Our Research
Key Publications
Scottish Brain Sciences is proud to be part of a large cutting-edge network of brain health organisations across the UK and United States, focussing on different aspects of development, understanding, and interventions that will be used to turn the tide on brain diseases and acquired brain disorders.
NEW PUBLICATION
Remote data collection speech analysis in people at risk for Alzheimer’s disease dementia: usability and acceptability results
Sarah Gregory, John Harrison, Janna Herrmann, Matthew Hunter, Natalie Jenkins, Alexandra König, Nicklas Linz, Saturnino Luz, Elisa Mallick, Hannah Pullen, Miles Welstead, Stephen Ruhmel, Johannes Tröger, Craig W. Ritchie
Published: 2023
Publication summary...
Digital cognitive assessments are gathering importance for the decentralized remote clinical trials of the future. Before including such assessments in clinical trials, they must be tested to confirm feasibility and acceptability with the intended participant group. This study presents usability and acceptability data from the Speech on the Phone Assessment (SPeAk) study. The results from this usability and acceptability analysis suggest that completing this brief battery of cognitive tests via a telephone call is both acceptable and feasible in a midlife-to-older adult population in the United Kingdom, living at risk for Alzheimer’s disease.
Download links...
Human astrocytes and microglia show augmented ingestion of synapses in Alzheimer’s disease via MFG-E8
Makis Tzioras, Michael J.D. Daniels, Caitlin Davies, Paul Baxter, Declan King, Sean McKay, Balazs Varga, Karla Popovic, Madison Hernandez, Anna J. Stevenson, Jack Barrington, Elizabeth Drinkwater, Julia Borella, Rebecca K. Holloway, Jane Tulloch, Jonathan Moss, Clare Latta, Jothy Kandasamy, Drahoslav Sokol, Colin Smith, Veronique E. Miron, Ragnhildur Thóra Káradóttir, Giles E. Hardingham, Christopher M. Henstridge, Paul M. Brennan, Barry W. McColl, Tara L. Spires-Jones
Published: 2023
Publication summary...
Synapse loss correlates with cognitive decline in Alzheimer’s disease (AD). Data from mouse models suggests microglia are important for synapse degeneration, but direct human evidence for any glial involvement in synapse removal in human AD remains to be established. Here we observe astrocytes and microglia from human brains contain greater amounts of synaptic protein in AD compared with non-disease controls, and that proximity to amyloid-β plaques and the APOE4 risk gene exacerbate this effect. In culture, mouse and human astrocytes and primary mouse and human microglia phagocytose AD patient-derived synapses more than synapses from controls. Inhibiting interactions of MFG-E8 rescues the elevated engulfment of AD synapses by astrocytes and microglia without affecting control synapse uptake. Thus, AD promotes increased synapse ingestion by human glial cells at least in part via an MFG-E8 opsonophagocytic mechanism with potential for targeted therapeutic manipulation.
Download links...
Practical pathway for the management of depression in the workplace: a Canadian perspective
Chokka P, Bender A, Brennan S, Ahmed G, Corbière M, Dozois DJA, Habert J, Harrison J, Katzman MA, McIntyre RS, Liu YS, Nieuwenhuijsen K and Dewa CS
Published: 2023
Publication summary...
Major depressive disorder (MDD) and other mental health issues pose a substantial burden on the workforce. Approximately half a million Canadians will not be at work in any week because of a mental health disorder, and more than twice that number will work at a reduced level of productivity (presenteeism). Although it is important to determine whether work plays a role in a mental health condition, at initial presentation, patients should be diagnosed and treated per appropriate clinical guidelines. However, it is also important for patient care to determine the various causes or triggers including work-related factors. Clearly identifying the stressors associated with the mental health disorder can help clinicians to assess functional limitations, develop an appropriate care plan, and interact more effectively with worker’s compensation and disability programs, as well as employers. There is currently no widely accepted tool to definitively identify MDD as work-related, but the presence of certain patient and work characteristics may help. This paper seeks to review the evidence specific to depression in the workplace, and provide practical tips to help clinicians to identify and treat work- related MDD, as well as navigate disability issues.
Download links...
What’s in a Score: A Longitudinal Investigation of Scores Based on Item Response Theory and Classical Test Theory for the Amsterdam Instrumental Activities of Daily Living Questionnaire in Cognitively Normal and Impaired Older Adults.
Dubbelman, M. A., Postema, M. C., Jutten, R. J., Harrison, J. E., Ritchie, C. W., Aleman, A., de Jong, F. J., Schalet, B. D., Terwee, C. B., van der Flier, W. M., Scheltens, P., & Sikkes, S. A. M.
Published: 2023
Publication summary...
Real world relevance is a key issue with respect to treatment efficacy. Many of the traditional scales fail to index key activities of daily living, such as emailing, internet purchasing, online banking, etc. The Amsterdam iADL was developed to remedy these failings. In this study we have sought to establish which of two scoring methods better captured change over time.
Objective: We aimed to investigate whether item response theory (IRT)-based scoring allows for a more accurate, responsive, and less biased assessment of everyday functioning than traditional classical test theory (CTT)-based scoring, as measured with the Amsterdam Instrumental Activities of Daily Living Questionnaire. Method: In this longitudinal multicenter study including cognitively normal and impaired individuals, we examined IRT-based and CTT-based score distributions and differences between diagnostic groups using linear regressions, and investigated scale attenuation. We compared change over time between scoring methods using linear mixed models with random intercepts and slopes for time. Results: Two thousand two hundred ninety-four participants were included (66.6 ± 7.7 years, 54% female): n = 2,032 (89%) with normal cognition, n = 93 (4%) with subjective cognitive decline, n = 79 (3%) with mild cognitive impairment, and n = 91 (4%) with dementia. At baseline, IRT-based and CTT-based scores were highly correlated (r = −0.92). IRT-based scores showed less scale attenuation than CTT-based scores. In a subsample of n = 1,145 (62%) who were followed for a mean of 1.3 (SD = 0.6) years, IRT-based scores declined significantly among cognitively normal individuals (unstandardized coefficient [B] = −0.15, 95% confidence interval, 95% CI [−0.28, −0.03], effect size = −0.02), whereas CTT-based scores did not (B = 0.20, 95% CI [−0.02, 0.41], effect size = 0.02). In the other diagnostic groups, effect sizes of change over time were similar. Conclusions: IRT-based scores were less affected by scale attenuation than CTT-based scores. With regard to responsiveness, IRT-based scores showed more signal than CTT-based scores in early disease stages, highlighting the IRT-based scores’ superior suitability for use in preclinical populations.
Download links...
Genetic risk factors of Alzheimer’s Disease disrupt resting‑state functional connectivity in cognitively intact young individuals
Ludmila Kucikova1,2 · Jianmin Zeng3 · Carlos Muñoz‑Neira1,4 · Graciela Muniz‑Terrera5,6 · Weijie Huang1,2,7 · Sarah Gregory5 · Craig Ritchie5,8 · John O’Brien4 · Li Su1,2,4
Published: 26 June, 2023
Publication summary...
Past evidence shows that changes in functional brain connectivity in multiple resting-state networks occur in cognitively healthy individuals who have non-modifiable risk factors for Alzheimer’s Disease. Here, we aimed to investigate how those changes differ in early adulthood and how they might relate to cognition.
We investigated the effects of genetic risk factors of AD, namely APOEe4 and MAPTA alleles, on resting-state functional connectivity in a cohort of 129 cognitively intact young adults (aged 17–22 years). We used Independent Component Analysis to identify networks of interest, and Gaussian Random Field Theory to compare connectivity between groups. Seed-based analysis was used to quantify inter-regional connectivity strength from the clusters that exhibited significant between-group differences. To investigate the relationship with cognition, we correlated the connectivity and the performance on the Stroop task.
The analysis revealed a decrease in functional connectivity in the Default Mode Network (DMN) in both APOEe4 carriers and MAPTA carriers in comparison with non-carriers. APOEe4 carriers showed decreased connectivity in the right angular gyrus (size = 246, p-FDR = 0.0079), which was correlated with poorer performance on the Stroop task. MAPTA carriers showed decreased connectivity in the left middle temporal gyrus (size = 546, p-FDR = 0.0001). In addition, we found that only MAPTA carriers had a decreased connectivity between the DMN and multiple other brain regions.
Download links...
Other Publications
Apart from the key publications listed here, you can also find a catalogue of other publications from our Scottish Brain Sciences colleagues: