Olfactory function declines during normal aging; however, accelerated olfactory decline is observed in neurodegenerative diseases, such as Alzheimer’s disease (AD). Moreover, olfactory deficits in pre-clinical AD are associated with future cognitive decline. Odor identification and memory deficits have been consistently reported in early stage AD indicating its potential sensitivity to AD pathophysiology in olfactory and limbic structures, yet few studies of olfaction have incorporated structural measures in a well-characterized cohort of older adults. In the current study we examined the association between odor identification impairment, cognition, and medial temporal lobe (MTL) sub-regions in cognitively unimpaired and impaired older adults.

We enrolled 140 participants (age=72.25±6.54, 56% female, years of education=16.30±2.63, 82% Caucasian, 15% Black/AA, 3% Multiracial) from the Penn Alzheimer’s Disease Research Center Clinical Cohort. Participants completed the Sniffin’ Sticks Odor Identification Test (SS-OIT), cognitive testing (NACC UDS2 or UDS3 and additional cognitive tests), and MRI scans (3T Siemens MAGNETOM Prisma MRI scanner). For the SS-OIT, participants were presented with 16 odorants using felt-tipped pen dispensers and asked to identify each odor from four multiple-choice options. Scores range from 0 to 16. Additionally, cognitive domains were created by averaging z-scores from tests within each domain: attention, memory, language, executive function, and visuospatial. This cohort was divided into participants with unimpaired cognition (n=96) and impaired cognition (MCI, dementia; n=44) using established normative data and consensus diagnosis. Linear regressions were performed to examine the association between SS-OIT score, each cognitive domain, and MTL measurements for unimpaired and impaired groups. For all analyses, we controlled for age, race, sex, education, smoking status, and hypertension and additionally for MOCA score and intracranial volume with MTL measurements.

In the unimpaired group, SS-OIT significantly associated with language (p<.05). In the impaired group, SS-OIT significantly associated with language and memory (p<.05). In the unimpaired group, SS-OIT significantly associated with right anterior hippocampal volume (p<.05). In the impaired group, significant associations were found between SS-OIT and right anterior hippocampal volume (p<.05) and left hippocampal mean thickness (p<.05). Additionally, SS-OIT significantly associated with left and right entorhinal cortex volume (p<.05) and mean thickness (p<.05).

This study reveals that lower odor identification performance is related to lower performance on measures of cognition and atrophy in MTL sub-regions in unimpaired and impaired older adults. Our findings support prior results demonstrating relationships between olfactory function, cognition, and MTL sub-regions. Specifically, olfactory function and episodic memory have been shown to follow similar patterns of decline in the course of AD, potentially reflecting AD pathology in shared regions of the MTL subserving episodic memory and olfactory function. Our findings demonstrate that reductions in both cortical thickness and grey matter volume of MTL regions are linked to olfactory deficits in individuals at risk for Alzheimer’s dementia. Future steps will include the analysis of longitudinal cognitive and imaging indices and the incorporation of fluid biomarker data.

Mobile, valid, and engaging cognitive assessments are essential for detecting and tracking change in research participants and patients at risk for Alzheimer’s Disease and Related Dementias (ADRDs). This pilot study aims to determine the feasibility and performance of app-based memory and executive functioning tasks included in the mobile cognitive app performance platform (mCAPP), to remotely detect cognitive changes associated with aging and preclinical Alzheimer’s Disease (AD).

The mCAPP includes three gamified tasks: (1) a memory task that includes learning and matching hidden card pairs and incorporates increasing memory load, pattern separation features (lure vs. non-lure), and spatial memory (2) a stroop-like task (“brick drop”) with speeded word and color identification and response inhibition components and (3) a digit-symbol coding-like task (“space imposters”) with increasing pairs and incidental learning components. The cohort completed the NACC UDS3 neuropsychological battery, selected NIH Toolbox tasks, and additional cognitive testing sensitive to pre-clinical AD, within six months of the mCAPP testing. Participants included thirty-seven older adults (60% female; age=72±4.4, years of education=17±2.5; 67% Caucasian, 30% Black/AA, 3% Multiracial) with normal cognition who are enrolled in the Penn Alzheimer’s Disease Research Center (ADRC) cohort. Participants completed one in-person session and two weeks of at-home testing, with eight scheduled sessions, four in the morning and four in the afternoon. Participants also completed questionnaires and an interview about technology use and wore activity trackers to collect daily step and sleep data and answered questions about mood, anxiety, and fatigue throughout the two weeks of at-home data collection.

The participants completed an average of 11 at-home sessions, with the majority choosing to play extra sessions. Participants reported high usability ratings for all tasks and the majority rated the task difficulty as acceptable. On all mCAPP tasks, participant performance declined in accuracy and speed with increasing memory load and task complexity. mCAPP tasks correlated significantly with paper and pencil measures and several NIH Toolbox tasks (p<0.05). Examination of performance trends over multiple sessions indicates stabilization of performance within 4-6 sessions on memory mCAPP measures and 5-7 sessions on executive functioning mCAPP measures. Preliminary analyses indicate differences in mCAPP measures and imaging biomarkers.

Participants were willing and able to complete at-home cognitive testing and most chose to complete more than the assigned sessions. Remote data collection is feasible and well-tolerated. We show preliminary construct validity with the UDS3 and NIH Toolbox and test-retest reliability following a period of task learning and performance improvement and stabilization. This work will help to advance remote detection and monitoring of early cognitive changes associated with preclinical AD. Future directions will include further evaluation of the relationships between mCAPP performance, behavioral states, and neuroimaging biomarkers as well as the utility of detection of practice effects in identifying longitudinal change and risk for ADRD-related cognitive decline.

Mobile, valid, and engaging cognitive assessments are essential for detecting and tracking change in research participants and patients at risk for Alzheimer’s Disease and Related Dementias (ADRDs). The mobile cognitive app performance platform (mCAPP) includes memory and executive functioning tasks to remotely detect cognitive changes associated with aging and preclinical Alzheimer’s disease. This study assesses participants’ comfort and subjective experiences with mCAPP as the potential utility and advantage of mobile app-based assessments for remote monitoring among older adults will depend upon usability and adoptability of such technology.

The mCAPP includes three gamified tasks: (1) a memory task involving learning and matching hidden card pairs (“Concentration”) (2) a stroop-like task (“Brick Drop”), and (3) a digit-symbol coding-like task (“Space Imposters”). Participants included 37 older adults (60% female; age=72±4.4; years of education=17±2.5; 67% White) with normal cognition enrolled in the Penn ADRC cohort. Participants completed one baseline session of mCAPP in-person, followed by two weeks of at-home use with eight scheduled sessions. Information on prior experience with mobile technology and games was collected, and usability of mCAPP was measured at baseline and after 2-weeks of use with the IBM Computer Usability Satisfaction Questionnaire and the mHeath App Usability Questionnaire (MAUQ) respectively. Feedback on perceived difficulty, enjoyment, and likelihood to play mCAPP games again on their own was collected.

Participants completed on average 11±4.9 sessions over 2 weeks, with each session lasting 11.5±2.5 minutes. 59% of participants reported using their mobile device to play games (“mobile game players”). Performance on mCAPP tasks was slower at baseline for non-players, with trend-level differences on higher-load blocks of Space Imposters (p=.057 and .059). No differences in game performance were seen between groups after playing 8 sessions at-home. There were no differences in usability of mCAPP between groups, with average usability 8.2±1.5 (IBM, 0-9 scale) at T1 and 6.2±0.8 (MAUQ, 1-7 scale) after completion of two weeks of at-home use (TLast). Reported enjoyment was moderate to high for both groups at baseline and increased over time. Likelihood to play Concentration and Brick Drop again trended lower among nonplayers at T1 (p=.061 and .054), but not at TLast. Further, change in likelihood to play mCAPP from T1 to TLast was positive among non-players, with change for Concentration significantly higher for non-players than for players (p=.037).

Participants were willing and able to complete at-home cognitive testing and most completed more than the assigned sessions. While participants who do not play games on their own mobile device were slower on some tasks at baseline, these differences dissipated with further play at-home. Usability and enjoyment of mCAPP games were high regardless of mobile game-playing status, and non-players demonstrated increased willingness to play mCAPP games again at the end of participation compared to baseline. This pilot study shows preliminary feasibility and adoptability of mobile app-based assessment regardless of prior experience with mobile games.