Brain and intracranial volumes are both enlarged and serve as potential risk factors in normal pressure hydrocephalus

Normal pressure hydrocephalus (NPH) is a poorly understood neurodegenerative condition leading to gait impairment and ultimately dementia. Prior work has shown larger intracranial volume (ICV) among those with NPH which has been taken to establish a link to Benign external hydrocephalus of infancy (BEH) as a predisposing factor. These studies have not evaluated brain volume which we hypothesize will also be elevated in NPH and account for the increase in ICV. Automated analysis was performed on CT head examinations from 305 NPH patients and 294 controls. Brain volume was ~ 4.8% larger in females (p < .001) and ~ 2.5% larger in males (p = .003) in NPH compared with controls and ICV was ~ 5.2% larger in females (p < .001) and ~ 3.7% larger in males (p < .001) with NPH compared with controls. The ratio of brain volume to intracranial volume in NPH versus controls was not significantly different for females (p = .4) or males, (p = .08). If BEH is a major cause of NPH this would then require that it also results in persistently enlarged brain volumes. Our data suggests large brain size itself is a risk factor for NPH and may help account for increased NPH risk among males.