Regional Fluorodeoxyglucose Metabolism and Instrumental Activities of Daily Living across the Alzheimer's Disease Spectrum

Article type: Research Article

Authors: Roy, Kamolika^{a; b; c} | Pepin, Lesley C.^d | Philiossaint, Marlie^d | Lorius, Natacha^{a; b; c} | Becker, J. Alex^d | Locascio, Joseph J.^c | Rentz, Dorene M.^{a; b; c} | Sperling, Reisa A.^{a; b; c} | Johnson, Keith A.^{a; b; c; d} | Marshall, Gad A.^{a; b; c; *} | 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] Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA | [d] 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-104H, Boston, MA 02115, USA. Tel.: +1 617 732 8085; Fax: +1 617 264 5212; E-mail: [email protected].

Note: [1] Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of the ADNI and/or provided data but did not participate in analysis or writing of this article. A complete listing of ADNI investigators can be found 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) begins as individuals with amnestic mild cognitive impairment (MCI) transition to Alzheimer’s disease (AD) dementia. IADL impairment in AD dementia has been associated with inferior parietal, inferior temporal, and superior occipital hypometabolism using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Objective:To investigate the relationship between regional FDG metabolism and IADL in clinically normal (CN) elderly, MCI, and mild AD dementia subjects cross-sectionally and longitudinally. Methods:One hundred and four CN, 203 MCI, and 95 AD dementia subjects from the Alzheimer’s Disease Neuroimaging Initiative underwent clinical assessments every 6 to 12 months for up to three years and baseline FDG PET. The subjective, informant-based Functional Activities Questionnaire was used to assess IADL. General linear models and mixed effects models were used, covarying for demographics, cognition, and behavior. Results:The cross-sectional analysis revealed middle frontal and orbitofrontal hypometabolism were significantly associated with greater IADL impairment. Additionally, the interaction of diagnosis with posterior cingulate and with parahippocampal hypometabolism showed a greater decline in IADL performance as metabolism decreased for the AD dementia relative to the MCI group, and the MCI group relative to the CN group. The longitudinal analysis showed that baseline middle frontal and posterior cingulate hypometabolism were significantly associated with greater rate of increase in IADL impairment over time. Conclusion:These results suggest that regional synaptic dysfunction, including the Alzheimer-typical medial parietal and less typical frontal regions, relates to daily functioning decline at baseline and over time across the early AD spectrum.

Keywords: ¹⁸F-fluorodeoxyglucose positron emission tomography, Alzheimer's disease, instrumental activities of daily living, mild cognitive impairment

DOI: 10.3233/JAD-131796

Journal: Journal of Alzheimer's Disease, vol. 42, no. 1, pp. 291-300, 2014