Investigating the clinico-anatomical dissociation in the behavioral variant of Alzheimer disease

Singleton, Ellen H.; Pijnenburg, Yolande A.  L.; Sudre, Carole H.; Groot, Colin; Kochova, Elena; Barkhof, Frederik; La Joie, Renaud; Rosen, Howard J.; Seeley, William W.; Miller, Bruce; Cardoso, M. Jorge; Papma, Janne; Scheltens, Philip; Rabinovici, Gil D.; Ossenkoppele, Rik

doi:10.1186/s13195-020-00717-z

Title: Investigating the clinico-anatomical dissociation in the behavioral variant of Alzheimer disease

Journal Article · Sat Nov 14 00:00:00 EST 2020 · Alzheimer's Research & Therapy

DOI:https://doi.org/10.1186/s13195-020-00717-z· OSTI ID:1816073

^[1]; Pijnenburg, Yolande A. L. ^[2]; Sudre, Carole H. ^[3]; Groot, Colin ^[2]; Kochova, Elena ^[2]; Barkhof, Frederik ^[4]; La Joie, Renaud ^[5]; Rosen, Howard J. ^[5]; Seeley, William W. ^[5]; Miller, Bruce ^[5]; Cardoso, M. Jorge ^[6]; Papma, Janne ^[7]; Scheltens, Philip ^[2]; Rabinovici, Gil D. ^[8]; Ossenkoppele, Rik ^[9]

Vrije Univ., Amsterdam (Netherlands). Amsterdam Neuroscience. Dept. of Neurology. Alzheimer Center Amsterdam
Vrije Univ., Amsterdam (Netherlands). Amsterdam Neuroscience. Dept. of Neurology. Alzheimer Center Amsterdam
King's College, London (United Kingdom). School of Biomedical Engineering and Imaging Sciences
Vrije Univ., Amsterdam (Netherlands). Dept. of Radiology and Nuclear Medicine; Univ. College London (United Kingdom). Dept. of Medical Physics and Biomedical Engineering. Center for Medical Image Computing
Univ. of California, San Francisco, CA (United States). Dept. of Neurology, Memory and Aging Center
King's College, London (United Kingdom). School of Biomedical Engineering and Imaging Sciences; Univ. College London (United Kingdom). Department of Medical Physics and Biomedical Engineering. CMIC. Translational Imaging Group
Erasmus Univ. Medical Center, Rotterdam (Netherlands). Dept. of Neurology; Erasmus Univ. Medical Center, Rotterdam (Netherlands). Dept. of Radiology
Univ. of California, San Francisco, CA (United States). Dept. of Neurology, Memory and Aging Center; Univ. of California, San Francisco, CA (United States). Dept. of Radiology and Biomedical Imaging; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics and Integrated Bioimaging Division; Univ. of California, Berkeley, CA (United States). Helen Wills Neurosciecne Inst.
Vrije Univ., Amsterdam (Netherlands). Amsterdam Neuroscience. Dept. of Neurology. Alzheimer Center Amsterdam; Lund Univ. (Sweden). Clinical Memory Research Unit

We previously found temporoparietal-predominant atrophy patterns in the behavioral variant of Alzheimer’s disease (bvAD), with relative sparing of frontal regions. Here, we aimed to understand the clinico-anatomical dissociation in bvAD based on alternative neuroimaging markers. We retrospectively included 150 participants, including 29 bvAD, 28 “typical” amnestic-predominant AD (tAD), 28 behavioral variant of frontotemporal dementia (bvFTD), and 65 cognitively normal participants. Patients with bvAD were compared with other diagnostic groups on glucose metabolism and metabolic connectivity measured by [¹⁸F]FDG-PET, and on subcortical gray matter and white matter hyperintensity (WMH) volumes measured by MRI. A receiver-operating-characteristic-analysis was performed to determine the neuroimaging measures with highest diagnostic accuracy. bvAD and tAD showed predominant temporoparietal hypometabolism compared to controls, and did not differ in direct contrasts. However, overlaying statistical maps from contrasts between patients and controls revealed broader frontoinsular hypometabolism in bvAD than tAD, partially overlapping with bvFTD. bvAD showed greater anterior default mode network (DMN) involvement than tAD, mimicking bvFTD, and reduced connectivity of the posterior cingulate cortex with prefrontal regions. Analyses of WMH and subcortical volume showed closer resemblance of bvAD to tAD than to bvFTD, and larger amygdalar volumes in bvAD than tAD respectively. The top-3 discriminators for bvAD vs. bvFTD were FDG posterior-DMN-ratios (bvADbvFTD, area under the curve [AUC] range 0.85–0.91, all p < 0.001). The top-3 for bvAD vs. tAD were amygdalar volume (bvAD>tAD), MRI anterior-DMN-ratios (bvAD

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1816073

Journal Information:: Alzheimer's Research & Therapy, Vol. 12, Issue 1; ISSN 1758-9193

Publisher:: BioMed CentralCopyright Statement

Country of Publication:: United States

Language:: English

References (43)

Frontal variant of Alzheimer’s disease masquerading as behavioural-variant frontotemporal dementia: a case study comparison Wong, Stephanie; Strudwick, Jessica; Devenney, Emma Neurocase, Vol. 25, Issue 1-2 https://doi.org/10.1080/13554794.2019.1609523	journal	March 2019
Accurate automatic estimation of total intracranial volume: A nuisance variable with less nuisance Malone, Ian B.; Leung, Kelvin K.; Clegg, Shona NeuroImage, Vol. 104 https://doi.org/10.1016/j.neuroimage.2014.09.034	journal	January 2015
Bullseye's representation of cerebral white matter hyperintensities Sudre, C. H.; Gomez Anson, B.; Davagnanam, I. Journal of Neuroradiology, Vol. 45, Issue 2 https://doi.org/10.1016/j.neurad.2017.10.001	journal	March 2018
Differentiating the Frontal Presentation of Alzheimer's Disease with FDG-PET Woodward, Michael C.; Rowe, Christopher C.; Jones, Gareth Journal of Alzheimer's Disease, Vol. 44, Issue 1 https://doi.org/10.3233/JAD-141110	journal	January 2015
Divergent network connectivity changes in behavioural variant frontotemporal dementia and Alzheimer’s disease Zhou, Juan; Greicius, Michael D.; Gennatas, Efstathios D. Brain, Vol. 133, Issue 5 https://doi.org/10.1093/brain/awq075	journal	April 2010
Episodic memory loss is related to hippocampal-mediated -amyloid deposition in elderly subjects Mormino, E. C.; Kluth, J. T.; Madison, C. M. Brain, Vol. 132, Issue 5 https://doi.org/10.1093/brain/awn320	journal	November 2008
Effects of White Matter Lesions and Lacunes on Cortical Function Reed, Bruce R.; Eberling, Jamie L.; Mungas, Dan Archives of Neurology, Vol. 61, Issue 10 https://doi.org/10.1001/archneur.61.10.1545	journal	October 2004
A Bayesian model of shape and appearance for subcortical brain segmentation Patenaude, Brian; Smith, Stephen M.; Kennedy, David N. NeuroImage, Vol. 56, Issue 3 https://doi.org/10.1016/j.neuroimage.2011.02.046	journal	June 2011
Frontal Variant Alzheimer Disease or Frontotemporal Lobe Degeneration With Incidental Amyloidosis? Scialò, Carlo; Ferrara, Michela; Accardo, Jennifer Alzheimer Disease & Associated Disorders, Vol. 30, Issue 2 https://doi.org/10.1097/WAD.0000000000000123	journal	January 2016
Early frontotemporal dementia targets neurons unique to apes and humans Seeley, William W.; Carlin, Danielle A.; Allman, John M. Annals of Neurology, Vol. 60, Issue 6 https://doi.org/10.1002/ana.21055	journal	December 2006
Frontotemporal lobar degeneration: A consensus on clinical diagnostic criteria Neary, D.; Snowden, J. S.; Gustafson, L. Neurology, Vol. 51, Issue 6 https://doi.org/10.1212/WNL.51.6.1546	journal	December 1998
Atrophy patterns in early clinical stages across distinct phenotypes of Alzheimer's disease: Origin and Spread of Atrophy in AD Variants Ossenkoppele, Rik; Cohn-Sheehy, Brendan I.; La Joie, Renaud Human Brain Mapping, Vol. 36, Issue 11 https://doi.org/10.1002/hbm.22927	journal	August 2015
Functional-Anatomic Fractionation of the Brain's Default Network Andrews-Hanna, Jessica R.; Reidler, Jay S.; Sepulcre, Jorge Neuron, Vol. 65, Issue 4 https://doi.org/10.1016/j.neuron.2010.02.005	journal	February 2010
Neurodegenerative Diseases Target Large-Scale Human Brain Networks Seeley, William W.; Crawford, Richard K.; Zhou, Juan Neuron, Vol. 62, Issue 1 https://doi.org/10.1016/j.neuron.2009.03.024	journal	April 2009
Metabolic connectivity: methods and applications Yakushev, Igor; Drzezga, Alexander; Habeck, Christian Current Opinion in Neurology, Vol. 30, Issue 6 https://doi.org/10.1097/WCO.0000000000000494	journal	January 2017
Long-term effects of amyloid, hypometabolism, and atrophy on neuropsychological functions Ossenkoppele, R.; van der Flier, W. M.; Verfaillie, S. C. J. Neurology, Vol. 82, Issue 20 https://doi.org/10.1212/WNL.0000000000000432	journal	April 2014
The behavioural/dysexecutive variant of Alzheimer’s disease: clinical, neuroimaging and pathological features Ossenkoppele, Rik; Pijnenburg, Yolande A. L.; Perry, David C. Brain, Vol. 138, Issue 9 https://doi.org/10.1093/brain/awv191	journal	July 2015
Typical and atypical appearance of early-onset Alzheimer's disease: A clinical, neuroimaging and neuropathological study: Typical and atypical early-onset AD Kawakatsu, Shinobu; Kobayashi, Ryota; Hayashi, Hiroshi Neuropathology, Vol. 37, Issue 2 https://doi.org/10.1111/neup.12364	journal	January 2017
Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer’s disease Ossenkoppele, Rik; Schonhaut, Daniel R.; Schöll, Michael Brain, Vol. 139, Issue 5 https://doi.org/10.1093/brain/aww027	journal	March 2016
The diagnosis of mild cognitive impairment due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease Albert, Marilyn S.; DeKosky, Steven T.; Dickson, Dennis Alzheimer's & Dementia, Vol. 7, Issue 3 https://doi.org/10.1016/j.jalz.2011.03.008	journal	April 2011
Dissociable Intrinsic Connectivity Networks for Salience Processing and Executive Control Seeley, W. W.; Menon, V.; Schatzberg, A. F. Journal of Neuroscience, Vol. 27, Issue 9 https://doi.org/10.1523/JNEUROSCI.5587-06.2007	journal	February 2007
The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer's disease McKhann, Guy M.; Knopman, David S.; Chertkow, Howard Alzheimer's & Dementia, Vol. 7, Issue 3 https://doi.org/10.1016/j.jalz.2011.03.005	journal	May 2011
Larger amygdala volumes in first depressive episode as compared to recurrent major depression and healthy control subjects Frodl, Thomas; Meisenzahl, Eva Maria; Zetzsche, Thomas Biological Psychiatry, Vol. 53, Issue 4 https://doi.org/10.1016/S0006-3223(02)01474-9	journal	February 2003
Frontal–subcortical neuronal circuits and clinical neuropsychiatry Tekin, Sibel; Cummings, Jeffrey L. Journal of Psychosomatic Research, Vol. 53, Issue 2 https://doi.org/10.1016/S0022-3999(02)00428-2	journal	August 2002
Progressive dysexecutive syndrome due to Alzheimer’s disease: a description of 55 cases and comparison to other phenotypes Townley, Ryan A.; Graff-Radford, Jonathan; Mantyh, William G. Brain Communications, Vol. 2, Issue 1 https://doi.org/10.1093/braincomms/fcaa068	journal	January 2020
Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia Rascovsky, Katya; Hodges, John R.; Knopman, David Brain, Vol. 134, Issue 9 https://doi.org/10.1093/brain/awr179	journal	August 2011
Saliency, switching, attention and control: a network model of insula function Menon, Vinod; Uddin, Lucina Q. Brain Structure and Function, Vol. 214, Issue 5-6 https://doi.org/10.1007/s00429-010-0262-0	journal	May 2010
Diverging patterns of amyloid deposition and hypometabolism in clinical variants of probable Alzheimer’s disease Lehmann, Manja; Ghosh, Pia M.; Madison, Cindee Brain, Vol. 136, Issue 3 https://doi.org/10.1093/brain/aws327	journal	January 2013
Metabolic connectivity by interregional correlation analysis using statistical parametric mapping (SPM) and FDG brain PET; methodological development and patterns of metabolic connectivity in adults Lee, Dong Soo; Kang, Hyejin; Kim, Heejung European Journal of Nuclear Medicine and Molecular Imaging, Vol. 35, Issue 9 https://doi.org/10.1007/s00259-008-0808-z	journal	May 2008
Functional connectivity of default mode network components: Correlation, anticorrelation, and causality Uddin, Lucina Q.; Clare Kelly, A. M.; Biswal, Bharat B. Human Brain Mapping, Vol. 30, Issue 2 https://doi.org/10.1002/hbm.20531	journal	January 2008
The Brain's Default Mode Network Raichle, Marcus E. Annual Review of Neuroscience, Vol. 38, Issue 1 https://doi.org/10.1146/annurev-neuro-071013-014030	journal	July 2015
Remembering the past to imagine the future: the prospective brain Schacter, Daniel L.; Addis, Donna Rose; Buckner, Randy L. Nature Reviews Neuroscience, Vol. 8, Issue 9 https://doi.org/10.1038/nrn2213	journal	September 2007
Distribution of Pathology in Frontal Variant Alzheimer's Disease Blennerhassett, Richard; Lillo, Patricia; Halliday, Glenda M. Journal of Alzheimer's Disease, Vol. 39, Issue 1 https://doi.org/10.3233/JAD-131241	journal	January 2014
Automated Anatomical Labeling of Activations in SPM Using a Macroscopic Anatomical Parcellation of the MNI MRI Single-Subject Brain Tzourio-Mazoyer, N.; Landeau, B.; Papathanassiou, D. NeuroImage, Vol. 15, Issue 1 https://doi.org/10.1006/nimg.2001.0978	journal	January 2002
Preserved Pontine Glucose Metabolism in Alzheimer Disease: A Reference Region for Functional Brain Image (PET) Analysis Minoshima, Satoshi; Frey, Kirk A.; Foster, Norman L. Journal of Computer Assisted Tomography, Vol. 19, Issue 4 https://doi.org/10.1097/00004728-199507000-00006	journal	January 1995
MRI Signatures of Brain Macrostructural Atrophy and Microstructural Degradation in Frontotemporal Lobar Degeneration Subtypes Zhang, Yu; Tartaglia, Maria Carmela; Schuff, Norbert Journal of Alzheimer's Disease, Vol. 33, Issue 2 https://doi.org/10.3233/JAD-2012-121156	journal	December 2012
Clinical phenotype, atrophy, and small vessel disease in APOE ε2 carriers with Alzheimer disease Groot, Colin; Sudre, Carole H.; Barkhof, Frederik Neurology, Vol. 91, Issue 20 https://doi.org/10.1212/WNL.0000000000006503	journal	October 2018
Neocortical origin and progression of gray matter atrophy in nonamnestic Alzheimer's disease Phillips, Jeffrey S.; Da Re, Fulvio; Dratch, Laynie Neurobiology of Aging, Vol. 63 https://doi.org/10.1016/j.neurobiolaging.2017.11.008	journal	March 2018
Fractionating the Default Mode Network: Distinct Contributions of the Ventral and Dorsal Posterior Cingulate Cortex to Cognitive Control Leech, R.; Kamourieh, S.; Beckmann, C. F. Journal of Neuroscience, Vol. 31, Issue 9 https://doi.org/10.1523/JNEUROSCI.5626-10.2011	journal	March 2011
Tau covariance patterns in Alzheimer's disease patients match intrinsic connectivity networks in the healthy brain Ossenkoppele, Rik; Iaccarino, Leonardo; Schonhaut, Daniel R. NeuroImage: Clinical, Vol. 23 https://doi.org/10.1016/j.nicl.2019.101848	journal	January 2019
Large-scale automated synthesis of human functional neuroimaging data Yarkoni, Tal; Poldrack, Russell A.; Nichols, Thomas E. Nature Methods, Vol. 8, Issue 8 https://doi.org/10.1038/nmeth.1635	journal	June 2011
Overlapping and non-overlapping brain regions for theory of mind and self reflection in individual subjects Saxe, Rebecca; Moran, Joseph M.; Scholz, Jonathan Social Cognitive and Affective Neuroscience, Vol. 1, Issue 3 https://doi.org/10.1093/scan/nsl034	journal	December 2006
Spatial Patterns of Hypometabolism and Amyloid Deposition in Variants of Alzheimer’s Disease Corresponding to Brain Networks: a Prospective Cohort Study Wang, Ying; Shi, Zhihong; Zhang, Nan Molecular Imaging and Biology, Vol. 21, Issue 1 https://doi.org/10.1007/s11307-018-1219-6	journal	June 2018

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Additional file 1 of Investigating the clinico-anatomical dissociation in the behavioral variant of Alzheimer disease Singleton, Ellen H.; Pijnenburg, Yolande A. L.; Sudre, Carole H. https://doi.org/10.6084/m9.figshare.13238654 The current record is supplemented by this text	text	January 2020
Additional file 2 of Investigating the clinico-anatomical dissociation in the behavioral variant of Alzheimer disease Singleton, Ellen H.; Pijnenburg, Yolande A. L.; Sudre, Carole H. https://doi.org/10.6084/m9.figshare.13238657.v1 The current record is supplemented by this text	text	January 2020
Additional file 3 of Investigating the clinico-anatomical dissociation in the behavioral variant of Alzheimer disease Singleton, Ellen H.; Pijnenburg, Yolande A. L.; Sudre, Carole H. https://doi.org/10.6084/m9.figshare.13238660.v1 The current record is supplemented by this text	text	January 2020
Additional file 4 of Investigating the clinico-anatomical dissociation in the behavioral variant of Alzheimer disease Singleton, Ellen H.; Pijnenburg, Yolande A. L.; Sudre, Carole H. https://doi.org/10.6084/m9.figshare.13238663.v1 The current record is supplemented by this text	text	January 2020
Additional file 5 of Investigating the clinico-anatomical dissociation in the behavioral variant of Alzheimer disease Singleton, Ellen H.; Pijnenburg, Yolande A. L.; Sudre, Carole H. https://doi.org/10.6084/m9.figshare.13238666.v1 The current record is supplemented by this text	text	January 2020
Additional file 6 of Investigating the clinico-anatomical dissociation in the behavioral variant of Alzheimer disease Singleton, Ellen H.; Pijnenburg, Yolande A. L.; Sudre, Carole H. https://doi.org/10.6084/m9.figshare.13238669.v1 The current record is supplemented by this text	text	January 2020
Additional file 7 of Investigating the clinico-anatomical dissociation in the behavioral variant of Alzheimer disease Singleton, Ellen H.; Pijnenburg, Yolande A. L.; Sudre, Carole H. https://doi.org/10.6084/m9.figshare.13238672.v1 The current record is supplemented by this text	text	January 2020
Additional file 8 of Investigating the clinico-anatomical dissociation in the behavioral variant of Alzheimer disease Singleton, Ellen H.; Pijnenburg, Yolande A. L.; Sudre, Carole H. https://doi.org/10.6084/m9.figshare.13238675.v1 The current record is supplemented by this text	text	January 2020
Investigating the clinico-anatomical dissociation in the behavioral variant of Alzheimer disease Singleton, Ellen H.; Pijnenburg, Yolande A. L.; Sudre, Carole H. https://doi.org/10.6084/m9.figshare.c.5207813 The current record is supplemented by this collection	collection	January 2020
Additional file 1 of Investigating the clinico-anatomical dissociation in the behavioral variant of Alzheimer disease Singleton, Ellen H.; Pijnenburg, Yolande A. L.; Sudre, Carole H. https://doi.org/10.6084/m9.figshare.13238654.v1 The current record is supplemented by this text	text	January 2020
Additional file 2 of Investigating the clinico-anatomical dissociation in the behavioral variant of Alzheimer disease Singleton, Ellen H.; Pijnenburg, Yolande A. L.; Sudre, Carole H. https://doi.org/10.6084/m9.figshare.13238657 The current record is supplemented by this text	text	January 2020
Additional file 5 of Investigating the clinico-anatomical dissociation in the behavioral variant of Alzheimer disease Singleton, Ellen H.; Pijnenburg, Yolande A. L.; Sudre, Carole H. https://doi.org/10.6084/m9.figshare.13238666 The current record is supplemented by this text	text	January 2020
Additional file 8 of Investigating the clinico-anatomical dissociation in the behavioral variant of Alzheimer disease Singleton, Ellen H.; Pijnenburg, Yolande A. L.; Sudre, Carole H. https://doi.org/10.6084/m9.figshare.13238675 The current record is supplemented by this text	text	January 2020
Additional file 3 of Investigating the clinico-anatomical dissociation in the behavioral variant of Alzheimer disease Singleton, Ellen H.; Pijnenburg, Yolande A. L.; Sudre, Carole H. https://doi.org/10.6084/m9.figshare.13238660 The current record is supplemented by this text	text	January 2020
Additional file 4 of Investigating the clinico-anatomical dissociation in the behavioral variant of Alzheimer disease Singleton, Ellen H.; Pijnenburg, Yolande A. L.; Sudre, Carole H. https://doi.org/10.6084/m9.figshare.13238663 The current record is supplemented by this text	text	January 2020
Additional file 7 of Investigating the clinico-anatomical dissociation in the behavioral variant of Alzheimer disease Singleton, Ellen H.; Pijnenburg, Yolande A. L.; Sudre, Carole H. https://doi.org/10.6084/m9.figshare.13238672 The current record is supplemented by this text	text	January 2020
Additional file 6 of Investigating the clinico-anatomical dissociation in the behavioral variant of Alzheimer disease Singleton, Ellen H.; Pijnenburg, Yolande A. L.; Sudre, Carole H. https://doi.org/10.6084/m9.figshare.13238669 The current record is supplemented by this text	text	January 2020

Title: Investigating the clinico-anatomical dissociation in the behavioral variant of Alzheimer disease

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