Davangere Devanand, MD: The State of Dementia Drug Development

There’s a growing sense of optimism in the prospects to treat dementia and Alzheimer’s disease—some informed by regulatory breakthroughs, and more inspired by what’s still to come in drug development. Primary to one expert in the field is that a refined treatment blueprint is taking shape.

In an interview with HCPLive during the American Psychiatric Association (APA) 2024 Annual Meeting in New York, NY, this week, Davangere P. Devanand, MD, director of geriatric psychiatry at Columbia University Medical Center, discussed the evolution of dementia and Alzheimer’s treatment strategy based on the introduction of new blood and plasma biomarkers—innovations in diagnostics that may trickle from specialist prescribing, down to primary care intervention.

While lifestyle and behavior modifications including exercise and cognitive training has been previously advocated for early-stage and at-risk patients, Devanand said it’s now better understood to have only a small effect. And the anti-amyloid lecanemab—the first drug approved to treat Alzheimer’s disease by the US Food and Drug Administration (FDA) in decades—is now well understood to provide little more than disease-modifying properties.

“While it doesn't improve patients, it changes the trajectory so instead of going downhill at a steep slope, they go at a moderate slope,” Devanand said. “So in terms of diagnosis, understanding the pathophysiology and management, there have been improvements in all these areas, although we are a long way from curing the disease.”

Relative to previously established dementia drugs like cholinesterase inhibitors and memantine—which may be associated with short-term improvement of cognitive symptoms—lecanemab’s most significant value seems to be a delay in disease progression. Untreated dementia may take another 2 - 3 more years to progress significantly in patients, giving them a maintained quality of life not previously afforded.

All the same, the primary treatment outcome when assessing lecanemab, cholinesterase inhibitors, or other treatments to come remains cognitive performance. But the outcome may be relative to patients based on their condition severity, their symptoms, and their response to treatment.

“For example, if a patient feels better—is less depressed or anxious, feels calmer—that may not be captured by the main outcomes for these cognitive enhancers,” Devanand said. “Or, the patient may feel better, even though on the paper-and-pencil cognitive test, we don't see much change. And function is very important.”