Neurocognitive composite accurately detected symptom worsening in Alzheimer’s

Key takeaways:

• A phase 2 study examined the Cognitive-Functional Composite among 219 individuals with Alzheimer’s symptoms.
• CFC demonstrated significant decline in both treatment and placebo groups from baseline to week 78.

Time-dependent worsening of cognition and function among a cohort of individuals with biomarker-proven Alzheimer’s disease or dementia was accurately detected by a composite neurocognitive measure.

“Cognitive-Functional Composite is a brief measure of both cognition and function, comprising seven existing cognitive tests focusing on memory and executive functioning and the Amsterdam IADL Questionnaire,” Sietske Sikkes, PhD, associate professor, neurology, at Amsterdam University Medical Centers, and colleagues wrote in a poster presented at CTAD. “CFC was previously demonstrated as a suitable assessment to capture clinically meaningful cognitive decline in early dementia.”

Sikkes and fellow researchers aimed to explore changes in CFC and its components across an 18-month follow-up in both treatment and placebo cohorts within a phase 2 clinical trial of a novel therapeutic in those with either mild cognitive impairment or mild dementia related to Alzheimer’s disease.

The study included 219 individuals randomized 1:1 to receive either T-817MA (Toyama Chemical) (n = 108; mean age 70.3 years; 58.3% female) or placebo (n = 111; mean age 69.1 years; 62.2% female) for 78 weeks. Secondary endpoints of cognition and function were measured by the CFC, which was assessed at baseline as well as at weeks 28, 52 and 78. The researchers analyzed differences between the treatment and placebo groups for total CFC score as well as utilizing mixed model for repeated measures for each subscale, with differences between each CFC assessment interval analyzed with paired samples t-test.

A total of 188 participants completed all 78 weeks of treatment.

According to results, time-dependent worsening in total CFC score was observed with significant change from baseline to all assessment intervals (weeks 28, 52, 78) for both treatment and placebo groups.

Estimated change from baseline of total CFC at week 78 was - 0.361 in the placebo group and -0.365 in patients treated with the novel therapy.

The researchers further found the difference in decline among both groups was not statistically significant (P = 0.959) while the cognitive and the functional component of the CFC showed significant decline over time from baseline to 28 weeks and beyond, an effect additionally observed across all CFC subscales.

“The observations of CFC decline in 18 months in the placebo group is valuable for designing future clinical trials and understanding drug effects,” Sikkes and colleagues wrote.