Cerebrovascular disease, neurodegeneration, and clinical phenotype in dementia with Lewy bodies.

We investigated whether cerebrovascular disease contributes to neurodegeneration and clinical phenotype in dementia with Lewy bodies (DLB). Regional cortical thickness and subcortical gray matter volumes were estimated from structural magnetic resonance imaging (MRI) in 165 DLB patients. Cortical and subcortical infarcts were recorded and white matter hyperintensities (WMHs) were assessed. Subcortical only infarcts were more frequent (13.3%) than cortical only infarcts (3.1%) or both subcortical and cortical infarcts (2.4%). Infarcts, irrespective of type, were associated with WMHs. A higher WMH volume was associated with thinner orbitofrontal, retrosplenial, and posterior cingulate cortices, smaller thalamus and pallidum, and larger caudate volume. A higher WMH volume was associated with the presence of visual hallucinations and lower global cognitive performance, and tended to be associated with the absence of probable rapid eye movement sleep behavior disorder. Presence of infarcts was associated with the absence of parkinsonism. We conclude that cerebrovascular disease is associated with gray matter neurodegeneration in patients with probable DLB, which may have implications for the multifactorial treatment of probable DLB.

Ferreira D ，Nedelska Z ，Graff-Radford J ，Przybelski SA ，Lesnick TG ，Schwarz CG ，Botha H ，Senjem ML ，Fields JA ，Knopman DS ，Savica R ，Ferman TJ ，Graff-Radford NR ，Lowe VJ ，Jack CR ，Petersen RC ，Lemstra AW ，van de Beek M ，Barkhof F ，Blanc F ，Loureiro de Sousa P ，Philippi N ，Cretin B ，Demuynck C ，Hort J ，Oppedal K ，Boeve BF ，Aarsland D ，Westman E ，Kantarci K ... -  《-》

An investigation of cerebrovascular lesions in dementia with Lewy bodies compared to Alzheimer's disease.

Cerebrovascular lesions on MRI are common in Alzheimer's disease (AD) dementia, but less is known about their frequency and impact on dementia with Lewy bodies (DLB). White-matter hyperintensities (WMHs) and infarcts on MRI were assessed in consecutive DLB (n = 81) and AD dementia (n = 240) patients and compared to age-matched and sex-matched cognitively normal subjects (CN) from a population-based cohort. DLB had higher WMH volume compared to CN, and WMH volume was higher in the occipital and posterior periventricular regions in DLB compared to AD. Higher WMH volume was associated with history of cardiovascular disease and diabetes but not with clinical disease severity in DLB. Frequency of infarcts in DLB was not different from CN and AD dementia. In DLB, WMH volume is higher than AD and CN and appears to be primarily associated with history of vascular disease.

Sarro L ，Tosakulwong N ，Schwarz CG ，Graff-Radford J ，Przybelski SA ，Lesnick TG ，Zuk SM ，Reid RI ，Raman MR ，Boeve BF ，Ferman TJ ，Knopman DS ，Comi G ，Filippi M ，Murray ME ，Parisi JE ，Dickson DW ，Petersen RC ，Jack CR Jr ，Kantarci K ... -  《-》

Frontal and subcortical contribution to visual hallucinations in dementia with Lewy bodies and Parkinson's disease.

Pezzoli S ，Cagnin A ，Antonini A ，Venneri A ... -  《-》

A multiparametric MRI study of structural brain damage in dementia with lewy bodies: A comparison with Alzheimer's disease.

Differential diagnosis between dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) is crucial for an adequate patients' management but might be challenging. We investigated with advanced MRI techniques gray (GM) and white matter (WM) damage in DLB patients compared to those with AD. 24 DLB patients, 26 age- and disease severity-matched AD patients, and 20 age and sex-matched controls performed clinical and neuropsychological assessment, and brain structural and diffusion-tensor MRI. We measured GM atrophy using voxel-based morphometry, WM hyperintensities (WMH) using a local thresholding segmentation technique, and normal-appearing WM (NAWM) damage using tract-based spatial statistic. DLB and AD patients exhibited mild-to-moderate-stage dementia. Compared to controls, GM damage was diffuse in AD, while limited to bilateral thalamus and temporal regions in DLB. Compared to DLB, AD patients exhibited GM atrophy in bilateral fronto-temporal and occipital regions. DLB and AD patients showed higher WMH load than controls, with no differences among each other. WMH in DLB were diffuse with relative prevalence in posterior parietal-occipital regions. Compared to controls, both DLB and AD patients showed reduced microstructural integrity of the main supratentorial and infratentorial NAWM tracts. AD patients exhibited greater posterior NAWM damage than DLB. DLB showed prominent WM degeneration compared to the limited GM atrophy, while in AD both tissue compartments were severely involved. In DLB, NAWM microstructural degeneration was independent of WMH, thus revealing two possible underlying processes. Different pathophysiological mechanisms are likely to drive GM and WM damage distribution in DLB and AD.

Caso F ，Agosta F ，Scamarcia PG ，Basaia S ，Canu E ，Magnani G ，Volontè MA ，Filippi M ... -  《-》

Cross-sectional Associations of β-Amyloid, Tau, and Cerebrovascular Biomarkers With Neurodegeneration in Probable Dementia With Lewy Bodies.

Although alpha-synuclein-related pathology is the hallmark of dementia with Lewy bodies (DLB), cerebrovascular and Alzheimer disease pathologies are common in patients with DLB. Little is known about the contribution of these pathologies to neurodegeneration in DLB. We investigated associations of cerebrovascular, β-amyloid, and tau biomarkers with gray matter (GM) volume in patients with probable DLB. We assessed patients with probable DLB and cognitively unimpaired (CU) controls with 11C-Pittsburgh compound B (PiB) and 18F-flortaucipir PET as markers of β-amyloid and tau, respectively. MRI was used to assess white matter hyperintensity (WMH) volume (a marker of cerebrovascular lesion load) and regional GM volume (a marker of neurodegeneration). We used correlations and analysis of covariance (ANCOVA) in the entire cohort and structural equation models (SEMs) in patients with DLB to investigate associations of WMH volume and regional β-amyloid and tau PET standardized uptake value ratios (SUVrs) with regional GM volume. We included 30 patients with DLB (69.3 ± 10.2 years, 87% men) and 100 CU controls balanced on age and sex. Compared with CU controls, patients with DLB showed a lower GM volume across all cortical and subcortical regions except for the cuneus, putamen, and pallidum. A larger WMH volume was associated with a lower volume in the medial and orbital frontal cortices, insula, fusiform cortex, and thalamus in patients with DLB. A higher PiB SUVr was associated with a lower volume in the inferior temporal cortex, while flortaucipir SUVr did not correlate with GM volume. SEMs showed that a higher age and absence of the APOE ε4 allele were significant predictors of higher WMH volume, and WMH volume in turn was a significant predictor of GM volume in medial and orbital frontal cortices, insula, and inferior temporal cortex. By contrast, we observed 2 distinct paths for the fusiform cortex, with age having an effect through PiB and flortaucipir SUVr on one path and through WMH volume on the other path. Patients with probable DLB have widespread cortical atrophy, most of which is likely influenced by alpha-synuclein-related pathology. Although cerebrovascular, β-amyloid, and tau pathologies often coexist in probable DLB, their contributions to neurodegeneration seem to be region specific.

Ferreira D ，Przybelski SA ，Lesnick TG ，Schwarz CG ，Diaz-Galvan P ，Graff-Radford J ，Senjem ML ，Fields JA ，Knopman DS ，Jones DT ，Savica R ，Ferman TJ ，Graff-Radford N ，Lowe VJ ，Jack CR ，Petersen RC ，Westman E ，Boeve BF ，Kantarci K ... -  《-》