The Relationship of Cerebrospinal Fluid Biomarkers and Cognitive Performance in Frontotemporal Dementia.

Objective: Currently available literature on the relationships between cerebrospinal fluid (CSF) biomarkers and cognitive performance in frontotemporal dementia (FTD) is very limited and inconclusive. In this study, we investigated the association of cognition, as measured with Montreal Cognitive Assessment (MoCA), with CSF levels of total tau (t-tau), phosphorylated tau at threonine 181 (p-tau181), and amyloid ß 1-42 (Aß1-42) in a group of patients with FTD and Alzheimer's disease (AD). Methods: We conducted a retrospective cohort study with participants selected from the electronic records of patients seen at Yale New Haven Hospital's Memory Clinic, CT, USA. We included 61 patients, 28 with FTD (mean age=64.1) and 33 with AD (mean age=66.8). Results: T-tau levels negatively and significantly correlated with total MoCA scores as well as the different MoCA index scores in both the FTD (r=-0.469, p<0.05) and AD (r=-0.545, p<0.01) groups. There were no significant associations with MoCA scores and p-tau181 levels in patients with FTD (r=-0.224, p>0.05), unlike patients with AD, who exhibited significant correlations (r=-0.549, p<0.01). Also, Aß1-42 levels were not significantly correlated with MoCA scores in either of the FTD and AD groups. Conclusion: CSF concentrations of t-tau are inversely correlated to cognitive performance in patients with FTD and both t-tau and p-tau181 in AD. These findings provide valuable insights into the relationship between clinical cognitive performance and tau-related pathology in FTD.

A review of the kappa opioid receptor system in opioid use.

The kappa opioid receptor (KOR) system is implicated in dysphoria and as an "anti-reward system" during withdrawal from opioids. However, no clear consensus has been made in the field, as mixed findings have been reported regarding the relationship between the KOR system and opioid use. This review summarizes the studies to date on the KOR system and opioids. A systematic scoping review was reported following PRISMA guidelines and conducted based on the published protocol. Comprehensive searches of several databases were done in the following databases: MEDLINE, Embase, PsycINFO, Web of Science, Scopus, and Cochrane. We included preclinical and clinical studies that tested the administration of KOR agonists/antagonists or dynorphin and/or measured dynorphin levels or KOR expression during opioid intoxication or withdrawal from opioids. One hundred studies were included in the final analysis. Preclinical administration of KOR agonists decreased drug-seeking/taking behaviors and opioid withdrawal symptoms. KOR antagonists showed mixed findings, depending on the agent and/or type of withdrawal symptom. Administration of dynorphins attenuated opioid withdrawal symptoms both in preclinical and clinical studies. In the limited number of available studies, dynorphin levels were found to increase in cerebrospinal fluid (CSF) and peripheral blood lymphocytes (PBL) of opioid use disorder subjects (OUD). In animals, dynorphin levels and/or KOR expression showed mixed findings during opioid use. The KOR/dynorphin system appears to have a multifaceted and complex nature rather than simply functioning as an anti-reward system. Future research in well-controlled study settings is necessary to better understand the clinical role of the KOR system in opioid use.

Relationship between neuroimaging and cognition in frontotemporal dementia: An FDG-PET and structural MRI study.

BACKGROUND AND PURPOSE: Frontotemporal dementia (FTD) is a clinically and pathologically heterogeneous neurodegenerative condition with a prevalence comparable to Alzheimer's disease for patients under 65 years of age. Limited studies have examined the association between cognition and neuroimaging in FTD using different imaging modalities. METHODS: We examined the association of cognition using Montreal Cognitive Assessment (MoCA) with both gray matter (GM) volume and glucose metabolism using magnetic resonance imaging and fluorodeoxyglucose (FDG)-PET in 21 patients diagnosed with FTD. Standardized uptake value ratio (SUVR) using the brainstem as a reference region was the primary outcome measure for FDG-PET. Partial volume correction was applied to PET data to account for disease-related atrophy. RESULTS: Significant positive associations were found between whole-cortex GM volume and MoCA scores (r = 0.46, p = .04). The association between whole-cortex FDG SUVR and MoCA scores was not significant (r = 0.37, p = .09). GM volumes of the frontal cortex (r = 0.54, p = .01), caudate (r = 0.62, p<.01), and insula (r = 0.57, p<.01) were also significantly correlated with MoCA, as were SUVR values of the insula (r = 0.51, p = .02), thalamus (r = 0.48, p = .03), and posterior cingulate cortex (PCC) (r = 0.47, p = .03). CONCLUSIONS: Whole-cortex atrophy is associated with cognitive dysfunction, and this association is larger than for whole-cortex hypometabolism as measured with FDG-PET. At the regional level, focal atrophy and/or hypometabolism in the frontal cortex, insula, PCC, thalamus, and caudate seem to be important for the decline of cognitive function in FTD. Furthermore, these results highlight how functional and structural changes may not overlap and might contribute to cognitive dysfunction in FTD in different ways.

Relationship between Neuroimaging and Cognition in Frontotemporal Dementia: A [18 F]FDG PET and Structural MRI Study.

Background: Frontotemporal dementia (FTD) is a clinically and pathologically heterogeneous condition with a prevalence comparable to Alzheimer's Disease for patients under sixty-five years of age. Gray matter (GM) atrophy and glucose hypometabolism are important biomarkers for the diagnosis and evaluation of disease progression in FTD. However, limited studies have systematically examined the association between cognition and neuroimaging in FTD using different imaging modalities in the same patient group. Methods: We examined the association of cognition using Montreal Cognitive Assessment (MoCA) with both GM volume and glucose metabolism using structural magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose positron emission tomography scanning ([18F]FDG PET) in 21 patients diagnosed with FTD. Standardized uptake value ratio (SUVR) using the brainstem as a reference region was the primary outcome measure for [18F]FDG PET. Partial volume correction was applied to PET data to account for disease-related atrophy. Results: Significant positive associations were found between whole-cortex GM volume and MoCA scores (r = 0.461, p = 0.035). The association between whole-cortex [18F]FDG SUVR and MoCA scores was not Significant (r = 0.374, p = 0.094). GM volumes of the frontal cortex (r = 0.540, p = 0.011), caudate (r = 0.616, p = 0.002), and insula (r = 0.568, p = 0.007) were also Significantly correlated with MoCA, as were SUVR values of the insula (r = 0.508, p = 0.018), thalamus (r = 0.478, p = 0.028), and posterior cingulate cortex (PCC) (r = 0.472, p = 0.030). Discussion: Whole-cortex atrophy is associated with cognitive dysfunction, and this effect is larger than for cortical hypometabolism as measured with [18F]FDG PET. At the regional level, focal atrophy and/or hypometabolism in the frontal lobe, insula, PCC, thalamus, and caudate seem to imply the importance of these regions for the decline of cognitive function in FTD. Furthermore, these results highlight how functional and structural changes may not overlap and might contribute to cognitive dysfunction in FTD in different ways. Our findings provide insight into the relationships between structural, metabolic, and cognitive changes due to FTD.