ABSTRACT
BACKGROUND AND PURPOSE: Brain atrophy occurs in the late stage of dementia, yet structural MRI is widely used in the work-up. Atrophy patterns can suggest a diagnosis of Alzheimer disease (AD) or frontotemporal dementia (FTD) but are difficult to assess visually. We hypothesized that the availability of a quantitative volumetric brain MRI report would increase neuroradiologists' accuracy in diagnosing AD, FTD, or healthy controls compared with visual assessment. MATERIALS AND METHODS: Twenty-two patients with AD, 17 with FTD, and 21 cognitively healthy patients were identified from the electronic health systems record and a behavioral neurology clinic. Four neuroradiologists evaluated T1-weighted anatomic MRI studies with and without a volumetric report. Outcome measures were the proportion of correct diagnoses of neurodegenerative disease versus normal aging ("rough accuracy") and AD versus FTD ("exact accuracy"). Generalized linear mixed models were fit to assess whether the use of a volumetric report was associated with higher accuracy, accounting for random effects of within-rater and within-subject variability. Post hoc within-group analysis was performed with multiple comparisons correction. Residualized volumes were tested for an association with the diagnosis using ANOVA. RESULTS: There was no statistically significant effect of the report on overall correct diagnoses. The proportion of "exact" correct diagnoses was higher with the report versus without the report for AD (0.52 versus 0.38) and FTD (0.49 versus 0.32) and lower for cognitively healthy (0.75 versus 0.89). The proportion of "rough" correct diagnoses of neurodegenerative disease was higher with the report than without the report within the AD group (0.59 versus 0.41), and it was similar within the FTD group (0.66 versus 0.63). Post hoc within-group analysis suggested that the report increased the accuracy in AD (OR = 2.77) and decreased the accuracy in cognitively healthy (OR = 0.25). Residualized hippocampal volumes were smaller in AD (mean difference -1.8; multiple comparisons correction, -2.8 to -0.8; P < .001) and FTD (mean difference -1.2; multiple comparisons correction, -2.2 to -0.1; P = .02) compared with cognitively healthy. CONCLUSIONS: The availability of a brain volumetric report did not improve neuroradiologists' accuracy over visual assessment in diagnosing AD or FTD in this limited sample. Post hoc analysis suggested that the report may have biased readers incorrectly toward a diagnosis of neurodegeneration in cognitively healthy adults.
ABSTRACT
Macrophages (MΦs) are heterogeneous and metabolically flexible, with metabolism strongly affecting immune activation. A classic response to proinflammatory activation is increased flux through glycolysis with a downregulation of oxidative metabolism, whereas alternative activation is primarily oxidative, which begs the question of whether targeting glucose metabolism is a viable approach to control MΦ activation. We created a murine model of myeloid-specific glucose transporter GLUT1 (Slc2a1) deletion. Bone marrow-derived MΦs (BMDM) from Slc2a1M-/- mice failed to uptake glucose and demonstrated reduced glycolysis and pentose phosphate pathway activity. Activated BMDMs displayed elevated metabolism of oleate and glutamine, yet maximal respiratory capacity was blunted in MΦ lacking GLUT1, demonstrating an incomplete metabolic reprogramming. Slc2a1M-/- BMDMs displayed a mixed inflammatory phenotype with reductions of the classically activated pro- and anti-inflammatory markers, yet less oxidative stress. Slc2a1M-/- BMDMs had reduced proinflammatory metabolites, whereas metabolites indicative of alternative activation-such as ornithine and polyamines-were greatly elevated in the absence of GLUT1. Adipose tissue MΦs of lean Slc2a1M-/- mice had increased alternative M2-like activation marker mannose receptor CD206, yet lack of GLUT1 was not a critical mediator in the development of obesity-associated metabolic dysregulation. However, Ldlr-/- mice lacking myeloid GLUT1 developed unstable atherosclerotic lesions. Defective phagocytic capacity in Slc2a1M-/- BMDMs may have contributed to unstable atheroma formation. Together, our findings suggest that although lack of GLUT1 blunted glycolysis and the pentose phosphate pathway, MΦ were metabolically flexible enough that inflammatory cytokine release was not dramatically regulated, yet phagocytic defects hindered MΦ function in chronic diseases.