Early Idiopathic Normal Pressure Hydrocephalus Patients With Neuropsychological Impairment Are Associated With Increased Fractional Anisotropy in the Anterior Thalamic Nucleus

In this study, we aimed to investigate the reactive changes in diffusion tensor imaging (DTI)-derived diffusion metrics of the anterior thalamic nucleus (AN), a relaying center for the Papez circuit, in early idiopathic normal pressure hydrocephalus (iNPH) patients with memory impairment, as well as its correlation with the patients’ neuropsychological performances. In total, 28 probable iNPH patients with symptom onset within 1 year and 17 control subjects were prospectively recruited between 2010 and 2013 for this institutional review board-approved study. Imaging studies including DTI and a neuropsychological assessment battery were performed in all subjects. Diffusion metrics were measured from the region of the AN using tract-deterministic seeding method by reconstructing the mammillo–thalamo–cingulate connections within the Papez circuit. Differences in diffusion metrics and memory assessment scores between the patient and control group were examined via the Mann–Whitney U test. Spearman correlation analyses were performed to examine associations between diffusion metrics of AN and neuropsychological tests within the patient group. We discovered that early iNPH patients exhibited marked elevations in fractional anisotropy, pure diffusion anisotropy, and axial diffusivity (all P < 0.01), as well as lower neuropsychological test scores including verbal and nonverbal memory (all P < 0.05) compared with normal control. Spearman rank correlation analyses did not disclose significant correlations between AN diffusion metrics and neuropsychological test scores in the patient group, whereas ranked scatter plots clearly demonstrated a dichotic sample distribution between patient and control samples. In summary, our study highlighted the potential compensatory role of the AN by increasing thalamocortical connectivity within the Papez circuit because memory function declines in early iNPH when early shunt treatment may potentially reverse the memory deficits.