Maura Malpetti (United Kingdom)
University of Cambridge
Department of Clinical Neurosciences
Maura Malpetti has been recently appointed as a Race Against Dementia and Alzheimer's Research UK fellow at the University of Cambridge (UK), where she earned her PhD in Clinical Neurosciences last year. She originally trained in Italy for a BSc in Psychology and an MSc in Cognitive Neurosciences, where she worked with FDG PET. She is interested in the study of neuropathology, biomarkers and clinical features of neurodegenerative diseases, with special interest in frontotemporal lobar degeneration and Alzheimer's disease. Her research focusses on multimodal biomarkers to investigate the pathophysiology of these conditions, in order to identify early diagnostic and prognostic markers. Specifically, she is studying novel PET tracers and other biomarkers for inflammation, tau and synaptic loss, with an interdisciplinary approach that integrates multimodal imaging and clinical data with fluid markers and post-mortem pathology.

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IN VIVO PET IMAGING OF INFLAMMATION AS A PROGNOSTIC TOOL IN FRONTOTEMPORAL DEMENTIA

Session Name
1070 - FTD, ALS; C9ORF72, TDP-43 AND PROGRANULIN (ID 52)
Session Type
SYMPOSIUM
Date
Fri, 18.03.2022
Session Time
09:10 AM - 10:55 AM
Room
ONSITE: 113
Lecture Time
10:25 AM - 10:40 AM
Presenter

Abstract

Aims

Across three main clinical syndromes of frontotemporal dementia (FTD), we used [11C]PK11195 PET uptake as an index of regional inflammation, and assessed its predictive power for future cognitive decline. Negative associations between inflammation and cognitive decline were hypothesised.

Methods

We recruited 30 patients, with clinical diagnoses of behavioural variant of FTD (N=10), non-fluent variant (N=10) and semantic variants of primary progressive aphasia (N=10). All patients underwent structural MRI and dynamic [11C]PK11195 PET at baseline, and cognitive assessment with the revised Addenbrooke's Cognitive Examination (ACE-R) every ~6 months up to 5 years. Regional [11C]PK11195 binding potentials were extracted, and averaged in 4 regions of interest: left and right frontal and temporal lobes. Linear mixed-effect models were used to estimate the annual rate of change (slope) in cognitive performance (Attention/Orientation ACE-R sub-scores) with regional inflammation as a predictor. Baseline cognitive performance, age and education were included as covariates.

Results

A negative predictive effect of [11C]PK11195 binding on cognitive performance over time was found for frontal regions (left: Estimate=-0.82, p=0.0009, p-FDR=0.0017; right: Estimate=-0.80, p=0.002, p-FDR=0.0212), also when diagnosis was included as a covariate. Bayesian correlations on cognitive slope and inflammation levels confirmed negative associations in left (r=-0.48, p=0.004, BF10=23.7) and right (r=-0.39, p=0.018, BF10=4.2) frontal regions. Adding grey-matter volumes to the models, inflammation in these regions provided additional information over atrophy (Estimate=-0.79, p=0.0006).

Conclusions

Inflammation PET in frontal regions provides useful information to predict cognitive decline in patients with FTD, across clinical syndromes. This result incentivises further exploration of immunomodulatory treatment strategies in FTD.

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