[p4–261]: Longitudinal Evaluation of Neuropsychological and Neuroimaging Progression in Posterior Cortical Atrophy
Year: 2017
Type: article
Study design: Observational Study
Abstract: Posterior cortical atrophy (PCA) is a clinico-radiological syndrome characterized by progressive decline in visual processing and atrophy of posterior brain regions. With the majority of cases attributable to Alzheimer's disease (AD) and recent evidence for genetic risk factors specifically related to PCA (Schott et al., 2016), the syndrome can provide important insights into selective vulnerability and phenotypic diversity in AD. The present study describes the first major longitudinal investigation of PCA disease progression. 92 patients fulfilling consensus criteria (Crutch et al., in press) for PCA-pure (age=64.3±7.9 [range=49–85]; MMSE=21.4±5.1 [range=6–30]; 38% female) and 63 typical AD (tAD) patients (age=65.7±7.7 [range=51–84]; MMSE=19.4±4.9 [range=7–28]; 54% female) underwent up to 5 annual assessments. At each visit participants completed a T1-weighted MRI scan and neuropsychological battery. Rates of whole brain and regional atrophy were compared between PCA and tAD using a differential equation model (Villemagne et al. 2013). An Event-Based Model (EBM) (Fontejin et al. 2012) estimated the order in which brain regions became abnormal. EBMs of the orders in which PCA and tAD participants failed cognitive tests were also constructed. Differential equation and EBM modelling results of brain imaging data are reported in Figure 1. These indicate a distinct pattern of longitudinal change in PCA as compared with tAD, with PCA showing progressive posterior to anterior involvement and medial temporal sparing until the latest stages. In the cognitive EBMs, tests sensitive to visuospatial dysfunction (e.g. A cancellation time) declined earlier in PCA than tAD whilst tests sensitive to working memory impairment (e.g. digit span backwards) declined earlier in tAD than PCA. Baseline cognitive profiles in PCA patients were also shown to correspond to distinct longitudinal patterns of atrophy. For the first time we describe the distinctive spatial and temporal dynamics of disease progression in a large sample of individuals with PCA, and quantify the extent and variability of neuroimaging and neuropsychological differences between PCA and typical AD at different disease stages. Such detailed characterization is required to understand the impact of genetic risk factors upon phenotype, age at onset, and disease progression rate. (A) Regional volume trajectory over time for PCA and AD, anchored using the biomarker value at patient baseline visit. The bootstraps indicate confidence intervals around the mean trajectory. (B) Snapshots of PCA, and (C) Snapshots of AD, brain volume loss from the Event-Based Model (stage numbers relate to EBM model stages not time).
Source: Alzheimer s & Dementia
Authors: Silvia Primativo, Razvan Valentin Marinescu, Nicholas C. Firth, Keir Yong, Timothy J. Shakespeare, Aida Suarez Gonzalez, Amelia M. Carton, Manja Lehmann, Catherine F. Slattery, Ross W. Paterson, Alexander J.M. Foulkes, Natalie S. Ryan, Elizabeth K. Warrington, Nick C. Fox, Daniel C. Alexander, Jonathan M. Schott, Sebastian J. Crutch
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2767190158