Methylene Blue Trial Conclusions

One therapy that aims at abnormal tau and therefore might be useful both in contexts of Alzheimer’s disease and FTD has unfortunately NOT shown significant efficacy in either dementia. The anti-tau agent was leuco-methylthioninium aka LMTM.

You may recall some buzz about this in late July: a trial in Alzheimer’s disease was negative, but the investigators were criticized for trying to make a case that a sub-analysis showed some good effects in  those participants who were taking only the investigational product and NOT typical Alzheimer’s standard of care. The level of evidence provided was NOT enough to get this drug approved by the FDA or for clinicians to stop FDA-approved medication to institute LMTM instead.

At the Munich International FTD Conference last month, results of a similar clinical trial but for participants with behavioral variant FTD were announced.  The CEO of the pharma company , Claude Wischik, reported no significant benefit for this group either.  Dedicated groups will continue the search.

Bloodtests for Tracking FTD Progression

For similar report applicable to Alzheimer’s disease, click here

Rohrer et al., an international collaborative that has been studying biomarkers and genetics in FTD, reported in late September that assaying serum for neurofilament light chain protein still holds promise. The UCSF group had presented some preliminary work in this area a few years ago, based on measurements from cerebrospinal fluid (which typically requires lumbar puncture to obtain). Now, just 2 years later, there may be a way to get this useful information through a blood draw.

The authors warned:

  • there was a lot of variability seen in measurements subgrouped by type of FTD (e.g., behavioral variant vs PPA)
  • while the serum level of neurofilament light chains increases as the size of the frontal lobes shrinks, more work is needed to know how predictive or diagnostic this measure can be.

The Paper: Serum neurofilament light chain protein is a measure of disease intensity in frontotemporal dementia. Neurology. 2016 Sep 27; 87(13): 1329–1336. doi:  10.1212/WNL.0000000000003154

Frontotemporal Dementia: Tracking Changes over the Course of Illness

O’Connor et al. (Australian group) followed and compared participants with behavioral variant FTD and semantic dementia (AKA semantic variant PPA) for 2- 4 years. In addition to looking at worsening of behavioral symptoms over time as we had done with data from UCSF, then Baycrest, these authors drew correlations between particular behavioral disturbances and ability to maintain one’s own activities of daily living. Of interest, but probably not news to you caregivers, was the finding that disability was not so related to disinhibition, but very much correlated with apathy. And counterintuitively, mental rigidity and compulsions in participants with semantic dementia (not bvFTD) seemed to bolster activity engagement.

I regret we don’t yet have a good symptomatic therapy for apathy despite its fairly unanimous priority as a symptom to target in therapy.

The paper:  Longitudinal change in everyday function and behavioral symptoms in frontotemporal dementia. Neurology Clinical Practice 

Bloodtests for Alzheimer’s Disease Progression

For similar report applicable to Frontotemporal Degenerations, click here

blooddraw Burnham et al. have been working an international collaboration to determine what type of biomarkers measurable in blood might give information that is as informative as samples of cerebrospinal fluid or PET imaging of the brain. Their longitudinal study (important to have repeat data points from individuals instead of drawing conclusions about progression from cross-sectional data) indicates that we may, in the future, be able to assess for amyloid-related risk for Alzheimer’s disease through blood samples. To use this methodology instead of lumbar punctures would be much  more comfortable for study participants and patients. To be able to avoid PET imaging would reduce the radiation exposure for participants and patients. The expense spared for clinical trials would be very significant as well.

The paper: Predicting Alzheimer disease from a blood-based biomarker profile: A 54-month follow-up. Neurology. 2016 Sep 13;87(11):1093-101. doi: 10.1212/WNL.0000000000003094.

Results from Small Open-Label Pilot of Light Therapy

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Thanks again, to those of you who responded to the recruitment ad that appeared on this blog earlier!

Here, with permission from the manufacturer and the 5 participants, are the de-identified aggregate results of the study. Please note that this level of evidence does NOT warrant a positive endorsement by me or the USC ATRI of the device for treatment of Alzheimer’s disease. This is intended to be informational, and you may decide what action to take (if any).

Direct Light Therapy for Sundowning: A Feasibility Study. Group Aggregate Results

8 Sept 2016

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If you’re interested in ordering or asking questions, please email lminikes@avstim.com

 

Not So Different Despite Age

istock-doctor-teenA recent paper summarizing the attitudes of teens diagnosed with multiple sclerosis demonstrated many similarities with families facing the diagnosis of dementia anew.

  • “…the road to diagnosis can be emotionally prolonged and emotionally taxing.” Due to the subtlety of symptoms and slow progression or even intermittent appearance of initial symptoms for both multiple sclerosis and dementia.
  • “…frustration with primary care physicians who lacked the knowledge base to handle the topic or efficiently make appropriate referrals…” We have yet to educate physicians across the board to recognize non-Alzheimer’s dementias
  • [on receiving a diagnosis] “Some experience a great sense of loss. Others are relieved to receive a diagnosis from an informed clinician.”
  • “However, stress secondary to miscommunication can occur.”
  • “adolescent [patients with MS] …report they often feel left out of consulations , which tend to focus on parental [caregiver] issues”
  • Parent [caregiver] reactions to diagnosis: “initial emotional distress upon learning of the diagnosis, and feeling a threat to their children’s wellbeing, which often was accompanied by a sense of devastation….feeling they were living in a nightmare.” “What is going to happen next we don’t know…But then it made us stop and think we don’t know what tomorrow brings anyway.”

Volunteering for the Research That’s Right for You

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Illustration from Jimmy’s Cambridge, UK. jimmyscambridge.net

Excerpted from The Memory Clinic, this is Appendix 2.

Whether you have dementia, think you’ll get it, or feel like you will live on as a healthy control, we need you to participate in research! And now that I work at a coordinating center for Alzheimer’s clinical trials, it’s my bailiwick to get you informed and motivated to consider volunteering.

To locate clinical trials, I always recommend http://www.clinicaltrials.gov. The entries onto this government-sponsored website are vetted to a small extent, in that proof of an ethics review board approval is required for all studies listed. However, some of the entries may be outdated (e.g., the study stopped recruiting a year ago) or the ethics review board that approved the study may not have the same high standards as others. As you pursue participation in a study, be VERY suspicious if:

  • there is no mechanism for someone to answer your questions about the study (and there is NO such thing as a stupid question)
  • you have not been informed equally well about benefits and risks of participating
  • there are penalties for withdrawing from the study
  • the patient with dementia can give consent in the absence of someone holding power of attorney

It is important to ask if you must stop medications the patient is already taking in order to participate. Depending upon whether you and your doctor think those medications are actively benefiting the patient, having to stop them for the study may be a deal-breaker.

Inquire after the number of visits entailed and the locations (not always a one-stop protocol!). We try not to design studies that require a swarm of visits, but there may be a lot of activity to get you rolling in the study (several visits, including imaging), then a slower visit schedule for the remainder of the study. Know what to expect.

Rights of the participant in a study should be stated on the informed consent form. These include:

  • a written explanation of all study procedures, purposes, risks, and benefits
  • the opportunity to ask questions and to feel that all questions have been answered satisfactorily before consenting to the study
  • ample time to consider the risks and benefits before consenting to the study
  • the ability to withdraw at any point in the study without penalties or adverse consequences to the patient’s clinical care
  • assurance of confidentiality

It is the researcher’s responsibility to help patients and their families feel comfortable enough with the study procedures that they will be inclined to complete participation. We are disappointed if you  have to leave the study early, but we know that your participation is voluntary. We do value your  contribution of time and energy and especially your trust that we will act in your  best interest in all events.

2016 Update

Do ask whether a placebo-controlled study will conduct an extension for study-completers. In the extension, all participants will typically have the opportunity to use the study drug (or Investigational Product, IP). This may offset your concerns about being assigned to the placebo group during the main study.

 

How Much Physical Activity Is Enough to Maintain Your Brain Health?

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For a while, I have seen researchers estimate and confirm that 20 minutes of rigorous exercise (something more than fast walking) 3 times weekly can give you benefits for Alzheimer’s prevention or maintenance of cognitive function. My personal bias is that we need at least that much physical activity to maintain a sense of lifestyle balance.

Dr. Mischley of Bastyr University presented data regarding Parkinson’s disease at the recent World Parkinson Congress – the results are not published in a peer-reviewed journal yet, but of interest to this discussion was the finding that people diagnosed with Parkinson’s disease who do 30 minutes of exercise DAILY show lower disease severity. [not clear to me which way the causality goes from the cross-sectional information I saw. This was not an interventional study in which exercise was “prescribed.”]

Re diet: under suspicion for worsening Parkinson’s disease: fried foods, diet soda, canned goods and iron…

See http://bastyr.edu/news/general-news/2016/10/diet-exercise-and-supplements-affect-parkinson%E2%80%99s

Next Chapter in the Transcranial Magnetic Stimulation Story for Primary Progressive  Aphasia?

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.