Altered medial temporal lobe responses during visuospatial encoding in healthy APOE*4 carriers

Borghesani, Paul R.; Johnson, L. Clark; Shelton, Amy L.; Peskind, Elaine R.; Aylward, Elizabeth H.; Schellenberg, Gerard D.; Cherrier, Monique M.

doi:10.1016/j.neurobiolaging.2007.01.012

« Previous Next »Neurobiology of Aging
Volume 29, Issue 7 , Pages 981-991, July 2008

Altered medial temporal lobe responses during visuospatial encoding in healthy APOE*4 carriers

Paul R. Borghesani
- Mental Illness Research, Education, and Clinical Center (MIRECC), Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA
- Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA
- Corresponding author at: Veterans Affairs Puget Sound Health Care System (VAPSHCS), S-116 6East, 1660 Columbian Way, Seattle, WA 98108, USA. Tel.: +1 206 277 1337; fax: +1 206 277 4856.
L. Clark Johnson
- Department of Psychosocial and Community Health Nursing, University of Washington School of Nursing, Seattle, WA 98195, USA
Amy L. Shelton
- Department of Psychological and Brain Sciences, Johns Hopkins University, Baltimore, MD 21218, USA
Elaine R. Peskind
- Mental Illness Research, Education, and Clinical Center (MIRECC), Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA
- Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA
- Geriatrics Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA
Elizabeth H. Aylward
- Department of Radiology, University of Washington School of Medicine, Seattle, WA 98195, USA
Gerard D. Schellenberg
- Geriatrics Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA
Monique M. Cherrier
- Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA
- Geriatrics Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA

Received 21 August 2006; received in revised form 5 January 2007; accepted 21 January 2007. published online 12 March 2007.

Abstract

The apolipoprotein ɛ4 allele (APOE*4) is a major genetic risk factor for Alzheimer's disease (AD) and has been associated with altered cortical activation as assessed by functional neuroimaging in cognitively normal younger and older carriers. We chose to evaluate medial temporal lobe (MTL) activation during encoding and recognition using a perspective-dependent (route or survey) visuospatial memory task by monitoring the blood-oxygen-level-dependent (BOLD) fMRI response in older, non-demented APOE*4 carriers (APOE*4+) and non-carriers (APOE*4−). During encoding, the APOE*4− group had greater average task-associated BOLD responses in ventral visual pathways, including the MTLs, as compared to the APOE*4+ group. Furthermore, MTL activation was greater during route encoding than survey encoding on average in APOE*4−, but not APOE*4+, subjects. During recognition, both groups performed similarly and no BOLD signal differences were found. Finally, within-group analysis revealed MTL activation during encoding was correlated with recognition performance in APOE*4−, but not APOE*4+ subjects. Reduced task-associated MTL activation that does not correlate with either visuospatial perspective or task performance suggests that MTL dysregulation occurs prior to clinical symptoms of dementia in APOE*4 carriers.

Keywords: Alzheimer, Apolipoprotein, Hippocampus, APOE*4, Perspective, Visuospatial learning, Encoding, Recognition, fMRI, Route, Survey