Joel Fredrik Astrup Aanerud

Cerebral blood flow, cerebral oxygen metabolism, and atrophy in healthy aging

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  • Manouchehr S. Vafaee, Aarhus University Hospital
  • ,
  • Per Borghammer
  • Joel Aanerud
  • Paul Cumming
  • ,
  • Albert Gjedde, Aarhus University Hospital

Introduction: It is debatable where and to what extent cerebral blood flow (CBF) and cerebral oxygen metabolism (CMRO2) decline with healthy aging. It is possible that neocortical atrophy could affect the measurements of these physiological factors in addition to the direct effects of aging on blood flow and metabolism. To tackle these issues and to shed some light on the cerebrometabolic changes following normal aging, we completed a series of CBF/CMRO2 PET studies on a healthy group. Material and methods: 12 healthy young males and females, aged (26±4 yrs), and 16 elderly healthy subjects, aged (58y±5 yrs), underwent one CBF and two identical CMRO2 quantitative 3-min PET scans in a state-of-rest. The cortical grey matter was extracted from the subjects MRI scans by means of an automated segmentation algorithm. We also performed a voxel-based subtraction of young and old and a voxel-wise regression of CBF and CMRO2 versus age. The magnitudes of CMRO2 and CBF were determined with the two-compartment weighted-integration methods. Mean subtracted image volumes (elderly minus young) were converted to zstatistic volumes. Significant focal differences of CBF and CMRO2 and grey matter intensity were identified on the basis of the 3D Gaussian random field theory and cluster analysis. Results: The average whole brain CBF in young subjects (53±5ml/min.hg) did not differ from the elderly population (52±6ml/min.hg). However, the average global CMRO2 in aged subjects (154±24μmol/min.hg) was lower than in the young subjects (166±13μmol/min.hg) but did not reach significance (p=0.1). Oxygen consumption had decreased more progressively than CBF in some regions and predominantly so in the neocortex, although clusters of CBF and CMRO2 decline overlapped extensively. CBF and CMRO2 decreased in most of the frontal lobe (except orbitofrontal cortex, M1, PMA and SMA), and L/R lateral parietal cortex and L posterior cingulate. Oxygen decline was more pronounced in the pre-central gyrus than CBF. A somewhat similar and significant pattern of decrease in grey matter intensity was seen, primarily in the frontal and lateral parietal cortices. Discussion: While it is accepted that many changes occur in the brain as a result of normal aging, it is not fully agreed to what degree and in which regions of the brain those changes take place. Our data indicate that global CMRO2 decreases (although not significantly) without concomitant decrease in global CBF. If so, the finding confirms that oxygen consumption is a more accurate index of neuronal work than blood flow. We observe overlapping areas of decreased CBF and CMRO2 and decline in grey matter intensity. It is thus likely that neocortical atrophy contributes to the decreased signal in these PET scans. However, the data also revealed non-overlapping areas. The decreases of CBF and CMRO2 in healthy aging are most likely due to combinations of atrophy and direct changes, such as functional deafferentation, changes in neurotransmitter systems, and cell death following healthy aging. The metabolic depression as a result of healthy aging suggests a dysfunction of neuronal circuits that underlie some age-related changes in cognitive function.

Original languageEnglish
JournalJournal of Cerebral Blood Flow and Metabolism
IssueSUPPL. 1
Publication statusPublished - 13 Nov 2007

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