A recent study published in Nature demonstrates the effectiveness of Cognivue Clarity in characterizing mild cognitive impairment (MCI) and Alzheimer's disease (AD). The research, involving 887 participants, highlights the tool's ability to differentiate between cognitively normal individuals, those with MCI, and those with probable AD, as well as its correlation with key AD biomarkers.
Study Design and Patient Population
The study evaluated 887 individuals who underwent both Cognivue Clarity testing and amyloid PET scans between April 2021 and November 2022. The cohort included 388 cognitively normal individuals, 282 with MCI, and 217 with probable AD. The mean age of participants was 71.8 years, with an average of 15.5 years of education. The sample was 56.4% female, and 37.3% were ApoE ε4 carriers. The ethnoracial composition was 78.8% non-Hispanic White, 9.6% Black, 9.8% Hispanic, and 1.8% Asian.
Cognivue Clarity Performance
The Cognivue Clarity global score and its 10 subtests effectively discriminated cognitively normal individuals from those with MCI and probable AD (p < 0.001 for all comparisons). Furthermore, the tool differentiated between MCI and probable AD (p < 0.001). Cognivue Clarity scores were also lower in ApoE4 carriers compared to non-carriers (63.9 vs. 61.2, p = 0.021).
The Cognivue Clarity global score demonstrated a very large effect size (Eta squared = 0.214; 95% CI: 0.168–0.258), and each subtest had medium to large effect sizes. The effect size for differentiating cognitively normal individuals from those with MCI was medium to large (Cohen’s d = 0.545; 95% CI: 0.388–0.701).
Impact of Sociodemographic Variables
Stratified analyses revealed that Cognivue Clarity global scores differentiated individuals with cognitive impairment across various sociodemographic variables. Non-impaired African Americans had lower Cognivue Clarity global scores compared to non-Hispanic Whites and Hispanics. Performance in impaired individuals did not differ significantly by ethnoracial identity. Differences in Cognivue Clarity global scores were observed by age and education but not by sex.
Correlation with Amyloid Status and AD Biomarkers
Cognivue Clarity effectively discriminated individuals with negative amyloid PET scans from those with positive scans (p < 0.001). The effect size for differentiating amyloid-negative from amyloid-positive individuals was medium to large (Cohen’s d = 0.568; 95% CI: 0.430–0.707).
Lower Cognivue Clarity global scores and subtest scores were strongly associated with higher amyloid PET SUVR and plasma pTau217 measurements (p < 0.001). Moderate correlations were observed between Cognivue Clarity scores and Aβ42/40 ratios, APS, pTau181, and Aβ42/pTau181 ratios. The correlation between Cognivue Clarity global scores and AD biomarkers was similar to the strength of association among the AD biomarkers themselves, with pTau217 showing the strongest association with amyloid PET.
Implications for Clinical Trials and Treatment
In a biomarker-confirmed subgroup, Cognivue Clarity differentiated between true controls, MCI due to AD, and AD dementia (p < 0.001). Cognivue Clarity scores were significantly lower in ApoE4 carriers within this subgroup (66.7 vs. 60.5, p < 0.001). ROC analyses in the biomarker-confirmed sample showed an improved AUC of 0.793 (95%CI: 0.75–0.83) for detecting cognitive impairment.
These findings suggest that Cognivue Clarity could serve as a valuable tool for identifying individuals at risk for AD, monitoring disease progression, and selecting appropriate candidates for clinical trials and emerging anti-amyloid therapies. The ability to differentiate MCI due to AD from non-AD MCI supports its utility in discerning early stages of cognitive impairment and the presence of amyloid pathology.
