NeurologyLive® Year in Review 2024: Top Stories in Alzheimer Disease and Dementia

In 2024, the NeurologyLive^® staff was a busy bunch, covering clinical news and data readouts from around the world across a number of key neurology subspecialty areas. From major study publications and FDA decisions to societal conference sessions and expert interviews, the team spent all year bringing the latest information to the website's front page.

Among our key focus areas is Alzheimer disease and dementia, a field that experienced massive shifts in the therapeutic paradigm in the past 12 months, among other progress. Although major news items often appear among the top pieces our team produces, sometimes smaller stories reach those heights for other reasons—clinical impact and interest, or concerns about the small- or big-picture parts of care, for example. Whatever the reason for the attention these stories got, their place here helps provide an understanding of the themes in this field over the course of 2024.

Here, we'll highlight some of the most-read content on NeurologyLive^® this year. Click the buttons to read further into these stories.

1. Phase 3 Trials of Aducanumab Highlight High Risk of Amyloid-Related Imaging Abnormalities in APOE Carriers

Published in Neurology, a genome-wide association study (GWAS) of the phase 3 ENGAGE (NCT02477800) and EMERGE (NCT02484547) trials of aducanumab (Aduhelm; Biogen) revealed a strong, significant link between apolipoprotein (APOE) carrier status and the risk of amyloid-related imaging abnormalities (ARIA). Overall, the research highlights the value genetics add to guiding clinical treatment decisions and the importance of reporting heterozygosity by genotype, given the substantially larger effects observed among ε4 homozygotes vs heterozygotes.

2. Novel Blood Test Shows High Accuracy in Identifying Alzheimer Disease Pathology

Published in JAMA Neurology, a cohort study showed that a novel and commercially available plasma phosphorylated tau217 (p-tau) immunoassay had high accuracy in identifying Alzheimer disease (AD) pathology. These findings suggest that wider availability of high-performing assays is essential for wider evaluation and implementation of AD blood tests in the clinical practice.

3. Combination of Ultrasound Blood-Brain Barrier Opening and Aducanumab Significantly Reduces Amyloid-β in Alzheimer Disease

Published in The New England Journal of Medicine, a prospective, open-label, single-group, single-institution, proof-of-concept trial of 3 patients showed that a combination of focused ultrasound to open the blood–brain barrier and administration of aducanumab (Aduhelm; Biogen), a recently discontinued treatment for Alzheimer disease (AD), resulted in significant reductions in amyloid-β (Aβ) levels^.

4. FDA Issues Revised Draft Guidance for Drug Development in Early Alzheimer Disease

The FDA has issued a revised draft guidance for industry leaders titled “Early Alzheimer's Disease: Developing Drugs for Treatment.” Once the guidance is finalized, the agency noted the information will help to provide recommendations for drug companies in development of treatments for patients in the early stages of Alzheimer disease (AD) that occur before the onset of overt dementia.

5. FDA Approves Eli Lilly's Donanemab for Early Symptomatic Alzheimer Disease

Less than a month following a positive recommendation from the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee, the agency has approved Eli Lilly and Company's donanemab, a 350 mg/20 mL once-monthly injection for IV infusion, for the treatment of adults with early symptomatic Alzheimer disease (AD). Marketed as Kisunla, donanemab is available to patients with mild cognitive impairment (MCI) as well as those with the mild dementia stage of AD, with confirmed amyloid pathology.

6. FDA Approves New-Generation Acetylcholinesterase Inhibitor ALPHA-1062 for Mild-to-Moderate Alzheimer Disease

The FDA has approved Alpha Cognition’s ALPHA-1062 (Zunveyl), a prodrug of an approved acetylcholinesterase inhibitor (AChEI), galantamine, as a treatment for patients with mild-to-moderate Alzheimer disease (AD). ALPHA-1062, a delayed-release oral tablet formulation, is considered a new-generation AChEI inhibitor, with expected minimal gastrointestinal adverse events (AEs).

7. Open Label Extension Data Shows Lecanemab’s Continued Effect on Alzheimer Disease After 3 Years

At the 2024 Alzheimer’s Association International Conference (AAIC), held July 28-August 1 in Philadelphia, Pennsylvania, Eisai presented new 3-year data from an open-label extension (OLE) of its pivotal phase 3 Clarity AD trial (NCT03887455) highlighting lecanemab (Leqembi), an FDA-approved therapy for early-stage Alzheimer disease (AD). At 3 years, investigators observed a continued clinically and personally meaningful benefit among treated patients, with continued positive impacts on biomarkers after plaque removal.

8. FDA Clears Cortechs.ai’s NeuroQuant 5.0 Software for Quantification and Segmentation of ARIA-E and ARIA-H

The FDA has granted 510(k) clearance for Cortechs.ai’s NeuroQuant 5.0 software, allowing for advanced segmentation and quantification capabilities for MRI lesions associated with T2*-weighted gradient recalled echo and susceptibility weighted imaging. This latest software development supports clinicians in the enhancement of segmentation for amyloid-related imaging abnormalities (ARIA) in patients who are undergoing antiamyloid treatment for Alzheimer disease (AD).

9. Highly Accurate Blood Test Enhances Alzheimer Diagnosis in Primary and Secondary Care

In a study presented at the 2024 Alzheimer’s Association International Conference, July 28 to August 1, in Philadelphia, Pennsylvania, use of the PrecivityAD2 (C2N Diagnostics) test was able to detect Alzheimer disease (AD) with high accuracy among patients who presented with cognitive symptoms compared with traditional diagnostic methods in primary and secondary care settings. The blood test, known as Amyloid Probability Score-2 (APS2), uses a combination of plasma phosphorylated-tau217 to not-phosphorylated-tau217 ratio (%p-tau217) and the ratio of 2 types of amyloid (Aβ42/Aβ40).

10. FDA Clears Icobrain Aria, First AI Tool for Safer ARIA Detection in Alzheimer Treatment

The FDA has cleared icobrain aria (icometrix), the first artificial-intelligence (AI) software approved to detect, measure, and grade amyloid-related imaging abnormalities (ARIA), a potential serious adverse effect of new anti-amyloid treatments for Alzheimer disease (AD).