Functional neuroanatomic validity of a novel, smartphone‐based remote assessment of processing speed in early Alzheimer’s Disease

Background

The quantification of information processing speed (IPS) and its changes over time is a cornerstone of neuropsychological assessment for early Alzheimer’s disease (eAD). Additionally, clinical practice and drug development increasingly require tools enabling the remote assessment of cognition. We previously reported the feasibility, reliability and clinical validity of a novel, smartphone‐based IPS test remotely self‐administered to healthy controls (HC) and individuals with subjective cognitive decline (SCD) and eAD. The present study performed whole‐brain voxel‐based morphometry (VBM) analyses to determine whether smartphone‐based IPS performance indeed correlated with atrophy of brain regions known to support processing speed.

Method

31 HC, 31 SCDn (amyloid‐PET negative), 31 SCDp (amyloid‐PET positive) and 30 eAD individuals participated in a Alzheimer’s Digital Assessment Suite (AD‐DAS) Proof‐of‐Concept study (https://www.isrctn.com/ISRCTN17035495). Participants performed 9 IPS assessments (90s digit‐symbol matching) over 28 days on provisioned smartphones. Each response sequence and digit‐symbol pairing was novel and matched for difficulty within/across sessions.

High‐resolution anatomic, T1‐weighted MRI were submitted to whole‐brain VBM analyses (Computational Anatomy Toolbox, SPM12/Matlab 2021) testing whether performance (number correct) correlated with gray matter signal intensities (covariates: age, gender, years of education, study site, total intracranial volume). The statistical parametric map was thresholded at p<0.001 uncorrected (voxel‐level) and family‐wise error corrected p<0.05 (cluster‐level). Peak voxel MNI coordinates and t‐values, cluster‐level p‐values are reported.

Result

Poor smartphone‐based IPS performance correlated with atrophy in five regions centered in: (1) right insula (57, ‐14, 15; t = 5.83; p<0.0001), (2) right lingual gyrus (14, ‐64, ‐8; t = 5.21; p = 0.006), (3) left hippocampus (‐36, ‐24, ‐16; t = 4.83; p = 0.021), (4) left precuneus (‐10, ‐57, 26; t = 4.73; p = 0.017), (5) right fusiform gyrus (27, ‐38, ‐15; t = 4.69; p = 0.043), replicating previous functional MRI findings with IPS (lingual gyrus, precuneus) and known neuroanatomical correlates of working memory (insula, hippocampus).

Conclusion

These findings support the functional neuroanatomic validity of a novel smartphone‐based IPS task and thus remote, clinically meaningful characterization of preclinical/early AD individuals’ IPS impairments in clinical monitoring and drug trials.