Ciara Treacy

We report on the feasibility, effectiveness, and cost-utility of implementing evidence-based PTSD treatment to quickly enhance the capacities of a French public hospital network, in the weeks after the November 15 Paris attacks. A 2-arm, multicentric preference clinical trial and economic-evaluation compared the use of Reconsolidation Therapy (RT) to treatment-as-usual (TAU) for 332 adults, mostly with post-traumatic stress disorder (PTSD). RT involves recalling trauma under propranolol during a weekly 25-minute session for six consecutive weeks. Feasibility endpoints included the number of trained hospital personnel over two days and the number of participants choosing RT as their preferred treatment modality. The primary effectiveness endpoint was the delta scores in PTSD symptoms from baseline to Week 52. Cost-utility was evaluated by comparing RT to TAU. A large number of therapists (n = 160) were trained at various hospital sites over two days, and more participants opted for RT (n = 262) than TAU (n = 70), supporting feasibility endpoints. After 1 year, the mean PTSD symptom score decreased by 38.14 points (SD = 0.10) in the RT group and by 35.02 (SD = 1.68) for TAU (p = .297), indexing significant improvement in both groups. A significant difference of 5.11 points (SD = 2.50) in favor of RT (p = .041) emerged at Week 7, suggesting a faster initial recovery with RT vs. TAU. RT had a 55.4% probability of being the more effective and cheaper treatment compared to only 8.4% for TAU, outperforming TAU with a point-estimate saving of 27 150€ per quality-adjusted life year (QALY). Annual sick leave costs were 4 147€ (95%CI: 3 394 - 5 012) for RT versus 7 386€ (95%CI: 5 416 - 10 340) for TAU (p = 0.01). Following massive trauma exposure, it is achievable to train mental health staff over 2 days in providing efficient evidence-based and cost-effective PTSD treatment. Findings await replication.

Inhibition represents a core executive function which underlies the ability to suppress interfering and/or distracting stimuli, thereby building resistance against task-irrelevant information. However, the impact of ageing on inhibitory functioning and the potential role of neuroplasticity - largely driven by predominant excitatory (glutamatergic) and inhibitory (GABAergic) neurochemicals – remains poorly understood. In this study, we investigated age relationships with neurochemical concentrations (GABA+ and Glx) and examined the associations between these neurochemicals and inhibitory sub-components in the context of healthy ageing. To this end, participants completed three inhibition tasks (i.e., flanker, Stroop and go/no-go), each measuring a different sub-component process, via the PsyToolkit platform. MRS data was acquired in the sensorimotor (SM1; n=71, mean age (SD) = 68.3 (±9.7) years, 39 females) and prefrontal (PFC; n=58, mean age (SD) = 67.6 (±9.6) years, 30 females) regions using a HERMES sequence and analysed using OSPREY’s pipeline. After correcting for gender and education, semi-partial correlations (rho) revealed no significant relationships between age and GABA+ or Glx concentrations in either the SM1 or PFC regions. Furthermore, through partial correlations (rho), after correcting for age, gender and education, we identified a significant negative relationship between SM1 Glx concentrations and go/no-go error rates, such that greater concentrations of Glx in the SM1 region were associated with greater accuracy on the go/no-go task. The null age-neurochemical results suggest that GABA+ and Glx may not uniformly decline during healthy ageing. This finding suggests that the relationship between older age and neurochemistry may be more nuanced than previously reported. In addition, our neurochemical-behavioural findings provide neurochemically-and-spatially specific evidence that SM1 Glx concentrations may be important for response inhibition. This result indicates a role for the glutamatergic system in supporting inhibition over the normal course of ageing.

The 2024 Lancet Commission on Dementia estimates that up to 45% of dementia cases could be prevented by addressing modifiable risk factors, emphasising both prevention opportunities and the need to understand the biological mechanisms. This study investigated neurophysiological mechanisms underlying modifiable dementia risk factors in cognitively unimpaired older adults. Seventy-nine cognitively unimpaired older adults underwent MRI brain scans, with spectroscopy measurements taken from the sensorimotor cortex (SMC) and prefrontal cortex (PFC), using a Hadamard Encoding and Reconstruction of MEGA-Edited Spectroscopy (HERMES) sequence, optimised for measuring GABA+. Modifiable dementia risk scores were calculated using the Assessment for Cognitive Health and Dementia Risk (CogDrisk). Hierarchical linear regression analyses revealed a significant negative relationship within the SMC, with lower GABA+ (β = −0.249, p = 0.009) associated with higher risk scores. In the PFC, lower tNAA and tCho concentrations significantly predicted higher risk scores (β = −0.168 and −0.170, respectively). These findings suggest that GABAergic system alterations may underlie the pathophysiology of modifiable dementia risk in healthy ageing, whilst changes in tNAA and tCho may reflect early alterations in neuronal integrity. These region-specific neurochemical findings may help identify potential early biomarkers for dementia risk, and suggest new therapeutic pathways for preventive interventions.

Objective:
The inhibition deficit hypothesis postulates that inhibitory functioning declines with age, which negatively impacts other cognitive abilities. Yet still, the impact of healthy ageing on inhibitory functioning remains unclear, with the multifaceted nature of inhibition often an overlooked factor. Moreover, no prior study has empirically tested whether inhibitory sub-components explain differential age-effects in sustained attention - an open question that this work aims to address.

Method:
In this cross-sectional study, we investigated the inhibition deficit hypothesis in a sample of eighty healthy older adults (mean age = 67.78 years, 44f). We utilised the PsyToolkit platform to administer three inhibition tasks (i.e., flanker, Stroop, and go/no-go), each targeting a distinct sub-component process, along with the Sustained Attention to Response Task (SART).

Results:
Semi-partial correlations (rho) of the three inhibition sub-component measures (correcting for gender and education) with age resulted in significant positive relationships with task performance on the Stroop and go/no-go, such that older individuals had more pronounced Stroop effects and worse go/no-go accuracy, respectively. Lastly, go/no-go performance completely mediated the relationship between ageing and sustained attention performance, whilst Stroop effects partially mediated this association.

Conclusion:
Age-related declines were observed in specific inhibition tasks, which speaks against a general inhibition deficit in healthy ageing and cautions against conflating these sub-components into a generalised concept of inhibition. The mediation findings demonstrate that inhibitory sub-components account for age-related declines in sustained attention, over and beyond ageing itself via an indirect path, representing an important cognitive domain to maintain throughout ageing.

Question:
Are different inhibitory sub-components associated with age, and do they mediate age-related changes in sustained attention?

Findings:
Different inhibition tasks were uncorrelated, demonstrating specific relationships with age and providing evidence that select inhibition tasks can explain differential age-effects in sustained attention.

Importance:
This study lends support for the inhibition deficit hypothesis and underlines the importance of considering inhibitions’ multifaceted nature.

Next steps:
Future research should adopt longitudinal designs to examine causal relationships