Preservation of neuronal number despite age-related cortical brain atrophy in elderly subjects without Alzheimer disease

Abstract

Cerebral volume loss has long been associated with normal aging, but whether this is due to aging itself or to age-related diseases, including incipient Alzheimer disease, is uncertain. To understand the changes that occur in the aging brain, we examined the cerebral cortex of 27 normal individuals ranging in age from 56 to 103 years. None fulfilled the criteria for the neuropathologic diagnosis of Alzheimer disease or other neurodegenerative disease. Seventeen of the elderly participants had cognitive testing an average of 6.7 months prior to death. We used quantitative approaches to analyze cortical thickness, neuronal number, and density. Frontal and temporal neocortical regions had clear evidence of cortical thinning with age, but total neuronal numbers in frontal and temporal neocortical regions remained relatively constant during a 50-year age range. These data suggest that loss of neuronal and dendritic architecture, rather than loss of neurons, underlies neocortical volume loss with increasing age in the absence of Alzheimer disease.

Figure 1

Scatterplots of cortical thickness versus age. Frontal cortical thickness in 27 cases demonstrated a significant correlation of decreasing cortical thickness with age (A). Temporal cortical thickness in 17 cases (B) and hippocampal CA1 sector area in 21 cases (C) also demonstrated decreasing cortical thickness or decreasing area of CA1 with increasing age.

Figure 2

Scatterplot of age and frontal cortical thickness of male and females demonstrating no differences based on gender.

Figure 3

Scatterplots of neuronal density versus age. Frontal cortical neuronal density (A) and temporal cortical neuronal density (B) show a small but not statistically significant increase with increasing age. Hippocampal neuronal density stays constant (C).

Figure 4

Scatterplots of neuronal number for frontal (A), and temporal regions (B) for estimated number of neurons in a cortical strip of 1 mm, by 1 mm, by calculated cortical thickness showing the neuronal number remaining constant with increasing age. Scatterplot of neuronal number in hippocampal CA1 region versus age (C) demonstrating loss of neurons with increasing age.

Figure 5

Scatterplots of last available Mini Mental State Examination (MMSE) score versus frontal cortical thickness in 17 cases (A) and temporal cortical thickness in 15 cases (B) demonstrating no correlation between cortical thickness and last available MMSE score (mean = 6.7 months prior to death).