Assessment of Cingulate Gyrus Integrity in Patients with Alzheimer’s Disease

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Michael J Larson and Dr. Ramona O Hopkins, Psychology and Neuroscience

Alzheimer’s disease (AD) is a neurogenerative disease that is characterized by memory loss, language impairments, impaired visuospatial skills, poor judgment, and mood changes. The pathophysiology of AD is typified by a loss of cholinergic cells in the basal forebrain, development of neuritic plaques in the cerebral cortex, neurofibrillary tangles that start in the temporal lobe and progress to other cortical regions, and generalized cerebral atrophy (Kolb & Whishaw, 2001). Increased atrophy is associated with increased severity of dementia (Fox, Scahill, Crum, & Rossor, 1999; O’Brien et al., 2001). The neuropathology and associated atrophy in AD progresses systematically, starting in the limbic system and progressing through the entorhinal cortex and medial temporal lobe (including the cingulate gyrus). Little is known about the effects of AD on the cingulate gyrus.

The cingulate gyrus is the largest of the limbic structures and is primarily involved in attention, affect, sensory processes, executive function, word processing, and memory (Devinsky, Morrell, & Vogt, 1995; Vogt, Finch, & Olson, 1992). There is a dichotomy in the functions of the anterior and posterior cingulate cortices (Vogt et al., 1992). Anterior damage of the cingulate gyrus results in changes in motivation, affect, and executive decision-making (Devinsky et al., 1995); posterior damage results in a change in monitoring of sensory events, spatial orientation, and memory (Vogt et al., 1992). A recent Positron Emission Tomography (PET) study of the cingulate gyrus found decreased glucose utilization in both the anterior and posterior cingulate in early AD (Minoshima et al., 1997). Additionally, Killiany et al. (2000) identified changes in the anterior cingulate as potential markers of AD progression.

To our knowledge no study has assessed morphological changes in the cingulate gyrus associated with AD using quantitative MRI analysis. The purpose of our study is to determine the effects of AD on the cingulate gyrus by assessing the cross-sectional surface area on midsagittal and para-sagittal MRI scans.

Methods

The data for this study come from archival data obtained from the Cache County project. Detailed descriptions of the Cache County study have been published elsewhere (Breitner et al., 1999). This study has IRB approval and informed consent was obtained from all participants. The data include information for 82 individuals with AD and 20 normal elderly control subjects all over age 65. Of the 82 AD patients there are 31 males and 51 females with a mean age of 83.17 + 6.59 years and a mean education level of 13.12 + 2.97 years. The elderly control subjects consist of 8 males and 12 females with a mean age of 76.7 + 6.38 years and a mean education level of 12.95 + 2.37 years.

Brain magnetic resonance (MR) images of the participants were performed on a 0.5 Tesla Philips scanner using a standard protocol (see Bigler et al., 2000). The area of the cingulate gyrus (CING_TOT) as well as the posterior (CING3), caudal (CING2), and anterior (CING1) portions of the cingulate were measured. Images were analyzed using NIH IMAGE. For each patient three images were used: the mid-sagittal slice and two para-sagittal slices 5mm to the right and left of the mid-saggital. One researcher, blinded to participant status, took two cross-sectional surface area measurements of each structure and averaged the results using the methodology described in Killiany et al. (2000). Pearson’s product moment correlation was used to establish the reliability of the measurements (CING_TOT: r = .93; CING3: r = .90; CING2: r = .92; CING1: r = .90). The MRI data were analyzed using analysis of variance (ANOVA)

Results and Conclusions

As expected, the overall surface area of the cingulate gyrus (CG) was significantly reduced in AD patients (F = 2.6, p = .05). Significant atrophy was also found in the posterior portion of the cingulate gyrus (F = 4.242, p = .02). The caudal and anterior portions of the CG were smaller in the AD participants compared to the controls although the difference did not reach statistical significance (CING2: F = 1.75, p = .09; CING1: F = .01, p = .49).

Cerebral atrophy associated with Alzheimer’s disease was found in the cingulate gyrus in this study. It is important to note, however, that the atrophy of the posterior CG was primarily responsible for the overall reduction of the CG surface area in AD patients. There are frontotemporal connections within the posterior CG, including input from the hippocampus, which is important in memory formation. This posterior CG atrophy, along with cerebral and hippocampal atrophy, may contribute to the reported memory impairments in patients with AD. The absence of anterior CG atrophy may be related to anatomical variability of the more anterior portions of the CG. In light of these results, we hope to compare the relationship between the cingulate gyrus and neurocognitive and emotional function.

References

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