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

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

Clinical Neuropsychology

Research output: Contribution to Journal › Article › Academic › peer-review

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.

Original language	English
Article number	24
Pages (from-to)	1-10
Number of pages	10
Journal	npj Digital Medicine
Volume	8
Early online date	13 Jan 2025
DOIs	https://doi.org/10.1038/s41746-024-01347-7
Publication status	Published - 2025

Bibliographical note

Funding

We would like to thank all study participants of the Harvard Aging Brain Study, Instrumental Activities of Daily Living study and Subjective Cognitive Decline study, as well as everyone involved in the data collection. The Harvard Aging Brain Study is funded by the National Institutes of Health/National Institute on Aging (NIH/NIA) (P01AG036694; Principal Investigators Sperling, Johnson) with additional support from several philanthropic organizations. The Instrumental Activities of Daily Living study (R01AG053184 and R01AG067021; Principal Investigator Marshall) and Subjective Cognitive Decline study (R01AG058825-01A; Principal Investigator Amariglio) are funded by the NIH. The current study was supported by the Davis Alzheimer Prevention Program and by the Vettel Alzheimer Innovation Fund. RJJ is supported by the Alzheimer\u2019s Association (AARF-22-967786).

Funders	Funder number
National Institutes of Health
Vettel Alzheimer Innovation Fund
National Institute on Aging	R01AG067021, P01AG036694, R01AG053184, R01AG058825-01A
Alzheimer's Association	AARF-22-967786

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Jutten, R. J., Soberanes, D., Molinare, C. P., Hsieh, S., Farrell, M. E., Schultz, A. S., Rentz, D. M., Marshall, G. A., Johnson, K. A., Sperling, R. A., Amariglio, R. E., & Papp, K. V. (2025). Detecting early cognitive deficits in preclinical Alzheimer's disease using a remote digital multi-day learning paradigm. npj Digital Medicine, 8, 1-10. Article 24. https://doi.org/10.1038/s41746-024-01347-7

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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.",

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AU - Farrell, Michelle E

AU - Schultz, Aaron S

AU - Rentz, Dorene M

AU - Marshall, Gad A

AU - Johnson, Keith A

AU - Sperling, Reisa A

AU - Amariglio, Rebecca E

AU - Papp, Kathryn V

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

Abstract

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Funding

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