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Principal Investigator  
Principal Investigator's Name: Eleni Aretouli
Institution: University of Deusto
Department: Psychology
Country:
Proposed Analysis: Dear ADNI Committee, We would like to request data from the ADNI study for the purpose of scientific investigation. Our research team is a collaborative group comprised from scientists from the Johns Hopkins University School of Medicine in the USA and the Faculty of Psychology of the University of Deusto in Spain. The investigators involved in the proposed project are: Principal Investigator: Eleni Aretouli, Ph.D. Co-investigators who will work on this project and have access to the ADNI data: 1. David Schretlen, PhD; Department of Psychiatry and Behavioral Sciences & Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, USA 2. Natalia Ojeda, PhD; Department of Methods and Experimental Psychology, School of Psychology, University of Deusto, Spain 3. Eleni Aretouli, PhD; Department of Methods and Experimental Psychology, School of Psychology, University of Deusto, Spain & Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, USA 4. Javier Pena, PhD; Department of Methods and Experimental Psychology, School of Psychology, University of Deusto, Spain 5. Naroa Ibarretxe, PhD; Department of Methods and Experimental Psychology, School of Psychology, University of Deusto, Spain The title, the rationale/background of our research proposal, our specific aims and methods are briefly described below. Title: Patterns of intraindividual variability in the transition from normal cognitive functioning to dementia. Background: Intraindividual variability (IIV) in cognitive performance has recently been suggested as a potential predictor of subsequent cognitive decline in healthy elderly persons or persons diagnosed with mild cognitive impairment (MCI) (Holtzer, Verghese, Wang, Hall, & Lipton, 2008). Using data from the Einstein Aging Study, a population-based longitudinal study of aging and dementia, Holtzer and his colleagues (2008) provided the first evidence that within-person across-neuropsychological test variability was associated with development of incident dementia independent of neuropsychological test performance and emphasized the need to confirm this finding in future studies. Recently, Tractenberg & Pietrzak (2011) pointed out that IIV can be defined with several various ways. Using data from the ADNI databases they found that when comparing healthy adults, persons with MCI and patients with dementia, the definition of IIV may produce between-groups differences with various effect sizes (Tractenberg & Pietrzak, 2011). However, they observed that within-test variation (IIV) at baseline did not provide much explanatory power for change in clinical functioning. It should be noted, however, that they included only 2 tests in their study design (MMSE and Clock Drawing Test) and also examined their predictive ability for a single follow-up after only 12 months. Thus, they found that only the IIV estimate derived from the items of the Clock Drawing Test predicted cognitive decline at the 12-month follow-up. Aims: Using a longitudinal study design we aim to test whether IIV across different cognitive domains can predict subsequent decline in healthy elderly persons or persons with MCI. Furthermore, we intend to use a novel approach in the definition and assessment of IIV. We intend to investigate the pattern of IIV as one transitions from normal cognitive functioning to dementia. We hypothesize that progressive dementia, such as that associated with Alzheimer’s disease (AD), will initially increase intraindividual variability and then decrease it as the dementia worsens. Methods: In order to accomplish our goal we request longitudinal data from the ADNI databases on all available cognitive tests and also some demographic and clinical information (demographics, family history, inclusion and exclusion criteria, diagnosis). More specifically, we would like to obtain data on the neuropsychological tests administered during the ADNI 1 and ADNI GO and ADNI 2 phases of the study (see Annex 1). We would be more interested in the participants that enrolled at baseline in ADNI 1 phase as NCs (N=200) or MCI (N=400) or diagnosed with dementia (N=200) and were follow-up at the second (ADNI GO) and third phase of the study (ADNI 2). However, depending on the attrition rates during the study, we may need data from persons recruited at the ADNI GO (N=200) phase or even at the ADNI 2 phase (N=550) as well. We will then analyze specific psychometric characteristics of the distributions of the cognitive performances of the participants in order to test our hypothesis. We hope you will approve our research proposal and allow us access to the data of your study. We remain at your disposal and would be happy to provide you with any further information regarding our research team or our proposal that you might need. Thank you for your consideration, Eleni Aretouli, Ph.D.
Additional Investigators  
Investigator's Name: David Schretlen
Proposed Analysis: Title: Patterns of intraindividual variability in the transition from normal cognitive functioning to dementia. Background: Intraindividual variability (IIV) in cognitive performance has recently been suggested as a potential predictor of subsequent cognitive decline in healthy elderly persons or persons diagnosed with mild cognitive impairment (MCI) (Holtzer, Verghese, Wang, Hall, & Lipton, 2008). Using data from the Einstein Aging Study, a population-based longitudinal study of aging and dementia, Holtzer and his colleagues (2008) provided the first evidence that within-person across-neuropsychological test variability was associated with development of incident dementia independent of neuropsychological test performance and emphasized the need to confirm this finding in future studies. Recently, Tractenberg & Pietrzak (2011) pointed out that IIV can be defined with several various ways. Using data from the ADNI databases they found that when comparing healthy adults, persons with MCI and patients with dementia, the definition of IIV may produce between-groups differences with various effect sizes (Tractenberg & Pietrzak, 2011). However, they observed that within-test variation (IIV) at baseline did not provide much explanatory power for change in clinical functioning. It should be noted, however, that they included only 2 tests in their study design (MMSE and Clock Drawing Test) and also examined their predictive ability for a single follow-up after only 12 months. Thus, they found that only the IIV estimate derived from the items of the Clock Drawing Test predicted cognitive decline at the 12-month follow-up. Aims: Using a longitudinal study design we aim to test whether IIV across different cognitive domains can predict subsequent decline in healthy elderly persons or persons with MCI. Furthermore, we intend to use a novel approach in the definition and assessment of IIV. We intend to investigate the pattern of IIV as one transitions from normal cognitive functioning to dementia. We hypothesize that progressive dementia, such as that associated with Alzheimer’s disease (AD), will initially increase intraindividual variability and then decrease it as the dementia worsens. Methods: In order to accomplish our goal we request longitudinal data from the ADNI databases on all available cognitive tests and also some demographic and clinical information (demographics, family history, inclusion and exclusion criteria, diagnosis). More specifically, we would like to obtain data on the neuropsychological tests administered during the ADNI 1 and ADNI GO and ADNI 2 phases of the study (see Annex 1). We would be more interested in the participants that enrolled at baseline in ADNI 1 phase as NCs (N=200) or MCI (N=400) or diagnosed with dementia (N=200) and were follow-up at the second (ADNI GO) and third phase of the study (ADNI 2). However, depending on the attrition rates during the study, we may need data from persons recruited at the ADNI GO (N=200) phase or even at the ADNI 2 phase (N=550) as well. We will then analyze specific psychometric characteristics of the distributions of the cognitive performances of the participants in order to test our hypothesis. Annex. Neuropsychological tests requested for the present proposal American National Adult Reading Test Mini Mental State Examination Logical Memory I and II (Wechsler Adult Intelligence Scale-Revised) Everyday Cognition (Ecog) Montreal Cognitive Assessment (MoCA) Digit Span Category Fluency, Category Fluency (Animals) Trail Making Test- Parts A & B Digit Symbol test (Wechsler Adult Intelligence Scale-Revised) Boston Naming Test Auditory Verbal Learning Test Geriatric Depression Scale Clock Drawing Test Neuropsychiatric Inventory Q ADAS-Cog ADAS-Cog 13 (with Delayed Word Recall and Number Cancellation) Clinical Dementia Rating Scale Activities of Daily Living (FAQ)