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P1‐277: Examining the regional specificity between Aβ burden and cognition
Author(s) -
Pike Kerryn E.,
Villemagne Victor L.,
Jones Gareth,
Ackermann Uwe,
O'Keefe Graeme,
Ames David,
Ellis Kathryn A.,
Masters Colin L.,
Rowe Christopher C.
Publication year - 2008
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.2008.05.867
Subject(s) - episodic memory , posterior parietal cortex , cognition , psychology , pittsburgh compound b , alzheimer's disease , neocortex , audiology , executive functions , neuroscience , cognitive impairment , disease , medicine
dementia onset. Promising biomarkers for identifying “at risk” individuals include CSF Abeta42, total tau (t-tau) and Abeta42/t-tau ratio and decreased cerebral glucose metabolism (CMRglu) on FDG-PET imaging. Parallel changes in CSF AD biomarkers and global or regional CMRglu have been observed in mild cognitive impairment and normal aging. Here, we used voxel-based correlation analyses to characterize CSF AD biomarker and CMRglu relationships in discrete cortical and subcortical brain regions in cognitively normal subjects. Methods: CSF was collected by lumbar puncture (LP) from 21 cognitively normal subjects, CSF Abeta42 and t-tau were measured by immunobead-based multiplex assays (Innogenetics), and brain PET imaging (10 mCi [F-18]FDG; GE Advance Scanner) was performed at rest. Subjects were age 63.0 12.4 (mean SD) years at LP; 65.4 11.5 years at PET; and time between LP and PET was 834.5 676.8 days. PET images were co-registered, transformed to standard stereotactic coordinates, and normalized to pontine activity using NEUROSTAT software (UW). Voxel-wise linear correlation maps (converted to Z values) were generated between normalized CMRglu and each CSF biomarker. Results: CSF Abeta42 and CMRglu were significantly positively correlated in frontal lobe (inferior and middle frontal gyri), temporal lobe, posterior and anterior cingulate cortices, insula and amygdala (Z’s 3.5); an overall pattern similar to that seen in amyloid PET imaging in AD. CSF t-tau and CMRglu were negatively correlated in hippocampus; cuneus; parietal lobe (inferior and superior); frontal cortex (superior, middle, inferior); anterior cingulate cortex; primary motor and sensory cortex; and thalamus. CSF Abeta42/t-tau ratios and CMRglu were negatively correlated in hippocampus; cuneus; precuneus; anterior cingulate cortex; frontal cortex (superior, middle, inferior); parietal cortex (superior, inferior), primary motor and sensory cortex; thalamus; and cerebellum. Conclusions: CSF Abeta42 and CMRglu are correlated in brain areas associated with amyloid plaque deposition in AD while CSF t-tau and Abeta42/t-tau ratio correlations with CMRglu are more widespread and include motor and sensory cortex usually spared in AD, suggesting that CMRglu may be differentially affected by amyloid and tau pathology. (Support: NIH AG023185, AG023670; NS045254 and the Dept. of Veterans Affairs).