HIPPOCAMPAL VOLUME IS PRESERVED AND FAILS TO PREDICT COGNITIVE DECLINE IN AGED RHESUS MONKEYS

J.L. Twining¹*; M.H. Buonocore²; J.A. Roberts³; D.G. Amaral⁴; P.R. Rapp¹; C.A. Barnes⁵

1. Kastor Neurobiol Aging Labs, Mt Sinai, New York, NY, USA
2. Radiology, Univ California, Davis, CA, USA
3. CNPRC, Davis, CA, USA
4. Psychiatry, Univ California, Davis, CA, USA
5. NSMA, Univ Arizona, Tucson, AZ, USA

Aged monkeys exhibit memory impairments indicative of hippocampal dysfunction that are similar to the effects of normal aging in humans. The current study quantified the volume of the hippocampus in vivo in 6 aged (24-29 years) and 6 young adult (9-12 years) rhesus monkeys (Macaca mulatta), a subset of which (4 young, 4 aged) were behaviorally characterized using a test of hippocampal memory (DNMS). The aim of this design was to determine if volumetric changes in the hippocampus predict the cognitive outcome of normal aging. Eighty contiguous 1mm coronal T1 images were acquired per monkey on a 1.5 Tesla GE Signa Horizon LX NV/i MRI system (GE Medical Systems, Waukesha, WI), using a RF-spoiled gradient sequence (3D SPGR) with TR:21ms, TE:7.9ms, flip angle:30o, FOV:16cm, Matrix:256x256, NEX:4, Bandwidth:15.63kHz. 3D reconstructions, aligned in a plane perpendicular to the long axis of the hippocampus, were generated using Analyze 5.0 software. The borders of the left and right hippocampi were digitized manually and the volumes calculated. The outcome of behavioral testing was similar to previous observations: aged monkeys exhibited robust deficits learning DNMS with a short delay (p < 0.001), and scored poorly relative to young subjects when memory was challenged with longer retention intervals (p < 0.01). However, hippocampal volume differed by less than 5% across the young (mean= 391mm3) and aged (mean= 375mm3) groups. Furthermore, there was no correlation between hippocampal volume and any measure of DNMS performance. These in vivo findings support the conclusion of post-mortem histological studies, suggesting that normal cognitive aging occurs independently of gross structural deterioration in the hippocampus.

Support Contributed By: AG003376, AG10606, AG09973 & RR-000169

Hippocampus, memory, aging, MRI