. 2019 Dec 13;9:19024. doi: 10.1038/s41598-019-54204-z

Table 4.

Contribution of tau biomarkers to prediction of clinical decline assessed by MMSE score (24 months).

	Biomarker	Mixed-model estimate (95% CI) of difference in clinical decline (24 months) versus reference, BM–/BM–	LRT P value	Hazard ratio estimate (95% CI) for outcome dementia within 6 years	LRT P value
ADNI	Aβ(1–42)\|pTau	–0.60 (–1.38 to 0.19)	–1.19 (–1.69 to –0.69)	–2.72 (–3.20 to –2.24)	<0.0001^a	2.05 (0.88 to 4.76)	3.46 (1.99 to 6.01)	6.61 (3.99 to 10.96)	0.0001^a
pTau/Aβ(1–42)\|pTau	0.02 (–1.07 to 1.11)	–1.34 (–1.90 to –0.79)	–2.40 (–2.84 to –1.96)	0.001^b	0.46 (0.06 to 3.36)	3.56 (2.19 to 5.80)	5.02 (3.34 to 7.54)	0.117^b
Visual PET\|pTau	0.02 (–0.87 to 0.92)	–0.82 (–1.38 to –0.26)	–2.33 (–2.81 to –1.85)	<0.0001^c	0.77 (0.10 to 5.89)	2.97 (1.46 to 6.04)	7.25 (4.02 to 13.11)	0.002^c
Aβ(1–42)\|tTau	–0.53 (–1.30 to 0.25)	–1.53 (–2.01 to –1.05)	–2.60 (–3.10 to –2.10)	<0.0001^d	1.73 (0.72 to 4.14)	3.94 (2.34 to 6.62)	6.09 (3.69 to 10.07)	0.013^d
tTau/Aβ(1–42)\|tTau	0.11 (–0.86 to 1.08)	–1.73 (–2.23 to –1.23)	–2.35 (–2.81 to –1.89)	0.001^e	0.44 (0.06 to 3.28)	4.70 (2.98 to 7.39)	5.19 (3.39 to 7.96)	0.551^e
Visual PET\|tTau	–0.07 (–0.91 to 0.76)	–1.00 (–1.51 to –0.49)	–2.54 (–3.05 to –2.03)	<0.0001^f	0.76 (0.10 to 5.88)	3.86 (2.03 to 7.35)	7.53 (4.10 to 13.82)	0.012 ^f
BioFINDER	Aβ(1–42)\|pTau	–0.18 (–1.45 to 1.10)	–0.99 (–1.65 to –0.33)	–1.46 (–2.15 to –0.76)	0.002^a	2.17 (1.06 to 4.45)	2.71 (1.72 to 4.27)	3.50 (2.25 to 5.45)	0.060^a
pTau/Aβ(1–42)\|pTau	0.26 (–1.40 to 1.93)	–1.75 (–2.53 to –0.98)	–1.44 (–2.09 to –0.78)	0.100^b	1.12 (0.38 to 3.27)	3.22 (1.82 to 5.71)	3.90 (2.39 to 6.35)	0.926^b
Visual PET\|pTau	–0.79 (–2.20 to 0.63)	–2.24 (–3.19 to –1.30)	–1.74 (–2.51 to –0.96)	0.058^c	1.12 (0.35 to 3.65)	3.57 (2.27 to 5.63)	3.33 (2.23 to 4.97)	0.743^c
Aβ(1–42)\|tTau	–0.19 (–1.32 to 0.94)	–1.05 (–1.71 to –0.38)	–1.42 (–2.13 to –0.71)	0.002^d	1.88 (0.95 to 3.73)	2.85 (1.80 to 4.50)	3.40 (2.15 to 5.37)	0.146^d
tTau/Aβ(1–42)\|tTau	0.08 (–1.26 to 1.41)	–1.71 (–2.47 to –0.94)	–1.37 (–2.03 to –0.71)	0.110^e	1.36 (0.54 to 3.42)	3.36 (1.87 to 6.04)	4.04 (2.46 to 6.65)	0.768^e
Visual PET\|tTau	–0.76 (–2.05 to 0.53)	–2.24 (–3.20 to –1.28)	–1.78 (–2.55 to –1.00)	0.056^f	1.10 (0.43 to 2.82)	3.73 (2.38 to 5.84)	3.24 (2.15 to 4.89)	0.623 ^f

Biomarker

Mixed-model estimate (95% CI) of difference in clinical decline (24 months) versus reference, BM–/BM–

LRT P value

Hazard ratio estimate (95% CI) for outcome dementia within 6 years

LRT P value

BM1–|BM2 +

BM1 + |BM2–

BM1 + |BM2 +

BM1–|BM2+

BM1+|BM2–

BM1+|BM2+

ADNI

Aβ(1–42)|pTau

–0.60

(–1.38 to 0.19)

–1.19

(–1.69 to –0.69)

–2.72

(–3.20 to –2.24)

<0.0001^a

2.05

(0.88 to 4.76)

3.46

(1.99 to 6.01)

6.61

(3.99 to 10.96)

0.0001^a

pTau/Aβ(1–42)|pTau

0.02

(–1.07 to 1.11)

–1.34

(–1.90 to –0.79)

–2.40

(–2.84 to –1.96)

0.001^b

0.46

(0.06 to 3.36)

3.56

(2.19 to 5.80)

5.02

(3.34 to 7.54)

0.117^b

Visual PET|pTau

0.02

(–0.87 to 0.92)

–0.82

(–1.38 to –0.26)

–2.33

(–2.81 to –1.85)

<0.0001^c

0.77

(0.10 to 5.89)

2.97

(1.46 to 6.04)

7.25

(4.02 to 13.11)

0.002^c

Aβ(1–42)|tTau

–0.53

(–1.30 to 0.25)

–1.53

(–2.01 to –1.05)

–2.60

(–3.10 to –2.10)

<0.0001^d

1.73

(0.72 to 4.14)

3.94

(2.34 to 6.62)

6.09

(3.69 to 10.07)

0.013^d

tTau/Aβ(1–42)|tTau

0.11

(–0.86 to 1.08)

–1.73

(–2.23 to –1.23)

–2.35

(–2.81 to –1.89)

0.001^e

0.44

(0.06 to 3.28)

4.70

(2.98 to 7.39)

5.19

(3.39 to 7.96)

0.551^e

Visual PET|tTau

–0.07

(–0.91 to 0.76)

–1.00

(–1.51 to –0.49)

–2.54

(–3.05 to –2.03)

<0.0001^f

0.76

(0.10 to 5.88)

3.86

(2.03 to 7.35)

7.53

(4.10 to 13.82)

0.012 ^f

BioFINDER

Aβ(1–42)|pTau

–0.18

(–1.45 to 1.10)

–0.99

(–1.65 to –0.33)

–1.46

(–2.15 to –0.76)

0.002^a

2.17

(1.06 to 4.45)

2.71

(1.72 to 4.27)

3.50

(2.25 to 5.45)

0.060^a

pTau/Aβ(1–42)|pTau

0.26

(–1.40 to 1.93)

–1.75

(–2.53 to –0.98)

–1.44

(–2.09 to –0.78)

0.100^b

1.12

(0.38 to 3.27)

3.22

(1.82 to 5.71)

3.90

(2.39 to 6.35)

0.926^b

Visual PET|pTau

–0.79

(–2.20 to 0.63)

–2.24

(–3.19 to –1.30)

–1.74

(–2.51 to –0.96)

0.058^c

1.12

(0.35 to 3.65)

3.57

(2.27 to 5.63)

3.33

(2.23 to 4.97)

0.743^c

Aβ(1–42)|tTau

–0.19

(–1.32 to 0.94)

–1.05

(–1.71 to –0.38)

–1.42

(–2.13 to –0.71)

0.002^d

1.88

(0.95 to 3.73)

2.85

(1.80 to 4.50)

3.40

(2.15 to 5.37)

0.146^d

tTau/Aβ(1–42)|tTau

0.08

(–1.26 to 1.41)

–1.71

(–2.47 to –0.94)

–1.37

(–2.03 to –0.71)

0.110^e

1.36

(0.54 to 3.42)

3.36

(1.87 to 6.04)

4.04

(2.46 to 6.65)

0.768^e

Visual PET|tTau

–0.76

(–2.05 to 0.53)

–2.24

(–3.20 to –1.28)

–1.78

(–2.55 to –1.00)

0.056^f

1.10

(0.43 to 2.82)

3.73

(2.38 to 5.84)

3.24

(2.15 to 4.89)

0.623 ^f

Analyses shown with adjustment for age, sex, years of education but without adjustment for APOEε4 status. Hazard ratio data also adjusted for baseline MMSE score (ADNI and BioFINDER) and baseline CDR-SB score (ADNI only). LRTs were used to assess the contribution of tau when combined with Aβ(1–42), Tau/Aβ(1–42) ratios or amyloid-PET, based on comparison of different four-categorical mixed models and Cox regression models. Data presented for ADNI MCI and BioFINDER MCS populations. LRT comparison: ^aAβ(1–42) versus Aβ(1–42)|pTau; ^bpTau/Aβ(1–42) versus pTau/Aβ(1–42)|pTau; ^cVisual PET versus visual PET|pTau; ^dAβ(1–42) versus Aβ(1–42)|tTau; ^etTau/Aβ(1–42) versus tTau/Aβ(1–42)|tTau; ^fVisual PET versus visual PET|tTau. MMSE, Mini-Mental State Examination; CI, confidence interval; BM–, biomarker-negative; BM + , biomarker-positive; LRT, likelihood ratio test; ADNI, Alzheimer’s Disease Neuroimaging Initiative; pTau, phosphorylated Tau; PET, positron emission tomography; tTau, total Tau; CDR-SB, Clinical Dementia Rating Scale Sum of Boxes; MCI, mild cognitive impairment; MCS, mild cognitive symptoms.