A three-minute computerized semantic paired associates test and plasma pTau217 status in older adults with and without cognitive impairment.

Abstract

Background: Plasma biomarkers for Alzheimer's disease (AD), including pTau217, are increasingly used to identify individuals at risk for underlying AD pathology. However, biomarkers alone do not capture the cognitive expression of disease, underscoring the need for brief cognitive measures capable of distinguishing impairment across biologically defined groups.

Objective: To evaluate the discriminative validity of the Brief Semantic Paired Associates Test (B-SPAT), a novel three-minute computerized cognitive screening test, among cognitively unimpaired and cognitively impaired older adults stratified by plasma pTau217 status.

Methods: Participants included 35 cognitively unimpaired (CU) older adults with negative plasma pTau217 (pTau217-), 22 cognitively impaired (CI) participants with pTau217-, and 20 CI participants with positive plasma pTau217 (pTau217+). All participants completed the B-SPAT, a fully digitized six-item semantic paired-associate learning task, along with a comprehensive neuropsychological battery.

Results: After adjustment for age, education, sex, and Mini-Mental State Examination scores, significant group differences in B-SPAT performance remained [F(2,70) = 8.28, p < 0.001]. Post-hoc analyses indicated that the CU pTau217- group performed significantly better than both cognitively impaired groups. Importantly, no significant differences were observed between the CI pTau217 + and CI pTau217- groups following covariate adjustment. Receiver operating characteristic analysis comparing CI pTau217 + and CU pTau217- participants yielded an area under the curve of 0.902 (SE = 0.041), with 95% sensitivity and 77.1% specificity.

Conclusions: The B-SPAT is a promising exploratory brief digital cognitive screening tool that differentiates cognitively impaired from cognitively unimpaired older adults across biomarker-defined groups and may have utility in community and primary care settings.