Resting-State Cardiac Workload is Related to Both Increased Neocortical Aggregation of Amyloid-β and Relative Impairments in Spatial Working Memory in Pre-Clinical Alzheimer’s Disease

Article type: Research Article

Authors: Santos, Cláudia Yang^a | Lim, Yen Ying^{b; c} | Wu, Wen-Chih^d | Machan, Jason Timothy^e | Polynice, Shahena^f | Schindler, Rachel^g | Maruff, Paul^{c; h} | Snyder, Peter Jeffrey^{a; b; *}

Affiliations: [a] Interdisciplinary Neuroscience Program, University of Rhode Island, Kingston, RI, USA | [b] Department of Neurology, Alpert Medical School of Brown University, Providence, RI, USA | [c] The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Victoria, Australia | [d] Division of Cardiology, Department of Medicine, Alpert Medical School of Brown University, Providence, RI, USA | [e] Lifespan Biostatistics Core, Lifespan Hospital System, Providence, RI, USA | [f] Department of Neuroscience, Brown University, Providence, RI, USA | [g] Pfizer Inc., New York, NY, USA | [h] Cogstate Ltd., Melbourne, Victoria, Australia

Correspondence: [*] Correspondence to: Peter J. Snyder, PhD, Suite 1.001, 1 Hoppin Street, Providence, RI 02903, USA. Tel.: +1 401 444 4117; Fax: +1 401 444 4100; E-mail: psnyder@lifespan.org.

Abstract: We sought to determine whether there is any association between a cardiac workload marker, rate pressure product (RPP), working memory, and cortical amyloid-β (Aβ) burden in 63 cognitively normal midlife adults (Mage = 62.8 years; range = 55 to 75 years) at risk for Alzheimer’s disease (AD). The results show a small-to-moderate relationship between increasing cardiac workload (at rest) and neocortical amyloidosis in individuals at the preclinical stage of AD. Moreover, increasing RPP was linearly related to increasing relative impairments on a spatial working memory task (R2 = 0.30), but only for those individuals with neuroimaging evidence suggestive of preclinical AD. These results support a relationship between the aggregation of Aβ protein plaques in the neocortex, increased cognitive impairment, and more inefficient myocardial oxygen use in the absence of significant metabolic demands.

Keywords: Alzheimer’s disease, amyloid beta-peptides, blood pressure, cardiovascular diseases, cerebrovascular disorders, comorbidity, memory, mild cognitive impairment, risk factors, short-term, workload

DOI: 10.3233/JAD-150576

Journal: Journal of Alzheimer's Disease, vol. 50, no. 1, pp. 127-131, 2016