Neuropsychological criteria for Mild Cognitive Impairment (MCI) best identify neuroimaging-based risk profiles: A Department of Defense/Alzheimer’s Disease Neuroimaging Initiative study

Abstract Objectives: Few studies have examined how differing diagnostic criteria for mild cognitive impairment (MCI) relate to neuroimaging markers of cerebrovascular disease and neurodegeneration in Veterans. We compared three MCI diagnostic schemes on their associations with white matter hyperintensity (WMH) burden, hippocampal volume, and cortical thickness in nondemented Vietnam-era Veterans. Methods: 228 Veterans (mean age = 69.65) were classified using: (1) Alzheimer’s Disease Neuroimaging Initiative (ADNI) criteria (subjective memory concerns, impaired Logical Memory, global Clinical Dementia Rating = 0.5); (2) neuropsychological criteria (>1 standard deviation [SD] below norms on two tests within a domain or one test across three domains); and (3) typical criteria (subjective memory concerns and >1.5 SD below norms on one test). Regression models predicting WMH burden adjusted for age and intracranial volume and included MCI status and hippocampal volume; ADNI-based models also included posttraumatic stress disorder symptom severity. Results: Neuropsychological criteria were associated with greater WMH burden ( β = 0.45, p = .024), whereas typical and ADNI criteria were not. Sensitivity analyses found that meeting neuropsychological criteria for amnestic MCI interacted with lower hippocampal volume to predict greater WMH burden ( β = −0.001, p = .028). No criteria were associated with cortical thickness. Conclusions: Neuropsychological criteria more sensitively identified Veterans with greater WMH burden and demonstrated a small, hippocampal volume-dependent effect in amnestic MCI. These findings support the clinical utility of multi-test neuropsychological approaches for detecting complex brain changes in high-comorbidity populations, with implications for risk stratification and targeted intervention in aging Veterans.