Atrophy Is Associated with Posterior Cingulate White Matter Disruption in Dementia with Lewy Bodies and Alzheimer’s Disease

Firbank MJ, Blamire AM, Krishnan MS, et al.
Neuroimage 2007;36:1–7

Background: Alzheimer disease (AD) and dementia with Lewy bodies (DLB) are associated with hippocampal and posterior cingulated hypometabolism. Studies have revealed functional connectivity of these two regions in resting state. The connection of both regions is given by the cingulum. Altogether, this network represents the structural and functional expression of the clinical presentation of AD and DLB with diminished episodic memory. To investigate the hypothesis of altered structure of the cingulum associated to hippocampal atrophy the special diffusion imaging, the diffusion tensor imaging (DTI) is an excellent tool. DTI allows imaging of the diffusion of water. As the axons are highly structured, the water tends to diffuse along the direction of the axons. Therefore, the DTI is a sensitive indicator of changes to the integrity of axons.

Patients and Methods: 15 subjects with AD and 16 with DLB as well as 15 healthy volunteers were scanned on a 1.5-T MRI system with a T1-weighted 3-D sequence (TR 10 ms, TE 4.6 ms, flip angle 20°). DTI sequence was used with a b value of 1,000 s/mm², TR of 6,000 ms, TE of 88 ms, TI of 2,000 ms, 24 images and SENSE factor of 2.SPM2 was used for gray and white matter distribution of the T1-weighted images. The mean gray matter volume was calculated for the regions of interest and compared among the three groups. Fractional anisotropy was calculated using FSL and correlated against hippocampal gray matter, global atrophy and disease group using again SPM.

Results: The three groups matched well in age, sex and years of education. The white matter hyperintensities were similar in all three groups. In correlation analyses a bilateral region adjacent to the posterior cingulated and encompassing a branch of the cingulum was found where global atrophy correlated with fractional anisotropy after controlling for diagnosis and hippocampal gray matter.

Conclusion: The results suggest the dementia progression as measured by global atrophy is associated with disruption of the white matter which connects the posterior cingulated and lateral temporal and parietal regions. Therefore, the regions which show a diminished metabolism in dementia are also disrupted in their connection. Further studies are needed to determine whether the disruption precedes or is a consequence of atrophy and hypometabolism.

Comment

The diagnosis and differential diagnosis of AD and other forms of dementia is a more and more important issue in clinical and experimental imaging due to the demographic alterations in many countries. Atrophy of the hippocampus is well described for AD but can also be found in other forms of dementia [1]. Furthermore, an early diagnosis of AD will be essential for some future therapy. The obvious atrophy is mainly associated with a later stage of disease where specific therapy will not, even with better substances as at this moment, have any benefit.

Therefore, further investigations leading to more detailed information especially for the early stage of AD or even the risk of AD are very important. The given study is not really focused on the early stage of AD and DLB but uses the altered brain volume and function at this later state with definite diagnosis to investigate some associated changes. The use of DTI to reveal the disruption of connecting structures is one further point in the whole diagnosis for AD and other dementias. As the authors exactly state at the conclusion, further studies have to reveal whether these changes in the DTI of the cingulated white matter may be present before the atrophy and metabolic changes of the connected brain regions.

This study should be seen in correlation to many others dealing with different aspects to come closer to an early diagnosis of AD. Here, the spectroscopic changes in AD and other dementias should be mentioned [2, 3]. Furthermore, with higher field strength, the hippocampal structures will be detectable in a higher resolution revealing not only a summarized volume loss at the manifest disease but maybe also reveal dysmorphic changes in some parts of the hippocampus. Even at 1.5 T some first results supported the early changes in hippocampal substructures [4]. These findings can also be correlated with functional MRI analyses and clinical tests [5].

Within the next future, clinical neuroradiologists should have these new developments more and more in mind and have do decide which steps in diagnosis for dementias have to be included in the clinical routine or which patients have to be sent to a center for special diagnostic work-up.

References

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2. Kantarci K, Weigand SD, Petersen RC, et al. Longitudinal (1)H MRS changes in mild cognitive impairment and Alzheimer’s disease. Neurobiol Aging 2006 July, epub, in print.
3. Griffith HR, den Hollender JA, Stewart CC. Elevated brain scyllo-inositol concentrations in patients with Alzheimer Disease. NMR Biomed 2007 Feb, epub, in print.
4. Csemansky JG, Wang L, Joshi S, et al. Preclinical detection of Alzheimer disease: hippocampal shape and volume predict dementia onset in elderly. Neuroimage 2005;25:783–92.
5. Kantarci K, Jack CR. Neuroimaging in Alzheimer disease: an evidence based review. Neuroimaging Clin N Am 2003;13:197–209.

(submitted June 10, 2007)

Elke R. Gizewski, Essen