Hippocampal and Clinical Trajectories of Mild Cognitive Impairment with Suspected Non-Alzheimer’s Disease Pathology

Article type: Research Article

Authors: Chung, Jun Ku^{a; b} | Plitman, Eric^{a; b} | Nakajima, Shinichiro^{b; c; d; e} | Caravaggio, Fernando^{b; c} | Iwata, Yusuke^{b; d} | Gerretsen, Philip^{b; c; e} | Kim, Julia^{a; b} | Takeuchi, Hiroyoshi^{c; d} | Shinagawa, Shunichiro^h | Patel, Raihaan^{f; g} | Chakravarty, M. Mallar^{f; g} | Graff-Guerrero, Ariel^{a; b; c; d; e; *} | for the Alzheimer’s Disease Neuroimaging Initiative¹

Affiliations: [a] Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Canada | [b] Multimodal Imaging Group - Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Canada | [c] Department of Psychiatry, University of Toronto, Toronto, Canada | [d] Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo, Japan | [e] Geriatric Mental Health Division, Centre for Addiction and Mental Health, Toronto, Canada | [f] Cerebral Imaging Centre, Douglas Mental Health Institute, McGill University, Montreal, QC, Canada | [g] Department of Psychiatry and Biomedical Engineering, McGill University, Montreal, QC, Canada | [h] The Jikei University School of Medicine, Tokyo, Japan

Correspondence: [*] Correspondence to: Ariel Graff-Guerrero, MD, PhD, Multimodal Imaging Group - Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario M5T 1R8, Canada. Tel.: +1 416 535 8501 /Ext. 4834; E-mail: ariel.graff@camh.ca.

Note: [1] Some 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 ADNI and/or provided data but did not participate in analysis or writing of this report. 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: Suspected non-Alzheimer’s disease pathology (SNAP) characterizes individuals showing neurodegeneration (e.g., hypometabolism) without amyloid-β (Aβ). Findings from previous studies regarding clinical and structural trajectories of SNAP are inconsistent. Using data from the Alzheimer’s Disease Neuroimaging Initiative, patients with amnestic mild cognitive impairment (MCI) were categorized into four groups: amyloid positive with hypometabolism (Aβ+ND+), amyloid only (Aβ+ND–), neither amyloid nor hypometabolism (Aβ–ND–), and SNAP (Aβ–ND+). Aβ+ND+(n = 33), Aβ+ND–(n = 32), and Aβ–ND–(n = 36) were matched to SNAP for age, gender, apolipoprotein E4 (apoE4) genotype, and scores on the Montreal Cognitive Assessment. Elderly controls (n = 40) were also matched to SNAP for age, gender, and apoE4 genotype. Longitudinal changes were compared across groups in terms of hippocampal volume, clinical symptoms, daily functioning, and cognitive functioning over a 2-year period. At baseline, no difference in cognition and functioning was observed between SNAP and Aβ+groups. SNAP showed worse clinical symptoms and impaired functioning at baseline compared to Aβ–ND–and controls. Two years of follow-up showed no differences in hippocampal volume changes between SNAP and any of the comparison groups. SNAP showed worse functional deterioration in comparison to Aβ–ND–and controls. However, Aβ+ND+ showed more severe changes in clinical symptoms in comparison to SNAP. Thus, patients with MCI and SNAP showed 1) more severe functional deterioration compared to Aβ–ND–and controls, 2) no differences with Aβ+ND–, and 3) less cognitive deterioration than Aβ+ND+. Future studies should investigate what causes SNAP, which is different from typical AD pathology and biomarker cascades.

Keywords: Functional decline, hippocampus, mild cognitive impairment, suspected non-Alzheimer’s pathology

DOI: 10.3233/JAD-170201

Journal: Journal of Alzheimer's Disease, vol. 58, no. 3, pp. 747-762, 2017