Mild Cognitive Impairment and Alzheimer's Disease and Related Dementias: Cross-national longitudinal prognosis and risk factors

Project Summary/Abstract
Tremendous growth in the prevalence of Alzheimer’s disease and related dementias (ADRD) is expected, with
estimates indicating that by 2050 two-thirds of adults with ADRD will reside in low- and middle-income countries
(LMICs). There is an urgent need to identify individuals at highest risk for ADRD at its earliest stages in order to
better target prevention and early intervention strategies. While mild cognitive impairment (MCI) is intended to
identify cognitively symptomatic individuals who are at greatest risk of progressing to dementia, most knowledge
regarding the measurement of MCI, its risk factors, and its prognosis comes from high-income countries. In
addition, MCI demonstrates significant variability in its course, given that large numbers of individuals with MCI
either revert to cognitively normal or remain with a stable MCI diagnosis over time. Differences in life-course
environmental determinants of cognitive health, biological risk, representativeness of study populations, MCI
criteria, and cognitive measurement methods may contribute to this variability. Moreover, little is known from a
global perspective about MCI measurement, its risk factors, and prognosis, particularly among LMICs which are
expected to carry the greatest future ADRD burden. The overall goal of this study is to improve the cross-national
measurement of MCI and to characterize its longitudinal course across populations with varied social, economic,
cultural, and healthcare life experiences. Data from the Harmonized Cognitive Assessment Protocol (HCAP)
Network offers a unique opportunity to generate harmonized MCI and dementia diagnoses and to investigate
the course and predictors of MCI cross-nationally. We will use data from 3 studies with longitudinal HCAP data:
the Health and Retirement (HRS) HCAP in the US; the Mexican Health and Aging Study’s (MHAS) ancillary
study on cognitive aging (Mex-Cog); and the Longitudinal Aging Study in India–Diagnostic Assessment of
Dementia (LASI-DAD). In Aim 1, we will harmonize MCI and dementia classifications cross-nationally and will
compare the longitudinal prognosis of MCI across the US, Mexico, and India. In Aim 2, we will investigate the
unique and shared sociodemographic, lifestyle, health, and biological risk factors associated with incident MCI
and dementia across the US, Mexico, and India. In Aim 3, we will study the unique and shared cognitive and
functional predictors of incident MCI and dementia risk cross-nationally and explore whether these predictors
are consistent across levels of educational attainment, sex/gender, and literacy. This proposal will enhance the
field of ADRD globally by improving the measurement of MCI and identifying the sociocultural and biological
pathways to ADRD from MCI to aid in the early identification of individuals at most risk of dementia, for whom
interventions should be prioritized.

Grant Number: 1RF1AG088009-01
NIH Institute/Center: NIH
Principal Investigator: Miguel Arce