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Table S1: Names and domains of all 24 neuropsychological tests in the ROS-MAP data.

Test name Cognitive test description Cognitive Domain

cts_wli word list episodic memory

cts_wlii word list recall episodic memory

cts_wliii word list recognition episodic memory

cts_ebmt East Boston immediate recall episodic memory

cts_ebdr East Boston immediate recall episodic memory

cts_story Logical memory I (immediate) episodic memory

cts_delay Logical memory II (delayed) episodic memory

cts_bname Boston naming (15 items) semantic memory

cts_catflu category fluency semantic memory

cts_animals category fluency - Animals semantic memory

cts_fruits category fluency - Fruits semantic memory

cts_read_nart reading test (10 items) semantic memory

cts_df digits forward working memory

cts_db digits backward working memory

cts_doperf digit ordering working memory

cts_lopair line orientation perceptual orientation

cts_pmat progressive matrices (16 items) perceptual orientation cts_pmsub progressive matrices (subset - 9 items) perceptual orientation

cts_sdmt symbol digits modality oral perceptual speed

cts_nccrtd number comparison perceptual speed

cts_stroop_cname stroop color naming perceptual speed

cts_stroop_wread stroop word reading perceptual speed

cts_idea Complex Ideational Matrix cts_mmse30 Mini Mental State Exam, 30 items

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Test Name Description

UDSBENTC Total score for copy of Benson figure UDSBENTD Total score for 10- to 15-minute delayed

ANIMALS Animals — Total number of animals named in 60 seconds VEG Vegetable— Total number of vegetables named in 60 seconds TRAILA Trail Making Test Part A — Total number of seconds to complete TRAILARR Part A — Number of commission errors

TRAILALI Part A — Number of correct lines

TRAILB Trail Making Test Part B — Total number of seconds to complete TRAILBRR Part B — Number of commission errors

TRAILBLI Part B — Number of correct lines

UDSVERFC Number of correct F-words generated in 1 minute UDSVERFN Number of F-words repeated in 1 minute

UDSVERNF Number of non-F-words and rule violation errors in 1 minute UDSVERLC Number of correct L-words generated in 1 minute

UDSVERLR Number of L-words repeated in 1 minute

UDSVERLN Number of non-L-words and rule violation errors in 1 minute UDSVERTN Total number of correct F-words and L-words

UDSVERTE Total number of F-word and L-word repetition errors UDSVERTI Total number of non-F/L-words and rule violation errors MOCATOTS MoCA Total Raw Score — uncorrected

CRAFTVRS Craft Story 21 Recall (Immediate) — Total story units recalled, verbatim scoring CRAFTURS Craft Story 21 Recall (Immediate) — Total story units recalled, paraphrase scoring DIGFORCT Number Span Test: Forward — Number of correct trials

DIGFORSL Number Span Test: Forward — Longest span forward DIGBACCT Number Span Test: Backward — Number of correct trials DIGBACLS Number Span Test: Forward — Longest span backward

CRAFTDVR Craft Story 21 Recall (Delayed) — Total story units recalled, verbatim scoring CRAFTDRE Craft Story 21 Recall (Delayed) — Total story units recalled, paraphrase scoring CRAFTDTI Craft Story 21 Recall (Delayed) — Delay time

MINTTOTS Multilingual Naming Test (MINT) — Total score

Table S2: Names and description of all 30 tests used in the NACC study data.

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Table S3: Number and percentage distribution of HV, MCI and AD across different subsets for NACC data set.

Distribution Values Percentage

Data set HV MCI AD HV MCI AD

1 54 18 11 65.06024 21.68675 13.25301

2 54 18 11 65.06024 21.68675 13.25301

3 60 12 11 72.28916 14.45783 13.25301

4 52 15 16 62.6506 18.07229 19.27711

5 60 12 11 72.28916 14.45783 13.25301

6 53 20 10 63.85542 24.09639 12.04819

7 58 16 9 69.87952 19.27711 10.84337

8 58 17 8 69.87952 20.48193 9.638554

Total 449 128 87 67.62048 19.27711 13.10241

Table S4: It presents the accuracy, sensitivity and specificity of prediction models for different data sets compared over 3 ML approaches namely, RF with ntree =800 and mtry =18, linear and radial SVM for NACC data.

Random Forests

Dataset Accuracy HV MCI AD

Sensitivity Specificity Sensitivity Specificity Sensitivity Specificity

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1 0.7229 0.8889 0.5862 0.16667 0.89231 0.8182 0.9444

2 0.7349 0.9444 0.5172 0.11111 0.92308 0.72727 0.95833

3 0.8072 0.9667 0.5652 0.08333 0.92958 0.72727 0.98611

4 0.7711 0.9615 0.6774 0.26667 0.89706 0.625 0.9701

5 0.8434 0.9167 0.7391 0.5 0.92958 0.8182 0.9722

6 0.7108 0.9057 0.4667 0.25 0.88889 0.6 0.9863

7 0.7349 0.8621 0.72 0.3125 0.83582 0.66667 0.94595

8 0.7711 0.931 0.72 0.17647 0.92424 0.875 0.90667

Linear Support Vector Machine

1 0.7349 0.9444 0.5517 0.05556 0.92308 0.8182 0.9444

2 0.7831 0.9815 0.6207 0.22222 0.93846 0.72727 0.95833

3 0.7711 0.9333 0.5217 0.08333 0.90141 0.63636 0.98611

4 0.759 0.9808 0.5806 0.2 0.92647 0.5625 0.9701

5 0.8193 0.9 0.7826 0.41667 0.90141 0.8182 0.9583

6 0.6988 0.9057 0.4667 0.2 0.90476 0.6 0.9589

7 0.7711 0.8966 0.64 0.375 0.8806 0.66667 0.97297

8 0.747 0.9138 0.68 0.23529 0.87879 0.625 0.93333

Radial Support Vector Machines

1 0.7711 0.9444 0.5862 0.11111 0.95385 1 0.9444

2 0.747 0.963 0.5172 0.11111 0.96923 0.72727 0.93056

3 0.8193 0.9833 0.5652 0.08333 0.94366 0.72727 0.98611

4 0.759 0.9423 0.5484 0.06667 0.95588 0.8125 0.9552

5 0.8554 0.95 0.6087 0.41667 0.98592 0.8182 0.9722

6 0.6988 0.8679 0.4667 0.2 0.92063 0.8 0.94521

7 0.7711 0.931 0.6 0.1875 0.92537 0.77778 0.94595

8 0.7952 0.9655 0.68 0.17647 0.95455 0.875 0.92

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Table S5: Contingency table for 4th data-set of NACC studies comparing the results from 3 different ML approaches, namely, Random Forests (800=ntree and 18=mtry), Linear and radial Support Vector Machine.

NACC

RF (800,18) SVM (Linear) SVM (Radial)

Acual HV

Actual MCI

Actual AD

Actual HV

Actual MCI

Actual AD

Actual HV

Actual

MCI Actual AD Pred

HV 50 9 1 51 10 3 49 12 2

Pred

MCI 2 4 5 1 3 4 2 1 1

Pred

AD 0 2 10 0 2 9 1 2 13

Total 52 15 16 52 15 16 52 15 16

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Table S6: Accuracy, sensitivity and specificity for prediction of HV, MCI, AD classes in different data sets for ROSMAP study, comparing few different combinations of tests (6,8 and 9 tests) with the results of whole battery of tests (24) using Random Forests [ntree = 800 and mtry = (no. of tests/2) meaning 12,3,4 and 4 respectively].

All 24 tests

Dataset Accuracy HV MCI AD

Sensitivity Specificity Sensitivity Specificity Sensitivity Specificity

1 0.9407 0.9786 0.9394 0.9259 0.9447 0.41667 1

2 0.9289 0.9779 0.8611 0.8095 0.9684 0.77778 0.9918

3 0.9368 0.9784 0.8971 0.8413 0.9684 0.6 0.9879

4 0.9249 0.9944 0.8493 0.8361 0.9583 0.33333 1

5 0.9644 1 0.918 0.8868 0.985 0.625 0.99592

6 0.9368 0.9944 0.8243 0.8116 0.9837 0.6 1

7 0.9526 0.9891 0.9143 0.8923 0.9734 0.4 0.99597

6 tests (wlii, mmse30, delay, wliii, pmsub, lopair)

1 0.9486 0.9786 0.9545 0.9444 0.9497 0.5 1

2 0.9368 0.9779 0.9028 0.8571 0.9632 0.66667 0.9918

3 0.9447 0.9892 0.9118 0.8413 0.9789 0.6 0.98387

4 0.9368 0.9944 0.8767 0.8689 0.9635 0.41667 1

5 0.9644 0.9948 0.9344 0.9057 0.98 0.625 0.99592

6 0.9526 0.9944 0.9054 0.8986 0.9728 0.2 1

7 0.9723 0.9945 0.9571 0.9538 0.9787 0.4 1

8 tests (wlii, mmse30, delay, wliii, pmsub, lopair, catflu, story)

1 0.9565 0.9786 0.9697 0.963 0.9548 0.58333 1

2 0.9447 0.9834 0.9167 0.8571 0.9737 0.77778 0.9877

3 0.9368 0.9784 0.9118 0.8413 0.9684 0.6 0.98387

4 0.9368 0.9944 0.8767 0.8689 0.9635 0.41667 1

5 0.9684 1 0.9344 0.9057 0.985 0.625 0.99592

6 0.9407 0.9944 0.8649 0.8551 0.9728 0.2 1

7 0.9684 0.9891 0.9571 0.9538 0.9734 0.4 1

9 tests (wlii, mmse30, delay, wliii, pmsub, lopair, catflu, story, sdmt)

1 0.9526 0.9786 0.9697 0.963 0.9497 0.5 1

2 0.9328 0.9834 0.875 0.8095 0.9737 0.77778 0.9877

3 0.9368 0.9838 0.8971 0.8254 0.9737 0.6 0.98387

4 0.9289 0.9944 0.863 0.8361 0.9583 0.41667 1

5 0.9644 0.9948 0.9344 0.9057 0.98 0.625 0.99592

6 0.9368 0.9944 0.8514 0.8406 0.9728 0.2 1

7 0.9605 0.9891 0.9429 0.9231 0.9734 0.4 0.995968

Table S7: Accuracy, sensitivity and specificity for prediction of HV, MCI, AD classes in different data sets, comparing combinations of 7 tests with the results of whole battery of tests for NACC data using Random Forests [ntree = 800 and mtry = (no. of tests/2) meaning 15 and 4 respectively].

All 30 tests

Dataset Accuracy HV MCI AD

Sensitivity Specificity Sensitivity Specificity Sensitivity Specificity

1 0.7349 0.8889 0.6207 0.16667 0.89231 0.9091 0.9444

2 0.7349 0.9444 0.5172 0.11111 0.92308 0.72727 0.95833

3 0.8072 0.9667 0.5652 0.08333 0.92958 0.72727 0.98611

4 0.759 0.9615 0.5806 0.13333 0.92647 0.6875 0.9701

5 0.8434 0.9333 0.6957 0.41667 0.94366 0.8182 0.9722

6 0.7108 0.9057 0.4667 0.25 0.88889 0.6 0.9863

7 0.747 0.8793 0.7200 0.3125 0.85075 0.66667 0.94595

8 0.7952 0.931 0.7600 0.29412 0.92424 0.875 0.92

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7 tests (CRAFTDRE, CRAFTDVR, MOCA, UDSBENTD, VEG, TRAILB, CRAFTVRS)

1 0.7349 0.8889 0.6207 0.22222 0.87692 0.8182 0.9583

2 0.759 0.9815 0.5172 0.11111 0.95385 0.72727 0.95833

3 0.8313 0.9667 0.5652 0.08333 0.95775 0.9091 0.9861

4 0.8072 0.9615 0.7419 0.3333 0.91176 0.75 0.9701

5 0.8193 0.8833 0.7391 0.5 0.90141 0.8182 0.9722

6 0.7108 0.9434 0.4667 0.2 0.90476 0.5 0.9726

7 0.759 0.8966 0.72 0.3125 0.86567 0.66667 0.94595

8 0.8072 0.931 0.8 0.35294 0.92424 0.875 0.92

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Supplementary Figure S1: Tuning of Random Forests: The figure describes how multiclass ROC values were used to find an optimum ntree, mtry value for Random Forests for one of the representative data subsets for ROSMAP study. The blue line represents mtry as 1, orange as 3, silver as 6, yellow as 9, light blue as 12 and green as 18.

100 200 300 400 500 600 700 800 900 1000 2000 5000 0.84

0.86 0.88 0.9 0.92 0.94 0.96

1 3

ntree

6 9 12 18

R O C

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Supplementary Figure S2: Finding important tests by the prediction accuracy pattern. The number of tests were arranged according to their discriminative power in Fischer’s score and then added one by one for one representative testing data subset of ROSMAP study; subsequently accuracy was predicted using Random Forests with different ntree (100,200-1200,2000,3000-5000) and mtry. The pattern shows the first 3 tests (wlii, mmse30, delay), 11

th

(wliii), 20

th

(pmsub) and 21

st

(lopair) tests to be important in all the 3 subfigures.

S2 (first subfigure) has mtry as (no. of tests/2), S2 (second subfigure) has mtry as (no. of tests/3) and S2 (third subfigure) has mtry as (no. of tests/1.414) for each iteration.

0 2 4 6 8 10 12 14 16 18 20 22 24 26

0.72 0.75 0.78 0.81 0.84 0.87 0.9 0.93

No. of tests

A cc u ra cy

0 2 4 6 8 10 12 14 16 18 20 22 24 26

0.73 0.75 0.77 0.79 0.81 0.83 0.85 0.87 0.89 0.91 0.93 0.95

No. of tests

A cc u ra cy

0 2 4 6 8 10 12 14 16 18 20 22 24 26

0.72 0.74 0.76 0.78 0.8 0.82 0.84 0.86 0.88 0.9 0.92 0.94 0.96

No. of tests

A cc u ra cy

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Supplementary Figure S3: Increment in accuracy for 6 important tests in one of the representative data subsets of ROSMAP data. The 6 tests were arranged in the following order: wlii, mmse30, delay, wliii, pmsub and lopair and we observed for the change in prediction accuracy if any of the following test was missing from the subset. It was done using Random Forests with different ntree (100,200-1200,2000,3000-5000) and mtry as (no. of tests/2). S3 (first subfigure) represents when pmsub was missing, S3 (second subfigure) represents when lopair was missing and S3 (third subfigure) represents when all 6 tests were present. It shows the dependence of all 6 tests to get the maximum prediction ability.

1 2 3 4 5

0.65 0.7 0.75 0.8 0.85 0.9 0.95

No. of Tests

A cc ur ac y

1 2 3 4 5

0.7 0.75 0.8 0.85 0.9 0.95

No. of Tests

A cc u ra cy

1 2 3 4 5 6

0.7 0.75 0.8 0.85 0.9 0.95 1

No. of Tests

A cc ur ac y

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Supplementary Figure S4: Ranking of 30 neuropsychological tests from NACC study.

Supplementary Figure S4A: Fischer’s score for 3 classes classification (HV, MCI, AD).

CRAFTDRE MOCATOTS

CRAFTDVR UDSBEN

TD

CRAFTURS CRAFTVRS

VEG TRAILB

AN IMALS

DIGBACCT TRAILBLI

DIGBACLS TRAILA

MINTTOTS DIGFORCT

UDSVER TN

UDSVER FC

UDSVER LC DIGFORSL

TRAILBR R

UDSBEN TC CRAFTDTI

TRAILALI UDSVER

TE

UDSVER FN

UDSVER LR UDSVER

TI

UDSVER LN

UDSVER NF TRAILAR

R 0

0.2 0.4 0.6 0.8 1 1.2 1.4 1.61.5

1.31.3

1.21.21.1

0.80.8 0.6

0.30.30.30.30.3

0.20.20.20.20.20.2

0.10.10.00.00.00.00.00.00.00.0

Test Name

F is ch er 's S co re

Supplementary Figure S4B: Average decrease in accuracy of prediction when a single test was removed iteratively.

UDSVER FN

TRAILB UDSBEN

TD

CRAFTDRE UDSVER

TE TRAILALI

DIGFO RCT CRAFTVR

S

UDSVER LCVEG

DIGBACCT TRAILBLI

TRAILA UDSVER

TI

TR AILAR

R

TRAILBR R

CRAFTURS DIGBACLS

UDSVER LR

UDSVER FC AN

IMALS DIGFO

RSL UDSBEN

TC

UDSVER NF CRAFTDTI

MINTTOTS UDSVER

LN

UDSVER TN

CRAFTDVR MOCATOTS -0.02

-0.01 -0.01 -0.01 -0.01 -0.01 0 0 0 0 0

Test Name

D ec re as e in A cc u ra cy

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