The clinical and pathophysiological correlates of locus coeruleus (LC) degeneration in Alzheimer's disease (AD) could be clarified using a method to index LC integrity in vivo, neuromelanin-sensitive MRI (NM-MRI). We examined whether integrity of the LCnorepinephrine system, assessed with NM-MRI, is associated with stage of AD and with neuropsychiatric symptoms (NPS), independent of cortical pathophysiology (amyloid-β and tau burden). Cognitively normal older adults (n=118), and individuals with mild cognitive impairment (MCI, n=44), and AD (n=28) underwent MR imaging and tau and amyloid-β positron emission tomography (with [ 18 F]MK6240 and [ 18 F]AZD4694, respectively). Integrity of the LC-norepinephrine system was assessed based on contrast-to-noise ratio of the LC on NM-MRI images. Braak stage of AD was derived from regional binding of [ 18 F]MK6240. NPS were assessed with the Mild Behavioral Impairment Checklist (MBI-C). LC signal contrast was decreased in tau-positive participants (t186=-4.00, p=0.0001) and negatively correlated to Braak stage (Spearman ρ=-0.31, p=0.00006). In tau-positive participants (n=51), higher LC signal predicted NPS severity (ρ=0.35, p=0.019) independently of tau burden, amyloid-β burden, and cortical gray matter volume. This relationship appeared to be driven by the impulse dyscontrol domain of NPS, which was highly correlated to LC signal (ρ=0.44, p=0.0027). NM-MRI reveals loss of LC integrity that correlates to severity of AD. However, LC preservation in AD may also have negative consequences by conferring risk for impulse control symptoms. NM-MRI shows promise as a practical biomarker that could have utility in predicting the risk of NPS or guiding their treatment in
Policies can impact the well-being of children both directly and indirectly. Despite the growing acceptance of children as active citizens, they are often neglected in decision-making regarding policy. The Canadian government, which is built on principles of liberty and respect of human rights has the duty to guarantee that children’s views and needs are taken into account. In this regard, the creation of a National Children’s Rights Commissioner is an essential step to the establishment of a system that is accountable to children and the entire community. In this paper, we present the arguments in support of the need for a National Commissioner of Children and Youth in Canada. Recent research on the beneficial impact of the National Commissioner and their successes across different Commonwealth countries will be presented, and implications will be discussed.
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