This paper considers the connection between fairness and unfairness from a theoretical standpoint, highlighting the importance of critically evaluating the potential impact of artificial intelligence (AI) tools on patients' perception of healthcare justice. The arguments and analysis are framed within the context of Hannah Arendt's concept of the 'banality of evil' and Miranda Fricker's concept of 'epistemic injustice'. The article suggests that the greatest threat to fairness and transparency when it comes to AI may not be people deliberately trying to cause harm, but rather a widespread culture of apathy and complacency that prevents people from taking action. The paper concludes that renewing patients' commitment to critical thinking and encouraging them to take greater personal responsibility are key. More active and engaged citizenship is also required. By cultivating critical reflection, prioritising data privacy, promoting collective support, building emotional resilience, and advocating for ethical AI, individuals can transform their healthcare into a formidable bulwark against those who seek to curtail their autonomy and stifle their voices. This comprehensive healthcare strategy is about more than just the individual's welfare. It is also about creating a fair, self-governing society in which the potential of each person as a smart, active participant is recognised and protected.

There is increasing recognition that a broader array of biological changes may contribute to the clinical expression of cognitive decline. As such, an emerging and often overlooked consideration in dementia is apathy, gait dysfunction, motoric-cognitive risk syndrome, and their interplay. Broadly, apathy, gait dysfunction, and motoric-cognitive risk may reflect changes across multiple physiological and neural systems acting as clinical markers bridging normal aging and overt dementia, thereby offering a framework to better understand and monitor dementia risk, management, and prognosis. This article synthesizes some key findings in this emerging field, highlighting their relevance to integrated screening and intervention strategies. The authors emphasize the clinical importance of recognizing apathy and gait slowing as early, observable features that often precede overt cognitive impairment and are commonly encountered across routine clinical settings.

BackgroundLate-life emergence of persistent behavioral changes has been recognized as a clinically meaningful sign of neurodegeneration. These neuropsychiatric symptoms, operationalized as mild behavioral impairment (MBI), represent a unique pathway through which early dementia symptoms may become observable. By capturing this neurobehavioral dimension of risk, MBI expands the traditional focus on cognitive decline and may provide a complementary framework for understanding the early manifestations of neurodegeneration.ObjectiveThis systematic review evaluated longitudinal evidence on the association between MBI and incident dementia, including conversion rates, dementia subtypes, domain-specific risk patterns, and biomarker correlates.MethodsWe systematically searched five databases up to November 2025. Eligible studies were longitudinal prospective or retrospective cohorts including adults ≥ 50 years without dementia at baseline, assessing MBI using ISTAART-aligned instruments and reporting incident dementia outcomes. Two reviewers independently screened studies and extracted data. Hazard ratios were synthesized using random-effects meta-analysis, with heterogeneity and publication bias formally assessed.ResultsDespite significant study heterogeneity, MBI was associated with increased risk of incident dementia. Alzheimer's disease was the most frequently reported outcome. Among different neurobehavioral domains, apathy and affective dysregulation emerged as particularly strong predictors of dementia risk. A few biomarker studies linked MBI to greater amyloid burden, elevated plasma phosphorylated tau, and structural brain changes, supporting a biological connection between MBI and early neurodegeneration.ConclusionsMBI seems to represent a clinically meaningful syndrome that identifies individuals at elevated risk for dementia. Future studies must confirm the clinical and epidemiological value of MBI and/or its subdomains, exploring their biological substrates.

Physical inactivity is a key modifiable risk factor for Alzheimer's disease (AD). However, emerging evidence suggests a bidirectional relationship where inactivity also serves as an early manifestation of AD pathology. This perspective synthesizes recent findings from long-term epidemiological cohorts, brainstem neuropathology, and digital phenotyping to reconceptualize the role of inactivity in preclinical AD. Early tau accumulation in catecholaminergic nuclei (locus coeruleus and ventral tegmental area) disrupts circuits essential for reward valuation and effort calculation. We hypothesize that this neurobiological failure may manifest as prodromal apathy and declining physical activity years before cognitive impairment. Standard metrics like step counts fail to capture these nuances. We propose a multidimensional digital phenotype - incorporating temporal complexity, circadian rhythms, and life-space mobility - to distinguish "behavioral" from "biologically constrained" inactivity. This framework has critical implications for trial enrichment and the design of personalized lifestyle interventions.

Monocyte chemoattractant protein-1 (MCP-1; also known as CCL2) is a chemokine implicated in neuroinflammatory pathways that may contribute to cognitive decline in Alzheimer's disease (AD). Elevated MCP-1 is associated with glial activation, blood-brain barrier dysfunction, and immune-cell recruitment. This study assessed the longitudinal association between peripheral MCP-1 and cognitive decline in biomarker-confirmed participants across the AD continuum and explored whether psychological stress was associated with longitudinal MCP-1 changes.

Late-life depression is associated with reduced treatment efficacy and age-related impairments in synaptic plasticity and stress responsiveness. Myo-inositol, an endogenous regulator of phosphoinositide signalling, has been proposed as candidate treatment for mood disorders, but its effects in age-related mood disorders remain unclear. Here, we investigated the impact of chronic myo-inositol supplementation on depressive behaviour and synaptic markers in aged male and female mice. Aged mice displayed reduced self-care behaviour in the sucrose splash test compared to young adults. Myo-inositol supplementation restored grooming behaviour in both sexes, an effect maintained following exposure to unpredictable chronic mild stress and independent of locomotor activity. Molecular analyses revealed sex-specific synaptic adaptations, with myo-inositol enhancing postsynaptic density protein 95 (PSD-95) levels in aged males, while increasing phosphorylation of the AMPA receptor subunit GluA1 at serine 845 and TARP expression in females. These findings demonstrate that myo-inositol dampens age-related apathetic alterations and is associated with sex-specific synaptic mechanisms, supporting its potential as a therapeutic strategy for late-life depression.

Late-life depression presenting with atypical features, progressive functional decline, behavioral changes, or poor response to treatment should prompt consideration of secondary causes. Olfactory groove meningiomas are slow-growing anterior skull base tumors that may remain clinically silent for prolonged periods and may present primarily with neuropsychiatric symptoms due to frontal lobe involvement. We report the case of a 64-year-old woman with a progressive depressive presentation characterized by marked functional decline, apathy, abulia, behavioral disinhibition, impaired insight, and executive dysfunction. Symptoms were initially interpreted as a primary depressive disorder in the context of bereavement and were poorly responsive to psychopharmacological treatment. Neuroimaging revealed a large extra-axial anterior skull base mass centered on the olfactory groove, measuring approximately 63 mm in maximum diameter, with homogeneous contrast enhancement, marked mass effect on the frontal lobes, and extensive vasogenic edema. The patient underwent surgical resection in January 2024. Histopathological examination confirmed a World Health Organization grade 2 olfactory groove meningioma, with brain invasion and spontaneous necrosis. Postoperative imaging showed a small probable residual lesion, and the patient subsequently underwent adjuvant radiotherapy with 60 Gy in 30 fractions using volumetric modulated arc therapy. Follow-up imaging demonstrated a slight reduction in the residual lesion. Clinically, the patient showed postoperative improvement, with preserved orientation and language functions, no focal neurological deficits, and a return to functional independence in daily life, although residual anosmia and non-specific orthostatic symptoms persisted. This case illustrates a strong clinical association between a large olfactory groove meningioma and a late-life neuropsychiatric presentation initially interpreted as depression. Such tumors should be considered when apparent late-life depression is accompanied by progressive functional deterioration, behavioral disinhibition, impaired insight, executive dysfunction, or poor response to adequate psychiatric treatment. Neuroimaging should be considered in these presentations to identify potentially treatable structural brain lesions.

Alzheimer's disease (AD) is the leading cause of dementia and represents a public health challenge in aging populations. Acetylcholinesterase inhibitors (AChEIs) remain first-line symptomatic therapy for mild to moderate AD, with real-world effectiveness largely influenced by tolerability, adherence, and treatment persistence. Galantamine and its inactive prodrug benzgalantamine are differentiated within the class by a dual mechanism that combines reversible acetylcholinesterase inhibition with positive allosteric modulation of nicotinic acetylcholine receptors. This narrative review synthesizes preclinical and clinical evidence examining galantamine-based therapy, with a focus on aspects related to nicotinic acetylcholine receptors: behavioral symptoms and sleep-related effects. Across randomized, observational, and longitudinal studies, galantamine has been associated with improvement or stabilization in behavioral domains including aberrant motor behavior, agitation/aggression, anxiety, apathy, delusions, disinhibition, and hallucinations. However, like other members of the AChEI class, gastrointestinal tolerability issues may affect treatment persistence. Benzgalantamine was developed to address gastrointestinal tolerability, with the aim of improving adherence and long-term treatment continuity.

Despite the success of combined antiretroviral therapy (cART) in achieving peripheral viral suppression, HIV-associated neurocognitive disorder (HAND) remains a persistent challenge, affecting approximately 50% of people living with HIV. This review identifies the prefrontal cortex (PFC) as a primary target of HIV-1 neurotoxicity, as HIV-1 can directly infect the brain, and cART fails to eliminate the production of viral proteins from latent HIV-microglial reservoirs. The blood-brain barrier receives several hits from HIV-1 proteins, leading to a leaky and highly permeable barrier. Several proteins drive chronic neuroinflammation through inflammasome activation and pyroptosis, and ferroptosis in microglia. Glutamatergic dysregulation in the CNS results in increased neuron excitability and neurotoxicity. Also, overactive complement-mediated synaptic pruning and microglial senescence disrupt the intricate neural networks required for higher-order signaling. Neuroimaging and PFC dysfunction can be linked to specific HIV-1 proteins and their effects on the brain. Clinical symptoms of HAND directly reflect specialized PFC dysfunction. Deficits include impaired executive processes, which can present as lacking foresight for goal-directed actions, poor planning, and difficulty switching between tasks. Significant behavioral changes, including disinhibition, impaired moral reasoning, and increased risk-taking, can also be seen. Patients experience apathy, emotional blunting, and rapid mood shifts. Cognitive impairments include working memory loss, distractibility, and inappropriate memory linking. PFC disruptions can escalate into neuropsychiatric sequelae, driven by damaged dopamine and serotonin pathways. Defining these viral-mediated mechanisms will facilitate the development of pharmacological strategies that target several HIV-mediated neurotoxic pathways to prevent the debilitating characteristics of HAND.