Amyloid-β associated cortical thinning in clinically normal elderly.
Bottom Line: We found that PiB retention in CN subjects was (1) age-related and (2) associated with cortical thickness reductions, particularly in parietal and posterior cingulate regions extending into the precuneus, in a pattern similar to that observed in mild AD.Hippocampal volume reduction was variably related to Aβ deposition.We conclude that Aβ deposition is associated with a pattern of cortical thickness reduction consistent with AD prior to the development of cognitive impairment.
Affiliation: Department of Radiology, Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.Show MeSH
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Mentions: While Aβ-associated thinning was observed in CN subjects as described above: (1) thinning was more anatomically extensive in the AD group; and (2) significantly more thinning per unit DVR was observed in the AD group (eg, 0.4mm/DVR in medial and lateral parietal areas) than in the CN group (see Fig 1). A vertex-level assessment of the difference revealed a significant interaction of the thickness-vs-Aβ coefficient and clinical status factor (CN vs AD) in posterior midline and inferior parietal regions (p < 1 × 10−4; data not shown). We related these observations to candidate time courses along the hypothetical CN–AD trajectory (see Supporting Information), in which the data were evaluated using sigmoid models to relate PCC cortical thickness and PiB retention. Assuming sigmoid time functions for PiB increase and loss of cortical thickness, both with the same rate-of-change achieved at the midpoint of the S-shaped portion of the curves, we calculated how far apart in time these midpoints would have to be in order to achieve the best fit to our data. In fitting this model to the age-adjusted CN and AD group data (Fig 3; r2 = 0.48; p < 1 × 10−4) we calculated this time lag parameter (see Supplemental Material) to be equal to 0.35 times the amyloid saturation time (the time to go from zero to maximum amyloid). For example, if a 10-year amyloid saturation time were hypothesized, the time lag between the rapid phases of PiB increase and cortical thinning would be 3.5 years.
Affiliation: Department of Radiology, Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.