Faculty Bibliography

Background: Rodent model and in vitro studies suggest brain temperature has the potential to bidirectionally interact with tau pathology in Alzheimer's Disease (AD): tau phosphorylation is robustly increased by small (<1degreeC) reductions in temperature within the human physiological range, and lower brain thermoregulatory areas may be among those first affected by AD pathology. Here, we evaluated the cross-sectional association between body temperature (Tb), as a proxy for brain temperature, and clinically accessible markers of tau pathology in cognitively normal older adults.
Method(s): Tb was measured continuously over 48 hours with ingestible telemetry combined with a novel pre-processing algorithm. This period included 2 nights of nocturnal polysomnography to facilitate delineation of Tb-tau pathology relationships according to waking vs sleeping time intervals. Tau pathology was assessed with both soluble markers including plasma P-tau (P-tau 181) and cerebrospinal fluid (CSF) P-tau, both sampled the following day, and aggregated tau, namely neurofibrillary tangle (NFT) burden in early (I-III) Braak stage areas imaged with MR-PET using the [18F]MK-6240 radio tracer on average ~ one month later Results: Plasma and CSF P-tau levels were highly correlated with one another and with tau tangle radio tracer uptake (NFT burden), p < 0.05 for all comparisons. Lower Tb (quantified by lower mean Tb and a greater proportion of time Tb was under 37.0degreeC) was associated with increased NFT burden and increased plasma and CSF P-tau levels, p < 0.05 all comparisons. For aggregated tau, lower Tb - tau pathology associations were seen during for Tb recorded during waking, but not during sleeping intervals.
Conclusion(s): Preliminary results suggest that lower body temperature in older adults may be associated with increased aggregated and soluble tau pathology

BACKGROUND:Converging evidence implicates the anterior hippocampus in the proximal pathophysiology of schizophrenia. Although resting state functional connectivity (FC) holds promise for characterizing anterior hippocampal circuit abnormalities and their relationship to treatment response, this technique has not yet been used in first-episode psychosis (FEP) patients in a manner that distinguishes the anterior from posterior hippocampus. METHODS:We used masked-hippocampal-group-independent component analysis with dual regression to contrast subregional hippocampal-whole brain FC between healthy controls (HCs) and antipsychotic naïve FEP patients (N = 61, 36 female). In a subsample of FEP patients (N = 27, 15 female), we repeated this analysis following 8 weeks of second-generation antipsychotic treatment and explored whether baseline FC predicted treatment response using random forest. RESULTS:Relative to HC, untreated FEP subjects displayed reproducibly lower FC between the left anteromedial hippocampus and cortical regions including the anterior cingulate and insular cortex (P < .05, corrected). Anteromedial hippocampal FC increased in FEP patients following treatment (P < .005), and no longer differed from HC. Random forest analysis showed baseline anteromedial hippocampal FC with four brain regions, namely the insular-opercular cortex, superior frontal gyrus, precentral gyrus, and postcentral gyrus predicted treatment response (area under the curve = 0.95). CONCLUSIONS:Antipsychotic naïve FEP is associated with lower FC between the anterior hippocampus and cortical regions previously implicated in schizophrenia. Preliminary analysis suggests that random forest models based on hippocampal FC may predict treatment response in FEP patients, and hence could be a useful biomarker for treatment development.

This chapter describes recent clinical trials for opioid use disorder (OUD), an area that has rapidly accelerated in response to the opioid overdose crisis in the USA and newly appropriated funding. Trials involve a wide range of compounds including cannabinoids and psychedelics, new and existing compounds targeting domains emerging from addiction neuroscience, agents repurposed from other indications, and novel strategies including vaccines, enzymes, and other biologicals. In parallel, new formulations of existing compounds offer immediate promise, as do a variety of web-based interventions and smartphone-delivered apps. Trials focused on implementing existing effective interventions in mainstream healthcare settings, and others focused on special populations, e.g., adolescents, criminal justice, pregnant women, native Americans, etc., have the potential to vastly expand treatment in the near term. Given the range of ongoing and recent trials, this chapter is not intended to be an exhaustive review but rather to present an overview of approaches within the framework of the opioid treatment cascade and the context of current OUD pharmacotherapies.

BACKGROUND AND PURPOSE/OBJECTIVE:Asymmetric atrophy of the hippocampus is an important clinical finding in normal aging and Alzheimer disease. In this study, we investigate the associations between the magnitude and asymmetry of hippocampal volumetric integrity and age, sex, and dementia severity. MATERIALS AND METHODS/METHODS:= 30). We used linear mixed-effects models to analyze the hippocampal parenchymal fraction and its asymmetry with respect to age, sex, dementia severity, and intracranial volume. RESULTS:After controlling for age, sex, and intracranial volume, we found that the magnitude of the hippocampal parenchymal fraction decreased and its asymmetry increased significantly with dementia severity. Also, hippocampal parenchymal fraction asymmetry was significantly higher in men after controlling for all other variables, but there was no sex effect on hippocampal parenchymal fraction magnitude. The magnitude of the hippocampal parenchymal fraction decreased and its asymmetry increased significantly with age in subjects who were cognitively healthy, but associations with age were different in nature in the mild cognitive impairment and Alzheimer disease groups. CONCLUSIONS:Hippocampal atrophy progresses asymmetrically with age in cognitively healthy subjects. Hippocampal parenchymal fraction asymmetry is significantly higher in men than women and in mild cognitive impairment/Alzheimer disease relative to cognitively healthy individuals.