Publication: Nature Communications

Sanne Simone Kaalund, Luca Passamonti, Kieren S. J. Allinson, Alexander G. Murley, Trevor W. Robbins, Maria Grazia Spillantini and James B. Rowe

4 February 2020

Summary:

The locus coeruleus is the major source of noradrenaline to the brain and contributes to a wide range of physiological and cognitive functions. Neurodegeneration and pathological aggregation of tau protein in the locus coeruleus are early features of progressive supranuclear palsy (PSP). It is proposed to contribute to the clinical expression of the disease, including the PSP Richardson’s syndrome. Researchers investigated whether the tau and neuronal loss are associated with clinical heterogeneity and severity in PSP.

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Publication: Journal of Neurology

David J. Lewis-Smith, Noham Wolpe, Boyd C. P. Ghosh & James B. Rowe

9 January 2020

Alien limb refers to movements that seem purposeful but are independent of patients’ reported intentions. Alien limb often co-occurs with apraxia in the corticobasal syndrome, and anatomical and phenomenological comparisons have led to the suggestion that alien limb and apraxia may be causally related as failures of goal-directed movements. Here, the researchers characterised the nature of alien limb symptoms in patients with the corticobasal syndrome and their relationship to limb apraxia.

Twenty-eight patients with corticobasal syndrome (93%) demonstrated significant apraxia and this was often asymmetrical, with the left hand preferentially affected in 23/30 (77%) patients. Moreover, 25/30 (83%) patients reported one or more symptoms consistent with alien limb. The range of these phenomena was broad, including changes in the sense of ownership and control as well as unwanted movements.

Regression analyses showed no significant association between the severity of limb apraxia and either the occurrence of an alien limb or the number of alien limb phenomena reported. Bayesian estimation showed a low probability for a positive association between alien limb and apraxia, suggesting that alien limb phenomena are not likely to be related to severity apraxia. The results shed light on the phenomenology of these disabling and as yet untreatable clinical features, with relevance to theoretical models of voluntary action.

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Publication: JAMA Neurology

Edwin Jabbari, Negin Holland, Viorica Chelban, P. Simon Jones, Ruth Lamb, Charlotte Rawlinson, Tong Guo, Alyssa A. Costantini, Manuela M. X. Tan, Amanda J. Heslegrave, Federico Roncaroli, Johannes C. Klein, Olaf Ansorge, Kieren S. J. Allinson, Zane Jaunmuktane, Janice L. Holton, Tamas Revesz, Thomas T. Warner, Andrew J. Lees, Henrik Zetterberg, Lucy L. Russell, Martina Bocchetta, Jonathan D. Rohrer, Nigel M. Williams, Donald G. Grosset, David J. Burn, Nicola Pavese, Alexander Gerhard, Christopher Kobylecki, P. Nigel Leigh, Alistair Church, Michele T. M. Hu, John Woodside, Henry Houlden,  James B. Rowe, Huw R. Morris

20 December 2019

This research looked at the distinguishing features of progressive supranuclear palsy and corticobasal syndrome subtypes and how they can be distinguished from Parkinson disease.

In this cohort study of 222 patients with atypical parkinsonian syndromes, recently defined progressive supranuclear palsy subtypes are almost as common as classic Richardson syndrome and share midbrain atrophy as a common hallmark. Distinct patterns of clinical trajectory, cognitive profile, serum neurofilament light chain level, genetic, and volumetric magnetic resonance imaging measures helped to distinguish the clinical subtypes of progressive supranuclear palsy and corticobasal syndrome; clinical trajectory and serum neurofilament light chain levels distinguished Parkinson disease from progressive supranuclear palsy and corticobasal syndrome

This study suggests that subtypes of progressive supranuclear palsy and corticobasal syndrome have distinct characteristics that may enhance their early diagnosis.

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Publication: The Lancet Neurology

Katrina M Moore, Jennifer Nicholas, Prof Murray Grossman, Corey T McMillan, David J Irwin, Lauren Massimo, PhD et al

3 December 2019

Frontotemporal dementia is a heterogenous neurodegenerative disorder, with about a third of cases being genetic. Most of this genetic component is accounted for by mutations in GRN, MAPT, and C9orf72. In this study, the researchers aimed to complement previous phenotypic studies by doing an international study of age at symptom onset, age at death, and disease duration in individuals with mutations in GRN, MAPT, and C9orf72.

The study showed that age at symptom onset and at death of people with genetic frontotemporal dementia is influenced by genetic group and, particularly for MAPT mutations, by the specific mutation carried and by family membership.

Although estimation of age at onset will be an important factor in future pre-symptomatic therapeutic trials for all three genetic groups, this study suggests that data from other members of the family will be particularly helpful only for individuals with MAPT mutations. Further work in identifying both genetic and environmental factors that modify phenotype in all groups will be important to improve such estimates.

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Publication: Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring

Audrey Low, Elijah Mak, Maura Malpetti, Leonidas Chouliaras, Nicolas Nicastro, Li Sua, Negin Holland, Timothy Rittman, Patricia Vázquez Rodríguez, Luca Passamonti, W Richard Bevan-Jones, PP Simon Jones, James B.Rowe, John T.O’Brien

1 December 2019

Widespread cortical asymmetries have been identified in Alzheimer’s disease (AD), but thalamic asymmetries and their relevance to clinical severity in AD remain unclear.

This research discovered that although overall asymmetry of the thalamus did not differ between groups, greater leftward lateralization of atrophy in the ventral nuclei was demonstrated in AD, compared with controls and amyloid-positive mild cognitive impairment. Increased posterior ventrolateral and ventromedial nuclei asymmetry were associated with worse cognitive dysfunction, informant-reported neuropsychiatric symptoms, and functional ability.

Leftward ventral thalamic atrophy was associated with disease severity in AD. The findings suggest the clinically relevant involvement of thalamic nuclei in the pathophysiology of AD.

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