Longitudinal fMRI in elderly reveals loss of hippocampal activation with clinical decline. Neurology 2010 Jun 15;74(24):1969-76
Date
05/14/2010Pubmed ID
20463288Pubmed Central ID
PMC2905893DOI
10.1212/WNL.0b013e3181e3966eScopus ID
2-s2.0-77953776221 (requires institutional sign-in at Scopus site) 251 CitationsAbstract
BACKGROUND: Previous cross-sectional fMRI studies in subjects with prodromal Alzheimer disease (AD) have reported variable results, ranging from hypoactivation, similar to patients with AD, to paradoxically increased activation or hyperactivation compared to cognitively normal older individuals. We have hypothesized that subjects in early phases of prodromal AD may experience a period of hippocampal hyperactivation, followed by loss of hippocampal activation as the disease progresses.
METHODS: We studied 51 older individuals without dementia (Clinical Dementia Rating [CDR] at baseline of 0, n = 21, and 0.5, n = 30) with longitudinal clinical and neuropsychological assessments, as well as fMRI during a face-name associative memory paradigm. Whole brain and region-of-interest analyses were applied to the longitudinal fMRI data.
RESULTS: Subjects classified as CDR 0 at baseline showed no difference in fMRI activity over 2 years, whereas those who were CDR 0.5 at baseline demonstrated a decrease in fMRI activity in the right hippocampus (p < 0.001). Dividing the subjects on the basis of their clinical and neuropsychological change over the 2 years, we found that subjects with more rapid decline demonstrated both the highest hippocampal activation at baseline, and the greatest loss of hippocampal activation. These findings remained significant after accounting for age, hippocampal volume, and APOE epsilon4 carrier status.
CONCLUSIONS: Clinical decline is associated with loss of hippocampal activation in older subjects. Longitudinal fMRI provides a reliable indicator of brain activation over time, and may prove useful in identifying functional brain changes associated with cognitive decline on the trajectory toward clinical Alzheimer disease.
Author List
O'Brien JL, O'Keefe KM, LaViolette PS, DeLuca AN, Blacker D, Dickerson BC, Sperling RAAuthor
Peter LaViolette PhD Vice Chair, Professor in the Radiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AgedAged, 80 and over
Aging
Cohort Studies
Dementia
Follow-Up Studies
Hippocampus
Humans
Longitudinal Studies
Magnetic Resonance Imaging
Neuropsychological Tests
Time Factors
