Life's Essential 8, Digital Cognitive Markers, and Alzheimer's Disease Risk - PROJECT SUMMARY Effective long-term drug treatments for Alzheimer’s disease (AD) remain elusive. Reducing major modifiable lifestyle and clinical risk factors, quantified by Life’s Essential 8 (LE8), may delay symptom onset or progression. The success of lifestyle intervention trials relies on the early detection of cognitive decline. Digital methods, such as the digital pen (dCDT), voice recordings (dVOICE), and other smartphone or wearable measures, enable easy, inexpensive, and frequent cognitive assessments in real-world settings, aiding early detection of cognitive changes in large populations. However, no study has evaluated the use of digital cognitive markers for monitoring cognitive changes in relation to longitudinal modifiable risk factors. It is urgent to address this knowledge gap. The Framingham Heart Study (FHS), a multi-generational cohort, possesses various digital measures, including dCDT and dVOICE measures collected from 2005 to 2014 (n~5000), digital Trail making and Stroop variables via smartphone from 2020 to 2023 (n~ 700), and additional digital cognitive assessments and voice data via a smartphone across the FHS generations from 2023 onward (n~5000). The FHS participants with digital cognitive measures have undergone regular health exams that collected demographic, lifestyle, and clinical measures, including those comprising the LE8, as well as longitudinal cognitive measures from standard cognitive tests, MRI measures of brain aging, plasma amyloid-β 40/42 biomarkers, and the ApoE genetic markers. We previously showed that several dCDT and dVOICE features are significantly associated with brain MRI measures, brain amyloid-β, cerebral microbleed of mixed types, and incident dementia. Our long-term goal is to utilize the relationship between longitudinal major modifiable risk factors and digital cognitive measures to monitor early cognitive decline in AD progression. We hypothesize that studying the relationship between the longitudinal LE8 metrics continuum and digital cognitive markers will effectively identify the major changepoint in cognitive decline. This hypothesis is supported by our recent findings that AD is associated with two clinical risk factors in LE8 in midlife but not in older age.6 To achieve the long-term goal, we will rigorously test the central hypotheses with three specific aims: Aim 1. Compare cross-sectional and longitudinal LE8 associations of digital cognitive measures (dNP) to conventional neuropsychological (cNP) test measures. Aim 2. Compare mild cognitive impairment (MCI) definitions and severity levels in predicting AD. Aim 3. Identify the changepoint of accelerated cognitive decline using LE8 metrics as during the preclinical phase of AD progression. The widespread use of mobile and wearable devices makes digital cognitive assessments more feasible, efficient, and cost-effective than traditional methods. Leveraging our expertise in digital neuropsychology and modifiable risk factors, our research will improve understanding of digital cognitive markers for diagnosing and predicting cognitive health. This includes monitoring cognitive health and examining how major modifiable risk factors relate to digital cognitive measures for early detection of cognitive decline in Alzheimer's disease across diverse populations.
