This study will use data from the Strong Heart Study (SHS) and the ancillary Cerebrovascular Disease and its Consequences in American Indians (CDCAI) study to evaluate cognitive function, AD risk factors, and MRIdefined biomarkers of AD in elderly AIs. SHS enrolled 4,549 AIs aged 45-74 years from 13 tribes in the U.S. Southwest, Southern Plains, and Northern Plains for 3 waves of data collection from 1988 to 2000.16,17 CDCAI assessed cognitive function and MRI-defined VBI in 818 surviving SHS participants in 2010-2013 (CDCAI-1), and begin reassessing surviving participants by repeating the same MRI and cognitive tests in 2017 (CDCAI- 2; recruitment will conclude in 2019). We will use statistical mapping software to reprocess MRIs from CDCAI-1 and 2; will quantify cerebral atrophy in brain regions preferentially affected by AD (including the hippocampus, the parahippocampal, medial temporal, and parietal regions, and the posterior cingulate cortex); and will create 3-dimensional brain maps for elderly AIs. We will compare structural patterns observed on MRI from CDCAI-1 and 2 with normative data on AD patients from other populations; define probable AD cases by assessing change in MRI-defined loss in regions selectively affected by AD, in combination with AD-related cognitive test performance and activities of daily living; and examine associations of probable AD with risk factors and functional outcomes. Our Specific Aims are to:

  1. Establish AI-specific normative values of MRI atrophy in brain regions selectively affected by AD, and evaluate AD-related regional atrophy in combination with cognitive and behavioral changes to calculate prevalence of probable AD in elderly AIs. We expect AD prevalence similar to that in non-AI populations.
  2. Use genetic, sociodemographic, and clinical data on risk factors for AD observed in other populations to identify correlates of probable AD in elderly AIs. We expect associations to be similar to those observed in other populations, with possible differences in magnitude.
  3. Estimate associations of MRI markers of probable AD with measures of cognitive and physical function, independent of the effects of VBI. We expect that AD will be a significant risk factor for functional loss in elderly AIs, and that volumetric loss in MRI markers will exhibit a dose-response relationship with poorer cognitive and physical function.

AD is the leading cause of dementia and one of the leading causes of death in the US.18 Effective therapies for its prevention and treatment are urgently needed, especially among AIs. The CDCAI study sample is the only population-based cohort of AIs with extant data on MRI and genetic biomarkers relevant to We will leverage these unparalleled data to address key elements of PM, namely, comprehensive risk assessment and detection of preclinical pathophysiologic processes of AD, in a population that is both understudied and underserved. This work will also inform efforts to improve the detection, treatment, and prevention of AD for people of other races and ethnicities.