Regional Cortical Thinning and Cerebrospinal Biomarkers Predict Worsening Daily Functioning Across the Alzheimer's Disease Spectrum

Article type: Research Article

Authors: Marshall, Gad A.^{a; b; c; d; *} | Lorius, Natacha^{a; b; c; d} | Locascio, Joseph J.^{c; d} | Hyman, Bradley T.^{c; d} | Rentz, Dorene M.^{a; b; c; d} | Johnson, Keith A.^{a; b; c; e} | Sperling, Reisa A.^{a; b; c; d} | for the Alzheimer's Disease Neuroimaging Initiative¹

Affiliations: [a] Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA | [b] Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA | [c] Massachusetts Alzheimer's Disease Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA | [d] Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA | [e] Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

Correspondence: [*] Correspondence to: Gad A. Marshall, MD, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, 221 Longwood Avenue, BL-104 H, Boston, MA 02115, USA. Tel.: +617 732 8085; Fax: +617 264 5212; E-mail: gamarshall@partners.org.

Note: [1] Data used in the preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (www.loni.ucla.edu\ADNI). The authors are site investigators and research staff for ADNI at Brigham and Women’s Hospital and Massachusetts General Hospital. The other site investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in the analysis or writing of this report. ADNI investigators include (complete listing available at http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf).

Abstract: Background:Impairment in instrumental activities of daily living (IADL) heralds the transition from mild cognitive impairment (MCI) to dementia and is a major source of burden for both the patient and caregiver. Objective:To investigate the relationship between IADL and regional cortical thinning and cerebrospinal fluid (CSF) Alzheimer’s disease (AD) biomarkers cross-sectionally and longitudinally in clinically normal (CN) elderly, MCI, and mild AD dementia subjects. Methods:Two hundred and twenty nine CN, 395 MCI, and 188 AD dementia subjects participating in the Alzheimer’s Disease Neuroimaging Initiative underwent baseline magnetic resonance imaging, baseline lumbar puncture, and clinical assessments, including the Functional Activities Questionnaire used to measure IADL, every 6 to 12 months up to 3 years. General linear regression and mixed effects models were employed. Results:IADL impairment was associated with the interactions between lower inferior temporal cortical thickness and diagnosis (p < 0.0001), greater lateral occipital cortical thickness and diagnosis (p < 0.0001), and greater amyloid-β 1-42 (Aβ1-42) and diagnosis (p = 0.0002) at baseline (driven by AD dementia). Lower baseline supramarginal (p = 0.02) and inferior temporal (p = 0.05) cortical thickness, lower Aβ1-42 (p < 0.0001), and greater total tau (t-tau) (p = 0.02) were associated with greater rate of IADL impairment over time. Conclusions:Temporal atrophy is associated with IADL impairment in mild AD dementia at baseline, while baseline parietal and temporal atrophy, lower CSF Aβ1-42, and greater t-tau predict worsening IADL impairment over time across the AD spectrum. These results emphasize the importance of assessing IADL at the stage of MCI and even at the transition from CN to MCI.

Keywords: Alzheimer's disease, cerebrospinal fluid, instrumental activities of daily living, magnetic resonance imaging, mild cognitive impairment

DOI: 10.3233/JAD-132768

Journal: Journal of Alzheimer's Disease, vol. 41, no. 3, pp. 719-728, 2014