Prediction of Cognitive Decline in Healthy Older Adults using fMRI

Article type: Research Article

Authors: Woodard, John L.^a | Seidenberg, Michael^b | Nielson, Kristy A.^{c; d} | Smith, J. Carson^e | Antuono, Piero^d | Durgerian, Sally^d | Guidotti, Leslie^b | Zhang, Qi^d | Butts, Alissa^c | Hantke, Nathan^c | Lancaster, Melissa^b | Rao, Stephen M.^{f; *}

Affiliations: [a] Department of Psychology, and Institute of Gerontology, Wayne State University, Detroit, MI, USA | [b] Department of Psychology, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA | [c] Department of Psychology, Marquette University, Milwaukee, WI, USA | [d] Department of Neurology, Medical College of Wisconsin, Milwaukee, WI, USA | [e] Department of Human Movement Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI, USA | [f] Neurological Institute, Cleveland Clinic, Cleveland, OH, USA

Correspondence: [*] Correspondence to: Stephen M. Rao, Ph.D., Schey Center for Cognitive Neuroimaging, Neurological Institute, Cleveland Clinic, 9500 Euclid Ave./U10, Cleveland, Ohio 44195, USA. Tel.: +1 216 444 7747; Fax: +1 216 445 7013; E-mail: [email protected].

Note: [] Handling Associate Editor: Diana Woodruff-Pak

Abstract: Few studies have examined the extent to which structural and functional MRI, alone and in combination with genetic biomarkers, can predict future cognitive decline in asymptomatic elders. This prospective study evaluated individual and combined contributions of demographic information, genetic risk, hippocampal volume, and fMRI activation for predicting cognitive decline after an 18-month retest interval. Standardized neuropsychological testing, an fMRI semantic memory task (famous name discrimination), and structural MRI (sMRI) were performed on 78 healthy elders (73% female; mean age = 73 years, range = 65 to 88 years). Positive family history of dementia and presence of one or both apolipoprotein E (APOE) ε4 alleles occurred in 51.3% and 33.3% of the sample, respectively. Hippocampal volumes were traced from sMRI scans. At follow-up, all participants underwent a repeat neuropsychological examination. At 18 months, 27 participants (34.6%) declined by at least 1 SD on one of three neuropsychological measures. Using logistic regression, demographic variables (age, years of education, gender) and family history of dementia did not predict future cognitive decline. Greater fMRI activity, absence of an APOE ε4 allele, and larger hippocampal volume were associated with reduced likelihood of cognitive decline. The most effective combination of predictors involved fMRI brain activity and APOE ε4 status. Brain activity measured from task-activated fMRI, in combination with APOE ε4 status, was successful in identifying cognitively intact individuals at greatest risk for developing cognitive decline over a relatively brief time period. These results have implications for enriching prevention clinical trials designed to slow AD progression.

Keywords: Aging, apolipoprotein E, cognitive decline, fMRI, hippocampal volume, neuroimaging, memory

DOI: 10.3233/JAD-2010-091693

Journal: Journal of Alzheimer's Disease, vol. 21, no. 3, pp. 871-885, 2010