Comparing Brain Amyloid Deposition, Glucose Metabolism, and Atrophy in Mild Cognitive Impairment with and without a Family History of Dementia

Article type: Research Article

Authors: Mosconi, Lisa^{a; b; c; *} | Andrews, Randolph D.^{a; b} | Matthews, Dawn C.^{a; b; *} | For the Alzheimer's Disease Neuroimaging Initiative (ADNI)

Affiliations: [a] Abiant Inc, Grayslake, IL, USA | [b] ADM Diagnostics, Chicago, IL, USA | [c] New York University School of Medicine, New York, NY, USA

Correspondence: [*] Correspondence to: Dr. Lisa Mosconi, New York University School of Medicine, 145 East 32nd Street, 5th floor, New York, NY 10016, USA. Tel.: +1 212 263 3255; Fax: +1 212 263 3270; E-mail: [email protected]; Dawn C. Matthews, ADM Diagnostics LLC, 10 West 35th St., Suite 10F4-2, Chicago, IL 60016. Tel.: +847 707 0370, Fax: +847 223 5018, E-mail: [email protected].

Abstract: This study compares the degree of brain amyloid-β (Aβ) deposition, glucose metabolism, and grey matter volume (GMV) reductions in mild cognitive impairment (MCI) patients overall and as a function of their parental history of dementia. Ten MCI with maternal history (MH), 8 with paternal history (PH), and 24 with negative family history (NH) received 11C-PiB and 18F-FDG PET and T1-MRI as part of the Alzheimer's Disease Neuroimaging Initiative. Statistical parametric mapping, voxel based morphometry, and Z-score mapping were used to compare biomarkers across MCI groups, and relative to 12 normal controls. MCI had higher PiB retention, hypometabolism, and GMV reductions in Alzheimer-vulnerable regions compared to controls. Biomarker abnormalities were more pronounced in MCI with MH than those with PH and NH. After partial volume correction of PET, Aβ load exceeded hypometabolism and atrophy with regard to the number of regions affected and magnitude of impairment in those regions. Hypometabolism exceeded atrophy in all MCI groups and exceeded Aβ load in medial temporal and posterior cingulate regions of MCI MH. While all three biomarkers were abnormal in MCI compared to controls, Aβ deposition was the most prominent abnormality, with MCI MH having the greatest degree of co-occurring hypometabolism.

Keywords: Alzheimer's disease, amyloid, family history, ¹⁸F-fluorodeoxyglucose (FDG), glucose metabolism, magnetic resonance imaging, mild cognitive impairment, positron emission tomography (PET) imaging, Pittsburgh Compound B

DOI: 10.3233/JAD-121867

Journal: Journal of Alzheimer's Disease, vol. 35, no. 3, pp. 509-524, 2013