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National Academy of Neuropsychology Conference San Antonio, Texas November 1999 |
July 1999 |
The relationship between specific neuropsychological measures of cognitive functioning in dementia and morphological measurements of the corpus callosum have not been established. This investigation examined these relationships in cognitively demented patients in an attempt to identify a neuroanatomical index of cortical and cognitive integrity. We hypothesized that mid-saggital regional measurements of the posterior corpus callosum would be related to the CVLT-9, a test of memory and language. Similarly, we predicted that regional measurements of the anterior corpus callosum would be related to a variety of assessments of executive function. Recent evidence indicates that the posterior corpus callosum is smaller in patients with Alzheimer's disease (AD). In contrast, patients with frontal systems deficits have degradation of the anterior corpus callosum. Thus, we predicted that selective degradation of anterior and posterior corpus callosum would discriminate between subcortical ischaemic vascular dementia (IVD) and Alzheimer's disease (AD), respectively. Participants included individuals diagnosed with AD (n=9) and IVD (n=8), who were comparable for age, education, level of dementia, depression, and handedness. Contrary to expectations, consistent, statistically significant negative correlations were found between measures of working memory and anterior regions of the corpus callosum (r=-.72, p=<.001). Also, anterior regions were positively correlated with measures of long delay verbal declarative memory (r=.55, p<.05), and semantic clustering during verbal recall (r=.56, p<.05). Also contrary to expectations, mid- and posterior regions of the corpus callosum were negatively correlated with clock drawing to command (r=-.64, p=<.01; r=-62. p<.01), and positively correlated with graphomotor perseverations (r=.51, p<.05). Regional measurements of the corpus callosum did not discriminate between diagnostic groups. Though unexpected, results consistently indicated that patients with a larger corpus callosum were indeed disadvantaged on the neuropsychological tests. These data are consistent with hemispheric interference notions of "reverse ontology" suspected in degenerative cortical and white matter dementias.
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The corpus callosum is the largest white matter tract in the brain and is responsible for integrating information between the cerebral hemispheres. Its cortical projections are organized efficiently such that connections to the frontal areas originate in the anterior portion of the corpus callosum, while temporal and parietal connections are rooted in the posterior. |
The most affected cortical neurons in Alzheimer's disease are the large pyramidal cells in cortical layer 3 (Glickstein & Whitteridge, 1976). This layer includes the largest number of neurons projecting into the corpus callosum found in various rodenta and non-human primates (Innocenti, 1986). Recent evidence has indicated that selective atrophy of the posterior corpus callosum also occurs in AD (Yamauchi et al., 1993; Janowsky et al., 1996; Kaufer et al., 1997; Hampel et al., 1998). Thus, it follows that the behavioral manifestations of the Alzheimer's neuropathology&endash; progressive memory and semantic language deficits&endash; may also be related to atrophy of the posterior corpus callosum. In fact, Yamauchi and colleagues (1994) claim that the extent of callosal atrophy may be a useful index of cognitive impairment.
Complementing the topographic projections first described by Pandya and Seltzer (1986), it follows that selective degradation of the anterior corpus callosum may be associated with changes in the executive functions of the frontal areas. Patterns of subcortical pathology and anterior degeneration of the corpus callosum have been found in corticobasal degeneration (Yamauchi et al., 1998), multiple sclerosis (Pozzilli et al., 1991), frontotemporal dementia (Kaufer, et al., 1997), progressive supranuclear palsy (Yamauchi et al., 1997), lacunar infarction and extensive leukoaraiosis (Yamauchi et al., 1994), and progressive subcortical vascular encephalopathy (Yamanouchi et al., 1990).
Purpose
Unfortunately, the constellation
of cognitive variables and their relationship to callosal atrophy in
healthy elderly and dementia populations has largely been overlooked,
or poorly specified by either using screening instruments (e.g.,
Mini-Mental Status Examination) or composite indices (e.g., Weschler
Adult Intelligence Scales). Thus, the purpose of this retrospective investigation
was to explore the relationship between the morphologic and
functional degradation of the corpus callosum in cognitively demented
patients.
Hypotheses & Predictions
Participants
All 17 participants met NINCDS-ADRDA and CADDTC criteria for AD and IVD respectively:
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(n=8) |
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sex (f/m) |
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(x2)=1.44 |
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age (years) |
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education |
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MMSE |
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GDS |
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Apparata
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MR studies
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Morphologic analysis
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Neuropsychological Variables of Interest
Results were contrary to expectation, specifically no between group differences were found and some correlations linked cognitive variables in different regions/different directions. The interpretation for these data is guarded, but are generally consistent with the notion that callosal area may be a sensitive, yet not a specific index of cortical integrity.
These data may also suggest that callosal integrity may be a liability for cognition. Teuber suggested this possibility when presented with Geschwind and Kaplan's classic disconnexion case study. Increased connectivity of the hemispheres may indeed facilitate interference effects. However, further investigation is warranted.
It is suggested, however, that future research employ a correlational design, with dementia and non-clinical groups. Additionally, specific measures of cognitive function are suggested, rather than gross measures.
Limitations
