Cerebrospinal Fluid Biomarkers and Reserve Variables as Predictors of Future “Non-Cognitive” Outcomes of Alzheimer’s Disease

Article type: Research Article

Authors: Ingber, Adam P.^a | Hassenstab, Jason^{b; e} | Fagan, Anne M.^{b; c; d} | Benzinger, Tammie L.S.^{b; f; k} | Grant, Elizabeth A.^{b; l} | Holtzman, David M.^{b; c; d; h} | Morris, John C.^{b; d; g; i; j} | Roe, Catherine M.^{b; d; *}

Affiliations: [a] Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY, USA | [b] Knight Alzheimer’s Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA | [c] Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USA | [d] Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA | [e] Department of Psychological and Brain Sciences, Washington University School of Medicine, St. Louis, MO, USA | [f] Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA | [g] Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA | [h] Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO, USA | [i] Department of Physical Therapy, Washington University School of Medicine, St. Louis, MO, USA | [j] Department of Occupational Therapy, Washington University School of Medicine, St. Louis, MO, USA | [k] Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO, USA

Correspondence: [*] Correspondence to: Catherine M. Roe, PhD, 660 S. Euclid Avenue, Campus Box 8111, St. Louis, MO 63110, USA. Tel.: +1 314 286 2435; E-mail: [email protected].

Note: [1] Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA.

Abstract: Background: The influence of reserve variables and Alzheimer’s disease (AD) biomarkers on cognitive test performance has been fairly well-characterized. However, less is known about the influence of these factors on “non-cognitive” outcomes, including functional abilities and mood. Objective: We examined whether cognitive and brain reserve variables mediate how AD biomarker levels in cognitively normal persons predict future changes in function, mood, and neuropsychiatric behavior. Methods: Non-cognitive outcomes were examined in 328 individuals 50 years and older enrolled in ongoing studies of aging and dementia at the Knight Alzheimer Disease Research Center (ADRC). All participants were cognitively normal at baseline (Clinical Dementia Rating [CDR] 0), completed cerebrospinal fluid (CSF) and structural neuroimaging studies within one year of baseline, and were followed for an average of 4.6 annual visits. Linear mixed effects models explored how cognitive reserve and brain reserve variables mediate the relationships between AD biomarker levels and changes in function, mood, and neuropsychiatric behavior in cognitively normal participants. Results: Education levels did not have a significant effect on predicting non-cognitive decline. However, participants with smaller brain volumes exhibited the worst outcomes on measures of mood, functional abilities, and behavioral disturbance. This effect was most pronounced in individuals who also had abnormal CSF biomarkers. Conclusions: The findings suggest that brain reserve plays a stronger, or earlier, role than cognitive reserve in protecting against non-cognitive impairment in AD.

Keywords: Alzheimer’s disease, biomarkers, cognitive reserve, dementia

DOI: 10.3233/JAD-150478

Journal: Journal of Alzheimer's Disease, vol. 52, no. 3, pp. 1055-1064, 2016