Detecting early cognitive deficits in preclinical Alzheimer's disease using a remote digital multi-day learning paradigm

Roos J Jutten; Daniel Soberanes; Cassidy P Molinare; Stephanie Hsieh; Michelle E Farrell; Aaron S Schultz; Dorene M Rentz; Gad A Marshall; Keith A Johnson; Reisa A Sperling; Rebecca E Amariglio; Kathryn V Papp

doi:10.1038/s41746-024-01347-7

Detecting early cognitive deficits in preclinical Alzheimer's disease using a remote digital multi-day learning paradigm

NPJ Digit Med. 2025 Jan 13;8(1):24. doi: 10.1038/s41746-024-01347-7.

Authors

Roos J Jutten¹, Daniel Soberanes², Cassidy P Molinare², Stephanie Hsieh², Michelle E Farrell^{3

4}, Aaron S Schultz³, Dorene M Rentz^{3

2}, Gad A Marshall^{3

2}, Keith A Johnson^{3

4}, Reisa A Sperling^{3

2}, Rebecca E Amariglio^{3

2}, Kathryn V Papp^{5

6}

Affiliations

¹ Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02129, USA. rjutten@mgh.harvard.edu.
² Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
³ Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02129, USA.
⁴ Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02129, USA.
⁵ Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02129, USA. kpapp@bwh.harvard.edu.
⁶ Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA. kpapp@bwh.harvard.edu.

Abstract

Remote, digital cognitive testing on an individual's own device provides the opportunity to deploy previously understudied but promising cognitive paradigms in preclinical Alzheimer's disease (AD). The Boston Remote Assessment for NeuroCognitive Health (BRANCH) captures a personalized learning curve for the same information presented over seven consecutive days. Here, we examined BRANCH multi-day learning curves (MDLCs) in 167 cognitively unimpaired older adults (age = 74.3 ± 7.5, 63% female) with different amyloid-β (A) and tau (T) biomarker profiles on positron emission tomography. MDLC scores decreased across ascending biomarker groups, with the A + T- group performing numerically worse (β = -0.24, 95%CI[-0.55,0.07], p = 0.128) and the A + T+ group performing significantly worse (β = -0.58, 95%CI[-1.06,-0.10], p = 0.018) than the A-T- group. Further, lower MDLC scores were associated with greater cortical thinning (β = 0.18, 95%CI[0.04,0.34], p = 0.013). Our results suggest that diminished MDLCs track with advanced AD pathophysiology, and demonstrate how a digital multi-day learning paradigm can provide novel insights about cognitive decline during preclinical AD.

Abstract

Grants and funding