King's College London

Research portal

Progressive callosal atrophy with stable memory impairment in familial British dementia

Research output: Chapter in Book/Report/Conference proceedingChapter

C A Lane, I B Malone, C H Sudre, R L Ahsan, E Manning, L Harper, S Ourselin, M J Cardoso, J M Schott

Original languageEnglish
Title of host publicationAlzheimer's and Dementia
Publication statusPublished - 2017

Publication series

NameAlzheimer's and Dementia
Volume13 (7)

King's Authors


Background: Familial British Dementia (FBD) is a rare autosomal dominant cerebral amyloid angiopathy (CAA) characterised by dementia, spastic tetraparesis and cerebellar ataxia. We describe the six-year follow up of an individual who presented with sudden onset memory impairment, and describe the longitudinal changes on magnetic resonance (MR) imaging. Methods: Single case study with multiple time-point neuropsychology and MR imaging (T1- MP-RAGE, T2, FLAIR, SWI sequences). Rates of brain atrophy were calculated using the brain boundary shift integral (BSI). Corpus callosum (CC) volumes were calculated using STEPS segmentation. Regional brain volume loss was assessed using nonlinear (fluid) registration (Figure 1). White matter hyperintensities (WMH) were automatically segmented using the longitudinal extension of an existing automated algorithm that models the data as a multivariate Gaussian mixture model (Figure 2). Genetic testing used next generation sequencing (NGS). Results: A 54 years old patient presented atypically with acute onset memory impairment which remained stable over the next six years (Table 1). NGS identified a c.799T>A heterozygous pathogenic mutation in the ITM2B gene, consistent with FBD. 2013 MR brain imaging revealed extensive white matter changes, lacunar infarcts, and multiple microbleeds (Figure 1). Fluid registration revealed progressive volume loss most prominently in the CC (Figure 1). BSI analysis demonstrated minimal global and hippocampal volume loss (Table 2). WMH segmentation confirmed progressive WMH accumulation (2013:82ml, 2015:101ml) with sparing of deep subcortical structures (Figure 3). Conclusions: Longitudinal imaging confirms previous cross-sectional findings that CC atrophy and accumulation of white matter disease are early features of FBD. Post-mortem studies report relatively little CAA within subcortical structures such as the basal ganglia, explaining the paucity of WMH in these regions. Whilst isolated episodicmemory impairment, themost consistent early neuropsychological feature in FBD, is usually considered to occur on a neurodegenerative basis, we suggest the very acute onset of memory impairment in this case is most consistent with a strategic vascular event. The documented stability in cognition and absence of other emerging symptoms/signs over several years are striking, perhaps suggesting that a vascular event led to the identification of otherwise asymptomatic prodromal atrophy.

View graph of relations

© 2018 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454