Revised Framingham Stroke Risk Profile: Association with Cognitive Status and MRI-Derived Volumetric Measures

Article type: Research Article

Authors: Pelcher, Isabelle^a | Puzo, Christian^a | Tripodis, Yorghos^b | Aparicio, Hugo J.^{a; c; d; e} | Steinberg, Eric G.^a | Phelps, Alyssa^a | Martin, Brett^f | Palmisano, Joseph N.^f | Vassey, Elizabeth^a | Lindbergh, Cutter^g | McKee, Ann C.^{a; c; d; h; i} | Stein, Thor D.^{a; d; e; h; i} | Killiany, Ronald J.^{a; j} | Au, Rhoda^{a; c; e; j; k} | Kowall, Neil W.^{a; c; d} | Stern, Robert A.^{a; c; j; l} | Mez, Jesse^{a; c} | Alosco, Michael L.^{a; c; *}

Affiliations: [a] Boston University Alzheimer’s Disease Center and CTE Center, Boston University School of Medicine, Boston, MA, USA | [b] Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA | [c] Department of Neurology, Boston University School of Medicine, Boston, MA, USA | [d] VA Boston Healthcare System, U.S. Department of Veteran Affairs, Boston, MA, USA | [e] Framingham Heart Study, National Heart, Lung, and Blood, Framingham, MA, USA | [f] Biostatistics and Epidemiology Data Analytics Center, Boston University School of Public Health, Boston, MA, USA | [g] Department of Neurology, University of California, San Francisco, San Francisco, CA, USA | [h] Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA, USA | [i] Department of Veterans Affairs Medical Center, Bedford, MA, USA | [j] Department of Anatomy & Neurobiology, Boston University School of Medicine, Boston, MA, USA | [k] Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA | [l] Department of Neurosurgery, Boston University School of Medicine, Boston, MA, USA

Correspondence: [*] Correspondence to: Michael L. Alosco, PhD, 72 E. Concord St, Robinson Building, Suite B7800, Boston MA 02118, USA. Tel.: +1 617 358 6029; E-mail: malosco@bu.edu.

Abstract: Background:The Framingham Stroke Risk Profile (FSRP) was created in 1991 to estimate 10-year risk of stroke. It was revised in 2017 (rFSRP) to reflect the modern data on vascular risk factors and stroke risk. Objective:This study examined the association between the rFSRP and cognitive and brain aging outcomes among participants from the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set (UDS). Methods:Cross-sectional rFSRP was computed at baseline for 19,309 participants (mean age = 72.84, SD = 8.48) from the NACC-UDS [9,697 (50.2%) normal cognition, 4,705 (24.4%) MCI, 4,907 (25.4%) dementia]. Multivariable linear, logistic, or ordinal regressions examined the association between the rFSRP and diagnostic status, neuropsychological test performance, CDR® Sum of Boxes, as well as total brain volume (TBV), hippocampal volume (HCV), and log-transformed white matter hyperintensities (WMH) for an MRI subset (n = 1,196). Models controlled for age, sex, education, racial identity, APOE ɛ4 status, and estimated intracranial volume for MRI models. Results:The mean rFSRP probability was 10.42% (min = 0.50%, max = 95.71%). Higher rFSRP scores corresponded to greater CDR Sum of Boxes (β= 0.02, p = 0.028) and worse performance on: Trail Making Test A (β= 0.05, p < 0.001) and B (β= 0.057, p < 0.001), and Digit Symbol (β= –0.058, p < 0.001). Higher rFSRP scores were associated with increased odds for a greater volume of log-transformed WMH (OR = 1.02 per quartile, p = 0.015). No associations were observed for diagnosis, episodic memory or language test scores, HCV, or TBV. Conclusion:These results support the rFSRP as a useful metric to facilitate clinical research on the associations between cerebrovascular disease and cognitive and brain aging.

Keywords: Alzheimer’s disease, cardiovascular disease, cerebrovascular disease, framingham stroke risk profile, stroke risk

DOI: 10.3233/JAD-200803

Journal: Journal of Alzheimer's Disease, vol. 78, no. 4, pp. 1393-1408, 2020