Longitudinal assessment of global and regional atrophy rates in Alzheimer's disease and dementia with Lewy bodies.

BACKGROUND & OBJECTIVE: Percent whole brain volume change (PBVC) measured from serial MRI scans is widely accepted as a sensitive marker of disease progression in Alzheimer's disease (AD). However, the utility of PBVC in the differential diagnosis of dementia remains to be established. We compared PBVC in AD and dementia with Lewy bodies (DLB), and investigated associations with clinical measures. METHODS: 72 participants (14 DLBs, 25 ADs, and 33 healthy controls (HCs)) underwent clinical assessment and 3 Tesla T1-weighted MRI at baseline and repeated at 12 months. We used FSL-SIENA to estimate PBVC for each subject. Voxelwise analyses and ANCOVA compared PBVC between DLB and AD, while correlational tests examined associations of PBVC with clinical measures. RESULTS: AD had significantly greater atrophy over 1 year (1.8%) compared to DLB (1.0%; p = 0.01) and HC (0.9%; p < 0.01) in widespread regions of the brain including periventricular areas. PBVC was not significantly different between DLB and HC (p = 0.95). There were no differences in cognitive decline between DLB and AD. In the combined dementia group (AD and DLB), younger age was associated with higher atrophy rates (r = 0.49, p < 0.01). CONCLUSIONS: AD showed a faster rate of global brain atrophy compared to DLB, which had similar rates of atrophy to HC. Among dementia subjects, younger age was associated with accelerated atrophy, reflecting more aggressive disease in younger people. PBVC could aid in differentiating between DLB and AD, however its utility as an outcome marker in DLB is limited.

Assessment of regional gray matter loss in dementia with Lewy bodies: a surface-based MRI analysis.

OBJECTIVE: To compare magnetic resonance imaging (MRI) patterns of cortical thinning in subjects with dementia with Lewy bodies (DLB), Alzheimer's disease (AD), and normal aging and investigate the relationship between cortical thickness and clinical measures. METHODS: Study participants (31 DLB, 30 AD, and 33 healthy comparison subjects) underwent 3-Tesla T1-weighted MRI and completed clinical and cognitive assessments. We used the FreeSurfer analysis package to measure cortical thickness and investigated the patterns of cortical thinning across groups. RESULTS: Cortical thinning in AD was found predominantly in the temporal and parietal areas extending into the frontal lobes (N = 63, df = 59, t >3.3, p <0.005, FDR-corrected). In DLB, cortical thinning was less diffuse with focal areas of cortical change predominantly affecting posterior structures (inferior parietal, posterior cingulate, and fusiform gyrus) (N = 64, df = 60, t >3.6, p <0.005, FDR-corrected). The average reduction in cortical thickness in medial temporal lobe structures was less in DLB (6%-10%) than in AD (15%-24%), and similar to the reduction in cortical thickness observed in other regions including inferior parietal, precuneus, and posterior cingulate (6%-9%). Associations between cortical thickness and clinical measures (MMSE and verbal fluency) were also observed in DLB (N = 31, df = 27, t >2.8, p <0.01 uncorrected). CONCLUSION: Cortical thickness may be a sensitive measure for characterising gray matter loss in DLB and highlights important structural imaging differences between the conditions.

Assessment of regional MR diffusion changes in dementia with Lewy bodies and Alzheimer's disease.

BACKGROUND: Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) are common forms of dementia, yet diagnosis is often difficult. Diffusion tensor imaging (DTI) is an MR technique used to assess neuronal microstructural integrity that may help develop a better understanding of the differences between the conditions. METHODS: We recruited subjects with DLB (n = 35), AD (n = 36), and similar aged healthy controls (n = 35). T1 weighted anatomical and diffusion MR images were acquired at 3 Tesla. Region of interest (ROI) analysis was used to measure fractional anisotropy (FA) and mean diffusivity (MD) in five structures: precuneus, thalamus, pons, midbrain, and amygdala. Where appropriate diffusivity measures (FA, MD) were correlated with selected clinical measures. RESULTS: Compared to controls, DLB subjects were characterized by reduced FA (p = 0.016) and increased MD (p = 0.007) in the precuneus. Amygdala diffusivity was positively correlated with UPDRS-III score in DLB (p = 0.003). In AD, reduced FA in the precuneus was also observed compared to controls (p = 0.026), and was associated with impaired global cognition (MMSE score) (p = 0.03). CONCLUSIONS: Our findings highlight the potential importance of the precuneus in the pathogenesis of DLB as well as AD. Diffusion tensor MRI may shed new light on the different neurobiological changes underpinning the key clinical features of DLB and AD.