Sex and age differences in atrophic rates: An ADNI study with n=1368 MRI scans

Laboratory of Neuro Imaging, Department of Neurology, UCLA School of Medicine, Los Angeles, CA 90095-1769, USA.
Neurobiology of aging (Impact Factor: 5.01). 08/2010; 31(8):1463-80. DOI: 10.1016/j.neurobiolaging.2010.04.033
Source: PubMed


We set out to determine factors that influence the rate of brain atrophy in 1-year longitudinal magnetic resonance imaging (MRI) data. With tensor-based morphometry (TBM), we mapped the 3-dimensional profile of progressive atrophy in 144 subjects with probable Alzheimer's disease (AD) (age: 76.5 +/- 7.4 years), 338 with amnestic mild cognitive impairment (MCI; 76.0 +/- 7.2), and 202 healthy controls (77.0 +/- 5.1), scanned twice, 1 year apart. Statistical maps revealed significant age and sex differences in atrophic rates. Brain atrophic rates were about 1%-1.5% faster in women than men. Atrophy was faster in younger than older subjects, most prominently in mild cognitive impairment, with a 1% increase in the rates of atrophy and 2% in ventricular expansion, for every 10-year decrease in age. TBM-derived atrophic rates correlated with reduced beta-amyloid and elevated tau levels (n = 363) at baseline, baseline and progressive deterioration in clinical measures, and increasing numbers of risk alleles for the ApoE4 gene. TBM is a sensitive, high-throughput biomarker for tracking disease progression in large imaging studies; sub-analyses focusing on women or younger subjects gave improved sample size requirements for clinical trials.

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Available from: Clifford R Jack
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    • "Brain tissue volumes, whether global or regional (notably hippocampus), are endophenotypes easily derivable from magnetic resonance imaging (MRI) that have been shown to be sensitive to aging and good predictors of dementia and cognitive decline in elderly individuals (Miller et al., 1980; Braak and Braak, 1998; Good et al., 2001; Den Heijer et al., 2002; Fjell and Walhovd, 2010). Using such brain phenotypes, many studies have investigated factors of morphological brain aging such as sex (Coffey et al., 1998; Resnick et al., 2003; Lemaître et al., 2005b; Abe et al., 2010; Hua et al., 2010; O'Dwyer et al., 2012; Ryan et al., 2014), genetics (Lemaître et al., 2005a; Crivello et al., 2010; Boada et al., 2012; Stein et al., 2012; Ryan et al., 2014) or lifestyle (Coffey et al., 1999; Sabia et al., 2014; Shpanskaya et al., 2014; Umene-Nakano et al., 2014). Others have demonstrated the effect on brain atrophy of cardiovascular risk factors such as obesity (Driscoll et al., 2012; Xu et al., 2013; Debette et al., 2014, 2011; Franke et al., 2014), hypertension (Debette et al., 2011; Maillard et al., 2012; Peters, 2012; Beauchet et al., 2013; Franke et al., 2014), hypercholesterolemia (Tendolkar et al., 2012; Van Velsen et al., 2013; Franke et al., 2014), diabetes (Biessels et al., 2005; Debette et al., 2011; Cherbuin et al., 2012; Franke et al., 2014) and tobacco smoking (Enzinger et al., 2005; Ikram et al., 2008; Debette et al., 2011; Durazzo et al., 2012; Hoogendam et al., 2012). "
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    ABSTRACT: We investigated the cross-sectional and longitudinal effects of tobacco smoking on brain atrophy in a large cohort of healthy elderly participants (65–80 years). MRI was used for measuring whole brain (WB), gray matter (GM), white matter (WM), and hippocampus (HIP) volumes at study entry time (baseline, N = 1451), and the annualized rates of variation of these volumes using a 4-year follow-up MRI in a subpart of the cohort (N = 1111). Effects of smoking status (never, former, or current smoker) at study entry and of lifetime tobacco consumption on these brain phenotypes were studied using sex-stratified AN(C)OVAs, including other health parameters as covariates. At baseline, male current smokers had lower GM, while female current smokers had lower WM. In addition, female former smokers exhibited reduced baseline HIP, the reduction being correlated with lifetime tobacco consumption. Longitudinal analyses demonstrated that current smokers, whether men or women, had larger annualized rates of HIP atrophy, as compared to either non or former smokers, independent of their lifetime consumption of tobacco. There was no effect of smoking on the annualized rate of WM loss. In all cases, measured sizes of these tobacco-smoking effects were of the same order of magnitude than those of age, and larger than effect sizes of any other covariate. These results demonstrate that tobacco smoking is a major factor of brain aging, with sex- and tissue specific effects, notably on the HIP annualized rate of atrophy after the age of 65.
    Full-text · Article · Nov 2014 · Frontiers in Aging Neuroscience
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    • "They concluded that a reduction in posterior cingulate glucose metabolism precedes a reduction in hippocampal volume or metabolism in cognitively normal persons at increased genetic risk for AD. It is thought that there are both Aβ-dependent and Aβindependent effects of APOE4 acting in concert to exacerbate the pathological and clinical phenotypes of AD (see Huang 2010; Liu et al. 2013 for reviews; see Fig. 2). Multimodal studies confirm this view, showing that the effects of APOE4 on brain structure and function is at least partly independent from its effect on Aβ deposition. "
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    ABSTRACT: The ε4 allele of the apolipoprotein E (APOE4) is associated with an increased risk of developing Alzheimer's disease (AD). Hence, several studies have compared the brain characteristics of APOE4 carriers versus non-carriers in presymptomatic stages to determine early AD biomarkers. The present review provides an overview on APOE4-related brain changes in cognitively normal individuals, focusing on the main neuroimaging biomarkers for AD, i.e. cortical beta-amyloid (Aβ) deposition, hypometabolism and atrophy. The most consistent findings are observed with Aβ deposition as most studies report significantly higher cortical Aβ load in APOE4 carriers compared with non-carriers. Fluorodeoxyglucose-positron emission tomography studies are rare and tend to show hypometabolism in brain regions typically impaired in AD. Structural magnetic resonance imaging findings are the most numerous and also the most discrepant, showing atrophy in AD-sensitive regions in some studies but contradicting results as well. Altogether, this suggests a graded effect of APOE4, with a predominant effect on Aβ over brain structure and metabolism. Multimodal studies confirm this view and also suggest that APOE4 effects on brain structure and function are mediated by both Aβ-dependent and Aβ-independent pathological processes. Neuroimaging studies on asymptomatic APOE4 carriers offer relevant information to the understanding of early pathological mechanisms of the disease, although caution is needed as to whether APOE4 effects reflect AD pathological processes, and are representative of these effects in non-carriers.
    Full-text · Article · Aug 2014 · Neuropsychology Review
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    • "Second, using the LONI pipeline processing environment (Rex et al., 2003; Dinov et al., 2009), the linearly aligned brains were registered via an intensity-based approach using a high-dimensional, elastic, non-linear algorithm (Leow et al., 2005a,b), an approach considered to be more accurate than feature-based methods (Chen et al., 2003). The registration algorithm employed a mutual information (MI) cost function and the symmetrized Kullback-Leibler (KL) distance as a regularizing term (Yanovsky et al., 2008, 2009; Hua et al., 2009, 2010a,b), a procedure that has been shown to be equivalent to considering both the forward and backward mapping in image registration (Leow et al., 2007). The KL-MI procedure is incorporated into a multi-scale bundle that uses multiple grid sizes to compute both regional and local deformations. "

    Full-text · Dataset · Oct 2013
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