The transitional association between b-amyloid pathology and regional XXXX .

@entity1010 @entity73 @entity194 @entity195
BACKGROUND: @entity195 ( @entity195 ) is characterized by the accumulation of b-amyloid (Ab) associated with @entity1010 and @entity73 . The functional form to model the association between Ab and regional @entity1010 has not been well defined. To determine the relationship between Ab and @entity194 , we compared the performance of the usual dichotomization of cerebrospinal fluid (CSF) Ab to identify subjects as Ab+ and Ab- with a trilinear spline model of CSF Ab. METHODS: One hundred and eighty-three subjects with mild @entity73 and 108 cognitively normal controls with baseline CSF Ab and up to 4  years of longitudinal magnetic resonance imaging data from the @entity195 Neuroimaging Initiative were analyzed using mixed-effects regression. Piecewise-linear splines were used to evaluate the nonlinear nature of the association between CSF Ab and regional @entity194 and to identify points of acceleration of @entity194 with respect to Ab. Several parameterizations of CSF Ab were compared using likelihood ratio tests and the Akaike information criterion. Periods of acceleration of @entity194 in which subjects transition from CSF Ab negativity to CSF Ab positivity were estimated from the spline models and tested for significance. RESULTS: Spline models resulted in better fits for many temporal and parietal regions compared with the dichotomous models. The trilinear model showed that periods of acceleration of @entity194 varied greatly by region with early changes seen in the insula, amygdala, precuneus, hippocampus, and other temporal regions, occurring before the clinical threshold for CSF Ab positivity. CONCLUSION: The use of piecewise-linear splines provides an improved model of the nonlinear association between CSF Ab and regional @entity194 in regions implicated in the progression of @entity195 . The important biological finding of this work is that some brain regions show periods of accelerated volume loss well before the CSF Ab42 threshold. This implies that signs of @entity1010 develop before the current conventional definition of "preclinical @entity195 ".
