ObjectiveTo investigate the status of the basal forebrain cholinergic system in primary progressive aphasia (PPA) as justification for cholinergic therapy.MethodsA cohort of 36 brains from PPA participants with the neuropathology of Alzheimer disease (PPA-AD, n = 14) or frontotemporal lobar degeneration (PPA-tau, n = 12; PPA-TDP, n = 10) were used for semiquantitative rating of degeneration and gliosis of basal forebrain cholinergic neurons (BFCN). A subpopulation of 5 PPA-AD and 7 control brains underwent detailed analysis of BFCN pathology and cortical cholinergic axonal loss employing immunohistochemical and histochemical methods and stereologic analysis.ResultsSemiquantitatively, 11 (∼80%) PPA-AD participants were rated as having moderate/severe BFCN loss and gliosis, whereas none of the PPA-tau and only 1 (10%) PPA-TDP participant received such a rating. Detailed analysis in the subpopulation of PPA-AD participants revealed substantial tangle formation, loss of BFCN, and degeneration of cortical cholinergic axons. Compared to controls, loss of p75 low affinity neurotrophin receptor-positive BFCN was detected in the PPA-AD participants (p < 0.01). Acetylcholinesterase-positive cholinergic axons in all cortical areas studied displayed loss in PPA-AD (p < 0.005–0.0001). The loss was more severe in the language-dominant left hemisphere and, within the left hemisphere, in language-affiliated cortical areas.ConclusionsOur results demonstrate prominent depletion of BFCN and cortical cholinergic axons in PPA-AD when compared with normal control or other neuropathologic variants of PPA. The demonstration of cholinergic denervation with an anatomy that fits the clinical picture suggests that cholinergic treatment is justified in patients with PPA who have positive AD biomarkers.

Oliver Goldsmith’s She Stoops to Conquer (1773) was staged only two weeks after the publication of his Essay on the Theatre, in which he famously compared sentimental comedies with what he described as laughing comedies. The play thus illustrates Goldsmith’s principles for his ideal laughing comedy. One of the aspects of this type of comedy, which has rarely been addressed, is its representation of the matrix of temporal and spatial elements, or what Mikhail Bakhtin calls a chronotope. The present study is thus aimed at investigating She Stoops to Conquer in terms of Bakhtinian chronotope. The study argues how different chronotopes have influenced the behaviours as well as the decisions of characters in the play. Moreover, it shows that the chronotopic framework can shed new light on the play’s portrayal of the class divisions in the eighteenth century, when the middle class was emerging in England’s social system.

Todd Phillips’ Joker (2019) is the latest cinematic portrayal of the notorious clown prince of Gotham City. Although the previous film adaptations would usually picture him as a villain to Batman’s hero, this version depicts him as a lonely man who has to cope with depression and struggles to be accepted by and fit in the society. Therefore, this version of the character carries a marked aura of socio-political consciousness. The present paper aims to analyze Todd Phillips’ Joker through the lens of the carnival ritual as put forward by Mikhail Bakhtin. The paper will discuss different carnivalesque elements present in Joker, and illustrate how the movie takes full advantage of them to mount an attack against the prevalent, official culture of Gotham. Moreover, it will argue how Joker forms a utopian condition where the constant anarchy results in freedom.