P4‐078: [18f]‐flutemetamol Amyloid PET Imaging in Patients with Normal Pressure Hydrocephalus

Normal pressure hydrocephalus (NPH) is a progressive condition associated with dementia, gait abnormalities, and urinary incontinence. Diagnosis is often difficult and other forms of dementia are frequently entertained. Indeed, prior work has suggested that a significant proportion of patients, more than half in some studies, with a clinical presentation of NPH have underlying Alzheimer's Disease (AD) pathology and that its presence may predict poorer response to ventriculo-peritoneal (VP) shunting. As such, an in vivo marker of AD pathology may provide important prognostic information. We utilized the novel PET amyloid imaging agent [18F]-flutemetamol to assess amyloid plaque burden in a cohort of NPH patients. [18F]-flutemetamol differs from Pittsburgh Compound-B (PiB) only with regard to the presence of a fluorine-18 radionuclide and has demonstrated considerable overlap in its imaging properties. A cohort of 7 patients who had a clinical diagnosis of NPH and underwent VP shunting were recruited. A high-resolution structural MRI and [18F]-flutemetamol PET scan was obtained. A composite standardized uptake value ratio (SUVR) with cerebellum as reference was calculated from regions typically associated with significant amyloid plaque burden in AD. PET imaging in the NPH group was compared to healthy controls (HC) and patients with Mild Cognitive Impairment (MCI) or AD. Data from the latter three cohorts were previously reported (Vandenberghe et al., Annals of Neurology, 2010). Composite SUVR results for the NPH group displayed a bimodal distribution with four patients having uptake very similar to the AD cohort while three others were in the HC range (Figure). This bimodal distribution was similar to MCI patients. Direct comparisons did not reveal a significant difference between the NPH group and patients with AD or MCI (p's > 0.1), but a higher composite SUVR than HC's (p < 0.05). [18F]-flutemetamol PET imaging is consistent with the notion that NPH represents a heterogeneous population in which a significant proportion of patients have evidence of AD pathology. Given the potential clinical implication of this pathology and its impact on shunt responsiveness, in vivo amyloid imaging may prove valuable in the evaluation of this condition. Composite standardized uptake value ratio values with cerebellum as reference (SUVRcer) in 4 groups (Alzheimer disease [AD], normal pressure hydrocephalus (NPH), healthy controls (HC), and mild cognitive impairment [MCI])