NeuroImage: Clinical Parallel ICA of FDG-PET and PiB-PET in three conditions with underlying Alzheimer’s pathology

The relationships between clinical phenotype, β -amyloid (A β ) deposition and neurodegeneration in Alzheimer’s disease (AD) are incompletely understood yet have important ramiﬁcations for future ther-apy. The goal of this study was to utilize multimodality positron emission tomography (PET) data from a clinically heterogeneous population of patients with probable AD in order to: (1) identify spatial patterns of A β deposition measured by ( 11 C)-labeled Pittsburgh Compound B (PiB-PET) and glucose metabolism mea- sured by FDG-PET that correlate with speciﬁc clinical presentation and (2) explore associations between spatial patterns of A β deposition and glucose metabolism across the AD population. We included all patients meeting the criteria for probable AD (NIA–AA) who had undergone MRI, PiB and FDG-PET at our center ( N = 46, mean age 63.0 ± 7.7, Mini-Mental State Examination 22.0 ± 4.8). Patients were subclassiﬁed based on their cognitive proﬁles into an amnestic / dysexecutive group (AD-memory; n = 27), a language-predominant group (AD-language; n = 10) and a visuospatial-predominant group (AD-visuospatial; n = 9). All patients were required to have evidence of amyloid deposition on PiB-PET. To capture the spatial distribution of A β deposition and glucose metabolism, we employed parallel independent component analysis (pICA), a method that enables joint analyses of multimodal imaging data. The relationships between PET components and clinical group were examined using a Receiver Operator Characteristic approach, including age, gender, education and apolipoprotein E (cid:3) 4 allele carrier status as covariates. Results of the ﬁrst set of analyses independently examining the relationship between components from each modality and clinical group showed three signiﬁcant components for FDG: a left inferior frontal and temporoparietal component associated with AD-language (area under the curve [AUC] 0.82, p = 0.011), and two components associated with AD-visuospatial (bilateral occipito-parieto-temporal [AUC 0.85, p = 0.009] and right posterior cingulate cortex [PCC] / precuneus and right lateral parietal [AUC 0.69, p = 0.045]). The AD-memory associated com- ponent included predominantly bilateral inferior frontal, cuneus and inferior temporal, and right inferior parietal hypometabolism but did not reach signiﬁcance (AUC 0.65, p = 0.062). None of the PiB components correlated with clinical group. Joint analysis of PiB and FDG with pICA revealed a correlated component pair, in which increased frontal and decreased PCC / precuneus PiB correlated with decreased FDG in the frontal, occipital temporal 0.75, 0.0001). multivariate data phenotype in is patterns of hypometabolism deposition. ﬁndings speciﬁc involvement of the default mode network in clinical variants of AD. β glucose metabolism in partially overlapping brain regions suggests that A β may exert both local and re- mote effects on brain metabolism. Applying multivariate approaches such as pICA to multimodal imaging data is a promising approach for unraveling the complex relationships between different elements of AD pathophysiology.