Mild Cognitive Impairment is Extremely Undiagnosed, Expert Says

Pharmacy Times interviewed John Showalter, MD, MSIS, dementia prevention and cognitive care internal medicine physician, and chief product and strategy officer at Linus Health, about mild cognitive impairment (MCI) and the significance of early detection. He noted that machine learning and artificial intelligence can be impactful in improving the accuracy of cognitive assessments. Additionally, Showalter described how pharmacists can be key players in the early detection of MCI through screening programs, notably for older patients who are prescribed antidepressants.

John Showalter, MD, MSIS: I'm John Showalter, I'm the Chief Product and Strategy Officer at Linus Health. I'm an internal medicine physician who's still practicing in dementia prevention and cognitive care.

PT®: What screening methods are available to detect mild cognitive impairment (MCI), and how can early interventions potentially alter progression of Alzheimer disease (AD) or other dementias?

Showalter: Right now, the best way to detect MCI is with a digital cognitive assessment, particularly [one] that has been tailored fit to screen and identify MCI. Classically, clinically, we've used paper and pencil tests like a [Mini-Mental State Examination (MMSE)], a [Montreal Cognitive Assessment (MoCA)], or a Mini-Cog. [MMSE is] not particularly sensitive, and the accuracy is not real great, so, identifying MCI in that way has not been particularly effective. But in the last few months to years, there's been a number of digital cognitive assessments that can really advance your ability to find those people and it's very important because dementia is a highly preventable condition. Over half of dementia can be prevented with lifestyle modifications, with correct control of diabetes and hypertension, there's 14 modifiable risk factors that have been identified, and the ability to intervene early is essential because we don't really have a whole lot that restores brain or restores function. We pause it at the place where it's been found, so the earlier that we find it, the more cognition and thinking that an individual can retain.

PT®: Can you discuss the significance of the FDA approval of donanemab for MCI, its mechanisms of action, and how is it a promising option for patients with MCI?

Showalter: It's particularly significant because [donanemab (Kisulna; Eli Lilly & Co.)] is now the second drug that is in a anti-amyloid classification that has been shown to slow the decline of cognitive impairment, slow the decline of dementia. They have some nuances on exactly where they attach to the to the amyloid molecules and when they attach, but essentially, both lecanemab (Leqembi; Eisai, Biogen) and donanemab are monoclonal antibodies that attach to amyloid and allow the body to, through the immune system, clear the amyloid plaques. Both of them have shown to substantially reduce the amyloid burden on the brain and slow progression of of Alzheimer disease (AD) between 20% and 30% and have translated to multiple months of increased independence for individuals with AD.

PT®: What role do pharmacists play in ensuring patients receive timely cognitive screenings and subsequent treatments? How might they collaborate with other health care workers?

Showalter: I think pharmacists have a huge role to play here. We know that there's an association between depression and AD, so if you are filling a new prescription for an SSRI—or other antidepressant—that someone over the age of 65 and they haven't had a cognitive assessment, that is a great time to talk to them about the importance of a cognitive assessment. In the future, there's some exciting possibilities of pharmacists becoming involved in delivering those cognitive assessments actually in the pharmacy. So, you could theoretically set up a protocol where all new antidepressants that you dispense in a pharmacy would trigger a technician to do a digital cognitive assessment right then and there, it'd be part of that screening piece. So, I'm excited about the future of pharmacists and cognitive care, and that also extends to patients that are on [donepezil] (Aricept; Eisai) and talking to them [patients] about what's actually been done, have they been considered for the anti-amyloid therapy, and understanding that medication recognition as an early sign that someone should be considered for additional treatment is super important. I am very excited for the role that that pharmacists can play in the screening and identification of MCI.

Over 90% of MCI is undiagnosed, and it's estimated that a third of people over 65 [years of age] have MCI, which means there's 20% of people over 65 walking around with MCI that don't know they have it. And the pharmacy's role and the pharmacist's role in helping those people get identified is huge.

Key Takeaways

Digital Cognitive Assessments Are Crucial for Early Detection: John Showalter, MD, MSIS, emphasizes the importance of digital cognitive assessments in identifying mild cognitive impairment (MCI). Traditional paper-based methods, such as the Mini-Mental State Examination, lack sensitivity and makes it harder to catch early signs of MCI. Early detection is essential because over half of dementia cases can be prevented through lifestyle changes and medical interventions aimed at controlling dementia risk factors.
Pharmacists Play a Vital Role in Cognitive Health: Pharmacists can significantly contribute to early detection of MCI by engaging with older adults who are prescribed antidepressants or cognitive medications. Showalter envisions a future where pharmacists perform digital cognitive screenings in pharmacies, helping identify undiagnosed MCI in people over the age of 65. This proactive role in screening can improve early intervention and treatment outcomes for patients at risk of Alzheimer disease and other dementias.
AI and Machine Learning Are Transforming Cognitive Screening: Advancements in artificial intelligence (AI) and machine learning are enhancing the accuracy of cognitive screenings. Showalter highlights the potential of AI to analyze cognitive assessments, such as the Mini-Cog, with better precision than human analysis. He also mentions upcoming technologies that assess voice and speech patterns for signs of cognitive impairment, further evolving how MCI is detected and treated in the near future.

PT®: How do you envision digital cognitive screenings evolving, especially with advancements in machine learning and artificial intelligence (Al)?

Showalter: I think machine learning and AI is going to continue to play a critical role. We just published a paper where it, essentially, was the AI analysis of Mini-Cog compared to the clinical analysis of Mini-Cog, showing marked superiority of detection of MCI using the AI analysis of the clock drawing and 3-word recall. There's a number of elements going into research now on voice and speech and [we are] going to be bringing voice and speech assessments to the clinical market very soon. We're finishing with our FDA registration around those, so the ability to do detailed voice analysis—pitch, tenor, cadence—and understand how that applies to cognitive impairment, not just the count of words, is really going to transform the ability to have a conversation with a patient and suss out that MCI that's currently undetected.

PT®: What new treatments or therapeutic options are on the horizon for MCI? Is there anything you are particularly excited for or want to highlight?

Showalter: There are 140 clinical trials going on right now on the therapeutic side. The one that I'm tracking most closely are the EVOKE trials (EVOKE [NCT04777396] and EVOKE+[NCT04777409]). So, that's the glucagon-like peptide-1 receptor agonists, semaglutide oral (Rybelsus; Novo Nordisk) both in dementia treatment and dementia prevention at MCI. That trial is supposed to end in October 2025, and the concept that we could be sitting in 2026 with a pill that slows or prevents dementia, or prevents the conversion of MCI to dementia, would completely change the landscape of treatment and it's something I'm very excited about in tracking as closely as you can.

Showalter: We talked [about it] a little bit, but given your audience, I just want to encourage the pharmacy group to lean into the detection of MCI. You know, if you imagined a world where we weren't doing blood pressure testing for hypertension, hemoglobin A1C testing for diabetes, mammography for breast cancer...[currently,] that's kind of where we're at with MCI, with 90% being undiagnosed, so, anybody from the clinical community...but I think pharmacies and pharmacists have a particularly trusted role in this, to lean into the detection of MCI would be huge. And as a clinician that treats these patients, I'd love to be hearing that they got detected early and got sent to me for treatment, as opposed to being detected really late when they finally have a problem.

Updated on October 4, 2024 at 5:00PM to correct a statement that said the MoCA test lacked sensitivity.