eTable 1 Description of original gait parameters.eTable 2 Overview of number of participants per cognitive and motor test.eTable 3 Characteristics of excluded study population.eFigure 1 Spiral test.eFigure 2 Gait domains.eFigure 3 Trajectories of cognitive and motor function stratified by educational level.eFigure 4 Trajectories of cognitive and motor function by APOE ε4 carrier status.

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eTable 1 Description of original gait parameters.

Parameter Description Indication of “worse” gait

Main underlying domain

Single support time The time elapsed between the last contact of the opposite foot and the first contact of the next footfall of the opposite foot when a foot touches the ground

Higher Rhythm

Swing time The time elapsed between the last contact of the current footfall to the first contact of the next footfall on the same foot in seconds

Higher Rhythm

Step time The time elapsed between the first contact of one foot and the first contact of the opposite foot

Higher Rhythm

Stride time The elapsed time between the first contacts of two consecutive footfalls of the same foot in seconds

Higher Rhythm

Cadence The number of steps/minute Lower Rhythm

stance time The time elapsed between the first contact and the last contact of two consecutive footfalls on the same foot in seconds. It is initiated by heel contact and ends with the toe off of the same foot

Higher Rhythm

Stride length SD The standard deviation in the stride length in centimeters

Higher Variability

Step length SD The standard deviation in the step length in centimeters

Higher Variability

Stride velocity SD The standard deviation in the stride velocity (stride length/stride time) in centimeters/second

Higher Variability

Stride time SD The standard deviation in the stride time in seconds

Higher Variability

Step time SD The standard deviation in the step time in seconds

Higher Variability

Stance time SD The standard deviation in the stance time in seconds

Higher Variability

Swing time SD The standard deviation in the swing time in seconds

Higher Variability

Single support time SD

The standard deviation in the single support time in seconds

Higher Variability

Double support time SD

The standard deviation in the double support time in seconds

Higher Variability

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Parameter Description Indication of “worse” gait

Main underlying domain

Single support (%GC)

The single support time as a percentage of the stride time

Lower Phases

Swing (%GC) The swing time as a percentage of the stride time

Lower Phases

Stance (%GC) The stance time as a percentage of the stride time

Higher Phases

Double support (%GC)

The double support time as a percentage of the stride time

Higher Phases

Double support time

The amount of time that two feet are on the ground at the same time within one footfall in seconds

Higher Phases

Stride length The distance between the heel points of two consecutive footprints of the same foot on the line of progression in centimeters

Lower Pace

Step length The distance between the heel points of two consecutive opposite footprints on the line of progression in centimeters

Lower Pace

Velocity The velocity in centimeters/second Lower Pace

Sum of feet surface The sum of the surfaces of the side stepsa as a percentage of the surface of a normal step

Higher Tandem

Sum of step distance

The sum of the distances of the side stepsa from the line on the walkway in centimeters

Higher Tandem

Double step A double-step was a step with one foot, followed by a step with the same foot, where both feet were on the line of the walkway

Higher Tandem

Turning step count The number of steps used within the Turning Time

Higher Turning

Turning time The turning time was defined as the time between the last contact of the second foot before the first turn foot and the first contact of the second foot with a normal angle coming out of the turn. In which the first turn foot is defined as the first foot deviating from the normal angle of the feet (subject dependent)

Higher Turning

Stride width SD The standard deviation in the stride width in centimeters

Higher Base of support

Stride width The distance from heel center of one footprint to the line of progression formed by two footprints of the opposite

Lower Base of support

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foot in centimeters

a A sidestep was defined as a step next to the line on the walkway, which was followed by a step with the same foot or a step with the other foot. Abbreviations: SD, standard deviation; %GC, as a percentage of the stride time.

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eTable 2 Overview of number of participants per cognitive and motor test.

Cognitive/motor test

Analysis of cognitive function

(N = 9,514)

Analysis of motor function

(N = 8,297)

Word Fluency Test 9,458 (99.4)

Letter-Digit Substitution Test 9,419 (99.0)

Stroop Test: Reading subtask 9,311 (97.9)

Stroop Test: Naming subtask 9,300 (97.8)

Stroop Test: Interference subtask 9,281 (97.6)

Word Learning Test: Immediate recall subtask 7,875 (82.8)

Word Learning Test: Delayed recall subtask 7,875 (82.8)

Word Learning Test: Recognition subtask 7,882 (82.8)

Design Organization Test 5,561 (58.5)

Purdue Pegboard Test 8,225 (99.1)

Archimedes Spiral Test 5,424 (65.4)

Gait assessments 4,154 (50.1)Numbers are presented as number of participants per cognitive or motor test (% of total number of participants for cognitive or motor tests).Abbreviations: N, number of participants.

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eTable 3 Characteristics of excluded participants.

Characteristic

Excluded participantsa

History of dementia, stroke, or

Parkinson’s disease at time

of first assessmentb

(N=3,873)

No cognitive or motor

assessments (N=1,494)

Aged ≥90 years at time of

first assessment

(N=33)

Agec, years, mean (SD) 73.0 (13.7) 72.6 (9.3) 88.2 (4.7)

Sex, women, n (%) 2,509 (64.8) 844 (56.5) 19 (57.6)

Educational level, n (%)

Primary 1,087 (28.1) 466 (31.2) 11 (33.3)

Lower 1,327 (34.3) 575 (38.5) 10 (30.3)

Intermediate 802 (20.7) 334 (22.4) 6 (18.2)

Higher 341 (8.8) 90 (6.0) 3 (9.1)

Body mass index, kg/m2, mean (SD) 26.6 (4.0) 26.4 (4.1) 25.6 (2.9)

Smoking, n (%)

Never 1,367 (35.3) 486 (32.5) 18 (54.5)

Past 1,403 (36.2) 567 (38.0) 11 (33.3)

Current 805 (20.8) 399 (26.7) 1 (3.0)

Alcohol use, n (%) 1,663 (42.9) 781 (52.3) 17 (51.5)

Systolic blood pressure, mmHg, mean (SD) 143 (22.9) 144 (23.6) 145 (18.9)

Type 2 diabetes, n (%) 527 (13.6) 211 (14.1) 5 (15.2)

APOE ε4 carrier, n (%) 714 (18.4) 364 (24.4) 6 (18.2)a In total, 5,405 out of 14,926 participants were excluded. Characteristics of participants without consent for follow-up (n=5) are

not shown. b Also comprises participants with insufficient data to determine a history of one of these diseases.c Age at study entry, not age at first assessment.

Characteristics are measured at study entry.

Missing values for all characteristics are not imputed and therefore numbers do not always sum up to 100%.

Abbreviations: N, number of participants; SD, standard deviation; IQR, interquartile range; APOE, Apolipoprotein E.

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eFigure 1 Spiral test.Example of a spiral-drawing quantification, showing an example of the calculation of quantitative measures of fine motor skills. The start and endpoint are indicated by a dot. The figure explains how deviation from template and crossings are defined.

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eFigure 2 Gait domains. To summarize gait parameters into independent domains, we conducted a principal component analysis. This yielded 7 independent gait domains: ‘base of support’, ‘pace’, ‘phases’, ‘rhythm’, ‘tandem’, ‘turning’, and ‘variability’. For each gait domain, a single gait parameter that has high correlation with the domain is illustrated.

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eFigure 3 Trajectories of cognitive and motor function stratified by educational level.

The thick black continuous line reflects the trajectory of performance for the total study population based on the results of the linear mixed model; the black dotted lines represent the 10th and 90th percentile curves. Furthermore, test performance was visualized per educational level in red for cognitive tests and in blue for motor tests.a Higher scores indicate worse performance. b Percentile curves could not be calculated and are therefore not shown, since the majority of the test scores was equal to 0.

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eFigure 4 Trajectories of cognitive and motor function stratified by APOE ε4 carrier status. Test performance was visualized for APOE ε4 carrier status level in red for cognitive tests and in blue for motor tests. Participants with unknown APOE ε4 carrier status were excluded for analysis regarding APOE ε4 carrier status (528 out of 9,514 participants for cognitive tests and 462 out of 8,297 participants for motor tests).a Higher scores indicate worse performance.

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