Improved biomarker associations using neuropsychological criteria versus ADNI criteria for diagnosis of MCI in Vietnam‐era veterans with head injury histories

Abstract

AbstractBackgroundCompared to conventional Petersen/Winblad criteria for mild cognitive impairment (MCI), our prior work has shown that neuropsychological or “actuarial” criteria more accurately predicts progression to dementia, and is more strongly associated with Alzheimer’s disease (AD) biomarkers and imaging profiles. However, research to date has been conducted in relatively healthy samples with few comorbidities. Given that history of traumatic brain injury (TBI) and post‐traumatic stress disorder (PTSD) is common in older veteran populations, and both conditions are well‐documented risk factors for AD, we compared Jak/Bondi neuropsychological and ADNI MCI criteria to examine cross‐sectional cognitive and biomarker profiles in a well‐characterized sample of Vietnam‐era veterans with history of TBI and PTSD.Method186 veterans (mean age = 70.11) from the DoD‐ADNI study with history of TBI were evaluated for MCI using (1) ADNI criteria: subjective memory concern, objective memory impairment using WMS‐R Logical Memory, and Clinical Dementia Rating Global = 0.5; and (2) neuropsychological criteria: >1 standard deviation (SD) below age‐appropriate norms on two tests within any cognitive domain, or >1 SD below age‐appropriate norms on one test across all domains. Accounting for age and education, linear regression evaluated relationships between MCI diagnosis and AD biomarkers (Aβ42, total tau [t‐tau], and phosphorylated tau [p‐tau]). Logistic regression evaluated whether PTSD symptoms (CAPS total score) predicted MCI.ResultRoughly 17% of the sample met neuropsychological criteria for MCI, while 13% met ADNI criteria. Agreement between criteria was poor (κ = .17). APOE4 carrier status did not predict diagnosis by either criteria. MCI diagnosis using neuropsychological criteria was associated with higher t‐tau (p = .049) and p‐tau (p = .04), but not Aβ42 (p = .15), while ADNI diagnosis was not associated with any biomarkers (p>.05). PTSD symptoms predicted MCI diagnosis using ADNI (p = .005) but not neuropsychological criteria (p = .19).ConclusionFindings showed that MCI diagnosis using sensitive neuropsychological methods is more strongly associated with AD biomarkers than conventional diagnostic methods. Additionally, ADNI criteria may be capturing false‐positive diagnoses secondary to PTSD. MCI diagnostics benefit from the incorporation of comprehensive neuropsychological methods, particularly in complex populations with medical and psychiatric comorbidities.