Cold-Activated Brown Adipose Tissue is Associated with Less Cardiometabolic Dysfunction in Young Adults with Obesity.

OBJECTIVE: This study aimed to test the hypothesis that young adults with obesity and cold-activated brown adipose tissue (BAT) are less likely to have metabolic dysfunction (dyslipidemia, insulin resistance, and hypertension) than those without cold-activated BAT. Previous studies have noted a potentially protective effect of BAT and higher adiponectin/leptin ratios, but they have acknowledged that the clinical implications of these findings remain uncertain. METHODS: Twenty-one females and twenty-three males with obesity (BMI ≥ 30 kg/m2 ) underwent a 2-hour cooling protocol before 18 F-fluorodeoxyglucose (18 F-FDG)-positron emission tomography/x-ray computed tomography scan to determine the prevalence, volume, and 18 F-FDG uptake of cold-activated BAT. RESULTS: Cold-activated BAT was identified in 43% of participants (11 female, 8 male); females had greater 18 F-FDG uptake. Those with cold-activated BAT had a lesser degree of metabolic dysfunction. Cold-activated BAT volume correlated with triglycerides (inversely) and adiponectin (concordantly). Body-mass-adjusted cold-activated BAT activity correlated with high-density lipoprotein cholesterol (concordantly). Males with cold-activated BAT had lower leptin and higher adiponectin/leptin ratio. CONCLUSIONS: A high prevalence of cold-activated BAT was found in the study participants. BAT could be important in decreasing metabolic dysfunction among young adults with obesity, making it a potential target for treating metabolically unhealthy obesity.

Relationship between 18F-Flutemetamol uptake and RBANS performance in non-demented community-dwelling older adults.

OBJECTIVE: The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) has been used extensively for clinical care and in research for patients with mild cognitive impairment and Alzheimer's disease (AD); however, relatively few studies have evaluated the relationship between RBANS performance and AD imaging biomarkers. The purpose of the current study was to evaluate the association between a relatively new amyloid positron emission tomography imaging biomarker and performance on the RBANS. METHODS: Twenty-seven nondemented community-dwelling adults over the age of 65 underwent 18F-Flutemetamol amyloid- positron emission tomography imaging, along with cognitive testing using the RBANS and select behavioral measures. Partial correlation coefficients were used to identify relationships between the imaging and behavioral markers. RESULTS: After controlling for age and education, amyloid deposition and RBANS Indexes of Immediate Memory, Delayed Memory, and Total Scale score were significantly correlated (p's < .001, r's = -.73 to -.77, d's = 2.13-2.39), with greater amyloid burden being associated with lower RBANS scores. The Delayed Memory Index was particularly highly associated with 18F-Flutemetamol binding (r2 = .59, p < .001, d = 2.39). Neither 18F-Flutemetamol binding nor RBANS performance was significantly correlated with levels of depression, subjective cognitive difficulties, or premorbid intellect. CONCLUSIONS: Because of the limited use of amyloid imaging in clinical settings due to high cost and lack of reimbursement, these findings suggest that in particular RBANS Delayed Memory Index may be a cost-efficient tool to identify early signs of AD pathology, and its use may enlighten clinical decision-making regarding potential progression to dementia due to AD.

Amyloid Positivity Using [18F]Flutemetamol-PET and Cognitive Deficits in Nondemented Community-Dwelling Older Adults.

Little research exists examining the relationship between beta-amyloid neuritic plaque density via [18F]flutemetamol binding and cognition; consequently, the purpose of the current study was to compare cognitive performances among individuals having either increased amyloid deposition (Flute+) or minimal amyloid deposition (Flute-). Twenty-seven nondemented community-dwelling adults over the age of 65 underwent [18F]flutemetamol amyloid-positron emission tomography imaging, along with cognitive testing using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and select behavioral measures. Analysis of variance was used to identify the differences among the cognitive and behavioral measures between Flute+/Flute- groups. Flute+ participants performed significantly worse than Flute- participants on RBANS indexes of immediate memory, language, delayed memory, and total scale score, but no significant group differences in the endorsed level of depression or subjective report of cognitive difficulties were observed. Although these results are preliminary, [18F]flutemetamol accurately tracks cognition in a nondemented elderly sample, which may allow for better prediction of cognitive decline in late life.

FDG and FLT-PET for Early measurement of response to 37.5 mg daily sunitinib therapy in metastatic renal cell carcinoma.

BACKGROUND: Metastatic renal cell carcinoma has a poor prognosis and an intrinsic resistance to standard treatment. Sunitinib is an oral receptor tyrosine kinase inhibitor that has been used as a first-line targeted therapy in metastatic renal cell carcinoma. While computed tomography (CT) is currently the gold standard for response assessment in oncological trials, numerous studies have shown that positron emission tomography (PET) imaging can provide information predictive of tumor response to treatment earlier than the typical interval for standard of care follow-up CT imaging. In this exploratory study we sought to characterize early tumor response in patients with metastatic renal cell carcinoma treated with continuous daily 37.5 mg sunitinib therapy. METHODS: Twenty patients underwent dynamic acquisition positron emission tomography (PET) imaging using (18) F-fluorodeoxyglucose (FDG) and (18) F-fluorothymidine (FLT) at baseline and early in treatment (after 1, 2, 3 or 4 weeks) with 37.5 mg continuous daily dosing of sunitinib. Semi-quantitative analyses were performed to characterize the tumor metabolic (FDG) and proliferative (FLT) responses to treatment. RESULTS: Proliferative responses were observed in 9/19 patients and occurred in 2 patients at one week (the earliest interval evaluated) after the initiation of therapy. A metabolic response was observed in 5/19 patients, however this was not observed until after two weeks of therapy were completed. Metabolic progression was observed in 2/19 patients and proliferative progression was observed in 1/19 patients. Baseline FDG-PET tumor maximum standardized uptake values correlated inversely with overall survival (p = 0.0036). Conversely, baseline (18) F-fluorothymidine PET imaging did not have prognostic value (p = 0.56) but showed a greater early response rate at 1-2 weeks after initiating therapy. CONCLUSIONS: While preliminary in nature, these results show an immediate and sustained proliferative response followed by a delayed metabolic response beginning after two weeks in metastatic renal cell carcinoma treated with a continuous daily dose of 37.5 mg sunitinib. The results provide evidence of tumor response to lower-dose sunitinib while also supporting the inclusion of PET imaging as a tool for early assessment in oncological clinical trials. TRIAL REGISTRATION: ID: NCT00694096.

Amyloid deposition and cognition in older adults: the effects of premorbid intellect.

Although amyloid deposition remains a marker of the development of Alzheimer's disease, results linking amyloid and cognition have been equivocal. Twenty-five community-dwelling non-demented older adults were examined with (18)F-flutemetamol, an amyloid imaging agent, and a cognitive battery, including an estimate of premorbid intellect and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). In the first model, (18)F-flutemetamol uptake significantly correlated with the Delayed Memory Index of the RBANS (r = -.51, p = .02) and premorbid intellect (r = .43, p = .03). In the second model, the relationship between (18)F-flutemetamol and cognition was notably stronger when controlling for premorbid intellect (e.g., three of the five RBANS Indexes and its Total score significantly correlated with (18)F-flutemetamol, r's = -.41 to -.58). Associations were found between amyloid-binding (18)F-flutemetamol and cognitive functioning in non-demented older adults. These associations were greatest with delayed memory and stronger when premorbid intellect was considered, suggesting that cognitive reserve partly compensates for the symptomatic expression of amyloid pathology in community-dwelling elderly.