Monday, Biogen and the FDA made history with the first approval of a disease-modifying treatment for Alzheimer’s disease (AD). Biogen will need to confirm that aducanumab provides benefit to patients with AD in order to retain the conditional approval. The internet has exploded with op eds, and I can let you read those yourself, but I do want to highlight points articulately written by the American Academy of Neurology (AAN) on the subject of healthcare system preparedness for this historic shift in the standard of care for AD. I’ve excerpted points from that letter to the FDA below:
The AAN is specifically concerned with the labeling for aducanumab if approved. Alzheimer’s disease currently affects more than 5 million people in the US. Due to the likely high demand for this drug if approved, the AAN believes that a broad label has the potential to overwhelm the healthcare system with treated patients who may or may not benefit and who might be at higher risk for adverse events, given age and comorbidities. The AAN believes that proof of amyloid biomarker abnormalities should be required for treatment, given the therapy’s mechanism of action. Absent this requirement, the AAN is concerned that this drug may be administered to patients for whom there is currently no evidence of clinical benefit. The AAN asks that the FDA carefully consider which patients would benefit from the therapy based on available evidence and that the label be targeted accordingly. Additionally, given the risk of adverse events, robust provider education will be necessary to protect patient safety. Education and guidance will be needed for administering providers, as well as radiologists, regarding monitoring for ARIA-related complications and dosing adjustments.
Although the AAN believes that identification of amyloid biomarker abnormalities should be required prior to administration of this drug, we are concerned as practitioners that there are substantial structural and policy constraints which could limit access to necessary testing and exceed the system’s capacity to meet the demand. The AAN notes that identification of amyloid positivity requires scans that are not currently covered by payors. Beta amyloid PET scans are very expensive exams, typically costing between $5,000-7,000 per study. The need for a PET scan prior to administration and current lack of coverage will present providers and patients with substantial barriers to access if aducanumab is approved. The AAN sees the cost and lack of coverage for necessary scans as a significant bottleneck issue that could result in substantial disparities in access to care. This is especially true if there are conflicts between the drug’s labeling and payors’ coverage for the drug. If the FDA approves a broad label, without a requirement of amyloid positivity, but payors require proof of amyloid positivity prior to authorizing administration of aducanumab, then there is likely to be a substantial increase in costs and administrative complexity associated with administering the drug and post-administration monitoring. The AAN has substantial concerns associated with an increase in prior authorization requirements that may result from an overly broad label and the accompanying administrative burden.
The AAN asks that the agency also take into consideration the potential cost of this drug. The AAN encourages a proactive discussion with the Centers for Medicare and Medicaid Services to consider novel milestone-based reimbursement schedules. There are open questions regarding the appropriate length of treatment for this therapy. The AAN questions whether there will be guidance in the data submitted to indicate treatment duration, or whether the drug will be indicated for continued use as the disease progresses into later stages. Given the questions surrounding appropriate length of treatment, the AAN envisions there being a significant potential for outcomes-based payment arrangements. Additionally, aducanumab is a novel drug with a very large potential market, with the majority of potential patients likely to be on a limited or fixed income. An extremely high price and resultant high cost sharing could be prohibitive and lead to disparities in access.
I read about the 5th Dementia, online musical interaction for patients living with neurodegenerative disorders, and loved just the name. But on further examination, I found this documentary about them!
Leong et al. have been researching the benefits of daytime napping. Their December publication was highlighted in one of my routine neurology journal reads, and I was delighted to see that those of us who nap show a benefit in retention of newly learned material post-nap.
Interesting nuances of the research:
These findings applied to participants aged 18-35 years, so it will be interesting to know whether napping is beneficial throughout the lifespan
This exact type of study design has not been used in patients with dementia yet
The study called for up to 90 minutes for each nap – much longer than I would let myself sleep, since anything over an hour can disrupt my ability to fall asleep when I want to go to bed the same evening
And the effects on memory performance were immediate- testing was performed on the same day not that long after patients would have either awakened from naps or had stayed awake over the same period of the day.
Taking a nap helped encoding of new information even among those participants who do not usually take a nap daily, which the authors interpret as non-nappers just not making the time to nap, as opposed to not wanting to nap.
How does it work? Was not answered by the study design.
If you’re in midlife (defined in many ways, but encompassed by ages 35-65 years), make sure you’re getting physical activity into your schedule! Palta et al. have just added another argument to the benefits of physical activity; this time, they looked at neuroimaging findings that come with aging, and it seems moderate-vigorous intensity physical activity is associated with* fewer cumulative white matter changes and small strokes in late life. Impressively, the data about physical activity were collected 25 years prior to the MRI scans of brain (when I was still in high school!). Talk about a long-term investment.
Moderate-vigorous intensity, per the scale they used, consisted of physical activity amounting to at least 75 minutes/week and meeting 2008/18 US Physical Activity Guidelines for the adult age group. To fill out the modified Baecke Physical Activity Questionnaire used in this study for yourself, click here.
*The association, as I’ve warned before in this blog, doesn’t mean causality, but it is tempting to think we can prevent the ravages of aging on the plumbing to our brains and the integrity between neuronal connections by getting our recommended physical activity. There are various other cerebrovascular lifestyle factors that may associate with moderate to vigorous levels of physical activity that were not included in this study, and those factors may play more causative roles in the improved outcome. For instance, consider the effects of lower fat, lower red meat diets, lower sugar intake as known cardiovascular (and cerebrovascular factors that tend to be associated with people who work moderate to high physical activity into their lives.
A friend once described himself as, “Exercising to eat.” Over time, I’ve had to reconsider that exercising a lot doesn’t give me a free pass to eat all the comfort foods I’d prefer. The struggle is real! We owe it to ourselves and those who might have to take care of us to do what we can to stave off brain injury.
This came out last month, so thanks go to my mom for calling it to my attention:
In this AARP article, Tony Bennett’s family opens up and describes his course of Alzheimer’s disease. I’ve always held Mr. Bennett in great regard for his support of up and coming talent (esp women!), but to know he has continued to do this while entering the Alzheimer’s path is very meaningful. It takes a lot of integrity to go on with one’s work for society despite a health challenge, and I am speculating, but I think the last 4 years have been productive because those artists working with him have met him halfway or more out of respect for his talent and also out of the kindness of caring for someone who might need a little more help.
And I like how Mr. Bennett’s story highlights that Alzheimer’s leads to changes, but sometimes hardwired activities or talents remain resilient. This retention becomes the focus of our ability to communicate meaningfully with friends and family and patients with Alzheimer’s.
Glen Campbell’s family similarly came forward and helped to destigmatize Alzheimer’s disease by telling their story in 2011, not that long after his diagnosis. Click here for interview with Dr. Ron Petersen, who was Mr. Campbell’s treating specialist.
Read all about it here. I frequently turn to this report to refresh my stats and check trends. I’m hoping in the near future we’ll have more in the Diversity section about Asian Americans.
Here are some excerpts:
Estimates for the US indicate that there are about 5 million Americans with Mild Cognitive Impairment, which is a fair parallel to the over 6 million Americans diagnosed with Alzheimer’s disease!
States with higher (near 30% increase in AD cases) projected over the next 5 years: Alaska (29.4%), Arizona (33.%), Nevada (30.6%), and Wyoming (30%). Are those 4 states ready for this? While California hands down had the largest number of cases of AD in 2020 at 690,000, our projected increase is only 21.7%, similar to that of Hawai’i (20.7%).
That old argument about whether women are more prone to AD than men! I have maintained for a long time that incidence is the same between men and women although prevalence is higher among women. I’m feeling vindicated with this year’s report: “The prevailing reason that there are more women living with Alzheimer’s or other dementias than men is most likely the fact that women live longer than men on average, and older age is the greatest risk factor for Alzheimer’s….Most studies of incidence in the US have found no significant difference between men and women in the proportion who develop Alzheimer’s or other dementias at any given age.” Do go to that page for their further review that intriguingly raises the possibility that sex differences may be regional or more education- than sex-based.
Unlike conferences organized by the AFTD, this conference is for health care professionals and researchers, but those with an interest in frontotemporal dementia, primary progressive aphasia, and progressive supranuclear palsy may appreciate the updates and discussion.
I’m especially delighted to see the Latin American contingent fielding a team of speakers!
For details and registration, see here. If you can’t attend in real time Mar 3-5, the conference proceedings will be available for 30 days on playback.
“LIVE STREAM MEETING This course will be offered as a live interactive virtual conference. Login instructions along with the digital syllabus will be shared with attendees a week before the meeting. Included in your registration fee is access to the course recordings on demand (available within a week after the conference) for any sessions that you miss, available for up to 30 days post-course.
All registrants will receive a webinar log-in link the week of the course. You will enter your full name and email address to “log-in” and authenticate yourself. Once completed, you will have access to the conference, and the system will email you an individualized access link to join the webinar at any time. For the rest of the conference you will use this link to join the webinar each day and you will never need to log-in again. If you click on the link but the webinar hasn’t started yet you will be placed in a waiting room. Attendees will be admitted from the waiting room into the webinar once we begin. All of the live content is recorded and hosted on the course webpage for 30 days post course so you can review anything that you might have missed. “
I know Body Mass Index (BMI) management is not as simple as refusing a donut, but DO make sure you have physical activity in your daily routine and eat more vegetables (OMG, I’ve turned into my mother) to help get to the less risky BMI. The BMI calculator doesn’t work for all body types, but the paper mentioned above showed a risk for those with BMI = 25-30 and an even higher risk (the 4x) for those with BMI > 30.