Evidence from theta-burst stimulation that age-related de-differentiation of the hippocampal network is functional for episodic memory.

Episodic memory is supported by hippocampal interactions with a distributed network. Aging is associated with memory decline and network de-differentiation. However, the role of de-differentiation in memory decline has not been directly tested. We reasoned that hippocampal network-targeted stimulation could test these theories, as age-related changes in the network response to stimulation would indicate network reorganization, and corresponding changes in memory would suggest that this reorganization is functional. We compared effects of stimulation on fMRI connectivity and memory in younger versus older adults. Theta-burst network-targeted stimulation of left lateral parietal cortex selectively increased hippocampal network connectivity and modulated memory in younger adults. In contrast, stimulation in older adults increased connectivity throughout the brain, without network selectivity, and did not influence memory. These findings provide evidence that network responses to stimulation are de-differentiated in aging and suggest that age-related de-differentiation is relevant for memory. This manuscript is part of the Special Issue entitled "Cognitive Neuroscience of Healthy and Pathological Aging" edited by Drs. M. N. Rajah, S. Belleville, and R. Cabeza. This article is part of the Virtual Special Issue titled COGNITIVE NEUROSCIENCE OF HEALTHY AND PATHOLOGICAL AGING. The full issue can be found on ScienceDirect at https://www.sciencedirect.com/journal/neurobiology-of-aging/special-issue/105379XPWJP.

ARMADA: Assessing reliable measurement in Alzheimer's disease and cognitive aging project methods.

INTRODUCTION: Early detection of cognitive decline in older adults is a public health priority. Advancing Reliable Measurement in Alzheimer's Disease and Cognitive Aging (ARMADA), a multisite study, is validating cognition, emotion, motor, and sensory modules of the National Institutes of Health Toolbox for Assessment of Neurological and Behavioral Function (NIHTB) in the aging spectrum from cognitively normal to dementia of the Alzheimer's type (DAT). METHODS: Participants 65 to 85 years old, in demographic groups racially proportional to the general US population, are recruited in one of three groups to validate the NIHTB: cognitively normal, amnestic mild cognitive impairment (aMCI), or mild DAT. Additional special emphasis cohorts include (1) Blacks in the three clinical groups; (2) Spanish-speakers in the three clinical groups; (3) cognitively normal, population-proportional, over age 85. DISCUSSION: Longitudinal study will determine whether NIHTB can predict cognitive decline and is associated with Alzheimer's disease biomarkers. Here, we detail the methods for the ARMADA study.