Atrophy is associated with posterior cingulate white matter disruption in dementia with Lewy bodies and Alzheimer’s disease
Introduction
In Alzheimer’s disease (AD) and dementia with Lewy bodies, (DLB) both hippocampal atrophy (Du et al., 2001, Matsuda et al., 2002, Tam et al., 2005) and decrease in blood perfusion in the posterior cingulate region (Colloby et al., 2002, Firbank et al., 2003a, Matsuda et al., 2002) are present. The posterior cingulate region is linked anatomically with the parahippocampal gyrus via the cingulum, a white matter tract which also connects it to the anterior cingulate and frontal cortex (Jellison et al., 2004, Mori et al., 2005). Studies have also shown functional connectivity between the regions, with activity in the posterior cingulate cortex covarying with hippocampal activity at rest (Greicius et al., 2003, Wang et al., 2006) and during memory recall (Ranganath et al., 2005).
In AD and DLB, regions in the medial and lateral parietal lobes show early hypometabolism, which is in excess of atrophy in the area (Chetelat et al., 2006, Firbank et al., 2003a). There is a large degree of overlap (Buckner et al., 2005) between these regions which show hypoperfusion and the ‘default network’ (Raichle et al., 2001) which is thought to be active during undirected mental activity. This network is involved in episodic memory (Cabeza and Nyberg, 2000), and its activity is diminished in AD (Greicius et al., 2003, Rombouts et al., 2005) and DLB (Sauer et al., 2006). It is unclear how the patterns of abnormal hypometabolism in dementia relate to underlying neuropathology (Buckner et al., 2005). One possibility is that hippocampal atrophy leads to secondary degeneration of the white matter connecting it to the cortical grey matter. Another possibility is that the lateral and medial parietal regions are affected directly by the disease process. The aim of this study was to use MR diffusion weighted imaging to investigate the neuropathological correlates of hippocampal atrophy.
Magnetic resonance (MR) diffusion weighted imaging (DWI) is a technique which allows images of the diffusion of water in the brain to be produced. Because of the highly structured nature of axons, water tends to diffuse along the direction of white matter axons rather than perpendicular to them. DWI is a sensitive indicator of changes to the integrity of axons (Bammer and Fazekas, 2002, Le Bihan, 2003, Moseley, 2002). Fractional anisotropy (FA) can be calculated from diffusion weighted images. The FA depends on the relative diffusivity of water in different directions and it varies from zero, where diffusion is equal in all directions, to 1, where diffusion occurs along a single direction. FA is high in regions of coherent white matter (such as the corpus callosum) since the fibres all go in the same direction. A decrease in FA indicates water diffusing more isotropically—this may be caused by damage to the walls of the axons, allowing water to diffuse perpendicular to the axon direction.
We hypothesised that atrophy of the hippocampus would be related to disrupted connectivity between it and cingulate and lateral parietal cortex and that this would be evident in terms of decreased fractional anisotropy.
Section snippets
Subjects/Methods
We recruited 15 people with Alzheimer’s disease and 16 with dementia with Lewy bodies, from clinical Old Age Psychiatry, Geriatric Medicine and Neurology Services. Fifteen healthy subjects of similar age were also recruited.
All subjects were aged over 60, had mild to moderate dementia (MMSE > 10) and did not have contra-indications for MRI. All Alzheimer’s disease subjects fulfilled criteria for probable AD according to NINCDS/ADRDA (McKhann et al., 1984). Dementia with Lewy body cases all met
Results
As can be seen in Table 1, the groups were well matched for age, sex, and years of education. Most of the patients were taking cholinesterase inhibitors, though there were no significant differences between the two dementia groups. The volumes of white matter hyperintensities were not significantly different between groups. The hippocampal volume was significantly reduced in both dementia groups, with AD having smaller volumes than DLB. There was increased whole brain atrophy (as measured by
Discussion
We found bilateral clusters adjacent to the posterior cingulate, encompassing a branch of the cingulum, where global atrophy correlated with reduction in FA. As can be seen from Fig. 2, and by comparison to studies of perfusion in AD (Herholz et al., 2002), the clusters are immediately adjacent to regions showing marked hypoperfusion in AD and DLB. These regions are also part of the ‘default network’ (Buckner et al., 2005).
Our finding of hippocampal atrophy in dementia, with DLB intermediate
Acknowledgment
This work was generously funded by a grant from the Newcastle Healthcare Charity.
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