Biomarkers of Vascular Risk, Systemic Inflammation, and Microvascular Pathology and Neuropsychiatric Symptoms in Alzheimer's Disease

Article type: Research Article

Authors: Hall, James R.^{a; b; *} | Wiechmann, April R.^{a; b} | Johnson, Leigh A.^{a; c} | Edwards, Melissa^d | Barber, Robert C.^{a; e} | Winter, A. Scott^a | Singh, Meharvan^{a; e} | O'Bryant, Sid E.^{a; c} | for the Texas Alzheimer's Research and Care Consortium

Affiliations: [a] Institute of Aging and Alzheimer's Disease Research, University of North Texas Health Science Center, Fort Worth, TX, USA | [b] Department of Psychiatry and Behavioral Health, University of North Texas Health Science Center, Fort Worth, TX, USA | [c] Department of Internal Medicine, University of North Texas Health Science Center, Fort Worth, TX, USA | [d] Department of Psychology, University of North Texas, Denton, TX, USA | [e] Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, USA

Correspondence: [*] Correspondence to: James R. Hall, PhD, Department of Psychiatry, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX 76107, USA. Tel.: +1 817 735 2326; Fax: +1 817 735 0615; E-mail: james.hall@unthsc.edu.

Abstract: Numerous serum and plasma based biomarkers of systemic inflammation have been linked to both neuropsychiatric disorders and Alzheimer's disease (AD). The present study investigated the relationship of clinical biomarkers of cardiovascular risk (cholesterol, triglycerides, and homocysteine) and a panel of markers of systemic inflammation (CRP, TNF-α, IL1-ra, IL-7, IL-10, IL-15, IL-18) and microvascular pathology (ICAM-1, VCAM-1) to neuropsychiatric symptoms in a sample with mild AD. Biomarker data was analyzed on a sample of 194 diagnosed with mild to moderate probable AD. The sample was composed of 127 females and 67 males. The presence of neuropsychiatric symptoms was gathered from interview with caretakers/family members using the Neuropsychiatric Inventory. For the total sample, IL-15, VCAM (vascular adhesion molecule), and triglycerides were significantly and negatively related to number of neuropsychiatric symptoms, and total cholesterol and homocysteine were positively related and as a group accounted for 16.1% of the variance. When stratified by gender, different patterns of significant biomarkers were found with relationships more robust for males for both total symptoms and symptom clusters. A combination of biomarkers of systemic inflammation, microvascular pathology, and clinical biomarkers of cardiovascular risk can account for a significant portion of the variance in the occurrence of neuropsychiatric symptoms in AD supporting a vascular and inflammatory component of psychiatric disorders found in AD. Gender differences suggest distinct impact of specific risks with total cholesterol, a measure of cardiovascular risk, being the strongest marker for males and IL-15, a marker of inflammation, being the strongest for females.

Keywords: Alzheimer's disease, biomarkers, gender, neuropsychiatric symptoms

DOI: 10.3233/JAD-122359

Journal: Journal of Alzheimer's Disease, vol. 35, no. 2, pp. 363-371, 2013