Reaction Time Is Negatively Associated with Corpus Callosum Area in the Early Stages of CADASIL

Reaction time was recently recognized as a marker of subtle cognitive and behavioral alterations in the early clinical stages of CADASIL, a monogenic cerebral small-vessel disease. In unselected patients with CADASIL, brain atrophy and lacunes are the main imaging correlates of disease severity, but MR imaging correlates of reaction time in mildly affected patients are unknown. We hypothesized that reaction time is independently associated with the corpus callosum area in the early clinical stages of CADASIL.

Twenty-six patients with CADASIL without dementia (Mini-Mental State Examination score > 24 and no cognitive symptoms) and without disability (modified Rankin Scale score ≤ 1) were compared with 29 age- and sex-matched controls. Corpus callosum area was determined on 3D-T1 MR imaging sequences with validated methodology. Between-group comparisons were performed with t tests or χ² tests when appropriate. Relationships between reaction time and corpus callosum area were tested using linear regression modeling.

Reaction time was significantly related to corpus callosum area in patients (estimate = -7.4 × 10³, standard error = 3.3 × 10³, P = .03) even after adjustment for age, sex, level of education, and scores of depression and apathy (estimate = -12.2 × 10³, standard error = 3.8 × 10³, P = .005). No significant relationship was observed in controls.

Corpus callosum area, a simple and robust imaging parameter, appears to be an independent correlate of reaction time at the early clinical stages of CADASIL. Further studies will determine whether corpus callosum area can be used as an outcome in future clinical trials in CADASIL or in more prevalent small-vessel diseases.