SUPPLEMENTAL TABLES:
Table e-1: Candidate variables as possible predictors of progression to frequent falls by visit 2, classified by blocks (MAO: Monoamine Oxidase; COMT: Catechol-O-Methyltransferase;
H&Y: Hoehn and Yahr; PDQ39: 39-Item Parkinson’s Disease Questionnaire; MSCI: Modified Care Giver Strain Index; TUG: Timed-Up-and-Go; DBS: Deep Brain Stimulation)
Variable Description
Block 1 Historical, demographic, and current treatment information Age
Sex Race
Living Situation Regular Care Partner Center
Disease duration Certainty of diagnosis Rest tremor
Motor fluctuations Falls in the last 3 months Number of comorbidities Cardiac comorbidity (y/n) Respiratory comorbidity (y/n) Diabetes (y/n)
Neurological comorbidity (y/n) Cancer (y/n)
Osteoarthritis(y/n) Other comorbidity (y/n) Hospital admissions Emergency room visits Injury-related (y/n) Pneumonia-related (y/n) Other infection-related (y/n) Cognitive changes-related (y/n) l-dopa (y/n)
dopamine agonist (y/n) MAO-B inhibitor (y/n) COMT inhibitor (y/n) Amantadine (y/n) Antidepressant (y/n) Anticholinergic (y/n) Antipsychotic (y/n) Cognitive enhancer (y/n) Physical therapy (y/n) Occupational therapy (y/n) Speech therapy (y/n) Exercise (y/n)
Social services/counseling (y/n) Mental health treatment (y/n) Deep brain stimulation (y/n)
At the time of baseline visit in years Male or Female
American Indian, Asian, Pacific Islander, African American, White, Multiple At Home, Skilled Care, Other
No, Spouse/Partner, Other Relative, Paid Caregiver, Other NPF COE where subject is followed
Years since diagnosis
Certainty of investigator regarding diagnosis of PD as > or < than 90 % Ever present vs. never present
History of motor fluctuations at the time of the visit
Used to derive the primary outcome measure (see Methods for details) Total number of positive categories below
History of any cardiac pathology at the time of the visit History of any respiratory pathology at the time of the visit History of diabetes at the time of the visit
History of neurological pathology besides PD at the time of the visit History of cancer at the time of the visit
History of osteoarthritis at the time of the visit
History of any other significant comorbidity at the time of the visit In the 12 months preceding the visit
In the 12 months preceding the visit Explanatory of hospital admissions Explanatory of hospital admissions Explanatory of hospital admissions Explanatory of hospital admissions
Treatment with L-dopa at the time of the visit Treatment with L-dopa at the time of the visit
Treatment with MAO-B inhibitor at the time of the visit Treatment with COMT inhibitor at the time of the visit Treatment with amantadine at the time of the visit Treatment with antidepressant at the time of the visit
Treatment with anti-PD anticholinergic at the time of the visit Treatment with antipsychotic at the time of the visit
Treatment with anticholinesterase or memantine at the time of the visit Treatment received in the last 12 months
Treatment received in the last 12 months Treatment received in the last 12 months
Currently engaged in a regular exercise program Treatment received in the last 12 months
Treatment received in the last 12 months History of Deep Brain Stimulation for PD
Block 2 Assessments during baseline visit
H&Y stage
PDQ-39 summary score MCSI
TUG (seconds) Semantic Fluency Immediate word recall Delayed word recall
At the time of the visit
Summary index expressed as percentage Summary index
A 6 sec penalty was assessed for use of gait assistive device Number of animals recited in 1 min
Immediate reciting of the 5 words from version 1 of the MoCA 5 min recall of same 5 words
Block 3 Treatments implemented during baseline visit
dopamine agonist MAO-B inhibitor COMT inhibitor Amantadine Antidepressant Cognitive enhancer Stimulant
Antipsychotic Anticholinergic Physical therapy Occupational therapy Speech therapy Exercise
Social services/counseling Mental health treatment DBS
Added or discontinued during visit Added or discontinued during visit Added or discontinued during visit Added or discontinued during visit Added or discontinued during visit Added or discontinued during visit Added or discontinued during visit Added or discontinued during visit Added or discontinued during visit
Ordered during visit or administered in the 3 months preceding the visit Ordered during visit or administered in the 3 months preceding the visit Ordered during visit or administered in the 3 months preceding the visit Recommended during the visit
Ordered during visit or administered in the 3 months preceding the visit Ordered during visit or administered in the 3 months preceding the visit Referred for DBS during the visit
Block 4 Changes in medical history between visits:
Change in comorbidities Cardiac comorbidity Respiratory comorbidity Diabetes
Neurological comorbidity Cancer
Osteoarthritis Other comorbidities Hospital admissions Emergency room visits Injury-related
Pneumonia-related Other infection-related Confusion-related Living situation
Change in total number of comorbidities between visits Emergence of new cardiac pathology between visits Emergence of new respiratory pathology between visits Emergence of diabetes between visits
Emergence of new neurological pathology besides PD between visits Emergence of new cancer between visits
Emergence of new osteoarthritis between visits Emergence of new other pathology between visits Change in number of hospital admissions between visits Change in number of emergency room visits between visits Change in injury-related admissions between visits
Change in pneumonia-related admissions between visits Change in other infection -related admissions between visits Change in confusion -related ad missions between visits Change in living situation between visits
HY: Hoehn & Yahr stage; PDQ-39: Parkinson’s Disease Questionnaire 39; MCSI: Multidimensional Caregiver Strain Index; TUG: Timed Up & Go; MAO:
monoamine oxidase; COMT: catechol-O-methyltransferase; DBS: Deep Brain Stimulation
Table e-2: Additional demographic and social data at the time of baseline visit
Variables Frequent faller at follow-up p-value Missing rate
No (n=2894) Yes (n= 382 )
Race American Indian 10 (0.3%) 4 (1.0%) 0.366 6 (0.18%)
Asian 75 (2.6%) 10 (2.6%)
Pacific Islander 3 (0.1%) 0
African American 61 (2.1%) 5 (1.3%)
White 2730 (94.3%) 361 (94.5%)
Multiple 10 (0.4%) 1 (0.3%)
Missing 5 (0.2%) 1 (0.3%)
Living Situation At Home 2829 (97.8%) 369 (96.9%) 0.268 3 (0.09%)
Skilled Care 38 (1.3%) 9 (2.4%)
Other 25 (0.9%) 3 (0.8%)
Regular Care Partner No 462 (16.0%) 48 (12.6%) <0.001 6 (0.18%)
Spouse/Partner 2260 (78.2%) 291 (76.4%) Other Relative 114 (3.9%) 28 (7.3%) Paid Caregiver 37 (1.3%) 12 (3.1%)
Other 16 (0.6%) 2 (0.5%)
Table e-3: Comorbidities in the study sample at the time of baseline visit
Variable Frequent faller at follow-up p-value Missing Rate
No (n=2894) Yes (n=382)
Cardiac No 2015 (69v7%) 263 (69.0%) 0.782 5 (0.15%)
Yes 875 (30.3%) 118 (31.0%)
Respiratory No 2522 (87.2%) 320 (84.0%) 0.078 4 (0.12%)
Yes 369 (12.8%) 61 (16.0%)
Diabetes No 2647 (91.5%) 338 (88.9%) 0.095 4 (0.12%)
Yes 245 (8.5%) 42 (11.1%)
Neurological No 2635 (91.2%) 328 (86.5%) 0.003 9 (0.27%)
Yes 253 (8.8%) 51 (13.5%)
Cancer No 2498 (86.5%) 327 (85.8%) 0.720 7 (0.21%)
Yes 390 (13.5%) 54 (14.2%)
Osteoarthritis No 1728 (59.8%) 205 (53.8%) 0.025 6 (0.18%)
Yes 1161 (40.2%) 176 (46.2%)
Other comorbidity No 2256 (79.2%) 290 (77.3%) 0.408 52 (1.59%)
Yes 593 (20.8%) 85 (22.7%)
Hospital admissions No 2352 (83.4%) 279 (74.8%) <0.0001 82 (2.5%)
Yes 469 (16.6%) 94 (25.2%)
Emergency room visits No 2295 (81.4%) 274 (73.7%) <0.001 84 (2.56%)
Yes 525 (18.6%) 98 (26.3%)
Injury-related admission No 2778 (96.0%) 357 (93.5%) 0.022 0
Yes 116 (4.0%) 25 (6.5%)
Other infection – related admission
No 2849 (98.4%) 370 (96.9%) 0.026 0
Yes 45 (1.6%) 12 (3.1%)
Pneumonia – related admission
No 2868 (99.1%) 378 (99.0%) 0.774 0
Yes 26 (0.9%) 4 (1.0%)
Confusion – related admission No 2872 (99.2%) 376 (98.4%) 0.106 0
Yes 22 (0.8%) 6 (1.6%)
Table e-4: Treatments in the study sample at the time of baseline visit (MAO: Monoamine Oxidase; COMT: Catechol-O-Methyltransferase)
Variable Frequent faller at follow-up p-value Missing Rate
No (n=2894) Yes (n= 382 )
L-dopa No 587 (20.3%) 29 (7.6%) <0.0001 0
Yes 2307 (79.7%) 353 (92.4%)
Dopamine agonist No 1691 (58.4%) 217 (56.8%) 0.545 0
Yes 1203 (41.6%) 165 (43.2%)
MAO-B inhibitor No 2156 (74.5%) 316 (82.7%) <0.002 0
Yes 738 (25.5%) 66 (17.3%)
COMT inhibitor No 2473 (85.5%) 303 (79.3%) 0.002 0
Yes 421 (14.5%) 79 (20.7%)
Amantadine No 2477 (85.6%) 316 (82.7%) 0.137 0
Yes 417 (14.4%) 66 (17.3%)
Antidepressant No 2181 (75.4%) 230 (60.2%) <0.0001 0
Yes 713 (24.6%) 152 (39.8%)
Cognitive enhancers No 2750 (95.0%) 337 (88.2%) <0.0001 0
Yes 144 (5.0%) 45 (11.8%)
Stimulants No 2863 (98.9%) 374 (97.9%) 0.083 0
Yes 31 (1.1%) 8 (2.1%)
Antipsychotics No 2811 (97.1%) 361 (94.5%) 0.006 0
Yes 83 (2.9%) 21 (5.5%)
Anticholinergics No 2736 (94.5%) 362 (94.8%) 0.856 0
Yes 158 (5.5%) 20 (5.2%)
Physical therapy No 1945 (67.2%) 224 (58.6%) 0.001 0
Yes 949 (32.8%) 158 (41.4%)
Occupational therapy No 2622 (90.6%) 332 (86.9%) 0.023 0
Yes 272 (9.4%) 50 (13.1%)
Speech therapy No 2620 (90.5%) 334 (87.4%) 0.056 0
Yes 274 (9.5%) 48 (12.6%)
Exercise program No 984 (34.0%) 151 (39.5%) 0.033 0
Yes 1910 (66.0%) 231 (60.5%)
Social worker/counseling No 2682 (92.7%) 344 (90.1%) 0.070 0
Yes 212 (7.3%) 38 (9.9%)
Mental Health tx or referral No 2633 (91.0%) 334 (87.4%) 0.026 0
Yes 261 (9.0%) 48 (12.6%)
Deep brain stimulation No 2702 (93.4%) 300 (78.5%) <0.0001 0
Yes 192 (6.6%) 82 (21.5%)
Table e-5: New treatments, or changes in treatment implemented between visits (MAO:
Monoamine Oxidase; COMT: Catechol-O-Methyltransferase; DBS: Deep Brain Stimulation)
Variable Frequent faller at follow-up p-value Missing Rate
No (n=2894) Yes (n= 382 )
L-dopa Continued 2771 (95.7%) 369 (96.6%) 0.565 0
Removed 26 (0.9%) 4 (1.0%)
Added 97 (3.4%) 9 (2.4%)
Dopamine agonist Continued 2791 (96.4%) 368 (96.3%) 0.714 0
Removed 33 (1.1%) 6 (1.6%)
Added 70 (2.4%) 8 (2.1%)
MAO-B inhibitor Continued 2799 (96.7%) 373 (97.6%) 0.448 0
Removed 28 (1.0%) 4 (1.0%)
Added 67 (2.3%) 5 (1.3%)
COMT inhibitor Continued 2845 (98.3%) 374 (97.9%) 0.841 0
Removed 17 (0.6%) 3 (0.8%)
Added 32 (1.1%) 5 (1.3%)
Amantadine Continued 2812 (97.2%) 367 (96.1%) 0.293 0
Removed 26 (0.9%) 3 (0.8%)
Added 56 (1.9%) 12 (3.1%)
Antidepressant Continued 2818 (97.4%) 372 (97.4%) 0.986 0
Removed 17 (0.6%) 2 (0.5%)
Added 59 (2.0%) 8 (2.1%)
Cognitive enhancers Unchanged 2869 (99.1%) 379 (99.2%) 0.762 0
Removed 4 (0.1%)
Added 21 (0.7%) 3 (0.8%)
Stimulants Continued 2887 (99.8%) 382 (100.0%) 0.336 0
Removed
Added 7 (0.2%)
Antipsychotics Continued 2883 (99.6%) 380 (99.5%) 0.498 0
Removed 2 (0.1%) 1 (0.3%)
Added 9 (0.3%) 1 (0.3%)
Anticholinergics Continued 2860 (98.8%) 377 (98.7%) 0.693 0
Removed 14 (0.5%) 3 (0.8%)
Added 20 (0.7%) 2 (0.5%)
Physical therapy No 1990 (68.8%) 231 (60.5%) 0.001 0
Yes 904 (31.2%) 151 (39.5%)
Occupational therapy No 2661 (91.9%) 328 (85.9%) <0.0001 0
Yes 233 (8.1%) 54 (14.1%)
Speech therapy No 2587 (89.4%) 316 (82.7%) <0.001 0
Yes 307 (10.6%) 66 (17.3%)
Exercise program No 2335 (80.7%) 306 (80.1%) 0.788 0
Yes 559 (19.3%) 76 (19.9%)
Social worker/counseling No 2720 (94.0%) 342 (89.5%) 0.001 0
Yes 174 (6.0%) 40 (10.5%)
Mental Health treatment or referral
No 2730 (94.3%) 344 (90.1%) 0.001 0
Yes 164 (5.7%) 38 (9.9%)
Deep brain stimulation No 2799 (96.7%) 359 (94.0%) 0.007 0
Yes 95 (3.3%) 23 (6.0%)
Table e-6: Multivariable model building: Block 1 (OR: Odds Ratio; DBS: Deep Brain Stimulation)
Effects Coefficient SEM p-value OR 95% CI for OR
Age of onset 0.029 0.00799 0.0003 1.029 (1.013, 1.046)
Female sex 1.9069 0.847 0.0244 6.732 (1.28, 35.411)
Age * Sex -0.0286 0.0126 0.0227 0.972 (0.948, 0.996)
Disease duration 0.0208 0.0101 0.0401 1.021 (1.001, 1.042)
Other Relative as Regular Care Partner 0.7191 0.2745 0.0088 2.053 (1.198, 3.515) Certainty of Diagnosis > 90% -0.6767 0.174 0.0001 0.508 (0.361, 0.715) Motor fluctuations at baseline visit 0.7077 0.1257 <0.0001 2.029 (1.586, 2.596) Prior admission for infection 0.7273 0.35 0.0377 2.069 (1.042, 4.109)
L-dopa at baseline visit 0.508 0.2156 0.0185 1.662 (1.089, 2.536)
Antidepressant at baseline visit 0.4648 0.1216 0.0001 1.592 (1.254, 2.02) Cognitive enhancers at baseline visit 0.5965 0.1989 0.0027 1.816 (1.229, 2.682) History of DBS at baseline visit 1.184 0.1704 <0.0001 3.267 (2.34, 4.563)
Table e-7: Multivariable model building: adding Block 2 to Block 1 (OR: Odds Ratio; DBS:
Deep Brain Stimulation; PDQ39: 39-Item Parkinson’s Disease Questionnaire; MCSI: H&Y:
Hoehn and Yahr)
Effects Coefficient SEM p-value OR 95%CI for OR
Female sex 1.7947 0.8827 0.042 6.017 (1.067, 33.942)
Age * Sex -0.0273 0.0131 0.0369 0.973 (0.948, 0.998)
Certainty of Diagnosis > 90% -0.3985 0.1896 0.0356 0.671 (0.463, 0.973) Motor fluctuations at baseline visit 0.454 0.1357 0.0008 1.575 (1.207, 2.054)
L-dopa at baseline visit 0.5946 0.2448 0.0151 1.812 (1.122, 2.928)
Antidepressant at baseline visit 0.3458 0.1302 0.0079 1.413 (1.095, 1.824) History of DBS at baseline visit 0.916 0.1759 <0.0001 2.499 (1.771, 3.528)
PDQ39 summary score 0.0217 0.00467 <0.0001 1.022 (1.013, 1.031)
MCSI 0.0122 0.0053 0.0217 1.012 (1.002, 1.023)
H&Y stage 2 (ref:1) 0.7273 0.2819 0.0099 2.069 (1.191, 3.596)
H&Y stage 3 (ref:1) 1.0232 0.3012 0.0007 2.782 (1.542, 5.021)
Semantic Fluency -0.0436 0.0114 0.0001 0.957 (0.957, 4.376)
Table e-8: Multivariable model building: adding Block 3 to Blocks 1 and 2 (OR: Odds Ratio;
DBS: Deep Brain Stimulation; PDQ39: 39-Item Parkinson’s Disease Questionnaire; H&Y:
Hoehn and Yahr)
Effects Coefficient SEM p-value OR 95% CI for OR
Female sex 1.8016 0.8895 0.0428 6.059 (1.06, 34.64)
Age * Sex -0.0276 0.0132 0.0363 0.973 (0.948, 0.998)
Certainty of PD Diagnosis > 90% -0.4215 0.1911 0.0274 0.656 (0.451, 0.954) Motor fluctuations at baseline visit 0.4244 0.1373 0.002 1.529 (1.168, 2.001)
L-dopa at baseline visit 0.5875 0.2456 0.0167 1.8 (1.112, 2.912)
Antidepressant at baseline visit 0.3262 0.131 0.0128 1.386 (1.072, 1.791) History of DBS at baseline visit 1.0263 0.1792 <0.0001 2.791 (1.964, 3.965)
PDQ39 summary score 0.0208 0.00471 <0.0001 1.021 (1.012, 1.03)
H&Y stage 2 (ref:1) 0.6813 0.2826 0.0159 1.976 (1.136, 3.439)
H&Y stage 3 (ref:1) 0.9489 0.3021 0.0017 2.583 (1.429, 4.669)
Semantic Fluency -0.046 0.0115 <0.0001 0.955 (0.934, 0.977)
Added Amantadine baseline visit 0.8332 0.3513 0.0177 2.301 (1.156, 4.58)
DBS (between visits) 0.6123 0.283 0.0305 1.845 (1.059, 3.212)
