Blood Biomarkers, Aducanumab and Setting Precedent for Dementia Care Advances

As the headline topic at the American Psychiatric Association (APA) 2022 Annual Meeting in New Orleans this week, “Social Determinants of Mental Health” provided many APA presenters an opportunity to consider the modern definitions of psychiatric and behavioral disease, and what influences that.

And that discussion around disease definition inherently opened the door to discuss what optimal care looks like for the affected patient.

In the second segment of an interview with HCPLive during APA 2022, Brent Forester, MD, MSc, chief of the division of geriatric psychiatry at McLean Hospital, discussed the inevitable convergence of blood-based testing innovations for Alzheimer’s disease and the standard for dementia—or neurocognitive disrders—in the Diagnostic and Statistical Manual of Mental Disorders (DSM).

“The challenge over the next 5 years is we know the clinical criteria in the DSM for the major and minor neurocognitive disorders—Alzheimer’s being the most common,” Forester said. “We know these dementias are based in neuropathology in the brain, and we can now visualize these neuropathological hallmarks with amyloid and tau PET imaging with CSF analysis, and increasingly with blood-based biomarkers.”

Forester is interested to see how true serum blood biomarkers that could be predictive to patient response to next-line therapies—in the case of Alzheimer’s disease, monoclonal antibodies.

“The coming together of biomarkers and clinical syndrome—we don’t have an example of that anywhere in psychiatry. But we will in Alzheimer’s disease,” Forester said. “That to me is truly exciting, and if we do it right, it will allow us to recognize people earlier.”

Later, Forester discussed the importance of merging pharmacotherapy strategies with proven patient behavioral changes—including exercise, diet, social engagement and cognitive stimulation—that have been proven to aide patients with dementia or Alzheimer’s disease even years after disease progression.

"If we could somehow incorporate those lifestyle interventions along with this increasingly knowledge of the biological interventions that are coming down the pike, we could see a huge change in the trajectory of Alzheimer’s disease,” he said.

Lastly, Forester—whose research program at McLean is a participant of the Biogen EMBARK trial—discussed the controversy surrounding the US Food and Drug Administration (FDA) approval of aducanumab (Aduhelm) for the treatment of Alzheimer’s disease last June.

“The problem that’s occurred since June 7, 2021 is that there’s been massive media attention on this, and I think it’s made the public but especially the medical community suspicious about these drugs and the intentions of pharmaceutical companies,” Forester said. “Everyone here intends to do the right thing.”

The landmark approval for the amyloid beta-targeting monoclonal antibody was met with great scrutiny from clinicians and investigators who challenged the supporting clinical data’s proof of benefit for patients. As Forester noted, though, it has been a well-received agent by eligible patients and various patient organizations even prior to the FDA decision.

As analysis of aducanumab’s absolute benefit for Alzheimer’s, as well as the FDA’s decision, continues to be reviewed amid consideration of yet another 2 monoclonal antibodies for the same indication, Forester expressed hope the backlash of last year’s decision doesn’t “sour the opportunity that’s still there.”

“We can’t be biologically reductionistic in our approach to Alzheimer’s, nor can we only look at psychosocial interventions,” Forester said. “It has to be both, and this is so obvious to all of us in psychiatry—but I will tell you, to the rest of the Alzheimer’s world, not so much.”