# Develop an ANS-based Personalized Cognitive Training for Mild Cognitive Impairment

> **NIH NIH R21** · STANFORD UNIVERSITY · 2022 · $203,015

## Abstract

Abstract
Speed of processing training (SOPT), practicing to enhance the information processing efficiency while
performing various perceptual and cognitive tasks, is the widest examined type computerized cognitive training
among aging populations, including those with mild cognitive impairment (MCI). However, the efficacy of existing
SOPTs in maintaining or improving older adults' cognitive health greatly varies across individuals. Our
preliminary studies identified that the flexibility of autonomic nervous system (ANS) is associated with learning
and cognitive and neural gains in existing SOPT in older adults with MCI. Our premise is that adaptation capacity,
which is primarily reflected by ANS flexibility, is a key contributor to the neuroplasticity underlying broad and
sustained effects of cognitive interventions. In this proposed study, we will combine this ANS response profile
with the traditional learning index to develop a “personalization engine”, called pSOPT, for better
reflecting individual adaptation capacity, and to test pSOPT's feasibility (R21 phase) and preliminary
effect (R33 phase) in MCI. In R21 phase (intervention refinement, Stage Ia), we will establish a
“personalization engine” for the SOPT by taking advantage of unique information derived from ANS
assessment that links to learning and test the feasibility in MCI. Advanced time-series data analysis
methods (e.g., shapelet analysis) will be used to develop a prototype of pSOPT based on the previously identified
ANS shapelet. Compliance and usability of the pSOPT will be examined using interviews, questionnaires, and
recorded performance data using a single group design in older adults with MCI (n = 10). Specific aims include
(1) Use the identified ANS shapelet to develop a “personalization engine” that can modulate SOPT according to
real-time measures of ANS; (2) Examine the feasibility of administering the pSOPT. In R33 phase (pilot test,
Stage Ib), we will test the preliminary effects of the pSOPT in MCI. A pilot double-blinded randomized
controlled trial (RCT). An MCI group (N = 50) will be randomized into a 6-week pSOPT (n = 25), or attention
control (n = 25). Cardiac monitor-based ANS signals will be recorded throughout training sessions across groups.
Learning is indexed by performing accurately across a consecutive set of trials in training tasks. Cognitive battery
(measuring cognitive gains) and BOLD fMRI-based brain function (measuring neural gains) will be assessed at
baseline, post training (7-week), and short-term follow-up (3-month); neurodegeneration (T1MRI and blood-
based Alzheimer's pathology) assessed at baseline. Specific aims include (1) Compare changes of cognitive
and neural gains between groups; (2) Explore whether pSOPT will enhance ANS flexibility in supporting cognitive
gains against baseline neurodegeneration. This study is a prerequisite to efficiently launch an efficacy trial of
pSOPT in slowing dementia progress.

## Key facts

- **NIH application ID:** 10488295
- **Project number:** 5R21AG073356-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Feng Vankee Lin
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $203,015
- **Award type:** 5
- **Project period:** 2021-09-15 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10488295

## Citation

> US National Institutes of Health, RePORTER application 10488295, Develop an ANS-based Personalized Cognitive Training for Mild Cognitive Impairment (5R21AG073356-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10488295. Licensed CC0.

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