Efficacy of Novel Treatments for Patients With Alzheimer Disease Reported in 3 New Clinical Trials

Potential new interventions for patients with Alzheimer disease are in the pipeline, as researchers recently reported the results of 3 new clinical trials at the Alzheimer’s Association International Conference 2022.

The Alzheimer’s Prevention Initiative Autosomal-Dominant Alzheimer’s Disease (ADAD) Trial1 is a prospective, randomized, double-blind, placebo-controlled study of the efficacy of crenezumab vs placebo in people who are asymptomatic PSEN1 E280A mutation carriers in Colombia.

Crenezumab, a monoclonal antibody, was found to be safe and well tolerated but did not have significant clinical or biomarker effects. The clinical trial is significant because the ADAD cohort is an understudied and underrepresented population that researchers have identified as critical for identifying prevention strategies that could change the disease course for people with preclinical Alzheimer disease.

“It turned out the drug was safe and well tolerated, there were minimal amyloid-related imaging abnormalities (ARIA), and no ARIA symptoms,” Banner Alzheimer’s Institute Executive Director, Eric M. Reiman, MD, concluded. “Unfortunately, there were no statistically significant effects on any of our clinical brain imaging or downstream Alzheimer’s disease biomarker measurements.”4

While the average rate of clinical and biomarker progression was slower in the treatment group vs the placebo group, it was not statistically significant. Additional analyses are still in progress.

Researchers also released the interim findings from the phase 2 PIONEER Study,2 which includes evidence of improved cognitive function, reduced decline of function, and improvement of executive function in patients with mild to moderate Alzheimer disease following treatment with the new medication candidate, T3D-595.

The interim results of the multi-center, randomized, double-blind placebo-controlled study show that T3D-595 appears to be safe and well tolerated through more than 32,000 treatment days.

The researchers in this study labeled Alzheimer disease as “a brain-specific form of diabetes” or “type 3 diabetes.” In the study, researchers say T3D-595 acts to correct dysfunctional glucose energy metabolism, correct dysfunctional lipid metabolism inherent in a brain with Alzheimer disease, and target multiple abnormalities (eg, amyloid plaques or neurofibrillary tangles).

Researchers expect to release topline results of the PIONEER Study in the second quarter of 2023.

Lastly, researchers reported the findings from the EXERT Trial,3 which included encouraging results in the study of nonpharmacological interventions in patients with dementia.

Study participants with mild cognitive impairment in both the aerobic exercise intervention arm and the stretching arm of the study showed no cognitive decline after 12 months. A comparison group, who experienced neither intervention, showed a significant cognitive decline over the same period.

The results of the randomized, controlled trial suggest that regular, mild physical activity may protect brain cells against damage.

“I think what is important here to note is that we conducted this trial and obtained these results during a pandemic, and I think for me, the benefit of this unfortunate experience is that we learned how to create a durable intervention for people who will encounter other life challenges,” researcher Laura Baker, PhD, concluded.4

Despite lockdowns and isolation, 80% of the study participants adhered to the exercise regimen and completed the study.


—Jessica Bard



  1. Tariot PN, Lopera F, Langbaum JB, et al; Alzheimer's Prevention Initiative. The Alzheimer's Prevention Initiative Autosomal-Dominant Alzheimer's Disease Trial: A study of crenezumab versus placebo in preclinical PSEN1 E280A mutation carriers to evaluate efficacy and safety in the treatment of autosomal-dominant Alzheimer's disease, including a placebo-treated noncarrier cohort. Alzheimers Dement (N Y). 2018;4:150-160. doi:10.1016/j.trci.2018.02.002
  2. Didsbury J, Strittmatter W, Chamberlain S, Gabriel H. The PIONEER Study: A multi-center, randomized, double-blind, placebo-controlled phase 2 trial of the effects of T3D-959 on safety, cognition, function and plasma biomarkers in mild to moderate Alzheimer’s disease subjects: Rationale and study design. Alzheimers Dement (N Y). 2020;16(suppl 9):e039922. doi:10.1002/alz.039922
  3.  Shadyab AH, LaCroix AZ, Feldman HH, et al; ADCS EXERT Study Group. Recruitment of a multi-site randomized controlled trial of aerobic exercise for older adults with amnestic mild cognitive impairment: The EXERT trial. Alzheimers Dement. 2021;17(11):1808-1817. doi:10.1002/alz.12401
  4. Reiman E, Didsbury J, Baker L. Expert briefing on advances in Alzheimer’s treatments: new clinical trial results. Talk presented: at Alzheimer’s Association International Conference (AAIC) 2022; July 31-August 4, 2022; San Diego, CA/virtual. Accessed August 2, 2022.