BACKGROUND: Knowledge of Alzheimer's disease (AD) manifestation in the pre-dementia stage facilitates the selection of appropriate measures for early detection and disease progression. OBJECTIVE: To examine the trajectories of cognitive performance, gray matter volume (GMV), and cerebrospinal fluid (CSF) biomarkers, together with the influence of apolipoprotein E (APOE) in subjects with amyloid-β (Aβ) deposits across the pre-clinical to dementia stages of AD. METHODS: 356 subjects were dichotomized into Aβ+ and Aβ- groups based on their CSF Aβ1-42 level. We derived AD-related atrophic regions (AD-ROIs) using the voxel-based morphometry approach. We characterized the trajectories of cognitive scores, GMV at AD-ROIs, and CSF biomarkers from preclinical to disease stages in Aβ+ subjects. The effect of APOE ε4 genotype on these trajectories was examined. RESULTS: Impairments in executive functioning/processing speed (EF/PS) and atrophy at the right supramarginal/inferior parietal gyrus were detected in cognitively normal Aβ+ subjects. Together with the APOE ε4 carrier status, these measures showed potential to identify cognitively normal elderly with abnormal CSF Aβ1-42 level in another independent cohort. Subsequently, impairment in memory, visuospatial, language, and attention as well as atrophy in the temporal lobe, thalamus, and mid-cingulate cortex were detectable in Aβ+ mild cognitive impairment (MCI) subjects. In MCI and dementia Aβ+ subjects, ε4 carriers had more severe atrophy of the medial temporal lobe and memory impairment but higher EF/PS compared to non-carriers. CONCLUSIONS: EF/PS decline and right parietal atrophy might act as non-invasive screening tests for abnormal amyloid deposition in cognitively normal elderly. APOE modulation on subsequent trajectories in cognition and atrophy should be taken into account when analyzing disease progression.
BACKGROUND: Knowledge of Alzheimer's disease (AD) manifestation in the pre-dementia stage facilitates the selection of appropriate measures for early detection and disease progression. OBJECTIVE: To examine the trajectories of cognitive performance, gray matter volume (GMV), and cerebrospinal fluid (CSF) biomarkers, together with the influence of apolipoprotein E (APOE) in subjects with amyloid-β (Aβ) deposits across the pre-clinical to dementia stages of AD. METHODS: 356 subjects were dichotomized into Aβ+ and Aβ- groups based on their CSF Aβ1-42 level. We derived AD-related atrophic regions (AD-ROIs) using the voxel-based morphometry approach. We characterized the trajectories of cognitive scores, GMV at AD-ROIs, and CSF biomarkers from preclinical to disease stages in Aβ+ subjects. The effect of APOE ε4 genotype on these trajectories was examined. RESULTS: Impairments in executive functioning/processing speed (EF/PS) and atrophy at the right supramarginal/inferior parietal gyrus were detected in cognitively normal Aβ+ subjects. Together with the APOE ε4 carrier status, these measures showed potential to identify cognitively normal elderly with abnormal CSF Aβ1-42 level in another independent cohort. Subsequently, impairment in memory, visuospatial, language, and attention as well as atrophy in the temporal lobe, thalamus, and mid-cingulate cortex were detectable in Aβ+ mild cognitive impairment (MCI) subjects. In MCI and dementia Aβ+ subjects, ε4 carriers had more severe atrophy of the medial temporal lobe and memory impairment but higher EF/PS compared to non-carriers. CONCLUSIONS: EF/PS decline and right parietal atrophy might act as non-invasive screening tests for abnormal amyloid deposition in cognitively normal elderly. APOE modulation on subsequent trajectories in cognition and atrophy should be taken into account when analyzing disease progression.
Authors: Li Juan Zheng; Yun Yan Su; Yun Fei Wang; U Joseph Schoepf; Akos Varga-Szemes; Jonathan Pannell; Xue Liang; Gang Zheng; Guang Ming Lu; Gui Fen Yang; Long Jiang Zhang Journal: Mol Neurobiol Date: 2017-05-13 Impact factor: 5.590
Authors: Michael W Weiner; Dallas P Veitch; Paul S Aisen; Laurel A Beckett; Nigel J Cairns; Robert C Green; Danielle Harvey; Clifford R Jack; William Jagust; John C Morris; Ronald C Petersen; Andrew J Saykin; Leslie M Shaw; Arthur W Toga; John Q Trojanowski Journal: Alzheimers Dement Date: 2017-03-22 Impact factor: 21.566
Authors: S Haller; M-L Montandon; C Rodriguez; M Ackermann; F R Herrmann; P Giannakopoulos Journal: AJNR Am J Neuroradiol Date: 2017-05-11 Impact factor: 3.825
Authors: Samantha L Allison; Erin M Jonaitis; Rebecca L Koscik; Bruce P Hermann; Kimberly D Mueller; Robert P Cary; Yue Ma; Howard A Rowley; Cynthia M Carlsson; Sanjay Asthana; Henrik Zetterberg; Kaj Blennow; Barbara B Bendlin; Sterling C Johnson Journal: Neurobiol Aging Date: 2021-02-04 Impact factor: 5.133