The Neural and Behavioral Profile of Older Adults at Risk for Developing Mild Cognitive Impairment

Improving the ability to detect Alzheimer’s disease (AD) at the earliest stages is essential to effectively treat afflicted individuals. Mild cognitive impairment (MCI) is thought to be an intermediary state between healthy aging and AD. The goal of the present dissertation was to examine older adults who are at heightened risk of developing AD – both patients with diagnosed MCI and a preclinical group of older adults at-risk for developing MCI. Our preclinical participants were undiagnosed and supposedly healthy members of the community, but were defined to be at-risk for MCI based on performance from a brief, standardized neuropsychological test. We administered a full neuropsychological battery after our screening and found that the preclinical group performed in the lowest quartile on measures that are conventionally impaired in MCI (Chapter 2). To establish a neural profile of this population, we investigated an ERP component associated with visual short-term memory (VSTM) capacity, the CDA (Chapter 2). We found that older adults at-risk for MCI had reduced VSTM and reduced differentiation of the CDA (Chapter 2). Additionally, we found that the P300, a well-characterized ERP component shown to be useful in determining conversion from MCI to AD, showed reduced amplitude in our at-risk group (Chapter 2). Electrophysiological signatures may be especially sensitive markers of the very earliest stages of AD. To further characterize the preclinical group, we administered an object discrimination task to older adults at-risk for developing MCI and diagnosed MCI patients (Chapter 3). We based the task design on previous research showing that the medial temporal lobe (MTL), a region damaged early in MCI, is necessary to resolve visual interference in this object discrimination task. Critically, we manipulated the level of visual interference across conditions, and found that both memory-impaired groups, but not controls, benefited from reduced interference on the perceptual task. Indeed, by reducing the requirement to bind features of an object together, performance in the memory-impaired group rose to the level of healthy controls. In Chapter 4, we sought to extend these findings by investigating the role of interference in a task assessing VSTM. We reduced interference by presenting a retroactive spatial cue (retrocue, providing a cue for binding object to location), which again elevated performance in patients with MCI and MTL amnesia to the level of their age-matched controls. The results of these experiments suggest that one of the most critical determinants of behavior is interference in the environment, and that increased vulnerability to interference may be one of the first symptoms of pathological aging.Ph.D