Relationship between F-18 florbetapir uptake in occipital lobe and neurocognitive performance in Alzheimer's disease.

PURPOSE: To determine the association between occipital amyloid-PET uptake and neurocognitive performance in Alzheimer's disease (AD). MATERIALS AND METHODS: Fifty-eight participants with normal aged, mild cognitive impairment (MCI) due to AD and AD subjects who underwent F-18 florbetapir brain PET/CT scans were divided into four groups (A, normal; B, MCI; C, mild AD; and D, moderate/severe AD). Semiquantitative analyses of SUVR images were performed. The differences between groups and the correlations between florbetapir uptake and Thai Mental State Examination (TMSE) scores were determined. Significant differences were defined using a P < 0.001, uncorrected, or a P < 0.05, FWE for the voxel-based analyses with Statistical Parametric Mapping (SPM). RESULTS: There was a slightly higher florbetapir uptake in the precuneus, parietal, and occipital association cortices in Group B > A. The occipital florbetapir uptake in Groups C and D was significantly higher than in Group A, in addition to the precuneus, anterior cingulate, posterior cingulate, temporoparietal, and frontal cortices. There was a strong negative correlation between TMSE scores and florbetapir uptake in the occipital lobe. CONCLUSIONS: Occipital amyloid uptake is associated with clinically advanced AD, and is inversely correlated with neurocognitive performance and may be useful for evaluating AD severity.

Relationships between amyloid levels, glucose metabolism, morphologic changes in the brain and clinical status of patients with Alzheimer's disease.

OBJECTIVE: The current study was conducted to improve the understanding of relationships between regional cortical amyloid load, glucose metabolism, cortical morphology (volume), and severity of clinical symptoms in patients with AD, MCI, and age-matched controls. METHODS: To objectivize the radiological evaluation of patients with suspected AD, head-to-head multi-modality imaging studies were conducted using MRI and PET/CT with [18F]FDG and [18F]AV45 for visualization and quantitation of brain morphology, glucose metabolism, and amyloid levels, respectively. A total of 84 subjects was studied, including 33 patients with AD, 31 patients with MCI, and 20 age-matched healthy controls (HC). A new quantitative index was calculated as a ratio of regional SUV of [18F]AV45 (normalized to cerebellar cortex) over the corresponding regional SUV of [18F]FDG, divided by the corresponding regional volume, measured from the co-registered MRI and normalized to the normal age-matched control group (AV45/FDG/NVol index). Relationships between clinical scores (TMSE, ADAS) and AV45/FDG/NVol indices for different structures of the brain in study groups were determined using linear regression analyses. RESULTS: A significant direct linear correlation was observed between the AV45/FDG/NVol index and ADAS-Cog test score and an inverse correlation with TMSE score at baseline and with the degree of changes in ADAS and TMSE scores assessed one year later (disease progression). The observed correlations between AV45/FDG/NVol index and clinical scores were higher than those with MRI-based cortical volumes, FDG SUV, or cerebellum-normalized AV45 SUV alone. CONCLUSIONS: Current study demonstrated that AV45/FDG/NVol index mapping of the brain is a novel quantitative molecular imaging biomarker that correlates with clinical neurocognitive status and may facilitate more accurate diagnosis, staging, and prognosis of AD. Additional larger scale clinical studies are required to further evaluate the efficacy of this new quantitative index as a diagnostic and prognostic biomarker of AD as well as for the evaluation of safety and efficacy of novel agents undergoing clinical trials for therapy of AD.

Changes in regional cerebral blood flow associated with a 45 day course of the ketogenic agent, caprylidene, in patients with mild to moderate Alzheimer's disease: Results of a randomized, double-blinded, pilot study.

BACKGROUND: Caprylidene is a ketogen that, when metabolized, produces the ketones beta-hydroxybutyrate and acetoacetate, which can cross the blood brain barrier. It has been hypothesized that ketone bodies can be used as an alternate energy source by neurons with impaired glucose utilization. Caprylidene has been shown to improve cognition in patients with mild-to-moderate Alzheimer's disease (AD) who lacked an AD-predisposing allele (ɛ4) of the gene for apolipoprotein E. In this pilot study, we examined the effects of caprylidene on regional cerebral blood flow (rCBF) in patients with mild to moderate AD. METHODS: Sixteen subjects with mild-to-moderate AD, based on NINCDS-ADRDA criteria, were enrolled in a double-blinded, placebo-controlled, randomized clinical trial. Fourteen subjects received treatment with caprylidene, and 2 subjects were given placebo. Subjects received 4 15O-water PET scans over the course of the study to assess rCBF: once before receiving a standard caprylidene or placebo dose and 90 min after the dose, on the first day and after 45 days of daily caprylidene or placebo consumption. The scans were examined by standardized volumes of interest (sVOI) and voxel-based statistical parametric mapping (spm) methods of analysis. RESULTS: Subjects lacking an ɛ4 allele had significantly elevated rCBF in the left superior lateral temporal cortex by sVOI analysis after adopting a caprylidene diet for 45 days (p = 0.04), which was further corroborated by spm. The anterior cerebellum, left inferior temporal cortex, and hypothalamus were also found by spm to be regions of long-term increase in rCBF in these subjects. In contrast, patients who possessed the ɛ4 allele did not display these changes in rCBF. CONCLUSION: Daily ingestion of caprylidene over 45 days was associated with increased blood flow in specific brain regions in patients lacking an apolipoprotein ɛ4 allele.

Utility of Adding SPECT/CT Imaging to Post-Therapeutic Radioiodine Whole-Body Scan in Patients with Differentiated Thyroid Cancer.

OBJECTIVE: To determine the usefulness of adding single-photon emission computed tomography/computed tomography (SPECT/CT) imaging to post-therapeutic radioiodine whole-body scan (RxWBS) in patients with differentiated thyroid cancer. MATERIAL AND METHOD: RxWBSs and SPECT/CT images of 93 consecutive patients were reviewed retrospectively by three experienced nuclear medicine physicians without knowledge of clinical data. RxWBSs were reviewed first followed by evaluation of RxWBS plus SPECT/CT imaging. Foci of increased radioiodine uptake were identified and localization was attempted. The findings obtained from RxWBS were compared with WBS plus SPECT/CT imaging to determine impact on lesion characterization, TNM staging, and management plan. RESULTS: Two hundred seventy seven lesions were identified by RxWBS alone. RxWBS plus SPECT/CT imaging detected eight additional pathologic lesions (4 in bones, two in neck, and one in lung and thyroid bed). RxWBS plus SPECT/CT studies reclassified 85 of 277 lesions (30.7%) detected by RxWBS. Most change occurred in neck region (57 lesions) followed by chest region (16 lesions). For impact on TNM staging, RxWBS plus SPECT/CT studies changed N stage of 21 patients (22.6%) and reclassified M stage of 10 patients (10.8%). These resulted in change of TNM stage group of 14 patients (15.1%) and changed management plan of 19 patients (20.4%). CONCLUSION: The addition of SPECT/CT imaging to RxWBS in patients with differentiated thyroid cancer improved disease localization and lesion characterization leading to more accurate N and M staging, which was mainly downstaged. SPECT/CT also had impact on plan of management in about one fifth of the patients. However, caution should be taken when interpreting lesion in lower chest and upper abdomen because misregistration of SPECT and CT images.