Vascular Risk and FDDNP-PET Influence Cognitive Performance

Article type: Research Article

Authors: Merrill, David A.^a | Siddarth, Prabha^a | Kepe, Vladimir^{b; c} | Raja, Pushpa V.^a | Saito, Nathan^a | Ercoli, Linda M.^a | Miller, Karen J.^a | Lavretsky, Helen^a | Bookheimer, Susan Y.^{d; e} | Barrio, Jorge R.^c | Small, Gary W.^{a; b; *}

Affiliations: [a] Division of Geriatric Psychiatry, Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience & Human Behavior, David Geffen School of Medicine, and Longevity Center, University of California, Los Angeles, CA, USA | [b] Alzheimer's Disease Research Center, University of California, Los Angeles, CA, USA | [c] Department of Molecular and Medical Pharmacology, Center for Health Sciences, University of California, Los Angeles, CA, USA | [d] Center for Cognitive Neurosciences, Semel Institute for Neuroscience & Human Behavior, University of California, Los Angeles, CA, USA | [e] Brain Mapping Center, University of California, Los Angeles, CA, USA

Correspondence: [*] Correspondence to: Gary W. Small, 760 Westwood Plaza, Room 38-251, Los Angeles, CA 90024, USA. Tel.: +1 310 825 0291; Fax: +1 310 825 3910; E-mail: gsmall@ucla.edu.

Abstract: The relationship of cerebrovascular risk and Alzheimer's disease (AD) pathology to cognition in pre-dementia has been extensively investigated and is well-established. Cerebrovascular risk can be measured using a Framingham Stroke Risk Profile (FSRP) score, while positron emission tomography (PET) scans with 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile (FDDNP) measure AD neuropathology (i.e., amyloid-β plaques and tau tangles). Here we report results of 75 healthy non-demented subjects (mean age, 63 years) who underwent neuropsychological testing, physical assessments, and FDDNP-PET scans. Controlling for AD family history, education, and APOE4 status in a general linear model, higher FSRP risk and global FDDNP-PET binding were each associated with poorer cognitive functioning. The interaction of FSRP and global FDDNP-PET binding was not significant in the model, indicating that stroke risk and plaque and tangle burden each contributed to worse cognitive performance. Within our healthy volunteers, age, blood pressure, and antihypertensive medication use were vascular risks that contributed significantly to the above findings. These findings suggest that even mild cerebrovascular risk may influence the extent of cognitive dysfunction in pre-dementia, along with amyloid-β and tau burden.

Keywords: Aging, Alzheimer's disease, amyloid-β plaques, FDDNP, Framingham stroke risk profile, mild cognitive impairment, older adults, positron emission tomography, tau tangles

DOI: 10.3233/JAD-121903

Journal: Journal of Alzheimer's Disease, vol. 35, no. 1, pp. 147-157, 2013