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.

The authors previously reported that excitotoxic lesions of both the perirhinal and entorhinal cortices in baboons induce remote neocortical and hippocampal hypometabolism reminiscent of that observed in Alzheimer disease (AD), suggesting that disconnection may play a role in AD. Because the cerebral metabolic rate of glucose (CMR ) was preferentially correlated with perirhinal damage, the area first affected by neurofibrillary tangles in both AD and normal aging, the present series of experiments aimed at assessing the specific metabolic effects of perirhinal lesions. Using PET, CMR was measured before surgery and sequentially over the ensuing 10 months. Compared with sham-operated baboons, perirhinal lesions induced significant-albeit late and transient-CMR decreases in several brain regions, which significantly correlated with histologic damage for some of these regions. Among them, the temporal and hippocampal regions are metabolically affected after extensive rhinal lesions, in early AD, and aging, while the prefrontal region is affected in aging only. Furthermore, in contrast to AD and rhinal lesions, the posterior cingulate cortex was spared. Both the progressive but significant metabolic effects and specific hypometabolic pattern after perirhinal lesions were confirmed by direct comparisons with previous data obtained after combined lesions of both rhinal areas. Thus, although perirhinal damage appears in itself insufficient to induce sustained CMR decreases, it may contribute to the hypometabolic profile of both AD and normal aging, most likely with a stronger contribution in the latter.

The authors previously reported that excitotoxic lesions of both the perirhinal and entorhinal cortices in baboons induce remote neocortical and hippocampal hypometabolism reminiscent of that observed in Alzheimer disease (AD), suggesting that disconnection may play a role in AD. Because the cerebral metabolic rate of glucose (CMR ) was preferentially correlated with perirhinal damage, the area first affected by neurofibrillary tangles in both AD and normal aging, the present series of experiments aimed at assessing the specific metabolic effects of perirhinal lesions. Using PET, CMR was measured before surgery and sequentially over the ensuing 10 months. Compared with sham-operated baboons, perirhinal lesions induced significant-albeit late and transient-CMR decreases in several brain regions, which significantly correlated with histologic damage for some of these regions. Among them, the temporal and hippocampal regions are metabolically affected after extensive rhinal lesions, in early AD, and aging, while the prefrontal region is affected in aging only. Furthermore, in contrast to AD and rhinal lesions, the posterior cingulate cortex was spared. Both the progressive but significant metabolic effects and specific hypometabolic pattern after perirhinal lesions were confirmed by direct comparisons with previous data obtained after combined lesions of both rhinal areas. Thus, although perirhinal damage appears in itself insufficient to induce sustained CMR decreases, it may contribute to the hypometabolic profile of both AD and normal aging, most likely with a stronger contribution in the latter.