I was saddened to learn that we have lost two colleagues who encouraged dementia researchers to think outside the box.
Dr. Dale Schenk wowed us in the mid-1990s with his Kodachrome(!) slides documenting the effect of the “mouse vaccine” against amyloid plaques.
Dr. Allan Roses helped keep NON-amyloid causes of Alzheimer’s disease on our radars.
Apologies, just discovered this in my drafts box, awaiting post since the Toronto AAIC meeting.
The Memory Clinic at the Jewish General Hospital/McGill in Montreal has begun to study patients with PPA who receive the intervention repetitive transcranial magnetic stimulation (rTMS). The presenter, Dr. Carlos Tyler Romero showed a before and DURING treatment video that evidenced remarkable effects. Improvement in naming illustrated items was sustained for two weeks. Caregivers reported better albeit variable spontaneous engagement in conversation. I’d like to see data from more participants before fully endorsing this modality, but I have been hoping for good news like this since my last post on the topic.
The effect shown on the video was surprising, but even less expected was that the researchers at McGill are aiming at a part of the brain that is not the most obviously affected. The parietal lobe was the target, a bold choice that makes sense because of its position in the speech production network, but certainly not the inferior frontal lobe that is more visibly shrunken in non-fluent/agrammatic PPA.
I definitely will keep an eye peeled for more data from this group to round out the several types of PPA on which they’re doing the test.
My favorite AAIC plenary lecture was delivered by Dr. Jane Ann Driver at Brigham and Women’s. She explained to us how recognizing that the multifaceted approach to finding a cure for cancer is not at all being pursued for AD motivated her bold mid-career shift from oncology research to AD research. See one of her papers here. In it, she begins her exploration of how cancer may protect against AD (not just by taking people when they’re too young to have dementia) and how some mechanisms in AD may have anti-cancer effects.
Whereas cancer research is being approached from many many angles, there’s relatively little is going on in current AD research! (I’m sorry I couldn’t post her slides here, but suffice to say 2 orders of magnitude less going on in AD.)
Funding for AD research is one reason for this wheel not having many spokes. At a separate presentation, I learned from the leaders of the National Alzheimer’s Plan Action that whereas AD research will hope for $2bil annually, cancer research receives $30bil. That’s a lot more zeroes.
…an opportunity to let your politicians know what’s important to you
Tune in to http://act.alz.org/site/PageServer?pagename=federalpriorities for some suggestions as to which policies to support dementia research or caregiver support you could call to your presidential candidate, senator, and congressperson’s attention.
image from 23andme
It’s hard not to wonder if there’s something genetic that is or will be running in the family after a blood relative is diagnosed with a dementia.
Start with the genetics counselor at the genetics clinic. We’re often so intent on finding out the results that we forget that the WRONG person finding out the results can have devastating consequences. The genetics counselor should go over two aspects of the testing from the outset:
- the rationale for ordering testing – it’s expensive, and not all cases warrant the testing! If you’re gonna test anyone, test the diagnosed patient first, but unless the diagnosed patient has other similarly affected family members OR is atypically young for the diagnosis, you are likely to leave the genetics clinic without having left a sample behind
- the process of identifying who wants to know, who doesn’t, who shouldn’t
Other tidbits to consider:
- what type of sample to give (blood, a swab from the inside of the cheek?)
- what mutations on what chromosomes exactly will be tested and reported (you can’t ask for “The Works”)
- Cost: Genetic testing for the 3 most common mutations related to FTD could cost you $250-1200 out of pocket to order in Canada in 2014.
- Are you willing to participate in research by giving enough sample for the clinic to share with investigators? If you give a sample for genetic testing during research, it is rare for the investigators to also report your results back to you as part of the study. This system works in your favor, because, as above, revealing results should be done with the guidance of a genetics counselor who has been trained on how to have these conversations in a constructive and professional manner, and the procedures for clinical genetic testing are more tight than those for research. For example, in clinical genetic testing, there are more safeguards and double-checks for matching identity to sample for extra certainty that the news they are providing is yours.
- Timeline: It can take the genetics team a year to gather all the important medical records for family members affected across a few generations to determine whether the occurrence of FTD was sporadic within the context of multiple causes for dementia within the family vs. shared among all affected family members, which then makes it familial.
- Interpreting the results: a negative test result does not rule out the possibility of familial FTD. The negative test result means that the family does not carry the most commonly occurring mutations.
- Interpreting the results: Some patients with FTD due to known mutations have a mild presentation of illness that lingers for 20 years, so having a mutation does not sentence one to rapid progression or more severe illness course.
Some tidbits about comparing the genetics of different dementias:
- Up to 40% of FTD patients have a family history, and the pattern of inheritance reflects autosomal dominance (Chow et al., Arch Neurol 1999). In retrospect, later studies have not shown this high a prevalence, and that might be due to the fact that more FTD patients but with a different presentation, wider variety of family histories, had genetic testing after 1999.50% of FAMILIAL FTD cases have known genetic mutations. [So that’s 50% of the 40% ~= 20% of FTD patients]
- There is a drastically lower % of patient with AD or the other dementias that have strong family histories, let alone autosomal dominant patterns of inheritance. This makes it rare for an elderly person who develops AD to warrant genetic testing unless s/he has that autosomal dominant pattern, but the most commonly occurring genetic mutations (presenilin) that cause autosomal dominant AD tend to show “anticipation” through the family’s generations, which means earlier and earlier age at onset
Autosomal dominant family histories in FTD subtypes reported by Seelar et al. in Neurology 2008:
–36% of behavioral variant FTD had autosomal dominant inheritance patterns (close to our 1999 report, and as I recall, most of the patients had this subtype of FTD)
–20% of FTD-MND (an oversimplified way of defining this is as a combination of FTD and ALS)
–8% Progressive non-fluent aphasia
–4% Semantic dementia..but per my Oct 24, 2014 post: I’d never thought to put it this way before, but genetics counselor Emily Dwosh at UBC pointed out that regardless of the variant of FTD diagnosed, there are both sporadic and familial cases described. This means that genetic testing may be indicated for individuals among all types of FTD presentation, even semantic dementia. In semantic dementia, we haven’t found a “culprit” genetic mutation yet, but there have been cases of multiple family members affected by the same aphasia.
The C9orf72 mutation has been a game-changer. At this point in clinical knowledge, if there are patients with ALS and patients with FTD in a given family, C9orf72 mutations would be more likely than progranulin mutations. [also from Oct 24, 2014 post]
Funded to provide 100 families with GPS devices. If you are interested in knowing which GPS device they went for, it was the GreatCall wearable. Please contact Alzheimer’s San Diego for deets or to donate so more families can benefit. Part of the recipe for this solution was partnership with the San Diego County Sheriff’s Department.
I want to be doing this:
A long jump competitor in the track and field events in New Jersey. Credit: Roger Kisby for The New York Times
Senior Games, covered by NY Times last weekend. I did not see anything about cognitive testing for eligibility…
The Commonwealth Publishing Group in Taiwan, in association with Taipei Medical University, has translated my 2013 book into complex Chinese characters! I’m thrilled they thought there might be a readership in Taiwan, Hong Kong and Macau. For those of you interested in the original English version, it’s still offered through Amazon.com. You can apparently even get the hardback book, used for US$4 (includes shipping). One of the sellers is offloading a copy that used to be a library book. Ouch!
But to end on a positive note, I do like how they put the cover of this edition together! And there are some lovely graphics on a few pages inside.
Since the 1990s, we have struggled with the significance of ApolipoproteinE typing. The shorthand term for this genetic test is APOE genotyping; sometimes it’s called APOE4 genotyping.
[the following is excerpted from my book] Apolipoprotein E is a protein that sets us and chimpanzees apart form the rest of the primates, and its function is to help us manage cholesterol gleaned from meat-eating. Although not many genetic culprits for Alzheimer’s disease have been identified, APOE remains the genetic finding most frequently related to risk of Alzheimer’s disease (AD)…
Single nucleotide polymorphisms determine the versions of APOE numbered ε2, ε3, or ε4. Each version contributes differently to a person’s risk of developing AD…Each of us carries two copies of the gene, which means that a person may have two copies of ε2 or a combination of two types, such as ε3 +ε4 or ε2 +ε4, and so on…In general, people harboring one copy of ε4 are at a higher risk for AD than people without any copies of it; a person who has 2 copies is at even higher risk of developing AD.
The update in August 9, 2016’s issue of Neurology is that whereas we have been thinking of 1-2 copies of ε2 as desirably protective against AD, Chang et al. report here that children aged 3-20 (quite a wide range to be considered children) with ε2 +ε4 show smaller hippocampi (an epicenter for AD pathology) and poorer scores on attention and working memory. This combo has not shown consistently that the 2 and the 4 cancel each other out for late life dementia risk.
Children with the double-dose of ε2 showed poorer attention and executive function. Considering other observations of what happens to ε2 homozygotes, it would seem that whereas individuals start out with the disadvantage described in this report, something takes effect over the lifespan that turns out to be preventive against late life onset of AD. We have to figure out what that is and bottle it.
I apologize I didn’t put this post up closer to December, 2015, when the article was published in Neurology. Here are some excerpts from this review submitted by Dr. Adeline Su Lyn Ng at the National Neuroscience Institute in Singapore:
- “The proportion of Asian patients with FTD who have a positive family history ranges form 9.5% to 20%, considerably lower than the 30-50% seen in Caucasian populations.”
- Whereas the C9orf72 mutation accounts for 25% of familial FTD in Western cohorts, the numbers are much lower for Asian cohorts, and the few found thus far seem to have a Scandinavian founder, “suggesting a common founder effect that spread from Northern Europe to East Asian in human migration history.”
- South Indian populations may have completely different genetic mutations associated with FTD, PSP and CBS there
- She raised the possibility of underreporting as a factor in the current conclusions. I agree with her statement, “…it is vital to raise awareness of FTD among nonneurologists.” To that end, please do consider referring others to www.lifeandminds.ca/whendementiaisinthehouse and www.theaftd.org whenever you can!