White matter structural integrity in healthy aging adults and patients with Alzheimer disease: a magnetic resonance imaging study.

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 (R( 2)) 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 R(2) (P<.001). In healthy individuals, the FLWM R(2) increased until the age of 38 years and then declined markedly with age. The R( 2) 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 R(2) 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 R(2), 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.