The Kerala-Einstein Study (KES) proposes to build on the successful activities in our previous funding period to conduct high quality and impact research into Alzheimer?s disease and related dementias in the southern Indian state of Kerala. The KES team successfully established clinical research center in Kerala, trained junior investigators, instituted uniform study procedures, developed culture-fair cognitive tests, built databases, created research neuroimaging protocols, established a biorepository, and had multiple publications. In this renewal, our focus is on risk factors and brain substrates of pre-dementia syndromes, especially Motoric Cognitive Risk syndrome (MCR). MCR is a recent and innovative concept proposed by Dr. Verghese and colleagues, and validated in multiple countries including low and middle-income countries (LMIC). MCR is a pre-dementia syndrome characterized by presence of cognitive complaints and slow gait. MCR predicts risk of both Alzheimer?s disease and vascular dementia even after accounting for overlap with Mild Cognitive Impairment syndrome (MCI). Unlike MCI, complex cognitive tests or assays are not needed to diagnose MCR, increasing its clinical utility in resource poor LMIC settings.
Aim 1. Examine clinical risk factors for pre-dementia syndromes (MCR and MCI) in 1000 Kerala seniors. We identified potentially modifiable risk factors (depression, sedentariness and obesity) for MCR in developed countries, but their association with MCR in LMIC is unknown. In addition, we will study novel risk factors for pre- dementia syndromes in India; apathy and mild traumatic brain injury, and cognitive reserve.
Aim 2. Explore risk factors for pre-dementia syndromes in 400 rural and 600 urban Kerala seniors. There is a paucity of cognitive studies in rural seniors globally; our urban and rural sites in Kerala will provide a valuable opportunity to compare and contrast risk factors for MCR and MCI. In this renewal, we propose to establish a new research center in a rural site.
Aim 3. Establish brain pathologies and substrates of MCR in Kerala seniors. Frontal lacunes and frontal gray matter thinning were associated with MCR in KES, implicating both vascular and neurodegenerative pathologies. Small vessel disease is associated with gray matter atrophy. We propose to test mechanistic hypotheses linking these two pathologies to MCR syndrome in 400 indivdiuals with neuroimaging. We will continue to examine the neurobiological basis of pre-dementia syndromes in the KES biorepository that contains genetic samples of over 500 clinically phenotyped patients (normal, MCI and dementia). Our studies have the potential to continue to have a major impact in continuing to build sustainable research capacity in India, foster research training in India and USA and elucidate the pathogenesis of dementia.

Public Health Relevance

The Kerala-Einstein Study (KES) proposes to build on the successful research collaboration in our last funding period to conduct high quality and impactful research into Alzheimer?s disease and related dementias in the Indian state of Kerala. In this renewal, we propose to target risk factors and brain substrates of pre-dementia syndromes, especially the recently Motoric Cognitive Risk syndrome (MCR). MCR is characterized by cognitive complaints and slow gait, and identifies older adults at high risk for both Alzheimer?s disease and vascular dementia. Our studies have the potential to have a major impact in building sustainable research capacity in India, foster research training in India and USA, elucidate the pathogenesis of dementia, and provide insights into modifiable risk factors for dementia; ultimately leading to development of treatment and prevention strategies that are applicable worldwide.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
2R01AG039330-07
Application #
9820441
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Anderson, Dallas
Project Start
2011-08-01
Project End
2024-05-31
Budget Start
2019-09-15
Budget End
2020-05-31
Support Year
7
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Type
DUNS #
081266487
City
Bronx
State
NY
Country
United States
Zip Code
10461
Callisaya, Michele L; Verghese, Joe (2018) The Association of Clinic-Based Mobility Tasks and Measures of Community Performance and Risk. PM R 10:704-711.e1
Beauchet, Olivier; Blumen, Helena M; Callisaya, Michele L et al. (2018) Spatiotemporal Gait Characteristics Associated with Cognitive Impairment: A Multicenter Cross-Sectional Study, the Intercontinental ""Gait, cOgnitiOn & Decline"" Initiative. Curr Alzheimer Res 15:273-282
George, Claudene; Verghese, Joe (2017) Polypharmacy and Gait Performance in Community-dwelling Older Adults. J Am Geriatr Soc 65:2082-2087
Sheelakumari, R; Kesavadas, C; Varghese, T et al. (2017) Assessment of Iron Deposition in the Brain in Frontotemporal Dementia and Its Correlation with Behavioral Traits. AJNR Am J Neuroradiol 38:1953-1958
Ezzati, Ali; Wang, Cuiling; Lipton, Richard B et al. (2017) Association Between Vascular Pathology and Rate of Cognitive Decline Independent of Alzheimer's Disease Pathology. J Am Geriatr Soc 65:1836-1841
Ezzati, Ali; Rundek, Tatjana; Verghese, Joe et al. (2017) Transcranial Doppler and Lower Extremity Function in Older Adults: Einstein Aging Study. J Am Geriatr Soc 65:2659-2664
Ravi Teja, Karru Venkata; Tos Berendschot, Tjm; Steinbusch, Harry et al. (2017) Cerebral and Retinal Neurovascular Changes: A Biomarker for Alzheimer's Disease. J Gerontol Geriatr Res 6:
Allali, Gilles; Launay, Cyrille P; Blumen, Helena M et al. (2017) Falls, Cognitive Impairment, and Gait Performance: Results From the GOOD Initiative. J Am Med Dir Assoc 18:335-340
Verghese, Joe (2017) Reply to Cognitive Reserve: Predictor of Onset of Postoperative Delirium in Older Adults? J Am Geriatr Soc 65:660-661
Beauchet, Olivier; Allali, Gilles; Sekhon, Harmehr et al. (2017) Guidelines for Assessment of Gait and Reference Values for Spatiotemporal Gait Parameters in Older Adults: The Biomathics and Canadian Gait Consortiums Initiative. Front Hum Neurosci 11:353

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