Cox proportional hazards regression models of all-cause mortality over 8 years for IIV_RT (left side) and Mean RT (right side).

<p>Cox proportional hazards regression models of all-cause mortality over 8 years for IIV_RT (left side) and Mean RT (right side).</p

Baseline characteristics based on vital status at 8 years.

<p>Baseline characteristics based on vital status at 8 years.</p

Correlations between age, cognitive measures CVD risk score.

<p>Correlations between age, cognitive measures CVD risk score.</p

Microstructural White Matter Changes, Not Hippocampal Atrophy, Detect Early Amnestic Mild Cognitive Impairment

<div><p>Background</p><p>Alzheimer’s disease (AD) is generally considered to be characterized by pathology in gray matter of the brain, but convergent evidence suggests that white matter degradation also plays a vital role in its pathogenesis. The evolution of white matter deterioration and its relationship with gray matter atrophy remains elusive in amnestic mild cognitive impairment (aMCI), a prodromal stage of AD.</p> <p>Methods</p><p>We studied 155 cognitively normal (CN) and 27 ‘late’ aMCI individuals with stable diagnosis over 2 years, and 39 ‘early’ aMCI individuals who had converted from CN to aMCI at 2-year follow up. Diffusion tensor imaging (DTI) tractography was used to reconstruct six white matter tracts three limbic tracts critical for episodic memory function - the fornix, the parahippocampal cingulum, and the uncinate fasciculus; two cortico-cortical association fiber tracts - superior longitudinal fasciculus and inferior longitudinal fasciculus; and one projection fiber tract - corticospinal tract. Microstructural integrity as measured by fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AxD) was assessed for these tracts.</p> <p>Results</p><p>Compared with CN, late aMCI had lower white matter integrity in the fornix, the parahippocampal cingulum, and the uncinate fasciculus, while early aMCI showed white matter damage in the fornix. In addition, fornical measures were correlated with hippocampal atrophy in late aMCI, whereas abnormality of the fornix in early aMCI occurred in the absence of hippocampal atrophy and did not correlate with hippocampal volumes.</p> <p>Conclusions</p><p>Limbic white matter tracts are preferentially affected in the early stages of cognitive dysfunction. Microstructural degradation of the fornix preceding hippocampal atrophy may serve as a novel imaging marker for aMCI at an early stage.</p> </div

Results from the regression model of white matter tracts in early and late aMCI.

<p>Abbreviation: PHC, parahippocampal cingulum; Fx, fornix; UF, uncinate fasciculus; WMHs, white matter hyperintensities; HV, hippocampal volume; FA, fractional anisotropy; MD, mean diffusivity.</p>a<p>the late aMCI group.</p>b<p>the early aMCI group.</p

Group comparisons of FA and MD measures in early aMCI, late aMCI, and controls.

<p>Abbreviation: PHC, parahippocampal cingulum; Fx, fornix; UF, uncinate fasciculus; ILF, inferior longitudinal fasciculus; SLF, superior longitudinal fasciculus; CST, corticospinal tract. aMCI, amnestic mild cognitive impairment; CN, cognitively normal; L, left; R, right.</p>*<p>Significance at p<0.05.</p>**<p>Significance at P<0.01.</p

Probability maps of white matter hyperintensities (WMHs) from early (A) and late aMCI (B).

<p>WMHs were shown in the red-yellow and superimposed on the MNI T1 template. The color bar denotes the percentage of subjects who had WMHs in each image voxel.</p

Demographic and cognitive profiles of the study participants.

<p>CN, cognitively normal; aMCI, amnestic mild cognitive impairment; WMHs, white matter hyperintensities; HV, hippocampal volume.</p>a<p>significant difference between late aMCI and cognitively normal controls.</p>b<p>significant difference between early aMCI and cognitively normal controls.</p>c<p>significant difference between late aMCI and early aMCI.</p>*<p>Significance at p<0.05.</p>**<p>Significance at P<0.001.</p

Apolipoprotein levels in different <i>APOE ε</i>4 carrier groups.

<p>Statistics details: ANCOVA, Post-hoc: Bon Ferroni Covariates: age, sex.</p>*<p>Compared to non<i>APOE</i> ε4 carrier, p<0.05, **Compared to non<i>APOE</i> ε4 carrier, p<0.0005.</p>§<p>Compared to <i>APOE</i> ε4 heterozygote carrier, p<0.0005.</p>#<p>When heterozygous and homozygous carriers are pooled and compared with non <i>APOE</i> ε4 carriers the ApoH values are statistically significant (n = 156, mean = 158.95±42.78, F = 4.23, p = 0.04). Pooling of data from heterozygous and homozygous carriers makes no difference to the statistical outcomes for any of the other apolipoproteins, though the significant p values all become even slightly lower.</p

Grey matter correlates of COWAT.

<p>Brain regions where voxel-based GM volumes are positively correlated with COWAT in 344 participants aged 70-90 years, are superimposed on the sagittal slices of the brain template. The slices are at 5 mm intervals between and including -80 mm and 75 mm. The colour bar represents the t score ranging from 0 to 5.5; and yellow indicates a higher t score than red. </p