delay symptoms in some people; they have no effect in others. Treatment won't change the underlying degeneration of your brain, or halt progression. If your family can't care for you, there's little chance you'll get good care in a nursing home, at least in the US.

This bleak reality has prompted Chuck Jackson and other members of the Dementia Support and Advocacy Network (DASN) to speak out about Alzheimer's. The majority of DASN members are persons with dementia or their care partners. Individual members of the group are working with organizations, the media and lawmakers to raise awareness about Alzheimer's.

"If doctors themselves would be more aware, I think they'd find there are a lot more afflicted with Alzheimer's disease than they realize," says Sarah Christianson, a DASN member and former office manager diagnosed with early onset Alzheimer's and frontotemporal dementia.

Sarah Christianson

But Dr. Peter Whitehouse advocates something different: a complete redefinition of Alzheimer's and how we treat it.

Dr. Whitehouse is Director of Integrative Studies and Professor of Neurology at Case Western Reserve University, and author of the forthcoming book The End of Alzheimer's [St. Martin's Press]. He is one of several scientists and doctors who have mentioned to me that they don't think Alzheimer's is a single disease.

Peter J. Whitehouse, M.D., Ph.D

"People suffer enormously from what I used to call Alzheimer's," he says. "But as a clinician, I'm aware of the variability of dementia symptoms and progression, so I'm suspicious of the claim that this is one disease and that it's different than aging."

Expressing doubts about Alzheimer's status as a disease is controversial, both among researchers and among persons with dementia. "Terribly wrong-headed," says Jay Smith, a DASN member from California who is working to organize a conference for people with dementia. "That kind of thinking (simplistic, not based in reality) is just dangerous." Jay was forced to leave his job when he was diagnosed with early onset Alzheimer's.

Jay Smith

Lisa Genova, another DASN member, neuroscientist and author of Still Alice, a novel about a fifty-year-old cognitive psychology professor diagnosed with Alzheimer's. "This IS a disease," she says, "œand not just a normal part of aging."

"Alzheimer's doesn't just happen to people in their 70's and 80's; it happens to people in their 40's & 50's and younger," says Jaye Lander, a Pennsylvania-based former Wall Street executive diagnosed with early onset dementia of the Alzheimer's type. "I turned 60 on Thanksgiving but have had brain tissue atrophy visible in MRI's for several years. As long as our brains start disintegrating on us in our primes, I think it is a terrible disease and not just a normal function of aging."

Many researchers assume early onset and late onset Alzheimer's disease are similar, but Dr. Whitehouse's comments were not meant to address early onset Alzheimer's. "Of course, if people are getting it in their 40s and 50s, it's hard to say that's aging. It's more reasonable to call what these people are suffering from a disease," he says.

He is much less certain about whether late onset dementia is really one disease. "As a clinician, I now avoid using the word Alzheimer's," Dr. Whitehouse says. "But what do I put on a billing form, and what do I say to a patient? The answers are more complicated than we like."

Cerebral Amyloid Angiopathy and Alzheimer's Disease: Dad's Double Burden

     Five years after Dad first had memory problems, we're starting to understand what caused his dementia.  Seven months after he died, we know what caused his hemorrhagic stroke.  I'm both relieved and sad to have a diagnosis.

     Last week I got a report from the Neuropathology Lab at Massachusetts General Hospital, where we sent some of Dad's brain tissue.  The report says he had severe cerebral amyloid angiopathy, or CAA.  In people with CAA, a destructive protein is deposited on the walls of the blood vessels in the brain. The protein causes the vessel walls to crack, allowing blood to leak out.  Every hemorrhage, large or small, damages brain cells and can cause dementia, difficulty speaking, or even paralysis.  Some CAA patients, like Dad, die of these hemorrhagic strokes.

     In a way, it's a relief to know that researchers don't yet understand what causes CAA, or how to treat it.  As Dad's memory problems slid into full-blown dementia, I felt like there was an answer, but we just couldn't find it.  This diagnosis means no one - not me, not my family, not his doctors - could have done anything to help him, no matter how hard we tried.

     My father also had a "moderate number" of the plaques and tangles characteristic of Alzheimer's disease in some areas of his brain.  According to the neuropathology report, these "contributed to his neurologic difficulties."  It's sad to think about him entangled by both Alzheimer's and CAA.

     On my birthday last year, Dad stayed on the phone with me longer than usual.  It was hard for him to find words, but he wanted to talk.

        Dad, Beau and Mom

     "Things are different here now," he said.  "But when I nap, Beau [their dog] stays with me.  He climbs up on me so I feel better. And Mom and I still push on each other [give each other backrubs], so that's good."

     "You've got a lot of good things, Dad."

     "Yes.  Hi from me to you...happy birthday," he said.  "I'm still older than you are!"

     Struggling under the double burden of CAA and Alzheimer's, Dad kept both his gratitude and his sense of humor.

The APOE Gene, Alzheimer's and Dementia

     Going through the thick folder containing Dad's medical records, I found the results of a genetic test:

Apolipoprotein E Genotype:  2 and 3.  Interpretation:  This individual does not possess an apoe 4 allele.  This result does not indicate whether this individual's dementia is due to Alzheimer's disease or other cause of dementia.

     The APOE or apolipoprotein E, gene makes a protein that carries cholesterol and other fats through the blood to be processed.  The three common variations of this gene are called e2, e3 and e4.  Everyone has two copies of this gene; Dad had one e2 and one e3 copy.  If you have one or two copies of the e4 variation, you may have a somewhat higher risk of developing Alzheimer's disease.

     But the connection between the APOE gene and Alzheimer's is not very strong.  Some people who don't have the e4 variation have Alzheimer's, and some people with Alzheimer's don't have the e4 variation.  My father didn't have the e4 variation, but still developed dementia.  The e2 variation he had is actually associated with a lower risk of developing Alzheimer's disease in some studies.

     The APOE gene may also influence the age at which people develop Alzheimer's.  People with the e4 variant who have Alzheimer's tend to develop it at a much earlier age than those who have Alzheimer's but not the e4 variant.  Even this influence is weak - in an article published in The American Journal of Human Genetics in 2000, researchers estimate that only 7 to 9% of the age of onset of Alzheimer's is explained by the e4 variation.

     Dad did not have the gene variation associated with higher risk of Alzheimer's

     Because the connection between the APOE gene and Alzheimer's or dementia isn't very strong, environmental factors and/or additional genes must play a role in determining whether someone develops dementia, and at what age.  The search for other genes involved with dementia is an intimidating task.  An overview of presentations at a recent conference on Alzheimer's notes that the AlzGene database of studies on genes and Alzheimer's contains information on over 300 candidate genes and 800 common variations.  So far, no one has found another gene that plays as significant a role as APOE.

     It could be a combination of genes determines whether or not someone will develop dementia.  For example, a study of 180 Alzheimer's patients and 120 non-demented volunteers identified three different gene combinations, each of which appeared to increase the risk of developing Alzheimer's by 800 percent for study participants.

     The US National Institute on Aging is sponsoring ongoing research to identify genes involved in Alzheimer's.  The study is recruiting siblings, at least one of whom must have been diagnosed with the disease.

     If the link between genes and dementia were better understood, genetic tests could be used to predict, diagnose and maybe even treat Alzheimer's and other dementias.  In the meantime, the association between the APOE gene and Alzheimer's isn't strong enough to be useful.  Testing for the e4 variation of the APOE gene didn't help us understand Dad's dementia at all.

Can loss of sense of smell predict Alzheimer's?

My father always hated chocolate, and so did I. No Snickers bars or chocolate chip cookies for us. Then at Christmas two years ago, Dad ate a piece of chocolate cake. “This is great,” he said happily as I watched in amazement. Mom later told me he had become less picky about what he ate.   She didn’t think he had much of a sense of smell left either.

I hadn’t given this much thought until I saw the March 22nd post on Brainblog about a Rush University Medical Center study that showed “impaired odor identification in old age is associated with impaired global cognition and more rapid decline in perceptual processing speed and episodic memory.” The blog’s author, a neuropsychologist named Anthony Risser, suggested I contact the University of Pennsylvania’s Smell and Taste Center for more information on how loss of the sense of smell may be related to Alzheimer’s and other dementias.

Richard Doty, PhD is a Professor at the University’s School of Medicine and Director of the Center. He co-authored a recent article about a study in which a brief 10-smell test was effective in predicting whether patients with “mild cognitive impairment” would develop Alzheimer’s Disease.

 

 

 

Richard Doty, PhD

 

Why are sense of smell and cognitive decline linked? “There is no consensus as to the reasons for the smell loss in AD [Alzheimer’s disease],” Dr. Doty says, “although AD-related neuropathology does show up relatively early in such structures as the olfactory bulb and anterior olfactory nucleus.”

Just because Dad couldn’t detect odors very well didn’t necessarily mean he had or would develop Alzheimer’s. Many factors, including illnesses other than Alzheimer’s, habits such as smoking, and even normal aging can diminish our ability to smell. So smell tests can’t be used to diagnose Alzheimer’s or other dementias, but they could be useful for identifying patients whose mild memory problems may develop into more serious dementia.

When Dad first complained of memory problems several years ago, I don’t think any of his doctors asked him about his sense of smell. I looked at the American Academy of Neurology practice guidelines for early detection of dementia and also at an American Academy of Family Physicians publication about early diagnosis of dementia . Neither document says anything about smell tests.

I asked Dr. Doty why doctors wouldn’t routinely use these tests for preliminary dementia screening. I wondered whether the tests are too expensive or time-consuming. It turns out Dr. Doty is involved with Sensonics , a company that manufactures smell test kits that could be used to screen for likelihood of developing dementia. “The 12-item test takes about 5 minutes,” he said.  “The cost of this test is $12.95 and it would seem to me reasonable for screening purposes.  But despite a relatively large literature on olfaction in the prediction of AD, there are few clinics that use such testing.”

Dr. Doty is sending me some smell kits so I can see what the tests are like. I’ll write more about this topic once I’ve tried them out.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

The Eye Exam Every Dementia Patient Should Have?

 

After reading that problems with blood vessels in the eye might be a sign of similar problems in the brain, I asked Mom to get Dad’s eye exam records.

A study published in the January issue of Stroke showed that for people with high blood pressure, abnormalities of the blood vessels in the eye are associated with small strokes that can be detected only with an MRI . Patients and their families might not notice any one of these strokes, but the combined effect could cause dementia.

These same abnormalities may mean a patient has a higher than normal risk of having a stroke (see http://www.thelancet.com/journals/lancet/article/PIIS0140673601062535/abstract - this requires free registration to The Lancet).

My father did not have high blood pressure, but because his autopsy results had tentatively shown “hypertensive arteriosclerosis” (thickening of the blood vessel walls associated with high blood pressure),  I thought it might be helpful to know if the blood vessels in his eye showed any problems.

Tien Wong, MD, PhD is co-author of the new study in Stroke and the two other studies I linked to above. He sent me this photograph below as a sample of the retinal blood vessel disease an eye doctor might see. The red spots are retinal hemorrhages and aneuryisms, he explained, while the yellow spot indicates a mini-stroke.

 

Retinal photograph courtesy of Tien Y Wong, MD, PhD, Centre for Eye Research Australia, University of Melbourne

It turns out that the blood vessels in Dad’s eyes were normal. I’m not sure if that would lead his neurologist to suspect my father’s microbleeds were not caused by hypertensive arteriosclerosis. Either way, I would think anyone with dementia would want to ask his eye doctor to check for signs of retinal blood vessel abnormalities, and report the results to his neurologist and other doctors.

 

 

 

 

 

 

 

 

The MRI every dementia patient should get?

At the neuroconference, Dr. Fleming put up a slide of images from Dad’s MRI. He pointed to several small dark spots.

 

 

 

 

 

 

 

 

“When we look on the T2* GRE sequence, we can clearly see microbleeds. But you have to do the correct MRI sequence to detect these bleeds! The GRE or Gradient Refocused Echo takes only an extra 45-55 seconds.”

“I went to the American Society of Neurological Imaging meeting this weekend, and kind of had a bee in my bonnet about this.” He then went through several slides on technical aspects of MRIs. “At every coffee break, I talked with my colleagues about it. Turns out at some centers, every brain gets a GRE, but at many top centers, they don’t routinely do it. When I asked why they don’t, people shrugged. ‘Well, if we find them, what are we going to do,’ they asked. I say, if we don’t find out what’s going on first, we can’t figure out what to do.”

“A sizeable part of the population will have these bleeds,” Dr. Fleming pointed out, bringing up a slide referring to studies showing an estimate 3-12% of various populations have microbleeds. The older you get, the higher the risk, according to this research.

It seemed to me he made a good point about the importance of documenting the microbleeds, even if there’s no treatment yet. Maybe some patients with “probable Alzheimer’s” diagnoses have dementia caused by microbleeds. And maybe there are certain prescription and over-the-counter medicines that should be avoided or used with caution for these patients. I’ll try to find out whether there are any guidelines about this.