dementia, and B) Parkinson`s disease or dementia, comparing patients with acromegaly to the

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Supplementary figure 1. Kaplan–Meier estimates of incidence probability for A) Parkinson`s disease, B) all-cause dementia, C) Alzheimer’s disease, and D) vascular dementia comparing patients with acromegaly to the age- and sex-matched controls during follow-up after

diagnosis of acromegaly

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Supplementary figure 2. Kaplan–Meier estimates of incidence probability for A) Non-AD

dementia, and B) Parkinson`s disease or dementia, comparing patients with acromegaly to the

age- and sex-matched controls during follow-up after diagnosis of acromegaly

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Supplementary table 1. Frequency, incidence rates, and hazard ratios of neurodegenerative diseases between patients with acromegaly and controls by stratified Cox proportional- hazards model

Number patients of

Number of events

Duration (person-

years)

Rate (Events per 1000

person-years) Model 1 P-value

Parkinson`s disease

Control 8055 33 60144 0.55 1 (ref.) 0.001

Acromegaly 1611 18 11722 1.54 3.559 (1.702, 7.443)

All-cause dementia

Control 8055 267 59534 4.48 1 (ref.) 0.606

Acromegaly 1611 54 11596 4.66 1.089 (0.788, 1.505)

Alzheimer’s disease

Control 8055 197 59534 3.31 1 (ref.) 0.793

Acromegaly 1611 38 11596 3.28 1.053 (0.716, 1.549)

Vascular dementia

Control 8055 42 59534 0.71 1 (ref.) 0.735

Acromegaly 1611 6 11596 0.52 0.85 (0.333, 2.172)

Non-AD dementia

Control 8055 28 59534 0.47 1 (ref.) 0.096

Acromegaly 1611 10 11596 0.86 2.121 (0.876, 5.135)

Dementia or Parkinson`s disease

Control 8055 283 59438 4.76 1 (ref.) 0.1566

Acromegaly 1611 66 11542 5.72 1.242 (0.92, 1.675)

Model 1: Adjusted for age, sex, household income, place, type 2 diabetes, hypertension, and

dyslipidemia.

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Supplementary table 2. Numbers of hospital visit between controls and patients with acromegaly

Controls Patients with

acromegaly p-value

Numbers of hospital visit during follow-up <0.001

Mean ± SD 146.77 ± 175.19 210.26 ± 203.74

Median (Q1 - Q3) 93 (39 - 187) 157 (89 - 262)

Numbers of hospital visit during first 3 years <0.001

Mean ± SD 51.92 ± 57.93 87.56 ± 72.25

Median (Q1 - Q3) 36 (16 - 68) 70 (48 - 105)

Supplementary table 3. Risk of neurodegenerative diseases between patients with acromegaly and controls with adjusting numbers of hospital visit.

Number patients of

Number of events

Duration (person-

years)

Control 8055 33 60144 0.55 1 (ref.) 0.001

Acromegaly 1611 18 11722 1.54 2.854 (1.521, 5.354)

Control 8055 267 59534 4.48 1 (ref.) 0.533

Acromegaly 1611 54 11596 4.66 1.103 (0.811, 1.501)

Control 8055 197 59534 3.31 1 (ref.) 0.546

Acromegaly 1611 38 11596 3.28 1.119 (0.777, 1.612)

Control 8055 42 59534 0.71 1 (ref.) 0.294

Acromegaly 1611 6 11596 0.52 0.619 (0.253, 1.515)

Non-AD dementia

Control 8055 28 59534 0.47 1 (ref.) 0.152

Acromegaly 1611 10 11596 0.86 1.760 (0.813, 3.811)

Control 8055 283 59438 4.76 1 (ref.) 0.107

Acromegaly 1611 66 11542 5.72 1.263 (0.951, 1.678)

Model 1: Adjusted for age, sex, household income, place, type 2 diabetes, hypertension, and

dyslipidemia, numbers of hospital visit.

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Supplementary table 4. Risk of neurodegenerative diseases between patients with acromegaly and controls with one-year lag.

Number patients of

Number of events

Duration (person-

years)

Control 8018 31 52045 0.60 1 (ref.) 0.009

Acromegaly 1593 15 10084 1.49 2.403 (1.243, 4.647)

Control 8018 253 51480 4.91 1 (ref.) 0.483

Acromegaly 1593 44 9987 4.41 0.889 (0.638, 1.237)

Control 8018 189 51480 3.67 1 (ref.) 0.645

Acromegaly 1593 32 9987 3.20 0.913 (0.62, 1.344)

Control 8018 38 51480 0.74 1 (ref.) 0.242

Acromegaly 1593 5 9987 0.50 0.564 (0.216, 1.473)

Non-AD dementia

Control 8018 26 51480 0.51 1 (ref.) 0.658

Acromegaly 1593 7 9987 0.70 1.216 (0.511, 2.893)

Control 8018 267 51402 5.19 1 (ref.) 0.797

Acromegaly 1593 55 9941 5.53 1.04 (0.77, 1.406)

Model 1: Adjusted for age, sex, household income, place, type 2 diabetes, hypertension, and

dyslipidemia.

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Supplementary table 5. Risk of neurodegenerative diseases between patients with acromegaly and controls with age scaling.

Number patients of

Number of events

Duration (person-

years)

Control 8055 33 60144 0.55 1 (ref.) 0.002

Acromegaly 1611 18 11722 1.54 2.609 (1.409, 4.829)

Control 8055 267 59534 4.48 1 (ref.) 0.990

Acromegaly 1611 54 11596 4.66 1.002 (0.739, 1.358)

Control 8055 197 59534 3.31 1 (ref.) 0.936

Acromegaly 1611 38 11596 3.28 1.015 (0.708, 1.456)

Control 8055 42 59534 0.71 1 (ref.) 0.237

Acromegaly 1611 6 11596 0.52 0.586 (0.242, 1.42)

Non-AD dementia

Control 8055 28 59534 0.47 1 (ref.) 0.256

Acromegaly 1611 10 11596 0.86 1.552 (0.727, 3.311)

Control 8055 283 59438 4.76 1 (ref.) 0.356

Acromegaly 1611 66 11542 5.72 1.141 (0.862, 1.509)

Model 1: Adjusted for age, sex, household income, place, type 2 diabetes, hypertension, and

dyslipidemia.

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Supplementary table 6. Frequency, incidence rates, and hazard ratios of All-cause dementia between patients with acromegaly and controls according to prespecified subgroups after adjusting for age, sex, household income, place, type 2 diabetes, hypertension, and dyslipidaemia

Subgroup Group Number

patients of

Number events of

Duration (person-

years)

Rate (Events

1000 per person-

years)

Adjusted hazard ratio*

(95% confidence interval)

value P- P for interaction

Parkinson`s disease Age

(years) <65 Control 6805 91 51081 1.78 1 (ref.) 0.399 0.303

Acromegaly 1361 16 10052 1.59 0.786 (0.449, 1.376)

65≤ Control 1250 176 8453 20.82 1 (ref.) 0.464

Acromegaly 250 38 1543 24.62 1.145 (0.797, 1.644)

Sex Male Control 3255 81 23703 3.42 1 (ref.) 0.399 0.435

Acromegaly 651 14 4659 3.00 0.775 (0.428, 1.402)

Female Control 4800 186 35831 5.19 1 (ref.) 0.411

Acromegaly 960 40 6937 5.77 1.161 (0.814, 1.657)

Diabetes

mellitus No Control 7360 220 54654 4.03 1 (ref.) 0.212 0.028

Acromegaly 1058 23 7723 2.98 0.758 (0.49, 1.171)

Yes Control 695 47 4879 9.63 1 (ref.) 0.113

Acromegaly 553 31 3873 8.00 1.469 (0.914, 2.363)

Hypertension No Control 6162 138 45979 3.00 1 (ref.) 0.536 0.283

Acromegaly 804 15 5825 2.57 0.839 (0.482, 1.461)

Yes Control 1893 129 13555 9.52 1 (ref.) 0.720

Acromegaly 807 39 5771 6.76 1.071 (0.736, 1.557)

Dyslipidaemia No Control 6961 207 52234 3.96 1 (ref.) 0.877 0.399

Acromegaly 1253 39 9193 4.24 0.972 (0.68, 1.389)

Yes Control 1094 60 7299 8.22 1 (ref.) 0.641

Acromegaly 358 15 2402 6.24 1.152 (0.635, 2.093)

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Supplementary table 7. Frequency, incidence rates, and hazard ratios of Parkinson`s disease between patients with acromegaly and controls according to prespecified subgroups after adjusting for age, sex, household income, place, type 2 diabetes, hypertension, and dyslipidaemia

Subgroup Group Number

patients of

Number events of

Duration (person-

years)

Rate (Events per

1000 person-

years)

Adjusted hazard ratio* (95%

confidence interval)

value P- P for interaction Parkinson`s disease

Age

(years) <65 Control 6805 19 51267 0.37 1 (ref.) 0.039 0.953

Acromegaly 1361 11 10063 1.09 2.353 (1.046, 5.292)

65≤ Control 1250 14 8877 1.58 1 (ref.) 0.035

Acromegaly 250 7 1659 4.22 2.834 (1.077, 7.459)

Sex Male Control 3255 14 23884 0.59 1 (ref.) 0.163 0.480

Acromegaly 651 6 4674 1.28 2.053 (0.747, 5.641)

Female Control 4800 19 36260 0.52 1 (ref.) 0.004

Acromegaly 960 12 7048 1.70 3.164 (1.433, 6.984)

Diabetes

mellitus No Control 7360 30 55154 0.54 1 (ref.) 0.030 0.367

Acromegaly 1058 10 7764 1.29 2.26 (1.08, 4.729)

Yes Control 695 3 4990 0.60 1 (ref.) 0.054

Acromegaly 553 8 3958 2.02 3.835 (0.98, 15.011)

Hypertension No Control 6162 21 46303 0.45 1 (ref.) 0.155 0.337

Acromegaly 804 5 5861 0.85 2.093 (0.756, 5.79)

Yes Control 1893 12 13841 0.87 1 (ref.) 0.023

Acromegaly 807 13 5862 2.22 2.623 (1.145, 6.01)

Dyslipidaemia No Control 6961 25 52734 0.47 1 (ref.) 0.005 0.343

Acromegaly 1253 15 9284 1.62 2.671 (1.341, 5.319)

Yes Control 1094 8 7410 1.08 1 (ref.) 0.266

Acromegaly 358 3 2438 1.23 2.308 (0.529, 10.06)

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