MRI and pathology of REM sleep behavior disorder in dementia with Lewy bodies

Murray, Melissa E.; Ferman, Tanis J.; Boeve, Bradley F.; Przybelski, Scott A.; Lesnick, Timothy G.; Liesinger, Amanda M.; Senjem, Matthew L.; Gunter, Jeffrey L.; Preboske, Gregory M.; Lowe, Val J.; Vemuri, Prashanthi; Dugger, Brittany N.; Knopman, David S.; Smith, Glenn E.; Parisi, Joseph E.; Silber, Michael H.; Graff‐Radford, Neill R.; Petersen, Ronald C.; Jack, Clifford R.; Dickson, Dennis W.; Kantarci, Kejal

doi:10.1212/01.wnl.0000435299.57153.f0

Cited by 64 publications

(44 citation statements)

References 31 publications

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“…Since LB or AD-related pathologies are not considered to affect preferentially one hemisphere over another, the ROI-based rates of atrophy were calculated as averages of right and left hemispheric ROIs. The hippocampus and amygdala were chosen for ROI analysis because these structures have received reasonable attention in the literature as proxies of AD and DLB on MRI (Burton, et al, 2012, Burton, et al, 2009, Kantarci, et al, 2012, Murray, et al, 2013, Vemuri, et al, 2011, Whitwell, et al, 2007), and can be consistently quantified with various softwares due to their distinct borders (Fischl, et al, 2002, Patenaude, et al, 2011). …”

Section: Methodsmentioning

confidence: 99%

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Pattern of brain atrophy rates in autopsy-confirmed dementia with Lewy bodies

Nedelská

Ferman

Boeve

et al. 2015

Neurobiology of Aging

118

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Dementia with Lewy bodies (DLB) is characterized by preserved whole brain and medial temporal lobe volumes compared to Alzheimer’s disease dementia (AD) on MRI. However, frequently coexistent AD-type pathology may influence the pattern of regional brain atrophy rates in DLB patients. We investigated the pattern and magnitude of the atrophy rates from two serial MRIs in autopsy-confirmed DLB (n=20) and mixed DLB/AD patients (n=22), compared to AD (n=30) and elderly non-demented controls (n=15), followed antemortem. DLB patients without significant AD-type pathology were characterized by lower global and regional rates of atrophy, similar to controls. The mixed DLB/AD patients displayed greater rates in the whole brain, temporo-parietal cortices, hippocampus and amygdala, and ventricle expansion, similar to AD patients. In the DLB and DLB/AD patients, the atrophy rates correlated with Braak neurofibrillary tangle stage, cognitive decline and progression of motor symptoms. Global and regional atrophy rates are associated with AD-type pathology in DLB, and can be used as biomarkers of AD progression in patients with LB pathology.

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Section: Methodsmentioning

confidence: 99%

“…Specifically, greater atrophy in the hippocampus and amygdala has been associated with a high Braak NFT stage (Kantarci, et al, 2012) and tau-NFT density (Murray, et al, 2013) in patients with LB pathology.…”

Section: Introductionmentioning

confidence: 99%

Pattern of brain atrophy rates in autopsy-confirmed dementia with Lewy bodies

Nedelská

Ferman

Boeve

et al. 2015

Neurobiology of Aging

118

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“…Atrophy in the limbic, temporal and parietal association cortices on structural MRI is a marker of neurodegeneration associated with tau neurofibrillary tangle pathology of Alzheimer's disease and DLB (Jack et al, 2004;Burton et al, 2009;Murray et al, 2013). In several studies, patients with probable DLB showed an Alzheimer's diseaselike pattern of atrophy (Whitwell et al, 2007b;Sabattoli et al, 2008;Zhong et al, 2014) while autopsy confirmation later showed that the presence of tau neurofibrillary tangles and their Braak stage (Braak and Braak, 1991) of Alzheimer's disease primarily explained the cross-sectional (Burton et al, 2009;Kantarci et al, 2012a;Murray et al, 2013) and longitudinal (Nedelska et al, 2015) atrophy observed in the medial temporal structures.…”

Section: Introductionmentioning

confidence: 99%

Amyloid-β deposition and regional grey matter atrophy rates in dementia with Lewy bodies

Sarro¹,

Senjem

Lundt

et al. 2016

Brain

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Alzheimer's disease pathology frequently coexists with Lewy body disease at autopsy in patients with probable dementia with Lewy bodies. More than half of patients with probable dementia with Lewy bodies have high amyloid-b deposition as measured with 11 C-Pittsburgh compound B binding on positron emission tomography. Biomarkers of amyloid-b deposition precede neurodegeneration on magnetic resonance imaging during the progression of Alzheimer's disease, but little is known about how amyloid-b deposition relates to longitudinal progression of atrophy in patients with probable dementia with Lewy bodies. We investigated the associations between baseline 11 C-Pittsburgh compound B binding on positron emission tomography and the longitudinal rates of grey matter atrophy in a cohort of clinically diagnosed patients with dementia with Lewy bodies (n = 20), who were consecutively recruited to the Mayo Clinic Alzheimer's Disease Research Centre. All patients underwent 11 C-Pittsburgh compound B positron emission tomography and magnetic resonance imaging examinations at baseline. Follow-up magnetic resonance imaging was performed after a mean (standard deviation) interval of 2.5 (1.1) years. Regional grey matter loss was determined on threedimensional T 1 -weighted magnetic resonance imaging with the tensor-based morphometry-symmetric normalization technique. Linear regression was performed between baseline 11 C-Pittsburgh compound B standard unit value ratio and longitudinal change in regional grey matter volumes from an in-house modified atlas. We identified significant associations between greater baseline 11 C-Pittsburgh compound B standard unit value ratio and greater grey matter loss over time in the posterior cingulate gyrus, lateral and medial temporal lobe, and occipital lobe as well as caudate and putamen nuclei, after adjusting for age (P 5 0.05). Greater baseline 11 C-Pittsburgh compound B standard unit value ratio was also associated with greater ventricular expansion rates (P 5 0.01) and greater worsening over time in Clinical Dementia Rating Scale, sum of boxes (P = 0.02). In conclusion, in patients with probable dementia with Lewy bodies, higher amyloid-b deposition at baseline is predictive of faster neurodegeneration in the cortex and also in the striatum. This distribution is suggestive of possible interactions among amyloid-b, tau and a-synuclein aggregates, which needs further investigation. Furthermore, higher amyloid-b deposition at baseline predicts a faster clinical decline over time in patients with probable dementia with Lewy bodies. Keywords: DLB; structural MRI; beta-amyloid; amyloid imaging; brain atrophy Abbreviations: AChEI = acetylcholinesterase inhibitor; CDR-SOB = Clinical Dementia Rating scale, Sum of Boxes; DLB = dementia with Lewy bodies; MMSE = Mini-Mental State Examination; PiB = 11 C-Pittsburgh compound B; SUVR = standardized uptake value ratio; TBM-SyN = tensor-based morphometry using symmetric diffeomorphic image normalization; UPDRS-III =

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“…7 Furthermore, while hippocampal phospho-tau burden is associated with hippocampal atrophy, a-synuclein burden does not appear to influence the global hippocampal volume in patients with Lewy body pathology. 9 Therefore preserved hippocampal volumes may predict progression to DLB vs AD in MCI.…”

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confidence: 99%

“…24 In particular, hippocampal atrophy suggests additional AD-related neurofibrillary tangle pathology in probable DLB cases and may differentiate patients with mixed AD and Lewy body disease pathology from those with DLB. [6][7][8][9] Preservation of hippocampal volumes is also observed in patients with hippocampal sparing AD, 25 therefore is not specific to DLB. We censored individuals who progressed to dementia syndromes other than AD dementia or probable DLB at the time of progression to dementia and several of these patients as well as those who received a clinical diagnosis of probable DLB or AD dementia may have had atypical AD pathology.…”

mentioning

confidence: 99%

IC‐02‐05: Hippocampal volumes predict risk of dementia with lewy bodies in mild cognitive impairment

Kantarci

Lesnick

Przybelski

et al. 2015

Alzheimer's & Dementia

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Objective: To predict the risk of probable dementia with Lewy bodies (DLB) competing with Alzheimer disease (AD) dementia by hippocampal volume (HV) in patients with mild cognitive impairment (MCI) with impairments in amnestic or nonamnestic cognitive domains.Methods: Patients with MCI (n 5 160) from the Mayo Clinic Alzheimer's Disease Research Center, who participated in an MRI study at baseline from 2005 to 2014, were followed with approximately annual clinical evaluations. HVs were analyzed from 3T MRIs using FreeSurfer (5.3). Hippocampal atrophy was determined from the most normal 10th percentile of the measurement distributions in a separate cohort of clinically diagnosed patients with AD dementia. The subdistribution hazard ratios for progression to probable DLB and AD dementia were estimated by taking into account the competing risks.Results: During a median (range) follow-up of 2.0 (0.7-8.1) years, 20 (13%) patients with MCI progressed to probable DLB, and 61 (38%) progressed to AD dementia. The estimated subdistribution hazard ratio (95% confidence interval) for normal HV relative to hippocampal atrophy for progression to AD dementia was 0.56 (0.34-0.91; p 5 0.02) after taking into account the competing risks. The estimated hazard ratio for normal HV relative to hippocampal atrophy for progression to probable DLB was 4.22 (1.42-12.6; p 5 0.01) after adjusting for age and after including the MCI subtype in the model. Identifying patients with mild cognitive impairment (MCI) who are at risk for dementia with Lewy bodies (DLB) is critical for early interventions. Amnestic subtype of MCI has been established on clinical grounds in order to identify individuals who are at risk for Alzheimer disease (AD) dementia.1,2 Patients with MCI who have impairments in nonamnestic cognitive domains may be at an increased risk of DLB. 3,4 We have previously demonstrated that the competing risk of progression to probable DLB vs AD is higher in patients with nonamnestic MCI compared to amnestic MCI. 5Hippocampal volumes on antemortem MRI are preserved in patients with DLB who have little or no additional AD pathology at autopsy.6-8 Hippocampal volumes are lower in patients with DLB with increasing Braak neurofibrillary tangle stage regardless of the severity of Lewy

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MRI and pathology of REM sleep behavior disorder in dementia with Lewy bodies

Abstract: Presence of pRBD is associated with a higher likelihood of DLB and less severe Alzheimer-related pathology in the medial temporal lobes, whereas absence of pRBD is characterized by Alzheimer-like atrophy patterns on MRI and increased phospho-tau burden.

Cited by 64 publications

References 31 publications

Pattern of brain atrophy rates in autopsy-confirmed dementia with Lewy bodies

Pattern of brain atrophy rates in autopsy-confirmed dementia with Lewy bodies

Amyloid-β deposition and regional grey matter atrophy rates in dementia with Lewy bodies

IC‐02‐05: Hippocampal volumes predict risk of dementia with lewy bodies in mild cognitive impairment

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