Evaluation of 10-minute post-injection 11C-PiB PET and its correlation with 18F-FDG PET in older adults who are cognitively healthy, mildly impaired, or with probable Alzheimer's disease.

OBJECTIVE: Positron emission tomography (PET) allows in vivo evaluation of molecular targets in neurodegenerative diseases, such as Alzheimer's disease. Mild cognitive impairment is an intermediate stage between normal cognition and Alzheimer-type dementia. In vivo fibrillar amyloid-beta can be detected in PET using [11C]-labeled Pittsburgh compound B (11C-PiB). In contrast, [18F]fluoro-2-deoxy-d-glucose (18F-FDG) is a neurodegeneration biomarker used to evaluate cerebral glucose metabolism, indicating neuronal injury and synaptic dysfunction. In addition, early cerebral uptake of amyloid-PET tracers can determine regional cerebral blood flow. The present study compared early-phase 11C-PiB and 18F-FDG in older adults without cognitive impairment, amnestic mild cognitive impairment, and clinical diagnosis of probable Alzheimer's disease. METHODS: We selected 90 older adults, clinically classified as healthy controls, with amnestic mild cognitive impairment, or with probable Alzheimer's disease, who underwent an 18F-FDG PET, early-phase 11C-PiB PET and magnetic resonance imaging. All participants were also classified as amyloid-positive or -negative in late-phase 11C-PiB. The data were analyzed using statistical parametric mapping. RESULTS: We found that the probable Alzheimer's disease and amnestic mild cognitive impairment group had lower early-phase 11C-PiB uptake in limbic structures than 18F-FDG uptake. The images showed significant interactions between amyloid-beta status (negative or positive). However, early-phase 11C-PiB appears to provide different information from 18F-FDG about neurodegeneration. CONCLUSIONS: Our study suggests that early-phase 11C-PiB uptake correlates with 18F-FDG, irrespective of the particular amyloid-beta status. In addition, we observed distinct regional distribution patterns between both biomarkers, reinforcing the need for more robust studies to investigate the real clinical value of early-phase amyloid-PET imaging.

Evaluation of 10-minute post-injection 11C-PiB PET and its correlation with 18F-FDG PET in older adults who are cognitively healthy, mildly impaired, or with probable Alzheimer's disease

Objective: Positron emission tomography (PET) allows in vivo evaluation of molecular targets in neurodegenerative diseases, such as Alzheimer's disease. Mild cognitive impairment is an intermediate stage between normal cognition and Alzheimer-type dementia. In vivo fibrillar amyloid-beta can be detected in PET using [11C]-labeled Pittsburgh compound B (11C-PiB). In contrast, [18F]fluoro-2-deoxy-d-glucose (18F-FDG) is a neurodegeneration biomarker used to evaluate cerebral glucose metabolism, indicating neuronal injury and synaptic dysfunction. In addition, early cerebral uptake of amyloid-PET tracers can determine regional cerebral blood flow. The present study compared early-phase 11C-PiB and 18F-FDG in older adults without cognitive impairment, amnestic mild cognitive impairment, and clinical diagnosis of probable Alzheimer's disease. Methods: We selected 90 older adults, clinically classified as healthy controls, with amnestic mild cognitive impairment, or with probable Alzheimer's disease, who underwent an 18F-FDG PET, early-phase 11C-PiB PET and magnetic resonance imaging. All participants were also classified as amyloid-positive or -negative in late-phase 11C-PiB. The data were analyzed using statistical parametric mapping. Results: We found that the probable Alzheimer's disease and amnestic mild cognitive impairment group had lower early-phase 11C-PiB uptake in limbic structures than 18F-FDG uptake. The images showed significant interactions between amyloid-beta status (negative or positive). However, early-phase 11C-PiB appears to provide different information from 18F-FDG about neurodegeneration. Conclusions: Our study suggests that early-phase 11C-PiB uptake correlates with 18F-FDG, irrespective of the particular amyloid-beta status. In addition, we observed distinct regional distribution patterns between both biomarkers, reinforcing the need for more robust studies to investigate the real clinical value of early-phase amyloid-PET imaging.

Inverse Association Between Hypothalamic N-Acetyl Aspartate/Creatine Ratio and Indices of Body Mass in Adolescents with Obesity.

BACKGROUND: Approximately 10% of adolescents worldwide are overweight or obese, hence the urgent and universal need to elucidate possible mechanisms that lead to obesity in the adolescent population. OBJECTIVES: We examined the hypothalamic metabolism and its relationship with physical development in obese and eutrophic adolescents. METHODS: We performed a case-control study with 115 adolescents between 11 and 18 years of age, to compare obese (BMI z-score ≥ 2) and nonobese individuals (eutrophic controls; BMI z-score ≤ 1). The following hypothalamic metabolite ratios were examined as primary outcomes: glutamate/creatine (Cr), the sum of glutamate and glutamine/Cr, N-acetylaspartate (NAA)/Cr, myoinositol/Cr, and total choline/Cr (glycerophosphocholine +  phosphocholine/Cr), quantified by magnetic resonance spectroscopy. BMI z-scores, pubertal status, and scores on the Yale Food Addiction Scale, the Binge Eating Scale, and the Child Depression Inventory were assessed as secondary outcomes. Pearson coefficients (r) or nonparametric Spearman correlation (rho) analyses were performed between hypothalamic metabolite ratios and other parameters, such as BMI z-scores, physical development, food habits, depression symptoms, and serum protein concentrations (cytokines, hormones, and neuropeptides). RESULTS: Adolescents with obesity showed a lower hypothalamic NAA/Cr ratio (0.70 ± 0.19) compared to their eutrophic counterparts (0.84 ± 0.20; P = 0.004). The NAA/Cr ratio was negatively correlated with BMI z-scores (r = -0.25; P = 0.03) and serum insulin (rho = -0.27; P = 0.04), C-peptide (rho = -0.26; P = 0.04), amylin (r = -0.27; P = 0.04), ghrelin (rho = -0.30; P = 0.02), and neuropeptide Y (r = -0.27; P = 0.04). Also, the NAA/Cr ratio was positively correlated with circulating IL-8 levels (rho = 0.26; P = 0.04). CONCLUSIONS: High BMI z-scores are associated with lower hypothalamic NAA/Cr ratios. The negative correlations found between the NAA/Cr ratio and serum cytokines, hormones, and neuropeptides suggest a broad cross-talk linking hormonal imbalances, neurohumoral alterations, and hypothalamic functions in adolescents with obesity.

Hippocampal subregional volume changes in elders classified using positron emission tomography-based Alzheimer's biomarkers of ß-amyloid deposition and neurodegeneration.

Changes in hippocampal subfield volumes (HSV) along the Alzheimer's disease (AD) continuum have been scarcely investigated to date in elderly subjects classified based on the presence of ß-amyloid aggregation and signs of neurodegeneration. We classified patients (either sex) with mild dementia compatible with AD (n = 35) or amnestic mild cognitive impairment (n = 39), and cognitively unimpaired subjects (either sex; n = 26) using [11 C]PIB-PET to assess ß-amyloid aggregation (A+) and [18 F]FDG-PET to account for neurodegeneration ((N)+). Magnetic resonance imaging-based automated methods were used for HSV and white matter hyperintensity (WMH) measurements. Significant HSV reductions were found in A+(N)+ subjects in the presubiculum/subiculum complex and molecular layer, related to worse memory performance. In both the A+(N)+ and A+(N)- categories, subicular volumes were inversely correlated with the degree of Aß deposition. The A-(N)+ subgroup showed reduced HSV relative to the A-(N)- subgroup also in the subiculum/presubiculum. Combining all (N)- subjects, HSV were lower in subjects presenting significant cognitive decline irrespective of A+/A- classification (controlling for WMH load); these between-group differences were detected again in the presubiculum, but also involved the CA4 and granular layer. These findings demonstrate that differential HSV reductions are detectable both in (N)+ and (N)- categories along the AD continuum, and are directly related to the severity of cognitive deficits. HSV reductions are larger both in A+(N)+ and A+(N)- subjects in direct proportion to the degree of Aß deposition. The meaningful HSV reductions detected in the A-(N)+ subgroup highlights the strength of biomarker-based classifications outside of the classical AD continuum.

In vivo imaging evidence of poor cognitive resilience to Alzheimer's disease pathology in subjects with very low cognitive reserve from a low-middle income environment.

INTRODUCTION: Reduced cognitive reserve (CR) due to very low educational (VLE) levels may influence high dementia rates in low-middle income environments, leading to decreased cognitive resilience (RES) to Alzheimer´s disease (AD) pathology. However, in vivo findings in VLE groups confirming this prediction are lacking. METHODS: Cognitively impaired patients (with clinically defined AD dementia or amnestic mild cognitive impairment) and cognitively unimpaired older adults (n = 126) were recruited for a positron emission tomography (PET) and magnetic resonance imaging (MRI) investigation in Brazil, including 37 VLE individuals (≤5 years of education). A CR score was generated combining educational attainment and vocabulary knowledge. RES indices to AD pathology were calculated using standardized residuals from linear regression models relating current cognitive performance (episodic memory or overall cognition) to amyloid beta (Aß) burden Pittsburgh compound-B ([11C]PiB-PET). RESULTS: Aß burden was lower in VLE relative to highly-educated subjects (controlling for age, sex, and Mini-Mental Status Exam [MMSE] scores) in the overall cognitively impaired sample, and in dementia subjects when the three clinically defined groups were evaluated separately. In bivariate regression analyses for the overall sample, the RES index based on a composite cognitive score was predicted by CR, socioeconomic status, and hippocampal volume (but not white matter hyperintensities or intracranial volume [ICV]); in the multivariate model, only CR retained significance (and similar results were obtained in the Aß-positive subsample). In the multivariate model for the overall sample using the RES index based on memory performance, CR, hippocampal volume, and ICV were significant predictors, whereas only CR retained significance in Aß-positive subjects. DISCUSSION: Lower CR consistently predicted less resilience to AD pathology in older adults from a low-middle income environment.

Grey and white matter volumes either in treatment-naïve or hormone-treated transgender women: a voxel-based morphometry study.

Many previous magnetic resonance imaging (MRI) studies have documented sex differences in brain morphology, but the patterns of sexual brain differences in transgender women - male sex assigned at birth - with a diagnosis of gender dysphoria (TW) have been rarely investigated to date. We acquired T1-weighted MRI data for the following four (n = 80) groups: treatment-naïve TW (TNTW), TW treated with cross-sex hormones for at least one year (TTW), cisgender men, and cisgender women (cisgender individuals as controls). Differences in whole-brain and regional white matter volume and grey matter volume (GMV) were assessed using voxel-based morphometry. We found lower global brain volumes and regional GMVs in a large portion of the posterior-superior frontal cortex in the cisgender women group than in the TTW and cisgender men groups. Additionally, both transgender groups exhibited lower bilateral insular GMVs than the cisgender women group. Our results highlight differences in the insula in both transgender groups; such differences may be characteristic of TW. Furthermore, these alterations in the insula could be related to the neural network of body perception and reflect the distress that accompanies gender dysphoria.