Distinct brain volume changes associated with the head-turning sign and Neucop-Q response patterns in Alzheimer's disease

Background The “head-turning sign” (HTS) and Neurocognitive Questionnaire (Neucop-Q) capture toritsukuroi (saving appearance) behaviors commonly observed in Alzheimer's disease (AD). Neucop-Q is a brief screening questionnaire assessing current event memory (News; N), self-awareness/concern (Consciousness; C), and engagement in pleasurable activities (Pleasure; P). Previously, HTS-positivity and impaired N/impaired C/normal P (NimpCimpPnor) combination show high specificity for amyloid PET positivity. Objective To investigate the neuroanatomical correlates of HTS and specific Neucop-Q response patterns across the AD continuum. Methods One hundred thirty-seven individuals (54 cognitively normal controls, 9 preclinical AD, 36 mild cognitive impairment, and 38 AD dementia patients) underwent clinical evaluation and structural MRI. Gray matter volumes were analyzed using voxel-based morphometry with MVision software based on a Multi-Atlas Likelihood Fusion approach. Regional volumes were normalized to intracranial volume and adjusted for age and sex. Group differences were tested with false discovery rate (FDR) correction, and logistic regression assessed associations between regional volume and Neucop-Q responses. Results HTS was significantly associated with right hippocampal atrophy (FDR-corrected p = 0.024). In the logistic regression analyses, none of the associations survived correction for multiple comparisons. The NimpCimpPnor combination was correlated with medial and inferior temporal lobe atrophy (FDR < 0.01) and larger globus pallidus (FDR = 0.034), with logistic regression surviving correction. Conclusions HTS reflected reduced right hippocampal volume, whereas NimpCimpPnor involved broader temporal atrophy with relatively larger pallidal volumes, suggesting distinct regional gray matter patterns across behavioral response profiles.