Synergistic interaction between amyloid and tau predicts the progression to dementia  Tharick A. Pascoal, Sulantha Mathotaarachchi, Monica Shin, Andrea L. Benedet, Sara Mohades, Seqian Wang, Tom Beaudry, Min Su Kang, Jean-Paul Soucy, Aurelie Labbe, Serge Gauthier, Pedro Rosa-Neto  Alzheimer's & Dementia: The Journal of the Alzheimer's Association  Volume 13, Issue 6, Pages 644-653 (June 2017) DOI: 10.1016/j.jalz.2016.11.005 Copyright © 2016 The Authors Terms and Conditions

Fig. 1 Schematic representation of the image analysis methods. Abbreviations: ADNI, Alzheimer's disease Neuroimaging Initiative; CSF, cerebrospinal fluid; GM, gray matter; MCI, mild cognitive impairment; MRI, magnetic resonance imaging; PET, positron emission tomography; SUVR, standardized uptake value ratio; WM, white matter. Alzheimer's & Dementia: The Journal of the Alzheimer's Association 2017 13, 644-653DOI: (10.1016/j.jalz.2016.11.005) Copyright © 2016 The Authors Terms and Conditions

Fig. 2 The amnestic MCI Aβ+/p-tau+ individuals present the lowest baseline scores and the highest rate of decline in most neuropsychological functions. The values are presented in z-scores anchored in normative data of a cognitively normal population. In the box and whisker plots, the lower and upper boundaries show the 25th and 75th percentiles, respectively, whereas the horizontal line shows the median. The dots represent mild cognitive impairment (MCI) individuals less than the fifth or higher than the 95th percentile. Bonferroni-corrected P values for multiple comparisons indicate the values assessed with analyses of covariance adjusted for age, gender, years of education, APOE ε4 status, and baseline neuropsychological test score for longitudinal analysis. Post hoc multiple comparison analysis provided significant differences between biomarker groups for each neuropsychological test at *P < .05 and **P < .001. (A) At baseline, the Aβ+/p-tau+ group presented the lowest baseline scores in Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS-Cog), logical memory immediate recall (LMI), and 30-minute delayed recall (LM30). The Aβ+/p-tau+ group showed worse performance in the Trail Making Test part B (TMT-B) than the Aβ−/p-tau− and Aβ−/p-tau+ groups. (B) The Aβ+/p-tau+ group presented the highest longitudinal impairment in all neuropsychological tests except TMT-A and MMSE. Aβ+/p-tau+ group showed higher decline in MMSE than Aβ−/p-tau− and Aβ−/p-tau+ groups. Notably, Aβ−/p-tau−, Aβ+/p-tau−, and Aβ−/p-tau+ groups did not differ from each other in any baseline or longitudinal cognitive performance. Abbreviations: Aβ, amyloid β; p-tau, phosphorylated tau. Alzheimer's & Dementia: The Journal of the Alzheimer's Association 2017 13, 644-653DOI: (10.1016/j.jalz.2016.11.005) Copyright © 2016 The Authors Terms and Conditions

Fig. 3 Aβ+/p-tau+ individuals drove the rate of progression to dementia over 2 years in the amnestic MCI population. Abbreviations: Aβ, amyloid β; MCI, mild cognitive impairment; p-tau, phosphorylated tau. Alzheimer's & Dementia: The Journal of the Alzheimer's Association 2017 13, 644-653DOI: (10.1016/j.jalz.2016.11.005) Copyright © 2016 The Authors Terms and Conditions

Fig. 4 Synergistic effect between [18F]florbetapir SUVR and CSF p-tau in temporal and inferior parietal cortices predicts progression to dementia. T-statistical parametric map, after correcting for multiple comparisons (random field theory at P < .001), overlaid in a structural magnetic resonance scan revealed that lateral and basal temporal and inferior parietal cortices were the brain regions where the synergism between [18F]florbetapir standardized uptake value ratio (SUVR) and cerebrospinal fluid (CSF) phosphorylated tau (p-tau) status was associated with an increased likelihood of progression to Alzheimer disease (AD) dementia over 2 years. Alzheimer's & Dementia: The Journal of the Alzheimer's Association 2017 13, 644-653DOI: (10.1016/j.jalz.2016.11.005) Copyright © 2016 The Authors Terms and Conditions