Joint‐label fusion brain atlases for dementia research in Down syndrome

Research suggests a link between Alzheimer's Disease in Down Syndrome (DS) and the overproduction of amyloid plaques. Using Positron Emission Tomography (PET) we can assess the in‐vivo regional amyloid load using several available ligands. To measure amyloid distributions in specific brain regions, a brain atlas is used. A popular method of creating a brain atlas is to segment a participant's structural Magnetic Resonance Imaging (MRI) scan. Acquiring an MRI is often challenging in intellectually‐imparied populations because of contraindications or data exclusion due to significant motion artifacts or incomplete sequences related to general discomfort. When an MRI cannot be acquired, it is typically replaced with a standardized brain atlas derived from neurotypical populations (i.e. healthy individuals without DS) which may be inappropriate for use in DS. In this project, we create a series of disease and diagnosis‐specific (cognitively stable (CS‐DS), mild cognitive impairment (MCI‐DS), and dementia (DEM‐DS)) probabilistic group atlases of participants with DS and evaluate their accuracy of quantifying regional amyloid load compared to the individually‐based MRI segmentations. Further, we compare the diagnostic‐specific atlases with a probabilistic atlas constructed from similar‐aged cognitively‐stable neurotypical participants. We hypothesized that regional PET signals will best match the individually‐based MRI segmentations by using DS group atlases that aligns with a participant's disorder and disease status (e.g. DS and MCI‐DS). Our results vary by brain region but generally show that using a disorder‐specific atlas in DS better matches the individually‐based MRI segmentations than using an atlas constructed from cognitively‐stable neurotypical participants. We found no additional benefit of using diagnose‐specific atlases matching disease status. All atlases are made publicly available for the research community.

[1]  Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring announces new editor‐in‐chief for open access, peer reviewed journal , 2021, Alzheimer's & dementia : the journal of the Alzheimer's Association.

[2]  A. Brickman,et al.  Down syndrome: Distribution of brain amyloid in mild cognitive impairment , 2020, Alzheimer's & dementia.

[3]  S. Potkin,et al.  Brain amyloid and the transition to dementia in Down syndrome , 2020, bioRxiv.

[4]  W. Klunk,et al.  Neuropathological correlates of amyloid PET imaging in Down syndrome , 2019, Developmental neurobiology.

[5]  J. Nunes,et al.  Neuroimaging assessment in Down syndrome: a pictorial review , 2019, Insights into Imaging.

[6]  A. Danek,et al.  Alzheimer's disease in Down syndrome: An overlooked population for prevention trials , 2018, Alzheimer's & dementia.

[7]  Sterling C. Johnson,et al.  Imaging neurodegeneration in Down syndrome: brain templates for amyloid burden and tissue segmentation , 2018, Brain Imaging and Behavior.

[8]  Justin K. Rajendra,et al.  Handling Multiplicity in Neuroimaging Through Bayesian Lenses with Multilevel Modeling , 2017, Neuroinformatics.

[9]  Young T. Hong,et al.  Brain-predicted age in Down syndrome is associated with beta amyloid deposition and cognitive decline , 2017, Neurobiology of Aging.

[10]  Young T. Hong,et al.  The Down syndrome brain in the presence and absence of fibrillar β-amyloidosis , 2017, Neurobiology of Aging.

[11]  Amy Lin,et al.  Dissociations in Cortical Morphometry in Youth with Down Syndrome: Evidence for Reduced Surface Area but Increased Thickness. , 2016, Cerebral cortex.

[12]  Young T. Hong,et al.  The pattern of amyloid accumulation in the brains of adults with Down syndrome , 2016, Alzheimer's & Dementia.

[13]  J. Hardy,et al.  Dementia in Down's syndrome , 2016, The Lancet Neurology.

[14]  D. Giavarina.  Understanding Bland Altman analysis , 2015, Biochemia medica.

[15]  Sterling C. Johnson,et al.  Cognitive functioning in relation to brain amyloid-β in healthy adults with Down syndrome. , 2014, Brain : a journal of neurology.

[16]  A. Towbin,et al.  Imaging findings in Down syndrome , 2014, Pediatric Radiology.

[17]  Paul A. Yushkevich,et al.  Multi-atlas segmentation with joint label fusion and corrective learning—an open source implementation , 2013, Front. Neuroinform..

[18]  N. Schupf,et al.  Intellectual Disability, Mild Cognitive Impairment, and Risk for Dementia. , 2013, Journal of policy and practice in intellectual disabilities.

[19]  Angela Hassiotis,et al.  Discrimination and Other Barriers to Accessing Health Care: Perspectives of Patients with Mild and Moderate Intellectual Disability and Their Carers , 2013, PloS one.

[20]  W. Silverman,et al.  Dementia and mild cognitive impairment in adults with intellectual disability: issues of diagnosis. , 2013, Developmental disabilities research reviews.

[21]  M. Mintun,et al.  Amyloid-β Imaging with Pittsburgh Compound B and Florbetapir: Comparing Radiotracers and Quantification Methods , 2013, The Journal of Nuclear Medicine.

[22]  W. Klunk,et al.  Imaging brain amyloid in nondemented young adults with Down syndrome using Pittsburgh compound B , 2012, Alzheimer's & Dementia.

[23]  J. O'Brien,et al.  PET imaging of brain amyloid in dementia: a review , 2011, International journal of geriatric psychiatry.

[24]  Arno Klein,et al.  A reproducible evaluation of ANTs similarity metric performance in brain image registration , 2011, NeuroImage.

[25]  R. Kirby,et al.  Updated National Birth Prevalence estimates for selected birth defects in the United States, 2004-2006. , 2010, Birth defects research. Part A, Clinical and molecular teratology.

[26]  Stylianos E. Antonarakis,et al.  Down Syndrome: From Understanding the Neurobiology to Therapy , 2010, The Journal of Neuroscience.

[27]  A. Dale,et al.  One-Year Brain Atrophy Evident in Healthy Aging , 2009, The Journal of Neuroscience.

[28]  W. Jagust,et al.  Amyloid Imaging in Aging and Dementia: Testing the Amyloid Hypothesis In Vivo , 2009, Behavioural neurology.

[29]  Anders M. Dale,et al.  An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest , 2006, NeuroImage.

[30]  Keith A. Johnson,et al.  P2-366 Amyloid deposition begins in the striatum of presenilin-1 mutation carriers from two unrelated pedigrees , 2006, Alzheimer's & Dementia.

[31]  H. Hampel,et al.  Neuroanatomy of Down Syndrome in vivo: A Model of Preclinical Alzheimer’s Disease , 2006, Behavior genetics.

[32]  N. Schupf,et al.  Dementia in adults with mental retardation: assessment at a single point in time. , 2004, American journal of mental retardation : AJMR.

[33]  K. Natarajan,et al.  Magnetic resonance imaging, Down's syndrome and Alzheimer's disease: research and clinical implications. , 2003, Journal of intellectual disability research : JIDR.

[34]  A. Dale,et al.  Whole Brain Segmentation Automated Labeling of Neuroanatomical Structures in the Human Brain , 2002, Neuron.

[35]  Paul Thompson,et al.  Disease-specific probabilistic brain atlases , 2000, Proceedings IEEE Workshop on Mathematical Methods in Biomedical Image Analysis. MMBIA-2000 (Cat. No.PR00737).

[36]  D. Brockmeyer.  Down Syndrome and Craniovertebral Instability , 1999, Pediatric Neurosurgery.

[37]  G D Pearlson,et al.  MRI brain changes in subjects with Down syndrome with and without dementia , 1998, Developmental medicine and child neurology.

[38]  N. Driesen,et al.  Selective neuroanatornic abnormalities in Down's syndrome and their cognitive correlates , 1995, Neurology.

[39]  A. Neuhold,et al.  Down syndrome: MR quantification of brain structures and comparison with normal control subjects. , 1991, AJNR. American journal of neuroradiology.

[40]  R. S. Williams,et al.  A prospective study of Alzheimer disease in Down syndrome. , 1989, Archives of neurology.

[41]  G. Hommel.  A stagewise rejective multiple test procedure based on a modified Bonferroni test , 1988 .

[42]  D. Altman,et al.  STATISTICAL METHODS FOR ASSESSING AGREEMENT BETWEEN TWO METHODS OF CLINICAL MEASUREMENT , 1986, The Lancet.

[43]  F. Cardemil.  Comparison analysis and applications of the Bland-Altman method: correlation or agreement? , 2017 .

[44]  G. Dinant,et al.  Bmc Family Practice Doctor-patient Communication with People with Intellectual Disability -a Qualitative Study , 2009 .

[45]  W. Silverman.  Down syndrome: cognitive phenotype. , 2007, Mental retardation and developmental disabilities research reviews.

[46]  Nikos Makris,et al.  Automatically parcellating the human cerebral cortex. , 2004, Cerebral cortex.

[47]  D. Mann,et al.  The prevalence of amyloid (A4) protein deposits within the cerebral and cerebellar cortex in Down's syndrome and Alzheimer's disease , 2004, Acta Neuropathologica.

[48]  M. LeMay,et al.  The relationship between enlargement of the temporal horns of the lateral ventricles and dementia in aging patients with Down syndrome , 2004, Neuroradiology.

[49]  A. Toga,et al.  New approaches in brain morphometry. , 2002, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[50]  S. Sato,et al.  Relation of EEG alpha background to cognitive function, brain atrophy, and cerebral metabolism in Down's syndrome. Age-specific changes. , 1990, Archives of neurology.

[51]  I. Lott,et al.  Dementia in Down's syndrome: observations from a neurology clinic. , 1982, Applied research in mental retardation.