There is growing recognition that conditions such as Alzheimer's disease (AD) occur years before a formal diagnosis is rendered and that available cognitive and functional assessment measures are not sufficiently sensitive to detect early changes associated with the condition. This is critical since new treatment approaches are likely to be most effective in the earliest stages of disease. Further, FDA guidelines indicate that changes in biomarker measures will not be considered as surrogate outcomes in clinical trials of emerging therapies for early AD, unless they are also shown to have a clinical impact. The proposed investigation is highly innovative and designed to examine the efficacy of the newly developed and novel cognitive tests of cued recall and semantic interference (LASSI-L), time and event related prospective memory (MPMT), and novel computer-based functional task simulations (FTS) in detecting subtle cognitive and functional impairments, and progression of these impairments over time. Our sample will include Spanish-speaking and English-speaking older adults diagnosed with traditional neuropsychological measures and clinical evaluations as: amnestic MCI (aMCI), pre-clinical MCI (PreMCI), or cognitively normal (NC). In the proposed investigation, we will further establish the reliability and validity of our novel cognitive and functional measures in distinguishing between diagnostic groups and predicting progression of cognitive and functional decline over time. We also predict that among aMCI and PreMCI subjects, baseline and change scores on the LASSI-L, MPMT, and FTS will exhibit stronger associations with increasing MRI atrophy over a minimum three-year period relative to traditional neuropsychological measures. An exciting exploratory aim of the study will be the exploration, among a subsample of PreMCI and aMCI participants, the association between amyloid, tau, and phosphorylated tau biomarker levels in the CSF and performance on the LASSI-L, MPMT and FTS.

Public Health Relevance

This is an innovative longitudinal study that will examine the utility of two novel cognitive measures (LASSI-L; MPMT) and a series of newly developed computer-based functional task stimulations (FTS) in the detection of amnestic mild cognitive impairment (aMCI) and PreMCI versus normal elderly subjects. We will examine performance on these novel measures with changes in brain MRI volumes over time as well as associations with amyloid, tau, and phosphorylated tau biomarker levels in the CSF.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG047649-05
Application #
9625738
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Silverberg, Nina B
Project Start
2015-02-01
Project End
2020-01-31
Budget Start
2019-02-01
Budget End
2020-01-31
Support Year
5
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Miami School of Medicine
Department
Psychiatry
Type
Schools of Medicine
DUNS #
052780918
City
Coral Gables
State
FL
Country
United States
Zip Code
33146
Loewenstein, David A; Curiel, Rosie E; DeKosky, Steven et al. (2018) Utilizing semantic intrusions to identify amyloid positivity in mild cognitive impairment. Neurology 91:e976-e984
Grassi, Massimiliano; Perna, Giampaolo; Caldirola, Daniela et al. (2018) A Clinically-Translatable Machine Learning Algorithm for the Prediction of Alzheimer's Disease Conversion in Individuals with Mild and Premild Cognitive Impairment. J Alzheimers Dis 61:1555-1573
Crocco, Elizabeth A; Loewenstein, David A; Curiel, Rosie E et al. (2018) A novel cognitive assessment paradigm to detect Pre-mild cognitive impairment (PreMCI) and the relationship to biological markers of Alzheimer's disease. J Psychiatr Res 96:33-38
Burke, Shanna L; Rodriguez, Miriam J; Barker, Warren et al. (2018) Relationship between Cognitive Performance and Measures of Neurodegeneration among Hispanic and White Non-Hispanic Individuals with Normal Cognition, Mild Cognitive Impairment, and Dementia. J Int Neuropsychol Soc 24:176-187
Loewenstein, David A; Curiel, Rosie E; Duara, Ranjan et al. (2018) Novel Cognitive Paradigms for the Detection of Memory Impairment in Preclinical Alzheimer's Disease. Assessment 25:348-359
Shea, Yat-Fung; Barker, Warren; Greig-Gusto, Maria T et al. (2018) Impact of Amyloid PET Imaging in the Memory Clinic: A Systematic Review and Meta-Analysis. J Alzheimers Dis 64:323-335
Rosselli, Mónica; Loewenstein, David A; Curiel, Rosie E et al. (2018) Effects of Bilingualism on Verbal and Nonverbal Memory Measures in Mild Cognitive Impairment. J Int Neuropsychol Soc :1-14
Grassi, Massimiliano; Loewenstein, David A; Caldirola, Daniela et al. (2018) A clinically-translatable machine learning algorithm for the prediction of Alzheimer's disease conversion: further evidence of its accuracy via a transfer learning approach. Int Psychogeriatr :1-9
Matias-Guiu, Jordi A; Cabrera-Martín, María Nieves; Curiel, Rosie E et al. (2018) Comparison between FCSRT and LASSI-L to Detect Early Stage Alzheimer's Disease. J Alzheimers Dis 61:103-111
Shea, Yat-Fung; Barker, Warren; Greig-Gusto, Maria T et al. (2018) Utility of Amyloid PET Scans in the Evaluation of Patients Presenting with Diverse Cognitive Complaints. J Alzheimers Dis 66:1599-1608

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