Region-Specific Hierarchy between Atrophy, Hypometabolism, and β-Amyloid (Aβ) Load in Alzheimer's Disease Dementia

Abstract

Gray matter atrophy, glucose hypometabolism, and ␤-amyloid A␤ deposition are well-described hallmarks of Alzheimer's disease, but their relationships are poorly understood. The present study aims to compare the local levels of these three alterations in humans with Alzheimer's disease. Structural magnetic resonance imaging, 18 F-fluorodeoxyglucose positron emission tomography (PET), and 18 Fflorbetapir PET data from 34 amyloid-negative healthy controls and 20 demented patients with a high probability of Alzheimer's disease etiology (attested using neuroimaging biomarkers as recently recommended) were analyzed. For each patient and imaging modality, age-adjusted Z-score maps were computed, and direct between-modality voxelwise comparison and correlation analyses were performed. Significant differences in the levels of atrophy, hypometabolism, and A␤ deposition were found in most brain areas, but the hierarchy differed across regions. A cluster analysis revealed distinct subsets of regions: (1) in the hippocampus, atrophy exceeded hypometabolism, whereas A␤ load was minimal; (2) in posterior association areas, A␤ deposition was predominant, together with high hypometabolism and lower but still significant atrophy; and (3) in frontal regions, A␤ deposition was maximal, whereas structural and metabolic alterations were low. Atrophy and hypometabolism significantly correlated in the hippocampus and temporo-parietal cortex, whereas A␤ load was not significantly related to either atrophy or hypometabolism. These findings provide direct evidence for regional variations in the hierarchy and relationships between A␤ load, hypometabolism, and atrophy. Altogether, these variations probably reflect the differential involvement of region-specific pathological or protective mechanisms, such as the presence of neurofibrillary tangles, disconnection, as well as compensation processes.

Cognitive and neuroimaging features and brain β-amyloidosis in individuals at risk of Alzheimer's disease (INSIGHT-preAD): a longitudinal observational study

“…The SUVR threshold to determine abnormality uptake was extracted performing linear correlation between our method 34 and the method used by Besson et al 35 using 53 PET scans from another French study, the IMAP cohort 36 .…”

Relationships between years of education and gray matter volume, metabolism and functional connectivity in healthy elders

“…Moreover, individuals were also screened for the presence of amyloid deposition using florbetapir-PET imaging. They were classified as amyloidnegative or amyloid-positive using a neocortical standardized uptake value ratio cut off value of 1.1 (see La Joie et al, 2012 for the full description of the procedure). Of the initial 39 subjects involved in the study, three subjects with a positive florbetapir-PET scan (i.e., amyloid-positive) were excluded.…”

Direct voxel-based comparisons between grey matter shrinkage and glucose hypometabolism in chronic alcoholism

“…The PET data were first corrected for CSF and WM PVEs, using the voxel-by-voxel 'modified Mu¨ller-Gartner' method described in detail in Quarantelli et al 30 and already used in our laboratory. 16,17 Using SPM5, the PVE-corrected PET data set were then co-registered (rigid-body co-registration) onto their respective native MRIs and normalised into the MNI space by reapplying the normalisation parameters estimated from the VBM protocol described above (final voxel size: 2 mm 3 ; matrix ¼ 79 Â 95 Â 79). When the direct and absolute quantification of glucose metabolism cannot be conducted due to the absence of arterial function measurement, as in the present study, a reference region must be chosen to control the inter-individual variations in PET measurements 31 (i.e.…”

“…17 In AD, two distinct profiles were found: (a) atrophy exceeding hypometabolism in medial temporal lobe and hippocampus and (b) more severe hypometabolism than GM atrophy in posterior associative areas that may have precede structural changes. 16 Regional variations in the hierarchy and relationship between atrophy and hypometabolism in AD have been reported to probably reflect the differential involvement of region-specific pathological (or protective) mechanisms. 16 AD-related changes in glucose metabolism are not redundant with GM structural changes: both imaging modalities provide at least partly complementary information about brain integrity.…”