Additional file 2: of Validation of the Erlangen Test of Activities of Daily Living in Persons with Mild Dementia or Mild Cognitive Impairment (ETAM)

ETAM evaluation and documentation form. (DOC 82 kb

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

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

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

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

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

Grey matter correlates of CF.

<p>Brain regions where voxel-based GM volumes are positively correlated with CF in 344 participants aged 70-90 years, superimposed on the sagittal slices of the brain template. The slices are at 4 mm intervals between and including -48 mm and -20 mm. The colour bar represents the t score ranging from 0 to 5.5; and yellow indicates a higher t score than red.</p

Grey matter correlates of BNT.

<p>Brain regions where voxel-based GM volumes are positively correlated with BNT in 344 participants aged 70-90 years, superimposed on the sagittal slices of the brain template. The slices are at 4 mm intervals between and including -48 mm and 44 mm. The colour bar represents the t score ranging from 0 to 5.5; and yellow indicates a higher t score than red.</p

Risk factors for mild cognitive impairment, dementia and mortality: The Sydney Memory and Ageing Study

Background The nature and commonality of late-life risk factors for mild cognitive impairment (MCI), dementia, and mortality remain unclear. Our aim was to investigate potential risk factors, simultaneously in a single cohort including many individuals initially with normal cognition and followed for 6 years. Methods We classified 873 community-dwelling individuals (70–90 years old and without dementia at baseline) from the Sydney Memory and Ageing Study as cognitively normal (CN), having MCI or dementia, or deceased 6 years after baseline. Associations with baseline demographic, lifestyle, health, and medical factors were investigated, including apolipoprotein (APOE) genotype, MCI at baseline, and reversion from MCI to CN within 2 years of baseline. Results Eighty-three (9.5%) participants developed dementia and 114 (13%) died within 6 years; nearly 33% had MCI at baseline, of whom 28% reverted to CN within 2 years. A core set of baseline factors was associated with MCI and dementia at 6 years, including older age (per year: odds ratios and 95% confidence intervals = 1.08, 1.01–1.14 for MCI; 1.19, 1.09–1.31 for dementia), MCI at baseline (5.75, 3.49–9.49; 8.23, 3.93–17.22), poorer smelling ability (per extra test point: 0.89, 0.79–1.02; 0.80, 0.68–0.94), slower walking speed (per second: 1.12, 1.00–1.25; 1.21, 1.05–1.39), and being an APOE ε4 carrier (1.84, 1.07–3.14; 3.63, 1.68–7.82). All except APOE genotype were also associated with mortality (age: 1.11, 1.03–1.20; MCI: 3.87, 1.97–7.59; smelling ability: 0.83, 0.70–0.97; walking speed: 1.18, 1.03–1.34). Compared with stable CN participants, individuals reverting from MCI to CN after 2 years were at greater risk of future MCI (3.06, 1.63–5.72). Those who reverted exhibited some different associations between baseline risk factors and 6-year outcomes than individuals with stable MCI. Conclusion A core group of late-life risk factors indicative of physical and mental frailty are associated with each of dementia, MCI, and mortality after 6 years. Tests for slower walking speed and poorer smelling ability may help screen for cognitive decline. Individuals with normal cognition are at greater risk of future cognitive impairment if they have a history of MCI