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P4–378: Cerebral amyloid‐associated changes in brain perfusion in autosomal dominant Alzheimer's disease
Author(s) -
Kim Albert,
McDade Eric,
James Jeffrey,
Minhas Davneet,
Ikonomovic Zana,
Lopez Oscar,
Snitz Beth,
Price Julie,
Becker James,
Mathis Chet,
Klunk William
Publication year - 2013
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2013.08.211
Subject(s) - cerebral blood flow , cerebral perfusion pressure , temporal lobe , perfusion , pathology , medicine , voxel , alzheimer's disease , pittsburgh compound b , cardiology , neuroscience , psychology , disease , radiology , epilepsy
Background: It is clear the deposition of cerebral fibrillar amyloid occurs years before symptoms in autosomal dominant Alzheimer’s disease (ADAD). Only recently studies have begun to identify the relationship between amyloid and other markers of the pathologic cascade in ADAD. In late onset AD early changes in cerebral perfusion have been identified, but perfusion changes have not been explored in ADAD. In this study, we sought to explore the relationship between cerebral amyloid and cerebral perfusion in ADAD using arterial spin labeled (ASL) MRI. Methods: This was a cross-sectional, voxel based PET/MRI study of 14 mutation carriers (CDR score1⁄40 (11); CDR1⁄40.5 (2), CDR1⁄41 (1); mean age 37.6 years).We measured global PiB binding (computed as the average SUVR (cerebellum reference) of 5 cortical regions plus the striatum [Mean 1.85 6 0.568]; range 1.18-3.18), and cerebral blood flow using MRI-based ASL. Using SPM8, we regressed cerebral blood flow (measured at the voxel level) on global PiB, age, gender and CDR score. The statistical threshold was set at p<0.01 (uncorrected). Results: With increasing PiB retention, we found a decrease in cerebral perfusion to the left lateral and inferior temporal lobes as well as the right dorsolateral frontal lobe (A) ; and a subtle increase in cerebral perfusion to the right anterior temporal lobe (B). No changes were observed in striatum. Conclusions: Using ASL-MRI we found that in this small group of mostly cognitively normal ADADmutation carriers that as amyloid load increased there were regional differences in associated changes in arterial perfusion, mostly limited to the heteromodal cortices. These preliminary findings support the growing appreciation of the complex relationship between the various biomarkers in ADAD. In particular, this preliminary work suggests that as cerebral amyloid increases there are distinct patterns of changes in cortical arterial perfusion. This work supports further exploration of the early interactions between arterial blood flow and cerebral amyloid accumulation in ADAD and late onset AD. Table 4 Hippocampal volume comparisons on ApoE E4 and E2 allele carriers with E3 homozygotes