Early Biomarkers of Alzheimer's Disease: Using Speech Markers to Detect Mild Cognitive Impairment - PROJECT SUMMARY
Detecting early signs of Alzheimer’s Disease (AD) and mild cognitive impairment (MCI) during the prodromal
stage of AD is becoming increasingly important for cost-effective clinical trials, developing targeted intervention
strategies, and gaining maximum benefit from currently available treatment plans. However, because of
substantial differences in the manifestation of cognitive impairment, preclinical cognitive changes are not
discernible from age-related cognitive decline. Although a combined approach of using neuropsychological, fluid,
and imaging biomarkers has relatively improved the timely diagnosis of AD, measurement of these biomarkers
is expensive and highly technology-dependent, making these techniques impractical for use in many older adults
across different settings. In addition, assessment of cognitive functions through the use of neuropsychological
batteries remains the gold-standard in clinical trials and evaluation of intervention efficacy. Thus, it is critical to
identify early detectors that are 1) sensitive to pathologies of AD, 2) strongly predictive of future change in
cognition, and 3) accessible and feasible across diverse settings. Based on our recent findings, which have
identified measures of speech motor control as a powerful aid in indexing early stages of neurodegenerative
diseases such as amyotrophic lateral sclerosis and primary progressive aphasia, we propose assessment of
speech markers as an alternative or complementary and ecologically valid strategy for identifying adults at risk
of developing cognitive impairment due to AD. Speech production is one of humans’ most complex motor
behaviors, as it relies on tight integration of cognition, sensory, and motor processes which are all subject to
change with advancing age. We hypothesize that the rate of age-related changes in speech motor control of
adults can be influenced by genetic susceptibility to develop AD. In addition, we hypothesize that measures of
speech elicited during cognitively-demanding speech tasks can differentiate carriers of APOE ε4 (i.e., the major
gene known to increase AD risk) from noncarriers and that baseline speech acoustic and kinematic measures
can predict later cognitive decline. The proposed research will innovatively use acoustics and articulatory
kinematics in combination with neuroimaging to pursue three Aims. In Aim 1, we will determine the effect of aging
on speech motor control of adults with APOE ε4 positive (ε4+) and APOE ε4 negative (ε4-) genotypes matched
in sex and education. In Aim 2, we will identify the brain structural and resting-state functional bases for age-
related changes in speech measures of adults with ε4+ and ε4- genotypes. Finally, in Aim 3, we will determine
1) whether baseline speech acoustic/ kinematic measures predict cognitive change over two years, as quantified
by Hopkins Learning Test-Revised (HVLT-R) and Trail Making Test (TMT) scores; and 2) if speech and cognitive
changes are mediated through alterations in brain structure and function. The findings of this study will provide
critical information about measures of speech motor control that can be efficiently incorporated into
neuropsychological testing to optimize the clinical assessment of AD.
