Neurology -- Correspondence for Mungas et al., 59 (6) 867-873

Correspondence published:

Reply to van der Flier: Dan Mungas (16 January 2003)

Volumetric MRI predicts rate of cognitive decline related to AD and cerebrovascular disease.: Wiesje M. van der Flier, Mark A. van Buchem and Huub A.M. Middelkoop (30 December 2002)

Reply to van der Flier 16 January 2003

Dan Mungas
Dept. of Neurology, University of California, Davis
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Re: Reply to van der Flier

dmmungas{at}ucdavis.edu Dan Mungas

We welcome the opportunity to clarify the questions raised by van der Flier et al. First, baseline cognitive status was associated with clear differences in baseline cognitive and MRI values and in longitudinal cognitive change. Baseline Global Cognition significantly differed among all cognitive impairment groups (CDR=0.0 – mean (sem) = 99.5 (1.6), CDR=0.5 – 90.6 (2.2), CDR greater than or equal to 1.0 – 72.1 (3.6)). These results correspond to average, low average, and impaired baseline cognitive status in the three groups, as would be expected. There were also significant differences among all three groups in hippocampal volume (CDR=0.0 – .42% (.008), CDR=0.5 – .36% (.011), CDR greater than or equal to 1.0 – .29% (.018)) and cortical gray matter volume (CDR=0.0 – 39.2% (.28), CDR=0.5 – 36.7% (.38), CDR greater than or equal to 1.0 – 35.1% .63)), both expressed as percent of total intracranial volume. Similarly, the three groups significantly differed in annual rate of change in Global Cognition (CDR=0.0 – +.36 (.42), CDR=0.5 – -2.89 (.70), CDR greater than or equal to 1.0 – -8.64 (1.27)). These numbers correspond to stable to improved performance in the CDR=0.0 group, and annual declines of about .20 s.d. and .60 s.d. in the latter two groups.
Second, this primary purpose of this study was not to address disease progression in dementia. Cognitive impairment is a continuously varying phenomenon, and similarly, the pathologies associated with Alzheimer’s disease (AD) and ischemic brain injury are continuous processes that likely lead to changes in structural MRI variables and cognition both before and after the threshold for dementia has been reached. By clarifying continuous relationships between MRI variables and cognition we can better understand how these pathologies relate to clinically important concepts like cognitive decline and dementia. The primary conclusions from this study were: 1) cortical gray matter volume was inversely related to rate of cognitive decline regardless of presence of lacunes, and 2) hippocampal volume was inversely related to cognitive change in cases without lacunes but not in cases with lacunes. We hypothesize that cortical atrophy results from both AD and ischemic brain injury, but that severe hippocampal atrophy is more likely due to AD. Demented cases in this study contributed substantially to results and conclusions. They were more likely to have disproportionate cortical and hippocampal atrophy, to be cognitively impaired at baseline, and to show rapid cognitive decline. We agree that further study is needed to examine rate of decline in demented patients, however, we strongly believe that use of neuropathologically diagnosed cases will be essential to address questions regarding the relative rate of decline in AD vs. vascular dementia.

Volumetric MRI predicts rate of cognitive decline related to AD and cerebrovascular disease. 30 December 2002

Wiesje M. van der Flier,
neuropsychologist
Leiden University Medical Center,
Mark A. van Buchem and Huub A.M. Middelkoop
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Re: Volumetric MRI predicts rate of cognitive decline related to AD and cerebrovascular disease.

W.M.van_der_Flier{at}lumc.nl Wiesje M. van der Flier, et al.

We read with interest the article by Mungas et al. [1] on volumetric MRI correlates of longitudinal cognitive decline in normal aging, AD, and subcortical cerebrovascular brain injury (SCVBI). The authors report that cortical gray matter atrophy predicted cognitive decline regardless of whether lacunes were present, whereas hippocampal atrophy predicted decline only in those without lacunes. The authors conclude that cortical atrophy is an index of disease severity in both AD and SCVBI, whereas hippocampal volume may index disease severity and predict progression in AD.
We would be interested in the baseline values of MRI variables and of the global cognitive score, as well as in the (yearly) cognitive decline that is observed in the several patient groups. Does the observed decline have clinical relevance?
Second, the authors report on disease progression in dementia. However, from their data it seems as though there are only seven demented patients with lacunes and seven demented patients without lacunes included in the study. Patients with a CDR-rating of 0.5 are mostly not demented but suffer some form of mild cognitive impairment. [2] The MMSE scores reported in Table 2 are consistent with this notion, as they are not in the demented range (mean MMSE for CDR=0.5 without lacunes = 27.1, and for CDR = 0.5 with lacunes mean MMSE = 28.1).
It seems unjustified to make conclusions with respect to dementia as demented patients are underrepresented in the study population. It is still conceivable that the findings generalize to dementia, but this remains to be demonstrated.
References
1. Mungas D, Reed BR, Jagust WJ, et al. Volumetric MRI predicts rate of cognitive decline related to AD and cerebrovascular disease. Neurology 2002; 59(6):867-873.
2. Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol 1999; 56(3):303-308.