Neurocognitive insights on conceptual knowledge and its breakdown

Conceptual knowledge reflects our multi-modal ‘semantic database’. As such, it brings meaning to all verbal and non-verbal stimuli, is the foundation for verbal and non-verbal expression and provides the basis for computing appropriate semantic generalizations. Multiple disciplines (e.g. philosophy, cognitive science, cognitive neuroscience and behavioural neurology) have striven to answer the questions of how concepts are formed, how they are represented in the brain and how they break down differentially in various neurological patient groups. A long-standing and prominent hypothesis is that concepts are distilled from our multi-modal verbal and non-verbal experience such that sensation in one modality (e.g. the smell of an apple) not only activates the intramodality long-term knowledge, but also reactivates the relevant intermodality information about that item (i.e. all the things you know about and can do with an apple). This multi-modal view of conceptualization fits with contemporary functional neuroimaging studies that observe systematic variation of activation across different modality-specific association regions dependent on the conceptual category or type of information. A second vein of interdisciplinary work argues, however, that even a smorgasbord of multi-modal features is insufficient to build coherent, generalizable concepts. Instead, an additional process or intermediate representation is required. Recent multidisciplinary work, which combines neuropsychology, neuroscience and computational models, offers evidence that conceptualization follows from a combination of modality-specific sources of information plus a transmodal ‘hub’ representational system that is supported primarily by regions within the anterior temporal lobe, bilaterally.     

Sending people to care homes in lower-income countries: A qualified defence

In recent years, a proportion of older Germans has been sent to relatively high-end care homes within lower-income countries where the care tends to be cheaper and more extensive than that in German care homes. Destination countries are found predominantly within Eastern Europe (e.g. Poland, Hungary, Czech Republic), but to a lesser extent also within South-East Asia (e.g. Thailand). At the same time, these expatriations have caused much controversy, with some German commentators calling them ‘inhumane’ and ‘shameful’. In this article, I argue that such criticisms are overdrawn. Although sending an older individual to a care home within a lower-income country can be morally impermissible, I find that there are at least three sets of conditions under which it is not.     

Economics and mental health: the current scenario

Economics and mental health are intertwined. Apart from the accumulating evidence of the huge economic impacts of mental ill‐health, and the growing recognition of the effects that economic circumstances can exert on mental health, governments and other budget‐holders are putting increasing emphasis on economic data to support their decisions. Here we consider how economic evaluation (including cost‐effectiveness analysis, cost‐utility analysis and related techniques) can contribute evidence to inform the development of mental health policy strategies, and to identify some consequences at the treatment or care level that are of relevance to service providers and funding bodies. We provide an update and reflection on economic evidence relating to mental health using a lifespan perspective, analyzing costs and outcomes to shed light on a range of pressing issues. The past 30 years have witnessed a rapid growth in mental health economics, but major knowledge gaps remain. Across the lifespan, clearer evidence exists in the areas of perinatal depression identification‐plus‐treatment; risk‐reduction of mental health problems in childhood and adolescence; scaling up treatment, particularly psychotherapy, for depression; community‐based early intervention and employment support for psychosis; and cognitive stimulation and multicomponent carer interventions for dementia. From this discussion, we pull out the main challenges that are faced when trying to take evidence from research and translating it into policy or practice recommendations, and from there to actual implementation in terms of better treatment and care.     

Looking beyond the hippocampus: old and new neurological targets for understanding memory disorders

Although anterograde amnesia can occur after damage in various brain sites, hippocampal dysfunction is usually seen as the ultimate cause of the failure to learn new episodic information. This assumption is supported by anatomical evidence showing direct hippocampal connections with all other sites implicated in causing anterograde amnesia. Likewise, behavioural and clinical evidence would seem to strengthen the established notion of an episodic memory system emanating from the hippocampus. There is, however, growing evidence that key, interconnected sites may also regulate the hippocampus, reflecting a more balanced, integrated network that enables learning. Recent behavioural evidence strongly suggests that medial diencephalic structures have some mnemonic functions independent of the hippocampus, which can then act upon the hippocampus. Anatomical findings now reveal that nucleus reuniens and the retrosplenial cortex provide parallel, disynaptic routes for prefrontal control of hippocampal activity. There is also growing clinical evidence that retrosplenial cortex dysfunctions contribute to both anterograde amnesia and the earliest stages of Alzheimer''s disease, revealing the potential significance of this area for clinical studies. This array of findings underlines the importance of redressing the balance and the value of looking beyond the hippocampus when seeking to explain failures in learning new episodic information.     

Mid-life leukocyte telomere length and dementia risk: An observational and mendelian randomization study of 435,046 UK Biobank participants

Telomere attrition is one of biological aging hallmarks and may be intervened to target multiple aging-related diseases, including Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD). The objective of this study was to assess associations of leukocyte telomere length (TL) with AD/ADRD and early markers of AD/ADRD, including cognitive performance and brain magnetic resonance imaging (MRI) phenotypes. Data from European-ancestry participants in the UK Biobank (n = 435,046) were used to evaluate whether mid-life leukocyte TL is associated with incident AD/ADRD over a mean follow-up of 12.2 years. In a subsample without AD/ADRD and with brain imaging data (n = 43,390), we associated TL with brain MRI phenotypes related to AD or vascular dementia pathology. Longer TL was associated with a lower risk of incident AD/ADRD (adjusted Hazard Ratio [aHR] per SD = 0.93, 95% CI 0.90–0.96, p = 3.37 × 10⁻⁷). Longer TL also was associated with better cognitive performance in specific cognitive domains, larger hippocampus volume, lower total volume of white matter hyperintensities, and higher fractional anisotropy and lower mean diffusivity in the fornix. In conclusion, longer TL is inversely associated with AD/ADRD, cognitive impairment, and brain structural lesions toward the development of AD/ADRD. However, the relationships between genetically determined TL and the outcomes above were not statistically significant based on the results from Mendelian randomization analysis results. Our findings add to the literature of prioritizing risk for AD/ADRD. The causality needs to be ascertained in mechanistic studies.