Correlations between visual recognition memory and neocortical and hippocampal glucose metabolism after bilateral rhinal cortex lesions in the baboon: implications for Alzheimer's disease

Abstract

In Alzheimer's disease (AD), the rhinal cortex is the area earliest and most affected by neurofibrillary tangles, and the degree of temporoparietal glucose hypometabolism and rhinal cortex atrophy are both correlated with dementia severity. In monkeys, damage to the rhinal cortex leads to severe impairment in declarative memory, which is also affected preferentially in early AD. To investigate the contribution of rhinal alterations to the interrelationships between cerebral hypometabolism and declarative memory impairment observed in AD, we studied the effects of excitotoxic bilateral rhinal lesions in baboons on cerebral glucose consumption (CMRglc) as measured by positron emission tomography and performance on a visual recognition memory task as assessed in parallel by a delayed nonmatching-to-sample task. We reported previously that these rhinal lesions induce both a long-lasting hypometabolism in several remote brain regions (Meguro et al., 1999) and impaired memory performance (Chavoix et al., 2002). The present analysis indicates that across lesioned and sham baboons, memory scores were significantly positively correlated (p < 0.05; Spearman) with concomitant CMRglc values of several brain areas, such as neocortical associative and posterior hippocampal regions. These findings, reminiscent of those reported in AD, suggest that the neurodegenerative process that affects the rhinal cortex in early AD plays a crucial role in the pattern of brain hypometabolism and consequently in the declarative memory impairments characteristic of this disease.

Fig. 1.

Schematic damage in baboon RH4 compared with intended lesion (gray areas). Shown inblack are the areas with >25% neuronal loss. Approximate rostrocaudal distance (in millimeters) from the anterior commissure (AC) is indicated below each coronal section.

Fig. 2.

Illustration of the correlations between CMRglc and performance on the DNMS task for the posterior hippocampal, inferior parietal, and prefrontal dorsolateral regions [n = 8 baboons (4 lesioned and 4 sham-operated) for each correlation]. The correlation coefficients (Spearman's ρ) and corresponding p (two-tailed) values are shown for each correlation.