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The presence of Alzheimer's disease (AD)-related neuropathology among cognitively normal individuals has been well documented. It has been proposed that these individuals may represent a pre-clinical AD population. Previous studies have demonstrated a negative association between the presence of both amyloid-β (Aβ) plaques and neurofibrillary tangles with ante-mortem cognitive performance, a relationship which is likely influenced by a number of factors including age and APOE ɛ4 carrier status. The present study determined whether the presence of neuritic plaques (NPs) and diffuse plaques (DPs) are associated with performance in a number of cognitive domains after accounting for APOE ɛ4 carrier status and neurofibrillary tangle presence in a cohort of 123 older participants from the Rush Religious Order Study who died with a premortem clinical diagnosis of no cognitive impairment (NCI). After adjusting for age at death, education, gender, Braak stage, and APOE ɛ4 carrier status, the presence of NPs was associated with lower performance in the cognitive domains of Global Cognition (p = 0.002), Episodic Memory (p = 0.03), Semantic Memory (p = 0.009), and Visuospatial performance (p = 0.006), while DPs showed no association with any cognitive domain examined. These results suggest that decreases in cognition in elderly NCI individuals are associated with an increase in NPs and not DPs when age at death, education, gender, APOE ɛ4 status, and Braak stage are taken into consideration.

Introduction: The early detection of cognitive impairment is one of the most important challenges in Alzheimer's disease (AD) research. The use of brief, short‐term repeated test sessions via mobile app has demonstrated similar or better reliability and validity compared to standard in‐clinic assessments in adult samples. The present study examined adherence, acceptability, and reliability for a remote, app‐based cognitive screening protocol in healthy older adults. Methods: Cognitively unimpaired older adults (N = 52, ages 60–80) completed three brief cognitive testing sessions per day within morning, afternoon, and evening time windows, for 8 consecutive days using a mobile app‐based cognitive testing platform. Cognitive tasks assessed visual working memory, processing speed, and episodic memory. Results: Participants completed an average of 93% (M = 22.3 sessions, standard deviation = 10.2) of the 24 assigned sessions within 8 to 9 days. Average daily adherence ranged from 95% of sessions completed on day 2 to 88% of sessions completed on day 8. There was a statistically significant effect of session time on adherence between the morning and afternoon sessions only F (1, 51) = 9.15, P =.004, η p 2 = 0.152, with fewer afternoon sessions completed on average. The within‐person reliabilities of average scores, aggregated across all 24 sessions, were exceptionally high, ranging from 0.89 to 0.97. Performance on the episodic memory task was positively and significantly associated with total score and word list recall score on the Telephone Interview for Cognitive Status. In an exit survey, 65% of participants reported that they "definitely" would complete the sessions again. Discussion: These findings suggests that remote, mobile app–based cognitive testing in short bursts is both highly feasible and reliable in a motivated sample of cognitively normal older adults. Limitations include the limited diversity and generalizability of the sample; this was a largely White, highly educated, and motivated sample self‐selected for AD research. [ABSTRACT FROM AUTHOR]