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Childhood conduct disorders, a serious mental health concern, put children at risk for significant mental health problems throughout development. Elevations on callous-unemotional (CU) traits designate a subgroup of youth with conduct disorders who have unique causal processes underlying their problem behavior and are at a particularly high risk for serious impairment relative to others with these disorders. As a result, these traits have recently been integrated into major diagnostic classification systems for conduct disorders. Given that CU traits are partly defined by deficits in empathy, we review research on empathy development in typically developing children and use this research to ( a) advance theories on the specific emotional deficits that may be associated with CU traits, ( b) explain the severe pattern of aggressive behavior displayed by children with elevated CU traits, and ( c) suggest possible ways to enhance prevention and treatment for children with conduct disorders and elevated CU traits. Expected final online publication date for the Annual Review of Clinical Psychology, Volume 17 is May 7, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Objective: To investigate optimal cutoff scores and the effects of normative adjustments on the performance of the Montreal Cognitive Assessment (MoCA) as a screening instrument for Mild Cognitive Impairment (MCI) and dementia due to Alzheimer’s disease (AD-dementia). Methods: 499 adults 48 to 91 years-old enrolled in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and were administered the MoCA during baseline. Participants were classified as either cognitively normal (CN), MCI, or AD-dementia by clinical assessment. Receiver operating characteristic (ROC) analyses were performed using raw MoCA scores, education-adjusted MoCA scores, and a regression-based adjustment derived from the National Alzheimer’s Coordinating Center data (NACC). Test performance characteristics were calculated for various cutoffs after each normative correction method. Results: Areas under the curve (AUC) were similar for raw, education-adjusted, and NACC-adjusted MoCA scores, and demonstrated minimal improvement when adjustments of increasing complexity were applied. Youden’s index indicated that the optimal cutoff score may be lower than the established cutoff of 26. Conclusions: This study adds to the understanding of how normative adjustments affect the sensitivity and specificity of the MoCA. Suggested corrections based on education alone do not yield improved test characteristics, but small improvements are attained when a regression-based correction that accounts for age, sex, and education is applied. Furthermore, optimal cutoffs for distinguishing CN from MCI or CN from AD-dementia were lower than previously reported. Optimal cutoffs to detect MCI and AD-dementia may vary in different populations, and further study is needed to determine appropriate use of the MoCA as a screening tool.

Background: Metabotropic glutamate subtype 5 receptors (mGluR5) modulate synaptic transmission and may constitute an important therapeutic target in Alzheimer's disease (AD) by mediating the synaptotoxic action of amyloid-β oligomers. We utilized the positron emission tomography (PET) radioligand [ 18 F]FPEB to investigate mGluR5 binding in early AD. Methods: Sixteen individuals with amnestic mild cognitive impairment (MCI) due to AD or mild AD dementia who were positive for brain amyloid were compared to 15 cognitively normal (CN) participants who were negative for brain amyloid. Diagnostic groups were well balanced for age, sex, and education. Dynamic PET scans were acquired for 60 min, starting at 60 min after the initial administration of up to 185 MBq of [ 18 F]FPEB using a bolus-plusconstant-infusion method (K bol = 190 min). Equilibrium modeling with a cerebellum reference region was used to estimate [ 18 F]FPEB binding (BP ND) to mGluR5. Analyses were performed with and without corrections for gray matter atrophy and partial volume effects. Results: Linear mixed model analysis demonstrated a significant effect of group (p = 0.011) and the group × region interaction (p = 0.0049) on BP ND. Post hoc comparisons revealed a significant reduction (43%) in mGluR5 binding in the hippocampus of AD (BP ND = 0.76 ± 0.41) compared to CN (BP ND = 1.34 ± 0.58, p = 0.003, unpaired t test) participants, and a nonsignificant trend for a reduction in a composite association cortical region in AD (BP ND = 1.57 ± 0.25) compared to CN (BP ND = 1.86 ± 0.63, p = 0.093) participants. Exploratory analyses suggested additional mGluR5 reductions in the entorhinal cortex and parahippocampal gyrus in the AD group. In the overall sample, hippocampal mGluR5 binding was associated with episodic memory scores and global function. Conclusions: [ 18 F]FPEB-PET revealed reductions in hippocampal mGluR5 binding in early AD. Quantification of mGluR5 binding in AD may expand our understanding of AD pathogenesis and accelerate the development of novel biomarkers and treatments.

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