The existing diagnostic criteria for Dementia with Lewy bodies (DLB) has been criticized for being inadequate at differentiating DLB from Alzheimer's disease (AD). The main focus of this grant is to improve the differential diagnosis of DLB relative to AD, and to better understand the neuropathologic underpinnings of DLB and predictors of decline. Specifically, we will determine whether the addition of vigilance and visual tasks improves our ability to distinguish DLB from AD. We will also expand on our prior findings of daytime drowsiness in DLB, by investigating whether DLB and not AD, is associated with disturbed sleep/wake mechanisms based on indices from polysomnography and multiple sleep latency tests. Neuropathologic analyses will help to determine whether our diagnostic accuracy shows improvement when REM sleep behavior disorder (RBD) and excessive daytime sleepiness are included as diagnostic features. In addition, the contribution of Lewy body, Lewy neurite and AD pathology will be examined in relation to clinical/cognitive presentation and rate of disease progression. A secondary focus of the grant is to characterize preclinical predictors of DLB by analyzing data from persons who convert from a diagnosis of Mild Cognitive Impairment (MCI) to dementia in the Mayo Alzheimer's Disease Patient Registry (ADPR) and Alzheimers'Disease Research Center (ADRC) (Mayo African American Normative Studies and Minority/Indigent program). We hypothesize that non-amnestic MCI (with visual and/or attention/executive dysfunction) and RBD will be predictive of subsequent progression to DLB and not AD. The overarching theme of this grant application is to improve the early detection and diagnostic accuracy of DLB. This has implications for symptom management, development of treatment options and for providing education and support to DLB patients and their caregivers.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG015866-10
Application #
7613342
Study Section
Adult Psychopathology and Disorders of Aging Study Section (APDA)
Program Officer
Hsiao, John
Project Start
1999-05-01
Project End
2011-04-30
Budget Start
2009-05-01
Budget End
2011-04-30
Support Year
10
Fiscal Year
2009
Total Cost
$366,258
Indirect Cost
Name
Mayo Clinic Jacksonville
Department
Type
DUNS #
153223151
City
Jacksonville
State
FL
Country
United States
Zip Code
32224
Ferman, Tanis J; Aoki, Naoya; Crook, Julia E et al. (2018) The limbic and neocortical contribution of ?-synuclein, tau, and amyloid ? to disease duration in dementia with Lewy bodies. Alzheimers Dement 14:330-339
Lapid, Maria I; Kuntz, Karen M; Mason, Sara S et al. (2017) Efficacy, Safety, and Tolerability of Armodafinil Therapy for Hypersomnia Associated with Dementia with Lewy Bodies: A Pilot Study. Dement Geriatr Cogn Disord 43:269-280
St Louis, Erik K; Boeve, Bradley F (2017) REM Sleep Behavior Disorder: Diagnosis, Clinical Implications, and Future Directions. Mayo Clin Proc 92:1723-1736
Sanchez-Contreras, Monica; Heckman, Michael G; Tacik, Pawel et al. (2017) Study of LRRK2 variation in tauopathy: Progressive supranuclear palsy and corticobasal degeneration. Mov Disord 32:115-123
Walton, Ronald L; Soto-Ortolaza, Alexandra I; Murray, Melissa E et al. (2016) TREM2 p.R47H substitution is not associated with dementia with Lewy bodies. Neurol Genet 2:e85
Heckman, Michael G; Soto-Ortolaza, Alexandra I; Contreras, Monica Y Sanchez et al. (2016) LRRK2 variation and dementia with Lewy bodies. Parkinsonism Relat Disord 31:98-103
Hassan, Anhar; Heckman, Michael G; Ahlskog, J E et al. (2016) Association of Parkinson disease age of onset with DRD2, DRD3 and GRIN2B polymorphisms. Parkinsonism Relat Disord 22:102-5
Nedelska, Zuzana; Schwarz, Christopher G; Boeve, Bradley F et al. (2015) White matter integrity in dementia with Lewy bodies: a voxel-based analysis of diffusion tensor imaging. Neurobiol Aging 36:2010-7
Nedelska, Zuzana; Ferman, Tanis J; Boeve, Bradley F et al. (2015) Pattern of brain atrophy rates in autopsy-confirmed dementia with Lewy bodies. Neurobiol Aging 36:452-61
McCarter, Stuart J; Tippmann-Peikert, Maja; Sandness, David J et al. (2015) Neuroimaging-evident lesional pathology associated with REM sleep behavior disorder. Sleep Med 16:1502-10

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