Estimated sample sizes with respect to age, per arm, to detect a 25% reduction in rate of change in MCI participants relative to age-matched change in HCs, at the p<0.05 level with 80% power assuming a 24 month trial with scans every six months.

<p>Sample sizes are estimated using a linear mixed effects model with fixed intercepts (no relative change at baseline) and random slopes and linear dependence on age applied to all data available up through 36 months. Dashed lines show the 95% confidence intervals.</p

Number of participants in each age group, for each class of measure analyzed, separately for longitudinal and baseline analyses.

<p>Clin  =  clinical measure: ADAS-Cog, CDR-SB, MMSE. CSF data were obtained at baseline for approximately half the study sample. Note that in each age bracket, age extends up to, but does not include, the highest age indicated (age groups do not overlap).</p

Mixed effects model fit for annual rates of clinical decline, allowing for linear change with age.

<p>Data points plotted, with 95% confidence intervals, are independent estimates of rates of change for successive 5-year intervals for a mixed effects model fit without an age-dependent term. Slopes and p-values of the linear fits for each diagnostic group are shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042325#pone-0042325-t003" target="_blank">Table 3</a>. Legend: red  = AD; blue  =  MCI; green  = HC.</p

Slopes and p-values for annual atrophy rates as a function of age shown in Figure 1.

<p>Bold underlined entries highlight slope values that significantly differ from zero. The three right hand columns give p-values for differences in slopes between cohorts. Two-sample t-test for independent samples with unequal variances (Satterthwaite’s method <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042325#pone.0042325-Rosner1" target="_blank">[37]</a>) was used to calculate p-values for pair-wise comparisons (last three columns).</p

MCI participant demographic and baseline data.

<p>See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0047739#pone-0047739-t001" target="_blank">Tables 1</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0047739#pone-0047739-t003" target="_blank">3</a> for key. MCI: mild cognitive impairment.</p>‡<p>Two MCI participants were not classified for MRI^+/− due to technical issues; both had cognitive data and were Aβ⁺; 1 was ptau⁻, the other ptau⁺.</p>*<p>166 (53.4%) of the 311 MCI subjects had CSF Aβ data. All have ptau; includes the two in ^‡.</p>$<p>167 (53.7%) of the 311 MCI subjects had CSF ptau data. One of these does not have Aβ data, but has cognitive data and is ptau⁺MRI⁺. The 167 include the two in ^‡.</p><p>∧Only 75 MRI⁻ had CSF Aβ and ptau data; only 89 MRI⁺ had CSF Aβ data; 90 MRI⁺ had ptau data.</p

Annual atrophy rates for MCI participants, with 95% confidence intervals, for AD-relevant cortical and subcortical ROIs, grouped with respect to baseline Aβ, ptau, and volumetric MRI status (top row).

<p>In the bottom row, all participants are Aβ-positive. N is the number of participants. Numerical values are in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0047739#pone.0047739.s001" target="_blank">File S1</a>, Tables S1A–F.</p

Slopes and p-values for annual rates of clinical decline as a function of age shown in Figure 2.

<p>Bold underlined entries highlight slope values that significantly differ from zero. The three right hand columns give p-values for differences in slopes between cohorts. P-values for the last three columns were calculated as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042325#pone-0042325-t002" target="_blank">Table 2</a>.</p

Estimated sample sizes with respect to age, per arm, to detect a 25% reduction in rate of change in MCI participants relative to age-matched change in HCs, at the p<0.05 level with 80% power assuming a 24 month trial with scans every six months.

<p>Sample sizes are estimated using a linear mixed effects model with fixed intercepts (no relative change at baseline) and random slopes and linear dependence on age applied to all data available up through 36 months. Dashed lines show the 95% confidence intervals.</p

P-values for significance of difference in sample size estimates (Table 3, Figure 3) from pairs of measures (rows) using particular enrichment specifications (columns).

<p>Values significant at the 5% level are underlined and bold. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0047739#pone-0047739-t003" target="_blank">Tables 3</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0047739#pone-0047739-t004" target="_blank">4</a> legends for key.</p><p>Calculation of p-values described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0047739#pone.0047739-Holland1" target="_blank">[50]</a>.</p

Mixed effects model fit for annual atrophy rates, allowing for linear change with age.

<p>Data points plotted, with 95% confidence intervals, are independent estimates of the atrophy rates for successive 5-year intervals for a mixed effects model fit without an age-dependent term. Slopes and p-values of the linear fits of atrophy rates with age for each cohort are shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042325#pone-0042325-t002" target="_blank">Table 2</a>. Note that atrophy rate is shown by a signed value; thus a reduction in atrophy rate with age is evidenced by a positive slope in the linear fit. Legend: red  = AD; blue  =  MCI; green  = HC.</p