QUESTIONABLE DEMENTIA: COURSE AND PREDICTORS OF OUTCOME

Summary

Principal Investigator: Davangere P Devanand
Abstract: DESCRIPTION (provided by applicant): In R01AG17761, 150 patients with mild cognitive impairment (MCI) and 63 age and sex-matched healthy control subjects are followed. With an average of 5 years'follow-up, specific neuropsychological test scores, odor identification deficits, patient-informant discrepancy in report of function, MRI hippocampal and entorhinal atrophy are highly significant predictors of conversion to AD (41 converters to date), apolipoprotein E e4 genotype is significant only in older patients, and SPECT medial temporal and posterior cingulate deficits are significant only in some analyses. Selective Reminding Test delayed recall, odor identification deficits, hippocampal volume, and entorhinal volume are the variables identified for the initial algorithm to predict MCI conversion to AD. This head-to-head comparison of predictors, and the initial predictive algorithm for MCI conversion to AD, are novel and unique, and have potential clinical impact. Completion of 9-year follow-up is needed to accurately identify all MCI converters to AD, and to improve accuracy for evaluation of the hypothesized predictors and the predictive algorithm. In order to achieve eventual clinical application, it is critical to build upon the ongoing study's findings by enhancing the signal to noise ratio, improving predictive accuracy by modifying and expanding specific assessments, and independently validating the findings in a new sample. Therefore, in a new study, 140 patients with amnestic MCI (with or without other cognitive domain deficits) and 50 control subjects will be recruited and systematically followed to test new potential predictors of MCI conversion to AD. These include more sensitive and specific cutting-edge brain imaging techniques that should enhance signal to noise ratio and predictive accuracy: improved structural MRI, [18F]-FDG, and p-amyloid imaging with [11C]-6-OH-BTA-1 (Pittsburgh compound B). New [11C]-6-OH-BTA-1 PET pilot data are very promising. Informant report of cognitive decline will be added, and the functional, olfactory and neuropsychological predictors will be modified and improved. In subjects who agree to lumbar puncture, CSF tau, phosphorylated tau (P- tauisi), AB42 and F2-isoprostanes will be assessed at baseline. The primary analyses in the new study will be restricted to the new study sample. Before combining the amnestic MCI patients across the two samples to generate the predictive algorithm for predictors common to the two studies, we will rediagnose the ongoing study sample's follow-up visits using the improved new study methods, ensure comparability in demographics/clinical features, and require that specific predictor by sample interaction criteria be met. Relevance. There are several clinical and public health implications. Accurate prediction of MCI conversion to AD will help identify patients who need early treatment, facilitate patient/family planning for their own future, and improve patient selection for clinical trials.
Funding Period: -----------------200 - ----------------2013
more information: NIH RePORT

Top Publications

  1. ncbi PET network abnormalities and cognitive decline in patients with mild cognitive impairment
    Davangere P Devanand
    Department of Biological Psychiatry, College of Physicians and Surgeons, New York State Psychiatric Institute, Columbia University, New York, NY 10032, USA
    Neuropsychopharmacology 31:1327-34. 2006
  2. pmc Lessons from epidemiologic research about risk factors, modifiers, and progression of late onset Alzheimer's Disease in New York City at Columbia University Medical Center
    Devangere Devanand
    Department of Psychiatry, Columbia University Medical Center, New York, NY 10032, USA
    J Alzheimers Dis 33:S447-55. 2013
  3. pmc Relapse risk after discontinuation of risperidone in Alzheimer's disease
    D P Devanand
    Division of Geriatric Psychiatry, New York State Psychiatric Institute, New York, New York 10032, USA
    N Engl J Med 367:1497-507. 2012
  4. pmc Combining early markers strongly predicts conversion from mild cognitive impairment to Alzheimer's disease
    Davangere P Devanand
    Division of Geriatric Psychiatry, New York State Psychiatric Institute, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
    Biol Psychiatry 64:871-9. 2008
  5. pmc Voxel-based analysis of 11C-PIB scans for diagnosing Alzheimer's disease
    Arthur Mikhno
    Department of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, New York, USA
    J Nucl Med 49:1262-9. 2008
  6. pmc Randomized double-blind placebo-controlled donepezil augmentation in antidepressant-treated elderly patients with depression and cognitive impairment: a pilot study
    Gregory H Pelton
    Late Life Depression Clinic, The Memory Disorders Center, and The Division of Geriatric Psychiatry, New York State Psychiatric Institute, NY, USA
    Int J Geriatr Psychiatry 23:670-6. 2008
  7. ncbi Item reduction in a scale for screening
    Xinhua Liu
    Department of Biostatistics, Columbia University, New York, NY 10032, USA
    Stat Med 26:4311-27. 2007
  8. ncbi Olfactory dysfunction as a predictor of neurodegenerative disease
    Mark W Albers
    Department of Neurology, Columbia UniversityCollege of Physicians and Surgeons, 710 West 168th Street, New York, NY 10032, USA
    Curr Neurol Neurosci Rep 6:379-86. 2006
  9. ncbi Neuropsychological prediction of conversion to Alzheimer disease in patients with mild cognitive impairment
    Matthias H Tabert
    Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, 1051 Riverside Dr, Unit 126, New York, NY 10032, USA
    Arch Gen Psychiatry 63:916-24. 2006
  10. ncbi Validation and optimization of statistical approaches for modeling odorant-induced fMRI signal changes in olfactory-related brain areas
    Matthias H Tabert
    Department of Biological Psychiatry, New York State Psychiatric Institute, New York, NY 10032, USA
    Neuroimage 34:1375-90. 2007

Scientific Experts

  • S Salloway
  • Mirjam I Geerlings
  • Deidre J Devier
  • Davangere Devanand
  • Matthias H Tabert
  • Xinhua Liu
  • Gregory H Pelton
  • Mark W Albers
  • Patrick J Brown
  • Arthur Mikhno
  • Elise Caccappolo
  • Gregory Pelton
  • Ramin V Parsey
  • Harold A Sackeim
  • Neil Upton
  • J John Mann
  • Robert Y Lai
  • Steven P Roose
  • Oliver L Harper
  • Vincenzo Libri
  • Katrina Cuasay
  • Roger Gunn
  • Nikolaos Scarmeas
  • David W Kern
  • Jason Steffener
  • Truman R Brown
  • Maria Michael
  • Zhezhen Jin
  • Haiying Tang
  • Marni Jacobs
  • Yaakov Stern
  • Madeleine Goodkind
  • Karen Bell
  • Jennifer J Manly
  • Sara Rosenblum
  • Diana Zamora

Detail Information

Publications23

  1. ncbi PET network abnormalities and cognitive decline in patients with mild cognitive impairment
    Davangere P Devanand
    Department of Biological Psychiatry, College of Physicians and Surgeons, New York State Psychiatric Institute, Columbia University, New York, NY 10032, USA
    Neuropsychopharmacology 31:1327-34. 2006
    ..Independent replication in larger samples is needed before clinical application can be considered...
  2. pmc Lessons from epidemiologic research about risk factors, modifiers, and progression of late onset Alzheimer's Disease in New York City at Columbia University Medical Center
    Devangere Devanand
    Department of Psychiatry, Columbia University Medical Center, New York, NY 10032, USA
    J Alzheimers Dis 33:S447-55. 2013
    ..These studies have advanced our knowledge about risk factors, modifiers, and progression of late onset Alzheimer's disease..
  3. pmc Relapse risk after discontinuation of risperidone in Alzheimer's disease
    D P Devanand
    Division of Geriatric Psychiatry, New York State Psychiatric Institute, New York, New York 10032, USA
    N Engl J Med 367:1497-507. 2012
    ..Among patients with Alzheimer's disease who have had a response to antipsychotic medication for psychosis or agitation-aggression, the risk of a recurrence of symptoms after discontinuation of the medication has not been established...
  4. pmc Combining early markers strongly predicts conversion from mild cognitive impairment to Alzheimer's disease
    Davangere P Devanand
    Division of Geriatric Psychiatry, New York State Psychiatric Institute, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
    Biol Psychiatry 64:871-9. 2008
    ..The utility of combining early markers to predict conversion from mild cognitive impairment (MCI) to Alzheimer's Disease (AD) remains uncertain...
  5. pmc Voxel-based analysis of 11C-PIB scans for diagnosing Alzheimer's disease
    Arthur Mikhno
    Department of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, New York, USA
    J Nucl Med 49:1262-9. 2008
    ..We assessed the use of data-determined standardized voxels of interest (VOIs) to improve the classification capability of 11C-PIB scans on patients with AD...
  6. pmc Randomized double-blind placebo-controlled donepezil augmentation in antidepressant-treated elderly patients with depression and cognitive impairment: a pilot study
    Gregory H Pelton
    Late Life Depression Clinic, The Memory Disorders Center, and The Division of Geriatric Psychiatry, New York State Psychiatric Institute, NY, USA
    Int J Geriatr Psychiatry 23:670-6. 2008
    ..To assess combined antidepressant and cognitive enhancer treatment in elderly patients presenting with depression plus cognitive impairment...
  7. ncbi Item reduction in a scale for screening
    Xinhua Liu
    Department of Biostatistics, Columbia University, New York, NY 10032, USA
    Stat Med 26:4311-27. 2007
    ..The method is illustrated with a data set on patients with and without high risk of developing Alzheimer's disease who were administered a 40-item test of olfactory function...
  8. ncbi Olfactory dysfunction as a predictor of neurodegenerative disease
    Mark W Albers
    Department of Neurology, Columbia UniversityCollege of Physicians and Surgeons, 710 West 168th Street, New York, NY 10032, USA
    Curr Neurol Neurosci Rep 6:379-86. 2006
    ....
  9. ncbi Neuropsychological prediction of conversion to Alzheimer disease in patients with mild cognitive impairment
    Matthias H Tabert
    Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, 1051 Riverside Dr, Unit 126, New York, NY 10032, USA
    Arch Gen Psychiatry 63:916-24. 2006
    ..The likelihood of conversion to Alzheimer disease (AD) in mild cognitive impairment (MCI) and the "optimal" early markers of conversion need to be established...
  10. ncbi Validation and optimization of statistical approaches for modeling odorant-induced fMRI signal changes in olfactory-related brain areas
    Matthias H Tabert
    Department of Biological Psychiatry, New York State Psychiatric Institute, New York, NY 10032, USA
    Neuroimage 34:1375-90. 2007
    ....
  11. ncbi Hippocampal and entorhinal atrophy in mild cognitive impairment: prediction of Alzheimer disease
    D P Devanand
    Department of Biological Psychiatry, New York State Psychiatric Institute, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    Neurology 68:828-36. 2007
    ..To evaluate the utility of MRI hippocampal and entorhinal cortex atrophy in predicting conversion from mild cognitive impairment (MCI) to Alzheimer disease (AD)...
  12. pmc Depressive symptoms, antidepressant use, and brain volumes on MRI in a population-based cohort of old persons without dementia
    Mirjam I Geerlings
    University Medical Center Utrecht, Julius Center for Health Sciences and Primary Care, Utrecht, The Netherlands
    J Alzheimers Dis 30:75-82. 2012
    ....
  13. pmc MRI hippocampal and entorhinal cortex mapping in predicting conversion to Alzheimer's disease
    D P Devanand
    Division of Geriatric Psychiatry, New York State Psychiatric Institute, College of Physicians and Surgeons, Columbia University, NY, USA
    Neuroimage 60:1622-9. 2012
    ..Using MRI surface morphometry mapping, to evaluate local deformations of the hippocampus, parahippocampal gyrus, and entorhinal cortex in predicting conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD)...
  14. pmc A 6-month, randomized, double-blind, placebo-controlled pilot discontinuation trial following response to haloperidol treatment of psychosis and agitation in Alzheimer's disease
    D P Devanand
    Division of Geriatric Psychiatry, New York State Psychiatric Institute, College of Physicians and Surgeons, Columbia University, NY, USA
    Int J Geriatr Psychiatry 26:937-43. 2011
    ..In patients with Alzheimer's disease (AD) with psychosis or agitation that respond to haloperidol treatment, to evaluate the risk of relapse following discontinuation...
  15. pmc Plasma Aβ and PET PiB binding are inversely related in mild cognitive impairment
    D P Devanand
    Divisions of Geriatric Psychiatry, New York State Psychiatric Institute, Columbia University, New York, NY 10032, USA
    Neurology 77:125-31. 2011
    ..To evaluate the relations between PET Pittsburgh compound B (PiB-PET) binding (amyloid imaging) and plasma Aβ in patients with mild cognitive impairment (MCI) and similarly aged controls...
  16. pmc Functional impairment in elderly patients with mild cognitive impairment and mild Alzheimer disease
    Patrick J Brown
    Division of Geriatric Psychiatry, New York State Psychiatric Institute, New York, NY 10032, USA
    Arch Gen Psychiatry 68:617-26. 2011
    ....
  17. pmc The antipsychotic discontinuation in Alzheimer disease trial: clinical rationale and study design
    D P Devanand
    Division of Geriatric Psychiatry, New York State Psychiatric Institute, College of Physicians and Surgeons, Columbia University, NY, USA
    Am J Geriatr Psychiatry 20:362-73. 2012
    ..Responders are randomized, double-blind, to one of three arms in Phase B: 1) continuation risperidone for the next 32 weeks, 2) risperidone for the next 16 weeks followed by placebo for 16 weeks, or 3) placebo for the next 32 weeks...
  18. pmc Predictive utility of type and duration of symptoms at initial presentation in patients with mild cognitive impairment
    Deidre J Devier
    Department of Neurology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA ddevie lsuhsc edu
    Dement Geriatr Cogn Disord 30:238-44. 2010
    ..To assess (1) the duration and symptoms present in participants with mild cognitive impairment (MCI) and (2) the impact of these variables on predicting conversion to Alzheimer's disease (AD)...
  19. pmc (99m)Tc hexamethyl-propylene-aminoxime single-photon emission computed tomography prediction of conversion from mild cognitive impairment to Alzheimer disease
    D P Devanand
    NYSPI, Columbia University, New York, NY 10032, USA
    Am J Geriatr Psychiatry 18:959-72. 2010
    ..To examine the utility of single-photon emission computed tomography (SPECT) to predict conversion from mild cognitive impairment (MCI) to Alzheimer disease (AD)...
  20. pmc Pittsburgh compound B (11C-PIB) and fluorodeoxyglucose (18 F-FDG) PET in patients with Alzheimer disease, mild cognitive impairment, and healthy controls
    D P Devanand
    Division of Geriatric Psychiatry, Columbia University, New York, USA
    J Geriatr Psychiatry Neurol 23:185-98. 2010
    ..These PET techniques provide complementary information in strongly distinguishing diagnostic groups in cross-sectional comparisons that need testing in longitudinal studies...
  21. pmc The impact of anxiety on conversion from mild cognitive impairment to Alzheimer's disease
    Deidre J Devier
    Louisiana State University Health Sciences Center, Department of Neurology, New Orleans, LA, USA
    Int J Geriatr Psychiatry 24:1335-42. 2009
    ..To compare state and trait anxiety in mild cognitive impairment (MCI) patients and matched control subjects, and to assess the impact of these variables in predicting conversion to Alzheimer's disease...
  22. pmc Olfactory identification deficits and MCI in a multi-ethnic elderly community sample
    D P Devanand
    Division of Geriatric Psychiatry, Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    Neurobiol Aging 31:1593-600. 2010
    ..These findings indicate that the predictive utility of olfactory identification deficits for decline from no MCI to MCI and AD needs to be assessed in longitudinal studies of elderly community samples...
  23. pmc A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease
    S Salloway
    Butler Hospital, The Warren Alpert Medical School of Brown University, 345 Blackstone Blvd, Providence, RI 02906, USA
    Neurology 73:2061-70. 2009
    ..Bapineuzumab, a humanized anti-amyloid-beta (Abeta) monoclonal antibody for the potential treatment of Alzheimer disease (AD), was evaluated in a multiple ascending dose, safety, and efficacy study in mild to moderate AD...