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Amyloid-β associated cortical thinning in clinically normal elderly.

Becker JA, Hedden T, Carmasin J, Maye J, Rentz DM, Putcha D, Fischl B, Greve DN, Marshall GA, Salloway S, Marks D, Buckner RL, Sperling RA, Johnson KA - Ann. Neurol. (2011)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.

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Related in: MedlinePlus

Modeling of PCC thickness as a function of PiB retention in CN and AD groups. Least squares fit (solid curve) of thickness-PiB functional relationship based on sigmoid time courses, with the maximum rate of thickness decline later in time than the maximum rate of PiB increase; compare solid (thickness) and dotted (PiB) sigmoids (inset graph). Dashed curves correspond to shorter time lags, long-dashed curves correspond to one-half the best-fit time lag, and short-dashed curves correspond to no lag. The inset shows the underlying sigmoid time courses for PiB (dotted) and thickness at the 2 time lags. As the time lag between thickness and PiB increases, the curvature of the thickness-PiB curve increases. Binding potential (which is equal to DVR − 1) was used as the PiB measure in the modeling since we assumed that PiB BP asymptotes to zero prior to disease onset.
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fig03: Modeling of PCC thickness as a function of PiB retention in CN and AD groups. Least squares fit (solid curve) of thickness-PiB functional relationship based on sigmoid time courses, with the maximum rate of thickness decline later in time than the maximum rate of PiB increase; compare solid (thickness) and dotted (PiB) sigmoids (inset graph). Dashed curves correspond to shorter time lags, long-dashed curves correspond to one-half the best-fit time lag, and short-dashed curves correspond to no lag. The inset shows the underlying sigmoid time courses for PiB (dotted) and thickness at the 2 time lags. As the time lag between thickness and PiB increases, the curvature of the thickness-PiB curve increases. Binding potential (which is equal to DVR − 1) was used as the PiB measure in the modeling since we assumed that PiB BP asymptotes to zero prior to disease onset.

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.


Amyloid-β associated cortical thinning in clinically normal elderly.

Becker JA, Hedden T, Carmasin J, Maye J, Rentz DM, Putcha D, Fischl B, Greve DN, Marshall GA, Salloway S, Marks D, Buckner RL, Sperling RA, Johnson KA - Ann. Neurol. (2011)

Modeling of PCC thickness as a function of PiB retention in CN and AD groups. Least squares fit (solid curve) of thickness-PiB functional relationship based on sigmoid time courses, with the maximum rate of thickness decline later in time than the maximum rate of PiB increase; compare solid (thickness) and dotted (PiB) sigmoids (inset graph). Dashed curves correspond to shorter time lags, long-dashed curves correspond to one-half the best-fit time lag, and short-dashed curves correspond to no lag. The inset shows the underlying sigmoid time courses for PiB (dotted) and thickness at the 2 time lags. As the time lag between thickness and PiB increases, the curvature of the thickness-PiB curve increases. Binding potential (which is equal to DVR − 1) was used as the PiB measure in the modeling since we assumed that PiB BP asymptotes to zero prior to disease onset.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3117980&req=5

fig03: Modeling of PCC thickness as a function of PiB retention in CN and AD groups. Least squares fit (solid curve) of thickness-PiB functional relationship based on sigmoid time courses, with the maximum rate of thickness decline later in time than the maximum rate of PiB increase; compare solid (thickness) and dotted (PiB) sigmoids (inset graph). Dashed curves correspond to shorter time lags, long-dashed curves correspond to one-half the best-fit time lag, and short-dashed curves correspond to no lag. The inset shows the underlying sigmoid time courses for PiB (dotted) and thickness at the 2 time lags. As the time lag between thickness and PiB increases, the curvature of the thickness-PiB curve increases. Binding potential (which is equal to DVR − 1) was used as the PiB measure in the modeling since we assumed that PiB BP asymptotes to zero prior to disease onset.
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.

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.

Show MeSH
Related in: MedlinePlus