The transitional association between beta-amyloid pathology and regional brain atrophy

• Introduction: Alzheimer's disease (AD) is characterized by the accumulation of beta-amyloid (A beta) associated with brain atrophy and cognitive decline. The functional form to model the association between A beta and regional brain atrophy has not been well defined. To determine the relationship between Ab and atrophy, we compared the performance of the usual dichotomization of cerebrospinal fluid (CSF) A beta to identify subjects as A beta+ and A beta- with a trilinear spline model of CSF A beta. Methods: One hundred and eighty-three subjects with mild cognitive impairment and 108 cognitively normal controls with baseline CSFA beta and up to 4 years of longitudinal magnetic resonance imaging data from the Alzheimer's Disease Neuroimaging Initiative were analyzed using mixed-effects regression. Piecewise-linear splines were used to evaluate the nonlinear nature of the association between CSF A beta and regional atrophy and to identify points of acceleration of atrophy with respect to A beta. Several parameterizations of CSFA beta were compared using likelihood ratio tests and the Akaike information criterion. Periods of acceleration of atrophy in which subjects transition from CSF A beta negativity to CSFA beta 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 atrophy 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 A beta positivity. Discussion: The use of piecewise-linear splines provides an improved model of the nonlinear association between CSF A beta and regional atrophy in regions implicated in the progression of AD. The important biological finding of this work is that some brain regions show periods of accelerated volume loss well before the CSFA beta(42) threshold. This implies that signs of brain atrophy develop before the current conventional definition of "preclinical AD". (C) 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Neurologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Neurology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Nyckelord

Alzheimer's disease

ADNI

Trilinear

Beta amyloid

Atrophy

mild cognitive impairment

accelerated cortical atrophy

alzheimers-disease

cerebrospinal-fluid

deposition

mri

biomarkers

patterns

decline

burden

Neurosciences & Neurology

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)