Focal atrophy in dementia with Lewy bodies on MRI: a distinct pattern from Alzheimer's disease

Abstract

Dementia with Lewy bodies (DLB) is the second most common cause of degenerative dementia after Alzheimer's disease. However, unlike the latter, the patterns of cerebral atrophy associated with DLB have not been well established. The aim of this study was to identify a signature pattern of cerebral atrophy in DLB and to compare it with the pattern found in Alzheimer's disease. Seventy-two patients that fulfilled clinical criteria for probable DLB were age- and gender-matched to 72 patients with probable Alzheimer's disease and 72 controls. Voxel-based morphometry (VBM) was used to assess patterns of grey matter (GM) atrophy in the two patient groups, relative to controls, after correction for multiple comparisons (P < 0.05). Study-specific templates and prior probability maps were used to avoid normalization and segmentation bias. Region-of-interest (ROI) analyses were also performed comparing loss of the midbrain, substantia innominata (SI), temporoparietal cortex and hippocampus between the groups. The DLB group showed very little cortical involvement on VBM with regional GM loss observed primarily in the dorsal midbrain, SI and hypothalamus. In comparison, the Alzheimer's disease group showed a widespread pattern of GM loss involving the temporoparietal association cortices and the medial temporal lobes. The SI and dorsal midbrain were involved in Alzheimer's disease; however, they were not identified as a cluster of loss discrete from uninvolved surrounding areas, as observed in the DLB group. On direct comparison between the two groups, the Alzheimer's disease group showed greater loss in the medial temporal lobe and inferior temporal regions than the DLB group. The ROI analysis showed reduced SI and midbrain GM in both patient groups, with a trend for more reduction of SI GM in Alzheimer's disease than DLB, and more reduction of midbrain in DLB than Alzheimer's disease. Significantly greater loss in the hippocampus and temporo-parietal cortex was observed in the Alzheimer's disease patients when the two patient groups were compared. A pattern of relatively focused atrophy of the midbrain, hypothalamus and SI, with a relative sparing of the hippocampus and temporoparietal cortex is, therefore, suggestive of DLB and this may aid in the differentiation of DLB from Alzheimer's disease. These findings support recent pathological studies showing an ascending pattern of Lewy body progression from brainstem to basal areas of the brain. Damage to this network of structures in DLB may affect a number of different neurotransmitter systems which in turn may contribute to a number of the core clinical features of DLB.

Structural grey matter changes in the substantia innominata in Alzheimer's disease and dementia with Lewy bodies: a DARTEL‐VBM study

“…In the present study, SI volume was reduced in dementia groups compared with healthy controls, which was consistent with previous studies (Grothe et al ., 2014; Hanyu et al ., 2005; Whitwell et al ., 2007). In addition, atrophic changes within the SI appeared to be associated with dementia severity and cognitive fluctuations in DLB.…”

“…Strengths of the current study include the relatively large AD and DLB cohorts, the acquisition of higher‐field 3 T MRI data compared with previous studies assessing the SI in DLB (Hanyu et al ., 2005; Whitwell et al ., 2007), the use of rigorous and validated methodologies for imaging and the extensive clinical and cognitive profiling of participants. There are several study limitations.…”

Brain Mapping as a Tool to Study Neurodegeneration

“…41 Ventricular enlargement appears to have a higher predictive value in the earlier transition stages as opposed to the later stagethat is, from normal cognition to MCI or AD and less so from MCI to AD. 13,42 VBM has also been used to reveal the spatial profile of aging and gender effects in normal subjects, 28,43,44 frontotemporal and Lewy body dementia, [45][46][47][48] Parkinson's disease, and even herpes simplex encephalitis. 49 For analysis of cortical gray matter atrophy, VBM may not be optimal.…”

“…A VBM study by Whitwell et al 48 recently reported a distinct cortical atrophy pattern in DLB that may help differentiate between DLB and AD, the two most common dementias: namely, hippocampal and inferior temporal preservation along with midbrain atrophy in DLB. Using the cortical pattern-matching technique, Ballmaier et al 80 demonstrated that preservation of the temporal and orbitofrontal cortices in demented subjects is suggestive of DLB, as opposed to AD.…”

Reduced CSF CART in dementia with Lewy bodies

“…Mutations in the CART gene in humans are associated with depression and anxiety [5]. Interestingly, in a recent MRI study DLB patients displayed hypothalamic atrophy whereas this region was not affected in AD patients [18]. We therefore hypothesized that CART levels would be reduced in CSF from patients with DLB as a sign of hypothalamic pathology and compared these to levels in age-matched AD patients as well as healthy controls.…”