Where the brain grows old: Decline in anterior cingulate and medial prefrontal function with normal aging

Jose V Pardo, Joel T. Lee, Sohail A. Sheikh, Christa Surerus-Johnson, Hemant Shah, Kristin R. Munch, John V Carlis, Scott M. Lewis, Michael A Kuskowski, Maurice W Dysken

Research output: Contribution to journalArticlepeer-review

105 Scopus citations


Even healthy adults worry about declines in mental efficiency with aging. Subjective changes in mental flexibility, self-regulation, processing speed, and memory are often cited. We show here that focal decreases in brain activity occur with normal aging as measured with fluorodeoxyglucose and positron emission tomography. The largest declines localize to a medial network including the anterior cingulate/medial prefrontal cortex, dorsomedial thalamus, and sugenual cingulate/basal forebrain. Declining metabolism in this network correlates with declining cognitive function. The medial prefrontal metabolic changes with aging are similar in magnitude to the hypometabolism found in Mild Cognitive Impairment or Alzheimer's disease. These results converge with data from healthy elderly indicating dysfunction in the anterior attention system. The interaction of attention in the anterior cingulate cortex with memory in the medial temporal lobe may explain the global impairment that defines dementia. Despite the implications for an aging population, the neurophysiologic mechanisms of these metabolic decreases remain unknown.

Original languageEnglish (US)
Pages (from-to)1231-1237
Number of pages7
Issue number3
StatePublished - Apr 15 2007

Bibliographical note

Funding Information:
The involvement of the anterior cingulate cortex in aging is supported by previous studies. Martin ( = − 0.61, < 0.01) between regional brain blood flow, also a marker for brain activity, and age in 30 resting, healthy subjects with ages 30–85 years. Moeller ( = − 0.63, < 0.001) and noted that these changes occurred in young and mid-life adults. Despite these key previous observations, the prominence of ACC and medial prefrontal declines with aging throughout the life span are not widely appreciated. Several reasons may account for this across the different studies: use of region of interest analyses; lack of adjustment for multiple comparisons; sparse data on cortical thinning; and older PET scanner technology with decreased axial sampling and decreased signal-to-noise ratios. Our study not only confirms and highlights ACC involvement in normal aging, but also relates the finding to age-associated cognitive decline. To our knowledge, this relationship has not been reported previously. Martin et al., 1991 ) found within the ACC a negative correlation ( r p Moeller et al., 1996 ) provided evidence for a decline in metabolism in the medial frontal region of 130 healthy volunteers with ages 21–90 years. Schultz ( Schultz et al., 1999 ) looked for age-related decreases in brain blood flow in 37 healthy subjects with ages 19–50 years. They found that the medial frontal cortex, including the ACC, showed the largest negative correlation ( r p


  • Aging
  • Alzheimer's disease
  • Anterior cingulate cortex
  • Attention
  • Brain metabolism
  • Mild cognitive impairment
  • Neurodegeneration
  • PET

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