Dataset Information

Network-targeted stimulation engages neurobehavioral hallmarks of age-related memory decline.

ABSTRACT:

Objective

To test whether targeting hippocampal-cortical brain networks with high-frequency transcranial magnetic stimulation in older adults influences behavioral and neural measures characteristic of age-related memory impairment.

Methods

Fifteen adults aged 64 to 80 years (mean = 72 years) completed a single-blind, sham-controlled experiment. Stimulation targets in parietal cortex were determined based on fMRI connectivity with the hippocampus. Recollection and recognition memory were assessed after 5 consecutive daily sessions of full-intensity stimulation vs low-intensity sham stimulation using a within-subjects crossover design. Neural correlates of recollection and recognition memory formation were obtained via fMRI, measured within the targeted hippocampal-cortical network vs a control frontal-parietal network. These outcomes were measured approximately 24 hours after the final stimulation session.

Results

Recollection was specifically impaired in older adults compared to a young-adult control sample at baseline. Relative to sham, stimulation improved recollection to a greater extent than recognition. Stimulation increased recollection fMRI signals throughout the hippocampal-cortical network, including at the targeted location of the hippocampus. Effects of stimulation on fMRI recollection signals were greater than those for recognition and were greater in the targeted network compared to the control network.

Conclusions

Age-related recollection impairments were causally related to hippocampal-cortical network function in older adults. Stimulation selectively modified neural and behavioral hallmarks of age-related memory impairment, indicating effective engagement of memory intervention targets in older adults.

SUBMITTER: Nilakantan AS

PROVIDER: S-EPMC6598819 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:An unfortunate result of the rapid rise in geriatric populations worldwide is the increasing prevalence of age-related cognitive disorders such as Alzheimer's disease (AD). AD is a devastating neurodegenerative illness that is characterized by a profound impairment of cognitive function, marked physical disability, and an enormous economic burden on the afflicted individual, caregivers, and society in general. The rise in elderly populations is also resulting in an increase in individuals with related (potentially treatable) conditions such as "Mild Cognitive Impairment" (MCI) which is characterized by a less severe (but abnormal) level of cognitive impairment and a high-risk for developing dementia. Even in the absence of a diagnosable disorder of cognition (e.g., AD and MCI), the perception of increased forgetfulness and declining mental function is a clear source of apprehension in the elderly. This is a valid concern given that even a modest impairment of cognitive function is likely to be associated with significant disability in a rapidly evolving, technology-based society. Unfortunately, the currently available therapies designed to improve cognition (i.e., for AD and other forms of dementia) are limited by modest efficacy and adverse side effects, and their effects on cognitive function are not sustained over time. Accordingly, it is incumbent on the scientific community to develop safer and more effective therapies that improve and/or sustain cognitive function in the elderly allowing them to remain mentally active and productive for as long as possible. As diagnostic criteria for memory disorders evolve, the demand for pro-cognitive therapeutic agents is likely to surpass AD and dementia to include MCI and potentially even less severe forms of memory decline. The purpose of this review is to provide an overview of the contemporary therapeutic targets and preclinical pharmacologic approaches (with representative drug examples) designed to enhance memory function.