The Tangled Neuron

What I've learned so far

When I first started looking for answers about Dad’s dementia, I focused on possible treatments to add to or replace Aricept, which I didn’t think was helping him.   As my list of possible treatments got longer and longer, I realized I was a bit naïve.

 

The Alzheimer Research Forum lists 51 drugs in clinical trials (although 15 of these trials have been discontinued).  That doesn’t include all the vitamins or supplements I’d read might help.   For each possible treatment, there are hundreds or even thousands of journal articles and abstracts describing various studies and trials.

 

Dad didn’t live long enough for me to get through my list.

 

Here’s what I've learned so far: 

• Many of the treatments available now are expensive, not very effective and have side effects.
•  The reason we don’t have effective treatments is that we still don’t understand what causes Alzheimer’s Disease and some other dementias.  You only have to skim through the 27 current hypotheses on the Alzheimer Research Forum site to see that there’s no consensus among scientists. 

It must be frustrating to be a neurologist.

Wigged out

My father’s wigs were a sort of shorthand for his sense of humor, and one of the ways he poked fun at himself.  The summer after my freshman year in college, I went home to Connecticut

to work in my parents’ retail lumberyard.  Several of my friends were also back in town, and I invited them over for brunch with my family.

“Hi Bones!  Hi Stretch!” Dad greeted each of them at the door, using nicknames he had given them over the years. “How do you like Providence College?  What are you up to this summer?”  He didn’t say anything about his dark sunglasses or the ill-fitting black wig that covered his mostly bald head, so neither did they.

          Over drinks on the back deck, there was still no mention of my father’s appearance.  He came out and poured himself a mimosa.   My guests were trying not to stare; I was trying not to giggle. “Do you like my new get-up?” he asked my friend Liz. “Uh – it’s great,” she replied. He laughed so hard he almost spit out his drink.  “I’ll bet you thought I was having a midlife crisis…”

Dad’s quirky sense of humor made our lives interesting.  One minute he would be talking with me about interest rates and measures of money supply, the next minute prancing down the stairs in my mother’s bathrobe and another wig.

His wigs were always perched on the front of his head, where researchers say the frontal lobes of the brain pull together signals from other parts of the brain to process and react to humor.  Are our personalities really just electrical signals in our brains?  And did the persistence of some of Dad’s sense of humor contain clues about the underlying causes of his dementia?

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.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Deaths in Aricept trial

Reuters is reporting that eleven patients have died during a clinical trial of Aricept for vascular dementia.  No patients receiving a placebo died. 

 

648 patients took Aricept during the trial; 326 took a placebo.

 

Thickened blood vessel walls probably caused Dad's microbleeds

“The question we were asked was ‘What was the etiology of the dementia?’” the pathologist took up where Dr. Fleming left off.  A slide showing a cross-section of Dad’s whole brain was up on the screen. I hoped Mom was OK, but was afraid if I looked at her, it would get us both upset.  I concentrated on taking notes, and tried not to think about it. 

“So here’s the brain - you can see the large hemorrhage on the right side.” I was relieved when he moved on to a slide showing a microscopic view.  He moved to the next slide and another pathologist spoke up.  “I looked at these slides with Joe.  This shows thickening of the vessel walls….” 

He launched into a detailed discussion of why it was hard to figure out what caused Dad’s blood vessel disease.

Fifteen minutes into the presentation, I started to see why the cardiovascular surgeon on the plane had warned me not to expect a lot of answers.    The pathology slides showed that Dad’s microbleeds were probably from thickening and degeneration of the walls of the small blood vessels in his brain.  But it wasn’t clear what caused that problem or whether the microbleeds caused his dementia.

Are all dementia autopsies so complicated?

At the neuroconference

Today, Mom and I sat down with twenty doctors around a conference table at Pitt Memorial Hospital in Greenville, North Carolina.  They were neurologists, neurosurgeons and pathologists from East Carolina Neurology and from the Brody School of Medicine at EastCarolinaUniversity.  All of us were here for Dr. Frank Fleming’s presentation of my Dad’s case.

One of the doctors gave us the handouts for the presentation – 85 slides!  I felt really good that Dr. Fleming had taken my questions on Dad’s dementia and his autopsy report so seriously.  But this was the first time I’d been back to Greenville and the hospital where Dad died, and if it was painful for me, it must have been worse for my mother.  We agreed that if she got upset, she would step out of the room, and I would stay and take notes. 

“OK, let’s get started,” Dr. Fleming said.  “Today I’m going to talk about microbleeds and discuss the case of a 73 year old gentleman who unfortunately died of a hemorrhagic stroke in November. Something quite unusual for these Neuroconferences – we have the family here today…”

                                                                                                                                          

The first few slides were about Dad’s medical history.  He started having problems finding nouns about four years ago.  By March 2004, he was having “minor trouble with arithmetic” and had difficulty drawing a clock.  Shortly before he died in 2005, he struggled to find any words, and was increasingly confused.

Tests showed my father had normal or low blood pressure, no thyroid problems, no “clinical stroke event.” His cholesterol was low, the arteries in his neck weren’t blocked, and he didn’t have the APOE4 gene associated with a higher risk of Alzheimer’s.  In short, there weren’t a lot of clues about what might have caused Dad’s dementia.

“But now we look at these images from his MRI in October 2005,” the doctor said.  “You see a dark area on the right side, a spot in the cerebellum here – all these hyperintensities are old hemosiderin deposits.”  He was telling us Dad’s brain had been bleeding for a long time.

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We just don't know much about the brain...

I’m learning a lot from my “seatmates” on this trip to meet with Dad’s doctors.  On the puddle-jumper flight from Charlotte to Greenville,  I sat next to a cardiovascular surgeon.  He had come to North Carolina from Wisconsin to learn how to use the new robot his hospital had bought for heart surgery.

“What brings you to Greenville?” he asked.  I told him I was looking for answers on my Dad’s dementia, and that his doctors were presenting the results of his autopsy. 

“Don’t expect a lot of answers,” he warned me.  “We just don’t know much about the brain.”

“But I thought you could get a definitive answer about whether someone had Alzheimer’s by looking for plaques and tangles in the brain during an autopsy.”

“Well, the problem is that when you do an autopsy, you see the endpoint, but you don’t see the process.  The endpoint might look the same for a lot of different diseases.”

“Hmm, so maybe Dad’s autopsy would show plaques and atrophy whether he had Alzheimer’s Disease, vascular disease, or something else?” 

“Yes, possibly, but I’m not a neurologist.”  I got the feeling he was happy to be working on hearts rather than brains.

My grandmother had a stroke too...

Dr. Fleming asked me to investigate my grandmother’s medical history to see if she had the same type of hemorrhagic stroke Dad did.  Her name was Amalie and she came from a very wealthy family in New Britain, Connecticut. 

She fell in love with my grandfather in high school, and married him despite her family’s objections about his poverty.  They lived next door to us when I was young, and I have a lot of fond memories of time spent with them.

In her early 70’s, my grandmother was still working as a home health aide, and was very sharp.  But in her mid-70’s, she was sometimes confused, and then had a major stroke when I was away at college.  No one in the family seems to know what kind of stroke it was, so I’ve sent for a copy of her death certificate and will try to get a copy of her medical records from the hospital in Connecticut where she was treated for her stroke.

I invited myself to a presentation on Dad's case

Dad’s neurologist, Dr. Fleming, called today.  “I want you to know we’re still working on your questions about your Dad’s autopsy.  We’ve gone back to the pathologist to try to get some answers, and I expect they may have to go back and do some stains on tissue and so forth.   I don’t know when we’ll have the results.”

 

“I remember that your Dad’s mother died of a stroke,” he continued.  “Do you know if it was a hemorrhagic stroke?  If there’s anyone still alive you can talk with to find out, that would be very interesting for us to know.”

 

I promised to try to get more information for him.

 

“The microbleeds your Dad had are so interesting that we plan to discuss his case – without using his name, of course - at our Neuroconference sometime in March.  Most likely I’ll be presenting the pathology slides myself.”

 

“Would it be possible for me to attend this conference and listen to your presentation?” I  asked, half expecting him to say he’d rather I wouldn’t.  “Yes, that would be fine,” he answered. “I’ll let you know when we schedule the presentation.”

 

I’m really excited about this – maybe now we’ll start to get some answers about what caused Dad’s dementia!