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A Magnetic Resonance Imaging Study

George Bartzokis, MD; Jeffrey L. Cummings, MD; David Sultzer, MD; Victor W. Henderson, MD; Keith H. Nuechterlein, PhD; Jim Mintz, PhD

Arch Neurol. 2003;60:393-398.

Background  Imaging and postmortem studies suggest that frontal lobe white matter (FLWM) volume expands until about the age of 44.6 years and then declines. Postmortem evidence indicates that the structural integrity of myelin sheaths deteriorates during normal aging, especially in late myelinating regions such as the frontal lobes.

Objectives  To assess the integrity of FLWM by magnetic resonance imaging and, thus, to provide an important index of brain aging and its relationship to Alzheimer disease (AD).

Design  Cross-sectional study.

Setting  Two metropolitan university hospitals and AD research centers.

Participants  Two hundred fifty-two healthy adults (127 men and 125 women), aged 19 to 82 years, and 34 subjects with AD (16 men and 18 women), aged 59 to 85 years.

Main Outcome Measure  Calculated transverse relaxation rate (R₂) of the FLWM (an indirect measure of the structural integrity of white matter).

Results  As expected from prior imaging data on FLWM volume, the quadratic function best represented the relationship between age and the FLWM R₂ (P<.001). In healthy individuals, the FLWM R₂ increased until the age of 38 years and then declined markedly with age. The R₂ of subjects with AD was significantly lower than that of a group of healthy control subjects who were of similar age and sex (P<.001).

Conclusions  The R₂ changes in white matter suggest that the healthy adult brain is in a constant state of change, roughly defined as periods of maturation continuing into middle age followed by progressive loss of myelin integrity. Clinically diagnosed AD is associated with more severe myelin breakdown. Noninvasive measures, such as the determination of the R₂, may have the potential to track prospectively the trajectory of deteriorating white matter integrity during normal aging and the development of AD and, thus, may be a useful marker for medication development aimed at the prevention of AD.

From the Department of Neurology (Drs Bartzokis and Cummings) and the Laboratory of Neuroimaging, Division of Brain Mapping (Dr Bartzokis), University of California, Los Angeles, UCLA School of Medicine; the VA Greater Los Angeles Healthcare System, West Los Angeles, Calif (Drs Bartzokis, Sultzer, and Mintz); the Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles (Drs Cummings, Sultzer, Nuechterlein, and Mintz); and the Departments of Geriatrics and Neurology, University of Arkansas for Medical Sciences, Little Rock (Dr Henderson).

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