Antonina Luca

Objectives: Hearing loss may contribute to mobility decline, but its relationship with gait in cognitively unimpaired adults and whether it differs by sex is unclear. Methods: In this cross‐sectional study, cognitively unimpaired adults aged 50–80 years from the DataCOG study were included. Gait was assessed using the instrumented Timed Up and Go test, and pure‐tone audiometry (better‐ear PTA exposure). Three prespecified composite gait outcomes (global duration, turning, walking duration) were modeled unadjusted, age/sex‐adjusted, and sex‐stratified, with HC3‐robust linear regression. The a priori criterion was Holm‐adjusted p < 0.05 across the three composites per model; sensitivity analyses added education, comorbidities/cognition, high‐frequency PTA, and a WHO 20 dB HL threshold. Sex‐stratified analyses were also performed. Results: A total of 172 participants were included (119 women; mean age 63.9 ± 8.1 years) all with complete exposure, outcome, age, sex, and education data. Unadjusted, worse hearing was associated with poorer performance on all three composites (Holm p ≤ 0.015). Adjusted for age and sex, global duration was borderline (Holm p = 0.050) and turning/walking duration no longer met the Holm‐adjusted threshold (Holm p = 0.064, 0.131). Sex‐stratified, age‐adjusted estimates were larger in men ( n = 53) than women ( n = 119), but neither sex reached the Holm‐adjusted threshold (men, Holm p = 0.054; women, Holm p ≥ 0.459). Conclusions: Worse peripheral hearing was associated with poorer unadjusted gait performance. Adjustment and multiplicity correction attenuated this to borderline or non‐significant, and apparent sex differences did not reach the prespecified threshold. These findings are hypothesis‐generating and warrant confirmation. Level of Evidence: 3.

Background/Objectives: Intranasal (IN) neuroactivation of trigeminal/nasolacrimal pathways—either pharmacologically (e.g., varenicline nasal spray) or via intranasal electrical neurostimulation—has been shown to increase tear production in dry eye disease (DED) and to improve patient-reported symptoms, with variable effects on ocular surface staining across studies. Intranasal administration can exploit olfactory and trigeminal pathways to access central nervous system (CNS); preclinical studies also report delivery to the optic nerve and ocular compartments (e.g., vitreous) with associated retinal ganglion cell/optic nerve neuroprotection, supporting further investigation of intranasal strategies for ocular neuroprotection. Methods: We conducted a narrative review on the basis of databases of PubMed/MEDLINE, Scopus, Web of Science, and the Cochrane Library, with ClinicalTrials.gov screened for complete and ongoing studies) through 5 January 2026. The search terms included “intranasal/nasal spray”, “dry eye/tear secretion”, “trigeminal/neurostimulation”, and “neuroprotection/retina/optic nerve”, prioritizing clinical trials, mechanistic studies, and comprehensive reviews. Results: Phase IIb–III randomized, vehicle-controlled trials of varenicline solution nasal spray (OC-01) exhibited statistically significant improvements in tear production (Schirmer test) vs. vehicle and improvements in patient-reported symptoms (with statistical significance found in several symptom endpoints), with tolerability characterized mainly by mild, transient non-ocular adverse events. The product received Food and Drug Administration (FDA) approval for dry eye disease in 2021. Open-label and meta-analytic evidence also supports efficacy of intranasal tear neurostimulation in DED. Preclinical and translational studies demonstrated that IN administration could rapidly deliver proteins and other agents to the eye, optic nerve, and brain, with neuroprotective benefits achieved in optic-nerve and retinal injury models. Reported advantages include bypass of the first-pass metabolism and the blood–brain barrier with non-invasive dosing. Major limitations include mucociliary clearance, dose volume constraints, inter-individual variability, and local nasal adverse events. Conclusions: Evidence supports IN delivery as a clinically relevant modality for DED and a promising platform for ocular neuroprotection. Priorities include standardized ocular/retinal pharmacokinetics after IN dosing, head-to-head comparisons with topical/injectable standards, long-term safety surveillance (including olfactory and nasal mucosa), and optimization of candidate molecules and regimens.

Background/Objectives: Cognitive decline and dementia represent a growing global crisis, affecting over 57 million individuals worldwide, projected to exceed 150 million by 2050. The 2024 Lancet Commission identified hearing loss as the single largest modifiable dementia risk factor (~7% population-attributable fraction). Obstructive sleep apnea (OSA), affecting ~936 million adults, is an increasingly recognized contributor yet remains underdiagnosed, especially in low- and middle-income countries (LMICs). This review synthesizes evidence on the global burden of cognitive decline associated with both conditions, evaluates causality debates, and identifies research gaps. Methods: Following SANRA guidelines, a search was conducted across PubMed, Scopus, Web of Science, and the Cochrane Library through February 2026. Original studies, systematic reviews, meta-analyses, and WHO/GBD reports were included; editorials and non-English publications were excluded. After deduplication, 3847 records were screened, and 96 studies met the inclusion criteria. Results: OSA has been linked to cognitive decline through several plausible mechanisms, including intermittent hypoxia, sleep fragmentation, impaired glymphatic clearance, and amyloid-beta accumulation, though the directionality of these associations requires confirmation from longitudinal studies. Hearing loss contributes to cognitive load, social isolation, and cortical reorganization. Both conditions disproportionately affect LMICs, where access to diagnosis and treatment remains limited. CPAP and hearing rehabilitation show cognitive benefits when initiated early, though evidence for reversing established impairment remains limited. A synergistic interaction between the two conditions is biologically plausible but empirically underexplored. Conclusions: OSA and hearing loss are highly prevalent conditions associated with increased dementia risk, though the certainty of causal relationships and the magnitude of intervention effects differ between the two conditions and across the available evidence. Integrated screening and early intervention could yield substantial neuroprotective benefits in high-risk populations and LMICs. Future longitudinal studies should examine combined cognitive trajectories and optimal intervention timing.

Introduction: Behavioural symptoms, including hallucinations, apathy, and depression, are frequent in Parkinson's disease (PD). This review evaluated the effectiveness of rivastigmine in treating neuropsychiatric symptoms in PD. Methods: A search of PubMed, MEDLINE and EBSCO (1 January 2000–1 October 2025) using terms related to PD and intervention (rivastigmine, anticholinesterase) was conducted. Case reports and case series were excluded. Results: Eight studies (5 randomized controlled trials and three open‐label studies) were selected. Due to the heterogeneity of the outcomes and methodological differences between studies, findings were summarized in a narrative way. In almost all studies, rivastigmine improved hallucinations. Data on the effect of apathy are mixed. Conclusions: The present review suggests that rivastigmine may improve hallucinations in selected PD patients. Future multicentre, adequately powered randomized controlled trials with a stratification by cognitive status, formulation, and dose of rivastigmine are needed. Despite the limited number of high‐quality studies and methodological heterogeneity, clinical practice consistently suggests the beneficial role of rivastigmine in managing behavioural disturbances in PD. In real‐world settings, rivastigmine is frequently associated with improvement of hallucinations and affective symptoms, particularly in individuals with co‐occurring cognitive impairment. While these observations cannot substitute for robust controlled evidence, they provide additional support for the therapeutic value of rivastigmine.

Background: Social cognition is increasingly recognized as part of the non-motor phenotype of essential tremor (ET). Available ET evidence suggests selective alterations in some socio-cognitive domains, whereas findings on self-reported empathy and alexithymia remain limited and inconsistent. Objectives: This cross-sectional study aimed to evaluate empathy and alexithymia in patients with ET compared with healthy controls (HC), and to explore their associations with global cognition and with each other. Methods: Forty ET patients and 40 HC underwent the Italian versions of the Montreal Cognitive Assessment (MoCA), the short Empathy Quotient (EQ-short), and the Toronto Alexithymia Scale (TAS-20). Results: ET patients had significantly lower MoCA scores than HC (22.1 ± 4.1 vs. 25.3 ± 3.2, p<0.001), whereas no between-group differences emerged for EQ-short or TAS-20 scores. In ET, MoCA was not significantly associated with empathy or alexithymia measures. In HC, higher MoCA scores were associated with greater emotional reactivity. Exploratory bivariate analyses suggested inverse associations between social skills and alexithymia in ET, but only the adjusted ET models remained significant. Conclusion: Our findings do not support a group-level deficit in self-reported empathy or alexithymia in ET. Rather, they suggest that socio-emotional functioning may be largely preserved at the group level, while the relationship between social skills and emotional self-description may differ in ET.

Background: Previous studies assessed the relationship between caregivers’ characteristics and caregiver burden. However, comprehensive evaluations of caregivers’ behavioral and psychological traits remain comparatively limited. Objective: To explore the possible association between the cognitive and behavioral characteristics of caregivers of patients with Alzheimer's disease (AD) and the burden they experience, with a focus on sex/gender differences. Methods: In this multicenter cross-sectional study within the SINdem “Sex and Gender Differences in Dementia” group, informal caregivers of non-institutionalized AD patients attending the Italian Memory Clinics were enrolled. Caregivers completed the Montreal Cognitive Assessment, Revised Scale for Caregiver Self-Efficacy, 20-Item Toronto Alexithymia Scale, Barratt Impulsiveness Scale-11, Brief COPE, 14-Item Resilience Scale, Ten-Item Big Five Inventory, Five Facet Mindfulness Questionnaire, Empathy Quotient–Short, and the Caregiver Burden Inventory. Sex was considered as a binary variable (female/male); gender-related dimensions were explored indirectly through caregivers’ behavioral and psychological characteristics. Results: 238 caregivers and 238 AD patients were enrolled. A higher burden was associated with more daily caregiving hours, lower self-efficacy, greater impulsivity, difficulties identifying feelings, acting without awareness, a stronger tendency to judge, and higher neuroticism. Female caregiver burden was associated with attentional/motor impulsiveness, lower mindfulness, lower resilience, and lower emotional empathy. Male caregivers showed associations with lower self-efficacy, greater reliance on emotion-focused coping, difficulties identifying feelings, lower non-judging, lower agreeableness, and reduced cognitive empathy. Conclusions: Caregiver burden was associated with caregivers’ own behavioral and psychological profiles and sex, beyond patient-related factors. These findings support the importance of integrating sex/gender perspectives and targeted interventions into caregiver assessment and support.