The Importance of Genetic Counseling


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:

  1. 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
  2. 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:

  1. 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]
  2. 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]

Now Available in Chinese

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 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. 

Update on ApolipoproteinE

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.

FTD in Asia

asia_southern_pol_2004I 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 and whenever you can!


“Update” on Survival in FTD


Bottom color (blue) = time from onset to seeking medical attention; middle of bar (gold) = diagnostic time; top color (green) = time to death after diagnosis made. bvFTD = behavorial variant; PSP = prog supranuclear palsy; CBS = corticobasal syndrome; nfvPPA = non-fluent variant primary progressive aphasia; svPPA = semantic dementia.  Coyle-Gilchrist et al. Neurology 2016;86:1736-1743.

The May 2016 issue of Neurology published the latest figures on survival in frontotemporal lobar degeneration (what they are using to include behavioral  and language variants of FTD as well as CBS and PSP; beware, other authors use FTLD to indicate autopsy-confirmed cases). Way back in 2003, the average survival quoted for FTD was only about 6 years following diagnosis. Some of you have heard me comment before that most of my patients survived for 10  years after initially being seen and diagnosed in clinic. They might have gone on for 2-4 years before that clinic visit!

Coyle-Gilchrist of Cambridge University et al. gave the stats on data collected from 200 cases in the PiPPIN catchment area (East of England) felt to have one of the FTD syndromes listed above. Findings of interest:

  • Time to diagnose (using caregiver’s retrospection) still ranges about 2-4 years, longest in behavioral variant and non-fluent agrammatic primary progressive aphasia
  • Diagnosis could take average of 1.8 years(!) for PSP patients
  • Most patients survived for something less than 9 years (from onset to death, not from diagnosis to death). I think this was lower than what I’ve stated because the survival for PSP patients was between 6-7 years and I typically have not included that group in my observation above.
  • Much higher incidence of cases from ages 70-84 years than I’d expected.
  • Prevalence of what they’re calling FTLD = 10.8/100,000
  • Estimated lifetime risk was reported as 1 in 742 (which seems higher than I expected)

Now Recruiting Spouse-Caregivers in San Diego County!

I was happy to learn today that the UCSD’s Psychiatry Department has spent the last 20 years on researching the effects of dementia caregiving on the physical and mental wellbeing of caregivers. (I was briefly involved in this work as a neurology resident.) They’ve been concentrating on the cardiovascular risks associated with caregivers who are partners to patients with dementia (as opposed to adult child caregivers), and the findings are of great interest.

Here’s the current study to which they are recruiting – of note, all study visits are done as housecalls, in an effort to make it easier for caregivers to participate. The region they can serve is pretty far North and East within San Diego County, so please consider!




How Do You Rate in Self-Compassion?

Self help concept.

Image courtesy of

I was reminded of this wonderful practice devised by Dr. Kristin Neff earlier this month – it fits into the same conversation as “If you would do ANYthing to help a friend, if it took only 20 minutes,…why won’t you spend 20 minutes on yourself?” I try to take this quiz annually. Even if you don’t answer honestly (ahem), the multiple choice responses will remind you what the right answers for you may be.



Back in Southern California and Speaking September 30th

Dr. Josh Grill kindly invited me to kick off the talks at UC Irvine MIND’s Friday, September 30th’s conference. Click on that link for info about the Caregiver Panel to be led by UCLA’s Jill Shapira and another link to registration (Early Bird discounts if you act before Sept 9th!). I’m on the schedule at 8:45:


I had hoped for my new organization to have its website up and running by this time, but we’ve been delayed, hence the late announcement. I’ve been with USC since November of last year; the Alzheimer’s Therapeutic Research Institute is located in North San Diego (lovely!). It’s been an honor and a privilege to be connected back to this field again.