[show abstract][hide abstract] ABSTRACT: 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.
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).
Two metropolitan university hospitals and AD research centers.
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.
Calculated transverse relaxation rate (R( 2)) of the FLWM (an indirect measure of the structural integrity of white matter).
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).
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.
[show abstract][hide abstract] ABSTRACT: It is suggested that Alzheimer's disease (AD) patients are able to recall more items on the digit span task than on immediate free recall from a supraspan word list. Two experiments were undertaken to verify this assertion and to understand the basis of the putative span/supraspan discrepancy. The first experiment, involving 35 mildly or moderately demented AD patients, confirmed that digit span significantly exceeded immediate recall from a 10-item supraspan word list. Although digit span also exceeded supraspan recall in 38 elderly non-demented control subjects, the discrepancy was significantly greater within the AD group. In a second experiment, 19 AD cases and 20 controls were assessed with a word span task that used nouns matched by frequency and word length to nouns on the supraspan task. The magnitude of the span/supraspan discrepancy was reduced, indicating that part of the initial discrepancy was due to differences in stimulus items (digits versus common nouns). As before, AD subjects recalled more words on the span task than the supraspan task. However, in striking contrast, NC subjects recalled more words on the supraspan task, further indicating that AD patients are particularly impaired on supraspan recall. Using combined data from 106 subjects in both experiments, digit span performance correlated significantly with supraspan recall for NC but not AD subjects. Moreover, within the AD group the magnitude of the discrepancy was inversely related to a working memory measure derived from the backward digit span. The magnitude of the span/supraspan discrepancy correctly classified 88% of patients with mild dementia and 74% of controls. Results indicate that AD patients are specifically vulnerable to information overload inherent in the supraspan task, a view consistent with the perspective that AD is characterized by prominent disturbances in working memory.
[show abstract][hide abstract] ABSTRACT: In a working memory framework, the forward memory span involves a subsidiary system that maintains information, and the backward span relies on a central executive system (CES) that allocates processing resources. The authors hypothesized that a measure of the CES derived from the backward span would distinguish Alzheimer's disease (AD) patients (
n&≠&₄9) from elderly controls without dementia (
n&≠&₄9), vary as a function of disease severity, and underlie other cognitive disturbances. Memory span procedures were Digit Span Forward and Backward and Visual Memory Span Forward and Backward. Derived CES measures discriminated between groups, predicted dementia severity, and predicted performance on some of the cognitive tasks examined. However, working memory subsidiary systems also appeared to be affected in AD, and some cognitive deficits in AD were independent of working memory disturbances. The visual memory span backward was the best predictor of group and of dementia severity. (PsycINFO Database Record (c) 2012 APA, all rights reserved)