White Matter Cerebral Changes Related to Cognition

abstracts & commentary

Sources: de Groot JC, et al. Cerebral white matter lesions and cognitive function: The Rotterdam scan study. Ann Neurol 2000;47:145-151; Smith CD, et al. White matter volumes and periventricular white matter hyperintensities in aging and dementia. Neurology 2000;54:838-842.

These two reports explore the relationships between cerebral white matter lesions and cognitive dysfunction in two different groups of elderly patients. During a single year, de Groot and colleagues obtained magnetic resonance images (MRIs) to determine the association of white matter lesions (WML) with cognitive scores in 1077 relatively healthy, elderly Dutch persons. The entire group was stratified into five quintiles of declining numbers between the ages of 60 and 90 years. Some severely demented individuals apparently were excluded. Average minimental scores for the seventh, eighth, and ninth decades ranged between 26.8 and 27.8 (perfect = 30). The total 80- to 89-year group, however, included less than half the number of persons of either the 70-79 or the 60-69 year group. Similarly, the group average median age of the 80-89 year patients was 1.5 years younger than the subjects aged 60-69 years. Smith and colleagues took a different approach. They studied the autopsied brains of 52 aged nuns and correlated the application of postmortem MRI brain imaging with direct pathological examinations of the brains at autopsy.

The Dutch study correlated the relationships between periventricular and subcortical (remote from the ventricular borders) WMLs either singularly or together with neurocognitive capability. Particular attention was given to psychomotor speed, memory performance, and global cognition. WMLs were measured by both proton density and T2-weighted MRIs. Periventricular zones of interest included frontal and occipital WML caps, plus similar adjacency to the walls of the lateral ventricles. Subcortical WML volumes were calculated on hard copy by their diameters and termed small (1-3 mm), medium (3-10 mm), or large (> 10 mm). Overall brain atrophy or numbers of cerebral infarctions were not influential. Increased WMLs found in both periventricular and subcortical areas were associated with worsening mental status. Persons in the older quintiles, however, who did not increase the periventricular WMLs did not change their cognitive index rating. Some of them, however, selectively increased their subcortical WMLs but remained cognitively stable.

The Smith group of 52 nuns all possessed a long history of good health, good nutrition, and an average 15-16 years of education. Their age of death averaged 89.1 ± 4.8 years. Thirty-three of the 52 met the pathological anatomic criteria for Alzheimer’s disease (AD), but only 19 of the 33 were clinically identified as demented by standard cognitive testing. Total brain and white matter volumes were lower than was found in the nondemented nuns and their brain weights were lower as well (P = 0.06). Of the remaining 19 nuns, three were clinically demented. Two of the latter showed hippocampal sclerosis and one possessed large infarcts and many lacunes.

The interesting finding is that postmortem studies using T-1- and T-2-weighted MRIs on the nuns’ brains failed to correlate periventricular areas with white matter hyperintensity with dementia. Nevertheless, the demented brains, whether with AD, had proportionately lower absolute overall white matter volumes, although total brain weight was reduced even more. De Groot et al conclude that "the cerebral atrophy found on MR imaging is strongly related to the presence of dementia" (despite) "a lack of association with hyperintensities" on MRI films.


These two informative reports might at first glance appear to be antithetical. Much neurological literature has emphasized that periventricular white matter hyperintensities, with or without subcortical white patches, associate with cognitive decline. DeGroot et al, who were dealing with five quintiles of age between 60 and 90 years, selectively excluded an increasing population of severe dementia at later ages. Not unexpectedly, the older the quintile, the greater the proportion of brains succumbing to progressive dementia associated with periventricular hyperdensities-WELs. This inference may explain why many fewer subjects older than 78 years could be found to have high minimental scores and still retain high amounts of periventricular WELs. Estimates of brain volumes were not performed, but by the third quintile group (age 78 years), periventricular damage appeared far more serious than subcortical lesions.

Now, examine Smith et al’s postmortem MRI findings of brain volumes and brain weights on old, old persons with a mean age of 89.1 ± 4.8 years. As presented, 33 of the 52 had pathological evidence of AD, but only 19 of the ADs expressed clinical dementia. Among the other 19 nuns free of AD by pathological criteria, two who were demented had hippocampal sclerosis and one more had multifocal brain infarction. Is it possible that the nuns managed to reach 89 years because none of them had acquired the leucoencephalopathy that deGroot found in younger persons? Is the periventricular leucoencephathy an early elderly illness associated with chronic hypertension, diabetes, hypercholesteremia, alcoholism, or, perhaps, AD? Whatever the answer, further analysis and management may generate some protection for many persons around the world as they move into their late eighth decade. —fp

Which statement is correct?

a. Both deGroot et al and Smith et al found comparative loss of brain white matter in elderly, demented patients.

b. Smith found dementia in 33 nuns, all with pathological Alzheimer’s disease.

c. Periventricular and subcortical leucoencephalography were equally associated with dementia in the Dutch study.

d. The Dutch study followed patients for five years, but the Smith study examined only postmortem brains.