Vascular Burden Score Impacts Cognition Independent of Amyloid PET and MRI Measures of Alzheimer’s Disease and Vascular Brain Injury

Article type: Research Article

Authors: DeCarli, Charles^{a; *} | Villeneuve, Sylvia^b | Maillard, Pauline^a | Harvey, Danielle^c | Singh, Baljeet^a | Carmichael, Owen^d | Fletcher, Evan^a | Olichney, John^a | Farias, Sarah^a | Jagust, William^e | Reed, Bruce^f | Mungas, Dan^a

Affiliations: [a] UC Davis Department of Neurology and Center for Neuroscience, Davis, CA, USA | [b] Douglas Mental Health University Institute, McGill University, Montreal, Canada | [c] Division of Biostatistics, School of Medicine, University of California at Davis, Davis, CA, USA | [d] Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA | [e] Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley CA, USA | [f] Center for Scientific Review, Division of Neuroscience, Development and Aging, NIH, Bethesda, MD, USA

Correspondence: [*] Correspondence to: Charles DeCarli, MD, University of California at Davis, 4860 Y Street, Suite 3700, Sacramento, CA 95817, USA. Tel.: +1 916 734 8413; Fax: +1 916 734 6525; E-mail: [email protected].

Abstract: Background/Objective:To determine the impact of vascular burden on rates of decline in episodic memory and executive function. We hypothesize that greater vascular burden will have an additive negative impact on cognition after accounting for baseline cognitive impairment, positron emission tomography (PET) amyloid burden, and magnetic resonance imaging (MRI) measures. Methods:Individuals were followed an average of 5 years with serial cognitive assessments. Predictor variables include vascular burden score (VBS), quantitative brain MRI assessment, and amyloid imaging. Subjects consisted of 65 individuals, 53% of whom were male, aged 73.2±7.2 years on average with an average of 15.5±3.3 years of educational achievement. Results:Baseline cognitive impairment was significantly associated poorer episodic memory (p < 0.0001), smaller hippocampal volume (p < 0.0001), smaller brain volume (p = 0.0026), and greater global Pittsburg Imaging Compound B (PiB) index (p = 0.0008). Greater amyloid burden was associated with greater decline in episodic memory over time (β= –0.20±0.07, p < 0.005). VBS was significantly associated with the level of executive function performance (β= –0.14±0.05, p < 0.005) and there was a significant negative interaction between VBS, cognitive impairment, and PiB index (β= –0.065±0.03, p = 0.03). Conclusions:Our results find a significant influence of VBS independent of standard MRI measures and cerebral amyloid burden on executive function. In addition, VBS reduced the amount of cerebral amyloid burden needed to result in cognitive impairment. We conclude that the systemic effects of vascular disease as reflected by the VBS independently influence cognitive ability.

Keywords: Alzheimer’s disease, cerebrovascular disorders, cognition, neuroimaging

DOI: 10.3233/JAD-180965

Journal: Journal of Alzheimer's Disease, vol. 68, no. 1, pp. 187-196, 2019