Aging brain

About: Aging brain is a research topic. Over the lifetime, 1255 publications have been published within this topic receiving 66405 citations.

ERP, fMRI and functional connectivity studies of brain response to odor in normal aging and Alzheimer's disease

Abstract: More than 14 million Americans over 50 suffer from smell impairment (Murphy et al., 2002). In a series of studies we have sought the underlying cortical substrates of olfactory loss with aging. We used psychophysical, neuropsychological, event related potentials (ERPs) and functional magnetic resonance imaging (fMRI) techniques to address the problem. Psychophysical investigations have revealed significant losses in olfactory threshold sensitivity, odor identification and odor memory. These impairments are significantly worse in patients with neurodegenerative diseases such as Alzheimer’s disease (AD) (Murphy, 2002). The earliest lesions of AD are in the mesial temporal regions of the brain critical to olfactory processing, thus the potential exists for reflection of incipient disease in olfactory tasks. The investigation of olfactory function in aging and AD is of basic science interest and may contribute to the development of more sensitive diagnostic batteries for AD (Murphy, 2002). ERPs provide real-time temporal information about the brain’s response to odor stimulation. We have used this technique to investigate brain response over the lifespan in the normally aging brain (Murphy et al., 2000) and in patients with neurodegenerative diseases such as Alzheimer’s disease (Morgan and Murphy, 2002). The results suggest that the odor evoked response of the brain is significantly reduced in amplitude and delayed in its latency in normally aging persons and dramatically more delayed in Alzheimer’s patients. These results confirm the importance of considering a central origin for the olfactory loss associated with aging and AD. fMRI is a powerful tool for investigation of brain structure and of functional activation in specific regions of interest (ROIs). We have used fMRI to investigate the cortical substrate of olfactory impairment in the elderly. The fMRI data were analyzed with individual, group and ROI analyses. Results are described in Cerf-Ducastel and Murphy (2003), Ferdon and Murphy (2003) and Wiser et al. (2000). Older adults showed less activation in important olfactory ROIs: entorhinal cortex, amygdala, insula and piriform cortex. Cerebellar activation was lower in areas Crus I and II. A number of approaches have been taken to achieve an understanding of integrated brain activity. Functional connectivity involves correlation between fMRI activity in two brain regions during performance of a task. The technique permits testing the hypothesis that interacting brain regions, rather than isolated regions of interest, are the cortical substrate for performance. We have approached functional connectivity with more than one analysis strategy. Calhoun-Haney et al. (2004) used the seed voxel method to examine correlations between individual voxels in hippocampus and in ROIs for olfactory processing during an olfactory task. A number of investigators have conducted connectivity analysis on regional brain activation using correlational methods (Horwitz, 1989). Here we aimed to identify significant correlations in fMRI activation among ROIs for olfactory tasks and to test the hypothesis that the pattern of correlations among these regions is significantly impacted by aging. Activity was correlated separately for young adults, older adults and AD patients.

The absence of the calcium-buffering protein calbindin is associated with faster age-related decline in hippocampal metabolism.

Abstract: Although reductions in the expression of the calcium-buffering proteins calbindin D-28K (CB) and parvalbumin (PV) have been observed in the aging brain, it is unknown whether these changes contribute to age-related hippocampal dysfunction. To address this issue, we measured basal hippocampal metabolism and hippocampal structure across the lifespan of C57BL/6J, calbindin D-28k knockout (CBKO) and parvalbumin knockout (PVKO) mice. Basal metabolism was estimated using steady state relative cerebral blood volume (rCBV), which is a variant of fMRI that provides the highest spatial resolution, optimal for the analysis of individual subregions of the hippocampal formation. We found that like primates, normal aging in C57BL/6J mice is characterized by an age-dependent decline in rCBV-estimated dentate gyrus metabolism. Although abnormal hippocampal fMRI signals were observed in CBKO and PVKO mice, only CBKO mice showed accelerated age-dependent decline of rCBV-estimated metabolism in the dentate gyrus. We also found age-independent structural changes in CBKO mice, which included an enlarged hippocampus and neocortex as well as global brain hypertrophy. These metabolic and structural changes in CBKO mice correlated with a deficit in hippocampus-dependent learning in the active place avoidance task. Our results suggest that the decrease in CB that occurs during normal aging is involved in age-related hippocampal metabolic decline. Our findings also illustrate the value of using multiple MRI techniques in transgenic mice to investigate mechanisms involved in the functional and structural changes that occur during aging.

Aging brain: prevention of oxidative stress by vitamin E and exercise.

Abstract: With aging, the brain undergoes neuronal loss in many areas. Although the loss of cells in the cerebral cortex, in particular the frontal cortex, has been recognized with aging, the influence of synaptic losses has a larger impact on cognitive decline. Much of the recent research on animals, as well as humans, has been aimed at slowing the cognitive decline through enrichment, and it has been found that the key factors are antioxidants and exercise. Several reports support the concept that regular supplementation of vitamin E and physical activity from as early as middle age can slow the cognitive decline observed during the later years. A few studies have also suggested that exercise is analogous to acetylcholine esterase inhibitors that are also used extensively to treat cognitive impairment and dementia in Alzheimer's disease. In addition, reports also support that vitamin E and exercise may act synergistically to overcome free radical injury and oxidative stress in the aging brain.