Background: Paracetamol (acetaminophen) is a widely used analgesic and antipyretic, including among older adults. Its activity within the central nervous system has raised questions about its possible effects on cognitive function. This study aims to evaluate human and preclinical evidence on the neurocognitive findings associated with paracetamol exposure across adulthood, with particular attention to older adults, and to outline potential underlying mechanisms. Methods: PubMed/MEDLINE was searched for English-language, peer-reviewed studies published up to October 2025. Eligible studies examined cognitive or neurobiological outcomes associated with paracetamol exposure in adult humans or animal models. Twenty original studies were included in a narrative synthesis. Results: Human evidence was limited and mixed. Acute or short-term intervention studies reported domain-specific, mixed, or nonsignificant findings. In contrast, observational studies reported associations with cognitive decline or dementia that remained vulnerable to confounding and reverse causation. Preclinical findings were heterogeneous: potentially favourable, no significant differences, and potentially adverse findings occurred across overlapping human-equivalent dose ranges and varied by model, exposure duration, and outcome domain. Biochemical and histopathological findings did not necessarily correspond to behavioural cognitive outcomes. Discussion: The divergence between mixed acute findings, confounded observational associations, and heterogeneous preclinical results precludes a unified interpretation, particularly for older adults. Conclusion: Current evidence establishes neither cognitive benefit nor cognitive harm in humans and does not support changes to the therapeutic use of paracetamol. In older adults, treatment should continue to follow established geriatric prescribing principles. Further well-controlled studies are needed to clarify long-term cognitive safety and the clinical relevance of preclinical findings.
Introduction: Psychiatric symptoms in Huntington’s disease, including mood, anxiety, OCD, and psychosis, significantly impact disease burden. Their variability and frequent polypharmacy complicate treatment. However, evidence on efficacy, acceptability, and tolerability remains limited, with therapeutic decisions largely based on clinical experience. Methods: This systematic review was conducted in accordance with the PRISMA 2020 guidelines. Studies were categorized based on drug type, and for each category, the total number of treated patients, sex ratio, and weighted mean age were calculated. Discontinuation rates and adverse events were also systematically analyzed. Results: We identified 995 unique articles, of which 96 met the eligibility criteria, including 34 clinical studies and 62 case reports. The included clinical studies examined antipsychotics (n = 9; total sample = 797; men = 49.18%; mean age = 51.57 years), antidepressants (n = 8; total sample = 6,510; men = 45.78%; mean age = 50.52 years), mood stabilizers (n = 4; total sample = 85; men = 43.42%; mean age = 46.61 years), and other drugs (n = 13; total sample = 699; men = 53.4%; mean age = 49.78 years). Discontinuation rates ranged from 4% to 11%, and adverse events occurred in 27% to 29% of patients. Discussion: Clinical studies portrayed a less favorable view of pharmacotherapy in Huntington’s disease compared to case reports, likely reflecting publication bias. Despite these limitations, antipsychotics, particularly second-generation antipsychotics, demonstrated some therapeutic benefits. Antidepressants yielded mixed outcomes, while mood stabilizers appeared more effective when used as adjunctive treatments. Conclusions: Evidence on the pharmacological treatment of psychiatric symptoms in HD is limited. Studies showed high heterogeneity, with low-quality evidence supporting SGAs and mood stabilizers as add-ons. Larger, more robust studies are needed.
Abstract: The classical theory of glucagon-like peptide-1 receptor agonists (GLP-1RAs) emphasizes peripheral metabolic regulation and satiety mediated by hypothalamic-brainstem homeostatic pathways. However, numerous clinical studies have shown that GLP-1RAs significantly suppress patients’ food cravings and simultaneously reduce cravings for non-food reinforcers such as alcohol and nicotine, suggesting that the effects of GLP-1RAs extend far beyond the regulation of energy balance. GLP-1 receptors are expressed in the ventral tegmental area, the nucleus accumbens, and the central amygdala; their activation exhibits phase-specific effects: during the reward anticipation phase, they reduce dopamine signaling in the nucleus accumbens, whereas during the intake phase, they enhance this signaling. GLP-1RAs can modulate the mesolimbic dopamine system, likely through a combination of direct central actions and indirect peripheral- to-central signaling pathways, dynamically modulating reward processing rather than simply inhibiting it. Given that the mesolimbic dopamine system serves as a common neural substrate for both food and drug addiction, the observed modulatory effects of GLP-1RAs on various reinforcers suggest preliminary potential for expanded application in the treatment of binge eating disorder and substance use disorders, although clinical evidence remains limited for most non-food indications. Future research should elucidate the central penetration characteristics of different agonists, their cell-type-specific mechanisms of action, and the persistence of their neuromodulatory effects to advance the development of precision therapeutic strategies targeting specific reward circuits.
Abstract: Traumatic Optic Neuropathy (TON) is a leading cause of vision loss after head or eye injury, with few effective treatments available. TON progression involves dynamic crosstalk among glial cells, immune cells, and neurons, which contributes to secondary damage as well as repair processes. Chemokines are key regulators of this intercellular communication. They influence immune cell recruitment, neuroinflammation, neuronal survival, and axon regeneration through receptor signaling. Although certain chemokines have been reported in TON, current findings remain fragmented, highlighting the necessity of an integrated overview that systematically links pathological mechanisms with therapeutic strategies. This review discusses recent advances in TON chemokine signaling, spotlights key mechanistic discoveries, and assesses the potential of targeting these pathways to limit damage and promote the survival of Retinal Ganglion Cells (RGCs), axonal regeneration, and functional recovery.
