Focal atrophy on MRI and neuropathologic classification of dementia with Lewy bodies

Kantarci, Kejal; Ferman, Tanis J.; Boeve, Bradley F.; Weigand, Stephen D.; Przybelski, Scott A.; Vemuri, Prashanthi; Murray, Melissa E.; Senjem, Matthew L.; Smith, Glenn E.; Knopman, David S.; Petersen, Ronald C.; Jack, Clifford R.; Parisi, Joseph E.; Dickson, Dennis W.

doi:10.1212/wnl.0b013e31826357a5

Cited by 86 publications

(88 citation statements)

References 41 publications

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“…Hippocampal AD pathology is also a feature of DLB, as previous imaging studies have consistently demonstrated that the level of hippocampal atrophy observed in DLB is less than in AD (Hashimoto et al, 1998; Tam et al, 2005; Burton et al, 2009; Watson et al, 2012), and the level of atrophy relates to concurrent AD pathology measured post mortem (Burton et al, 2009; Kantarci et al, 2012). The extent of the atrophy may also influence the subsequent clinical course of DLB, as individuals with higher levels of hippocampal atrophy have a shorter survival time compared with those with lower levels of atrophy (Graff‐Radford et al, 2016).…”

Section: Introductionmentioning

confidence: 96%

The influence of hippocampal atrophy on the cognitive phenotype of dementia with Lewy bodies

Elder

Mactier

Colloby

et al. 2017

Int J Geriat Psychiatry

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ObjectiveThe level of hippocampal atrophy in dementia with Lewy bodies (DLB) is typically less than that observed in Alzheimer's disease (AD). However, it is not known how the cognitive phenotype of DLB is influenced by hippocampal atrophy or the atrophy of adjacent medial temporal lobe structures.MethodsDementia with Lewy bodies (n = 65), AD (n = 76) and control (n = 63) participants underwent 3T magnetic resonance imaging and cognitive Cambridge Cognitive Examination and Mini‐Mental State Examination (CAMCOG and MMSE) assessments. Hippocampal volume, and parahippocampal, entorhinal and temporal pole cortical thickness, was compared between groups. Regression models were used to investigate whether hippocampal volume and cortical thickness associated with global cognition and cognitive subdomains.ResultsDementia with Lewy bodies, AD and control participants showed significantly different hippocampal, parahippocampal and entorhinal cortical thinning, where atrophy was greatest in AD and intermediate in DLB. Temporal pole thickness was reduced in DLB and AD compared with control participants. In DLB, but not AD, hippocampal volume associated with total CAMCOG, CAMCOG memory and MMSE scores. In DLB, parahippocampal, entorhinal and temporal pole thickness associated with total CAMCOG and CAMCOG memory scores, parahippocampal thickness associated with MMSE scores, and entorhinal thickness associated with CAMCOG executive function scores.ConclusionsIn this large sample, these results are in agreement with other studies indicating that hippocampal atrophy is less severe in DLB than AD. Hippocampal atrophy and medial temporal lobe cortical thickness were associated with the severity of cognitive symptoms, suggesting that atrophy in these structures, as a potential proxy of AD pathology, may partly mediate specific DLB cognitive symptoms. © 2017 The Authors. International Journal of Geriatric Psychiatry Published by John Wiley & Sons Ltd.

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Section: Introductionmentioning

confidence: 96%

The influence of hippocampal atrophy on the cognitive phenotype of dementia with Lewy bodies

Elder

Mactier

Colloby

et al. 2017

Int J Geriat Psychiatry

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“…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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“…5 Hippocampal volumes on antemortem MRI are preserved in patients with DLB who have little or no additional AD pathology at autopsy. [6][7][8] Hippocampal volumes are lower in patients with DLB with increasing Braak neurofibrillary tangle stage regardless of the severity of Lewy body disease pathology. 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.…”

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confidence: 99%

“…[6][7][8] Hippocampal volumes are lower in patients with DLB with increasing Braak neurofibrillary tangle stage regardless of the severity of Lewy body disease pathology. 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.…”

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confidence: 99%

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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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Focal atrophy on MRI and neuropathologic classification of dementia with Lewy bodies

Cited by 86 publications

References 41 publications

The influence of hippocampal atrophy on the cognitive phenotype of dementia with Lewy bodies

The influence of hippocampal atrophy on the cognitive phenotype of 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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