Alzheimer's Disease Research

 

On March 24, 2022, the “godfather of the MoCA” cognitive assessment, Dr. Jeffrey L. Cummings, gave a seminar on “The Alzheimer’s Drug Development Pipeline: Innovations and New Directions.” Dr. Cummings, who is the Research Professor, Department of Brain Health Director, Chambers-Grundy Center for Transformative Neuroscience at UNLV, was introduced as the “rock star of Alzheimer’s disease [AD] research.” He is a world-renowned Alzheimer’s researcher and leader of clinical trials. Dr. Cummings told the attendees that sadly, “the clinical diagnosis of AD is too often wrong.”

As a gerontologist, I have been writing about misdiagnosis and presenting at scientific meetings on the misdiagnosis topic. Scientists estimate that around 20% of AD patients are misdiagnosed. Some due to lack of imaging based on clinical observations. Some due to other conditions that mimic dementia. Always get a second opinion and do not accept an AD diagnosis without imaging.

First, Dr. Cummings described how new drugs get approval by the FDA. Phases 1-3 must be completed before FDA review, which analyzes efficacy, safety, biomarkers, and how to use the drug. To improve probability of advancing any drug in clinical trial development, five “rights” of drug development must be met:

1.   Right target

2.   Right drug

3.   Right biomarker

4.   Right participants

5.   Right trial

There are 143 drugs now in 172 trials! Of these, thirty-one are in Phase 3. He stated that 83% of these drugs are Disease Modifying Therapy [DMTs] drugs which do not cure AD but slow the progression. As in all scientific research, Dr. Cummings reiterated that “the drugs follow the science.” The target most represented in the AD pipeline is inflammation and immunity, about 72%, with inflammation as a primary or secondary target.

    The media has recently discussed Aducanumab, known as Aduhelm. [See YouTube resource below dated Jul 28, 2020.] This controversial drug was approved even though it did not meet the outcomes by showing improvement in cognition. While it was shown to reduce plaques, the cost is over $28,000 annually. [BTW, any drug that reduces a-beta plaques has “umab” at the end.] Aduhelm is an anti-amyloid antibody monthly infusion and has shown 30% slowing via plaque burden for participants with MCI and mild AD. Slowing, not improvement. However, ARIA is a primary harmful side effect. What is ARIA? Amyloid-related imaging abnormality is a type of brain edema that causes headache, confusion, nausea, and gait changes. Therefore, APOE genotyping is recommended for patients, and that requires MRIs and PET scans. According to Dr. Cummings, this poses new and unprecedented demands and potentially a significant bottleneck, as clinicians often are reluctant to order MRIs. 

 

Resources for Dr. Cummings:

https://www.unlv.edu/news/expert/dr-jeffrey-l-cummings

 

Jeffrey Cummings, MD, ScD: Where Aducanumab Stands in Alzheimer Clinical Pipeline. Jul 28, 2020.

https://www.youtube.com/watch?v=miIjHPOYW4I

 

Jeffrey L. Cummings, MD, ScD: Optimal Therapeutic Targets for Addressing Alzheimer Disease. Aug 12, 2019.

https://www.youtube.com/watch?v=tlOxUMx6gbc

 

Jeffrey L. Cummings, MD, ScD: Agitation, Psychosis in Alzheimer Disease. Jul 29, 2019.

https://www.youtube.com/watch?v=ZEM1PtcUgck

 

DocPanel. September 12, 2018. Alzheimer's Misdiagnosis & the Benefit of a Radiology Second Opinion. https://www.docpanel.com/blog/post/alzheimers-disease-and-benefit-radiology-second-opinion