Publication: Annals of Clinical and Translational Neurology

Nicolas Nicastro, Ajenthan Surendranathan, Elijah Mak, James B. Rowe, John T. O’Brien

10 September 2019

There is evidence of increased microglial activation in Parkinson’s disease (PD) as shown by in vivo PET ligand such as 11C‐PK11195. In addition, diffusion tensor imaging (DTI) imaging reveals widespread changes in PD, especially when the associated dementia develops.

The researchers studied five subjects with Parkinson’s disease dementia (PDD). Their findings suggest that while DTI metrics mirror cognitive severity, higher 11C‐PK11195 binding seems to be associated with a relative preservation of both white matter tracts and cognition.

Longitudinal studies are warranted to tackle the complex relationship between microglial activation and structural abnormalities in neurodegenerative conditions.

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Publication: Diagnostics

Jeremy M. Brown, Julie Wiggins, Kate Dawson, Timothy Rittman, James B. Rowe

12 August 2019

This research paper summarises the current status of two novel short cognitive tests (SCT), known as Test Your Memory (TYM) and Test Your Memory for Mild Cognitive Impairment (TYM-MCI). The history of and recent research on the TYM and TYM-MCI are summarised in applications for Alzheimer’s and non-Alzheimer’s dementia and mild cognitive impairment.

In this NIHR Cambridge-BRC funded research, the researchers found out that the TYM test can be used in a general neurology clinic and can help distinguish patients with Alzheimer’s disease (AD) from those with no neurological cause for their memory complaints. An adapted tele-TYM test administered by telephone to patients produces scores which correlate strongly with the clinic-administered Addenbrooke’s Cognitive Examination revised (ACE-R) test and can identify patients with dementia.

This is important because the team showed that patients with AD decline on the TYM test at a rate of 3.6–4.1 points/year.

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Publication: The Journal of Neuroscience

L. Passamonti, K.A. Tsvetanov, P.S. Jones, W.R. Bevan-Jones, R. Arnold, R.J. Borchert, E. Mak, L. Su, J.T. O’Brien and J.B. Rowe

18 July 2019

Neuroinflammation is a key part of the etio-pathogenesis of Alzheimer’s disease. The researchers tested the relationship between neuroinflammation and the disruption of functional connectivity in large-scale networks, and their joint influence on cognitive impairment.

Patients showed significantly higher [11C]PK11195 binding relative to controls, in a distributed spatial pattern including the hippocampus, medial, and inferior temporal cortex. Patients with enhanced loading on this [11C]PK11195 binding distribution displayed diffuse abnormal functional connectivity. The expression of a stronger association between such abnormal connectivity and higher levels of neuroinflammation correlated with worse cognitive deficits.

This study suggests that neuroinflammation relates to the pathophysiological changes in network function that underlie cognitive deficits in Alzheimer’s disease. Neuroinflammation, and its association with functionally-relevant reorganisation of brain networks, is proposed as a target for emerging immuno-therapeutic strategies aimed at preventing or slowing the emergence of dementia.

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The analysis of neural circuits can provide crucial insights into the mechanisms of neurodegeneration and dementias, and offer potential quantitative biological tools to assess novel therapeutics. Here the researchers used behavioral variant frontotemporal dementia (bvFTD) as a model disease.

They demonstrated that inversion of canonical microcircuit models to noninvasive human magnetoencephalography, using dynamic causal modeling, can identify the regional- and laminar-specificity of bvFTD pathophysiology, and their parameters can accurately differentiate patients from matched healthy controls.

The research team suggests that this approach provides an in vivo platform for testing mechanistic hypotheses about disease progression and pharmacotherapeutics.

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Publication: Journal of Neurology, Neurosurgery and Psychiatry

Stefano Gazzina, Mario Grassi, Enrico Premi, Maura Cosseddu, Antonella Alberici, Silvana Archetti, Roberto Gasparotti, John Van Swieten, Daniela Galimberti, Raquel Sanchez-Valle, Robert Jr Laforce, Fermin Moreno, Matthis Synofzik, Caroline Graff, Mario Masellis, Maria Carmela Tartaglia, James B Rowe, Rik Vandenberghe, Elizabeth Finger, Fabrizio Tagliavini, Alexandre de Mendonça, Isabel Santana, Christopher R Butler, Simon Ducharme, Alex Gerhard, Adrian Danek, Johannes Levin, Markus Otto, Giovanni Frisoni, Sandro Sorbi, Alessandro Padovani, Jonathan D Rohrer, Barbara Borroni

10 June 2019

Cognitively engaging lifestyles have been associated with reduced risk of conversion to dementia. Multiple mechanisms have been advocated, including increased brain volumes (ie, brain reserve) and reduced disease progression (ie, brain maintenance). In cross-sectional studies of presymptomatic frontotemporal dementia (FTD), higher education has been related to increased grey matter volume. Here, the researchers examined the effect of education on grey matter loss over time.

Highly educated at-risk subjects had better cognition and higher grey matter volume at baseline; moreover, higher educational attainment was associated with slower loss of grey matter over time in mutation carriers.

This longitudinal study demonstrates that even in presence of ongoing pathological processes, education may facilitate both brain reserve and brain maintenance in the presymptomatic phase of genetic FTD.

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