PROJECT SUMMARY Can regular mental exercises in building cognitive maps delay the onset of Alzheimer’s disease (AD) or decelerate the progression of AD? The neuropathology of Alzheimer’s disease (AD) begins in the entorhinal cortex, leading to spatial navigation impairment that differentiates patients with mild cognitive impairment (MCI) and AD from healthy aging adults. Specifically, MCI and AD patients suffer declining abilities to allocentric navigation that requires developing a cognitive map (aka mental map) as an internal representation of the environment with places and features independent of one’s current location or orientation. A system of spatial cells in the hippocampal formation subserves cognitive map building with the spatial periodicity of grid- cell firing fields to form the brain’s metric coordinate system for allocentric navigation. Studies showed that grid cells could gradually lose their spatial periodicity during periods of reduced theta oscillations and hippocampal inactivation. Will mental exercises in building cognitive maps excite theta oscillations and hippocampal activation and strengthen spatial periodicity of grid-cell firing fields? Findings of structural brain changes in London taxi drivers and spatial information retrieval support the potential of such excitatory effects. Further, less is known about the role of the posterior parietal cortex (PPC) in the storage and retrieval of cognitive maps, and how this region changes with AD. The proposed study hypothesizes that regular mental exercises on cognitive map building can evoke such excitatory effects to delay AD onset and decelerate AD progression. In this exploratory proposal, we venture into the links amongst geographic environments, allocentric navigation, cognitive maps, and AD development: a more complex environment imposes a higher demand on cognitive maps to navigate even on daily commutes and routine errands, and frequent mental exercises of building and retrieving cognitive maps lead to preservation of spatial cognition relevant gray matter regions and consequently impede AD development. We will use data from the National Alzheimer’s Coordinating Center (NACC) and US-based Health and Retirement Study (HRS), respectively (1) to compare MCI/AD populations in geographic areas with varying degrees of environmental complexity and (2) to investigate MCI/AD populations with occupations of high dependency on cognitive maps, such as realtors, police officers, first responders, and the other occupations. The NACC databases contain participant’s 3-digit zip-codes and types of residence which will allow MCI/AD mapping to potential neighborhoods across the US, whereas HRS restricted data include occupation data and cross-wave geographic information at street-level. Findings from the exploratory project will support subsequent experimental research to model the role of gray matter volume, refine the research framework of the excitatory effects of environment complexity and cognitive mapping to MCI/AD development, and examine the potential MCI/AD detriments of GPS-enabled navigation devices.

PROJECT NARRATIVE A delay of AD onset for five years can reduce medical care costs by $511,208 per person in 2050. Despite recent failures in clinical trials and drug development, delaying impending MCI and progressing AD remain high priorities. The study explores new research directions in mitigating AD development via spatial cognitive mapping, and if proven effective, will shed light on beneficial navigation activities and implications for redesigning GPS navigation systems.