Completed Brain & Nervous System Psychology & Behaviour

Characterising survival heterogeneity in frontotemporal lobar degenerative syndromes.

Funder AMS (part of Academy)
Recipient organisation University of Cambridge
Funding £29K
Period Mar 2025 — Jul 2026

In plain English

AI plain-English summary

A fifth of people with Progressive Supranuclear Palsy or Corticobasal Syndrome die within three years of their first symptoms, while another fifth survive more than twelve years—and no one knows why. This survival gap matters because both diseases are aggressive, incurable forms of dementia that destroy movement, thinking, and behaviour. Without understanding what drives the difference, clinical trials cannot reliably tell whether a drug is working or simply testing a lucky or unlucky group of patients. The researcher will analyse blood biomarkers, brain scans, genetic variants, and socioeconomic data from roughly 300 deeply-characterised patients to identify which factors predict short versus long survival. If the work succeeds, it will give trial designers a way to stratify patients by expected prognosis, making smaller, faster, and more reliable studies possible. It may also reveal underlying disease mechanisms—for example, whether certain blood proteins or brain atrophy patterns drive rapid decline—pointing toward new treatment targets. This is fundamental science with a direct translational payoff: better trials today, better therapies tomorrow.

View original technical description
There is a pressing need to understand the determinants of clinical and prognostic variation in dementias. Such determinants can help prioritise strategies for prevention and treatment. This project is set in the context of two rapidly progressive syndromes caused by neurodegeneration with “4R-tauopathy”. The syndromes are Progressive Supranuclear Palsy (PSP, caused by PSP-pathology), and Corticobasal Syndrome (CBS, often caused by corticobasal degeneration pathology or PSP-pathology). They both affect cognition, behaviour and movement, and lack disease-modifying treatments. They have striking heterogeneity in survival (a fifth surviving >12 years from onset and a fifth <​3 years), which is challenging for the design of disease modifying clinical trials. The causes of this heterogeneity are unknown. I aim to determine the blood, brain and socioeconomic background correlates of survival variance. I will test prognostic value in (i) blood biomarkers and pre-specified blood-based genetic variants, (ii) structural brain imaging metrics; and (iii) background demographic factors, using mathematical modelling on ~300 deeply-phenotyped patients. Characterising the role of each factor in predicting survival is an opportunity to better understand underlying disease mechanism and targets for intervention, and improve trials design by evidence based stratification and monitoring.

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Researchers

Negin Holland (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Investigation of the genetic and functional determinants of disease progression in Progressive Supranuclear Palsy
Profiling neuroinflammatory signatures of disease heterogeneity in C9orf72-associated ALS-FTD
Neuropathology of disorders of movement and cognition
PROgressive Supranuclear Palsy CorTico-Basal Syndrome Multiple System Atrophy Longitudinal Study UK
PROgressive Supranuclear Palsy CorTicoBasal Syndrome Multiple System Atrophy Longitudinal Study UK (PROSPECTMUK)

Original classification

Starter Grant for Clinical Lecturers

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.