Functional neural correlates of anosognosia in Alzheimer s disease. University Medical Center Groningen

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1 Functional neural correlates of anosognosia in Alzheimer s disease Jaime D. Mondragón M.D., M.S. Prof. Dr. Natasha M. Maurits Prof. Dr. Peter P. De Deyn April 13 th, 2018 Department of Neurology Clinical Neuroengineering Alzheimer Research Center Groningen University Medical Center Groningen

2 Outline 1. Introduction Impact Biomarkers Imaging modalities Anosognosia 2. Results Neural correlates of anosognosia Past and Future projects

3 Impact, Biomarkers, Imaging Modalities, and Anosognosia INTRODUCTION

4 Impact Alzheimer s disease Estimated worldwide cost (billions of dollars) 35,6 million worldwide (2010) 54% developing countries 60-80% of dementias World estimated prevalence 2030: 65,7 million 2050: 115,4 million Mexico 2030: 2,7 million Direct and indirect costs Jack Jr et al. (2013). Lancet Neurology; 12: Sosa-Ortiz et al. (2012). Archives of medical research; 43: Wimo et al. (2013). Alzheimer & Dementia; 9: 1-13.

5 Model of dynamic biomarkers Biological o o CSF Serum Bateman et al. (2012). N Engl J Med.; 367(9): Jack Jr et al. (2013). Lancet Neurology; 12:

6 Model of dynamic biomarkers Imaging o o Structural Functional Bateman et al. (2012). N Engl J Med.; 367(9): Jack Jr et al. (2013). Lancet Neurology; 12:

7 Multifactorial causal model Iturria-Medina et al. (2016). Nat. Commun; 7: Iturria-Medina et al. (2017). Neuroimage; 152:

8 Overview of neuroimaging modalities Grinvald and Hildesheim. (2004). Nature reviews neurosci; 5(11):

9 Anosognosia From the Greek, α = without, νόσϛ = disease, γνώσιϛ = knowledge Joseph Babinski in 1914, Revue Neurologie Dorland s medical dictionary Unawareness or denial of a neurological deficit such as hemiplegia The lack of awareness of motor, visual or cognitive deficits in patients with neurological diseases Di Perri et al. (2014). Epilepsy Behav; 30: Dorland and Newman. (2012). Dorland's illustrated medical dictionary; 32: 96. Nurmi and Jehkonen. (2014). Cortex; 61:

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11 Anosognosia classification Subtypes or etiology: Hemiplegic, cortical blindness, Anton s syndrome, visual field defect, traumatic brain injury, multiple sclerosis, Parkinson s disease, Alzheimer s disease, mild cognitive impairment, frontotemporal dementia and Huntington s disease. Anosognosia in Alzheimer s disease Anosognosia Questionnaire-Dementia (AQ-D) Dementia Deficits Scale (DDS) Adjusted Memory Awareness Rating Scale (MARSA) Vannini et al. (2017). Neuropsychologia; 99: Nurmi and Jehkonen. (2014). Cortex; 61:

12 Neural Correlates of Anosognosia RESULTS

13 Neural correlates of anosognosia Systematic review PubMed, EMBASE and PsycINFO on March 2018 Identical research strategy with a priori variables was realized on each database following the PRISMA statement (Moher et al., 2009). Keywords: anosognosia, self-appraisal, insight, awareness, and consciousness combined with each of the following terms dementia, Alzheimer, mild cognitive impairment Supplementary search was performed using MRI, PET, SPECT, connectivity, activation, hypometabolism, and hypermetabolism. Mondragón et al. (2018). Neurosci Biobehav Rev.; in press.

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15 Highlights Abnormal frontotemporal activity occurs in MCI and AD with anosognosia MCI patients with anosognosia (MCIwa) have reduced parietotemporal metabolism MCIwa have reduced cortical midline (CM) perfusion and activation Anosognosia in AD reduces DMN activation and within network connectivity Reduced neural activity pattern in anosognosia: CM, parietotemporal, frontotemporal Mondragón et al. (2018). Neurosci Biobehav Rev.; in press.

16 Neural correlates of anosognosia Figure 2. Graphical representation of the neural correlates in MCI patients with anosognosia. Mondragón et al. (2018). Neurosci Biobehav Rev.; in press.

17 Neural correlates of anosognosia Figure 3. Graphical representation of the neural correlates of unawareness in MCI. Mondragón et al. (2018). Neurosci Biobehav Rev.; in press.

18 Neural correlates of anosognosia Figure 4. Graphical representation of the neural correlates in mild to moderate AD patients with anosognosia. Mondragón et al. (2018). Neurosci Biobehav Rev.; in press.

19 Neural correlates of anosognosia Figure 5. Graphical representation of the neural correlates of unawareness in mild to moderate AD. Mondragón et al. (2018). Neurosci Biobehav Rev.; in press.

20 Mondragón et al. (2018). Neurosci Biobehav Rev.; in press.

21 Hippocampal volume Mondragón et al. (2016). Dement Geriatr Cogn Dis Extra; 6:

22 Hippocampal volume Mondragón et al. (2016). Dement Geriatr Cogn Dis Extra; 6:

23 Hippocampal volume Mondragón et al. (2016). Dement Geriatr Cogn Dis Extra; 6:

24 Future projects Neural correlates of anosgnosia in Alzheimer s Disease Neuroimaging Initiative Neural correlates of anosgnosia in Parelsnoer Initiative

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