ALTERNATIVE CEREBRAL GLUCOSE UPTAKE METRICS DETECT EARLY METABOLIC CHANGES IN THE 5XFAD MOUSE MODEL OF ALZHEIMER'S DISEASE

Abstract

Background: Changes in visual and auditory function have been reported in patients with clinical Alzheimer’s disease (AD) and mild cognitive impairment (MCI), but the relationship of these measures to known biomarkers of AD neuropathology is unknown. Thus, the goal of this study was to test the hypothesis that sensory measures, including visual (contrast sensitivity) and auditory function (pure tone audiometry), are associated with neuroimaging biomarkers of AD, including amyloid deposition (measured with [11 C]PiB PET) and hippocampal volume. Methods: 31 participants, including 13 healthy age-matched controls (HC), 6 euthymic older adults with subjective cognitive decline (SCD) but no neuropsychological deficits, and 12 patients with MCI, were included in the present analysis. All participants underwent a test of contrast sensitivity, measured using frequency doubling technology (FDT-2) as previously described [1], pure tone audiometry to test tonal hearing, and structural MRI. A subset of participants also underwent [11 C]PiB PET imaging (n1⁄412 [3 HC, 3 SCD, 6 MCI]). Structural MRI scans were processed using FreeSurfer version 5.1. [11 C]PiB PET scans were processed using standard techniques in SPM8. Mean PiB standardized uptake value ratio (SUVR) was extracted from a global cortical grey matter region of interest. Contrast sensitivity (duration of FDT-2 exam) and tonal hearing at high frequency (mean tonal intensity at 8000Hz) were compared between diagnostic groups. The relationship of these sensory measures to global PiB uptake and hippocampal atrophy was evaluated using a linear regression model. Results: No significant difference between diagnostic groups was observed for either visual function or tonal hearing at 8000 Hz in this small sample (Fig. 1A & 1B). However, visual function (duration of FDT-2 exam) was significantly associated with amyloid deposition (p1⁄40.001, Fig. 1C). Tonal hearing and hippocampal volume were also significantly associated (p1⁄40.001, Fig. 1D). Conclusions: Visual and auditory changes in individuals at risk and during prodromal stages of AD are associated with neuroimaging biomarkers of AD pathology, including amyloid deposition and neurodegeneration. Non-invasive and inexpensive measures of visual and auditory sensory function warrant further investigation as potential biomarkers of early stage AD pathology. [1] Risacher et al. (2013) Neurobiol Aging. IC-P-098 ALTERNATIVE CEREBRAL GLUCOSE UPTAKE METRICS DETECT EARLY METABOLIC CHANGES IN THE 5XFAD MOUSE MODEL OFALZHEIMER’S DISEASE Drew R. DeBay, Ian R. Macdonald, G. Andrew Reid, Tim P. O’Leary, Courtney T. Jollymore, Meghan K. Cash, GeorgeMawko, Steve Burrell, Earl Martin, Chris V. Bowen, Richard E. Brown, Sultan Darvesh, Dalhousie University, Halifax, Nova Scotia, Canada; Mount Saint Vincent University, Halifax, Nova Scotia, Canada. Contact e-mail: drdebay@dal.ca