Alzheimer’s Disease Biomarkers and Future Decline in Cognitive Normal Older Adults

Article type: Research Article

Authors: Dumurgier, Julien^{a; b} | Hanseeuw, Bernard J.^a | Hatling, Frances B.^a | Judge, Kelly A.^{c; d} | Schultz, Aaron P.^d | Chhatwal, Jasmeer P.^a | Blacker, Deborah^e | Sperling, Reisa A.^d | Johnson, Keith A.^c | Hyman, Bradley T.^a | Gómez-Isla, Teresa^{a; *}

Affiliations: [a] Department of Neurology, Massachusetts Alzheimer Disease Research Center, Massachusetts General Hospital, Boston, MA, USA | [b] INSERM U942 and Memory Clinical Center, Saint Louis - Lariboisiere - Fernand Widal Hospital, AP-HP, University Paris VII Denis Diderot, Paris, France | [c] Department of Radiology, Massachusetts Alzheimer Disease Research Center, Massachusetts General Hospital, Boston, MA, USA | [d] Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women’s Hospital, Boston, MA, USA | [e] Department of Psychiatry, Massachusetts Alzheimer Disease Research Center, Massachusetts General Hospital, Boston, MA, USA

Correspondence: [*] Correspondence to: Dr. Teresa Gómez-Isla, MD, PhD, MassGeneral Institute for Neurodegenerative Disease, Building 114, 16th Street –2008, Charlestown, MA 02129-4404, USA. Tel.: +1 617 643 5562; Fax: +1 617 724 1480; E-mail: tgomezisla@partners.org.

Abstract: Background:Identifying older adults at risk of cognitive decline represents a challenge as Alzheimer’s disease (AD) modifying therapies move toward preclinical stages. Objective:To investigate the relationship between AD biomarkers and subsequent change in cognition in a cohort of cognitively intact older adults. Methods:84 cognitively normal subjects (mean age 72.0 years, 59% women) were recruited through the Massachusetts Alzheimer’s Disease Research Center and the Harvard Aging Brain Study and followed over 3 years. Measurements of amyloid-β 1–42 (Aβ42), total Tau (t-Tau), and Tau phosphorylated at threonine 181 (p-Tau181) in the cerebrospinal fluid (CSF) at study entry were available in all cases. Baseline brain MRI, FDG-PET, and PiB-PET data were available in the majority of participants. Relationship between baseline AD biomarkers and longitudinal change in cognition was assessed using Cox proportional hazard regression and linear mixed models. Results:14% participants increased their global Clinical Dementia Rating (CDR) score from 0 to 0.5 during follow-up. A CDR score increase was associated with higher baseline CSF t-Tau and p-Tau181, higher global cortical PiB retention, and lower hippocampal volume. The combination of high CSF t-Tau and low Aβ42 or low hippocampal volume was more strongly related to cognitive outcome than each single biomarker. Higher CSF t-Tau was the only biomarker associated with subsequent decline in MMSE score. Conclusions:Baseline CSF t-Tau and p-Tau181, in vivo amyloid load, and hippocampal volume were all independently associated with future decline in cognition. The discriminatory ability of these biomarkers to predict risk of cognitive decline, however, was only modest.

Keywords: Biomarkers, cognitive decline, cerebrospinal fluid, epidemiology, neuroimaging

DOI: 10.3233/JAD-170511

Journal: Journal of Alzheimer's Disease, vol. 60, no. 4, pp. 1451-1459, 2017