ABSTRACT
BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is frequently associated with concomitant amyloid-ß (Aß) pathology. OBJECTIVE: To compare the [11C]PIB PET uptake in the patients with suspected iNPH to Aß and hyperphosphorylated-tau (HPτ) in the right frontal cortical biopsy, the cerebrospinal fluid (CSF) Aß, the response to a CSF shunt, and the final clinical diagnosis of Alzheimer's disease (AD). METHODS: Patients (nâ=â21) from Kuopio NPH Registry (http://www.uef.fi/nph) with intraventricular pressure monitoring, immunostaining for Aß and HPτ in the right frontal cortical biopsies, and a Mini-Mental State Examination and a Clinical Dementia Rating underwent [11C]PIB PET. Aß, total tau, and Pτ181 were measured by ELISA from the ventricular (nâ=â15) and the lumbar (nâ=â9) CSF. Response to the shunt was seen in 13 out of the 15 shunted patients. AD was diagnosed in 8 patients during a median follow-up of 6 years (mean 7.3±2.4 years, range 3-1). RESULTS: [11C]PIB uptake in the right frontal cortex (ρ=â0.60, pâ<â0.01) and the combined neocortical [11C]PIB uptake score (ρ=â0.61, pâ<â0.01) were associated with a higher Aß load in the right frontal cortical biopsy. Excluding one (1/15) outlier, [11C]PIB uptake was also associated with the ventricular CSF Aß (ρ=â-0.58, pâ=â0.03). CONCLUSIONS: The findings show that [11C]PIB PET can reliably detect simultaneous amyloid pathology among the iNPH patients. Further studies will show whether amyloid PET could predict a clinical response to the shunt operation. In addition, the presence of Aß pathology in the patients with iNPH might also warrant treatment with current AD drugs.
Subject(s)
Carbon Radioisotopes/pharmacology , Frontal Lobe , Hydrocephalus, Normal Pressure , Positron-Emission Tomography/methods , Aged , Biopsy/methods , Female , Finland , Follow-Up Studies , Frontal Lobe/diagnostic imaging , Frontal Lobe/metabolism , Frontal Lobe/pathology , Humans , Hydrocephalus, Normal Pressure/diagnosis , Hydrocephalus, Normal Pressure/metabolism , Hydrocephalus, Normal Pressure/pathology , Hydrocephalus, Normal Pressure/psychology , Male , Mental Status and Dementia Tests , Reproducibility of Results , Ventricular Pressure , Ventriculoperitoneal Shunt/methods , tau Proteins/metabolismABSTRACT
PURPOSE: The aim of this study was to evaluate the visual assessment of positron emission tomography images of N-[methyl-11C]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole ([11C]PIB) in a patient population with mild to moderate memory impairment or dementia. METHODS: We compared the visual ratings of two readers using kappa statistics and correlated the results of visual and quantitative region of interest (ROI) analyses. The one reader had good experience in evaluating PIB images and the other had little previous experience. The sensitivity and specificity of the visual assessment was determined using quantitative data from 18 healthy controls previously examined: [11C]PIB uptake was considered as abnormal if it was more than 2 SD above the mean of the healthy subjects. RESULTS: The evaluation of visual classification as "normal" or "abnormal" showed good interobserver agreement (kappa = 0.90). There was a clear correlation between visual and quantitative analysis (r = 0.47-0.79, p < 0.001). The most difficult visually assessed brain area was the putamen (kappa = 0.11; correlation with quantitative analysis: reader A r = 0.22; reader B r = 0.60). CONCLUSION: Our study shows that visual evaluation of [(11)C]PIB images conforms with quantitative analyses also in a clinical patient population supporting the feasibility of visual evaluation in clinical settings.
Subject(s)
Benzothiazoles , Cognition Disorders/diagnostic imaging , Positron-Emission Tomography/methods , Aged , Aged, 80 and over , Aniline Compounds , Benzothiazoles/metabolism , Cognition Disorders/metabolism , Dementia/diagnostic imaging , Dementia/metabolism , Female , Humans , Male , Memory Disorders/diagnostic imaging , Memory Disorders/metabolism , Middle Aged , Positron-Emission Tomography/standards , Reference Standards , ThiazolesABSTRACT
OBJECTIVE: To compare carbon 11-labeled Pittsburgh Compound B ([11C]PiB) positron emission tomography (PET) findings in patients with and without Alzheimer disease lesions in frontal cortical biopsy specimens. DESIGN: Cross-sectional study of [11C]PiB PET findings in patients with or without beta-amyloid (Abeta) aggregates in frontal cortical biopsy specimens. SETTING: Two university hospitals in Finland. Patients Ten patients who had undergone intraventricular pressure monitoring with a frontal cortical biopsy (evaluated for Abeta aggregates and hyperphosphorylated tau) for suspected normal-pressure hydrocephalus. INTERVENTIONS: [11C]PiB PET and evaluation for cognitive impairment using a battery of neuropsychological tests. MAIN OUTCOME MEASURES: Immunohistochemical evaluation for Abeta aggregates and hyperphosphorylated tau in the frontal cortical biopsy specimen and [11C]PiB PET. RESULTS: In patients with Abeta aggregates in the frontal cortical biopsy specimen, PET imaging revealed higher [11C]PiB uptake (P < .05) in the frontal, parietal, and lateral temporal cortices and in the striatum as compared with the patients without frontal Abeta deposits. CONCLUSIONS: Our study supports the use of noninvasive [11C]PiB PET in the assessment of Abeta deposition in the brain. Large prospective studies are required to verify whether [11C]PiB PET will be a diagnostic aid, particularly in early Alzheimer disease.