Corticosteroids, but not NSAIDs, are associated with less Alzheimer neuropathology

Abstract

The objective of this study was to test the hypothesis that corticosteroid and nonsteroidal anti-inflammatory drug (NSAID) medications are associated with less global and regional Alzheimer's disease (AD) neuropathology. This postmortem study was based on 694 brains of subjects from the Mount Sinai School of Medicine Brain Bank who did not have neuropathologies other than neuritic plaques (NPs), neurofibrillary tangles (NFTs), or cerebrovascular disease. Densities of NPs and of NFTs were assessed in several neocortical regions and in the hippocampus, entorhinal cortex, and amygdala. Counts of NPs in several neocortical regions were also assessed. For each neuropathology measure, analyses of covariance controlling for age at death and sex compared subjects who received only corticosteroids (n = 54) or those who received only NSAIDs (n = 56) to the same comparison group, subjects who received neither (n = 576). Subjects receiving corticosteroids had significantly lower ratings and counts of NPs for all neuropathological measures, and NFTs overall and in the cerebral cortex and amygdala. In contrast, no measures were significant for subjects who received NSAIDs. Use of corticosteroids was associated with approximately 50% fewer NPs and NFTs in most brain regions examined, compared with nonmedicated subjects. In contrast, use of NSAIDs was not substantially associated with the reductions in hallmark lesions of AD. Because corticosteroids have anti-inflammatory as well as a myriad of other neurobiological effects, more direct studies in model systems could reveal novel therapeutic targets and mechanisms for AD lesion reduction.

Figure 1

Comparison of the extent of AD neuropathology in subjects who had a history of corticosteroids use (n=54) to controls (n=576) or of NSAIDs use (n=56) to controls Upper Panel Legend (p-values for corticosteroids comparisons; p-values for NSAIDs comparisons): NP Hippo-neuritic plaque CERAD ratings in the hippocampus (0.002;0.25); NP EC- neuritic plaques in the entorhinal cortex (0.017;0.39); NP Amyg- neuritic plaques in the amygdala (0.029;0.49); NFT Hippo- neurofibrillary tangles CERAD ratings in the hippocampus (0.032;0.86); NFT EC- neurofibrillary tangles in the entorhinal cortex (0.083;0.74); NFT amyg- neurofibrillary tangles in the amygdala (0.004;0.68). Lower Panel Legend (p-values for corticosteroids comparisons; p-values for NSAIDs comparisons): NP cortex- sum of CERAD ratings of neuritic plaques in four cortical regions (0.001;0.26); NP sum- sum of CERAD ratings of NPs in the hippocampus, entorhinal cortex, amygdala, and cortex (0.001; 0.26); NFT cortex- sum of CERAD ratings of neurofibrillary tangles in four cortical regions (0.002; 0.20); NFT sum- sum of CERAD ratings of NFTs in the same regions as in NPsum (0.001; 0.55). *p≤0.05; **p≤0.005

Figure 1

Comparison of the extent of AD neuropathology in subjects who had a history of corticosteroids use (n=54) to controls (n=576) or of NSAIDs use (n=56) to controls Upper Panel Legend (p-values for corticosteroids comparisons; p-values for NSAIDs comparisons): NP Hippo-neuritic plaque CERAD ratings in the hippocampus (0.002;0.25); NP EC- neuritic plaques in the entorhinal cortex (0.017;0.39); NP Amyg- neuritic plaques in the amygdala (0.029;0.49); NFT Hippo- neurofibrillary tangles CERAD ratings in the hippocampus (0.032;0.86); NFT EC- neurofibrillary tangles in the entorhinal cortex (0.083;0.74); NFT amyg- neurofibrillary tangles in the amygdala (0.004;0.68). Lower Panel Legend (p-values for corticosteroids comparisons; p-values for NSAIDs comparisons): NP cortex- sum of CERAD ratings of neuritic plaques in four cortical regions (0.001;0.26); NP sum- sum of CERAD ratings of NPs in the hippocampus, entorhinal cortex, amygdala, and cortex (0.001; 0.26); NFT cortex- sum of CERAD ratings of neurofibrillary tangles in four cortical regions (0.002; 0.20); NFT sum- sum of CERAD ratings of NFTs in the same regions as in NPsum (0.001; 0.55). *p≤0.05; **p≤0.005