Faculty Collaboration Database

Genetic risk for Alzheimer's disease alters the five-year trajectory of semantic memory activation in cognitively intact elders. Neuroimage 2015 May 01;111:136-46

Date

02/18/2015

Pubmed ID

25687593

Pubmed Central ID

PMC4387085

DOI

10.1016/j.neuroimage.2015.02.011

Scopus ID

2-s2.0-84923327069 (requires institutional sign-in at Scopus site)   37 Citations

Abstract

Healthy aging is associated with cognitive declines typically accompanied by increased task-related brain activity in comparison to younger counterparts. The Scaffolding Theory of Aging and Cognition (STAC) (Park and Reuter-Lorenz, 2009; Reuter-Lorenz and Park, 2014) posits that compensatory brain processes are responsible for maintaining normal cognitive performance in older adults, despite accumulation of aging-related neural damage. Cross-sectional studies indicate that cognitively intact elders at genetic risk for Alzheimer's disease (AD) demonstrate patterns of increased brain activity compared to low risk elders, suggesting that compensation represents an early response to AD-associated pathology. Whether this compensatory response persists or declines with the onset of cognitive impairment can only be addressed using a longitudinal design. The current prospective, 5-year longitudinal study examined brain activation in APOE ε4 carriers (N=24) and non-carriers (N=21). All participants, ages 65-85 and cognitively intact at study entry, underwent task-activated fMRI, structural MRI, and neuropsychological assessments at baseline, 18, and 57 months. fMRI activation was measured in response to a semantic memory task requiring participants to discriminate famous from non-famous names. Results indicated that the trajectory of change in brain activation while performing this semantic memory task differed between APOE ε4 carriers and non-carriers. The APOE ε4 group exhibited greater activation than the Low Risk group at baseline, but they subsequently showed a progressive decline in activation during the follow-up periods with corresponding emergence of episodic memory loss and hippocampal atrophy. In contrast, the non-carriers demonstrated a gradual increase in activation over the 5-year period. Our results are consistent with the STAC model by demonstrating that compensation varies with the severity of underlying neural damage and can be exhausted with the onset of cognitive symptoms and increased structural brain pathology. Our fMRI results could not be attributed to changes in task performance, group differences in cerebral perfusion, or regional cortical atrophy.

Author List

Rao SM, Bonner-Jackson A, Nielson KA, Seidenberg M, Smith JC, Woodard JL, Durgerian S

Author

Kristy Nielson PhD Professor in the Psychology department at Marquette University

MESH terms used to index this publication - Major topics in bold

Aged
Aged, 80 and over
Aging
Alzheimer Disease
Apolipoprotein E4
Atrophy
Brain
Female
Genetic Predisposition to Disease
Humans
Longitudinal Studies
Magnetic Resonance Imaging
Male
Memory, Long-Term