A Study to Identify the Correlates of Pseudobulbar Affect in Patients with Parkinsonian Disorders and ALS Neepa Patel, M.D., Michele K. York, Ph.D., Cecile Phan, M.D. and Joohi Jimenez-Shahed, M.D.

Parkinson’s Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, Texas Amyotrophic Lateral Sclerosis Association Center, Department of Neurology, Baylor College of Medicine, Houston, Texas

RESULTS (continued…)

DISCUSSION

REFERENCES

BACKGROUND Pseudobulbar affect (PBA) is a frontal disinhibition syndrome associated with

inappropriate laughter and crying to minor stimulus, independent of affective disturbance1.

PBA has been primarily studied in amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS)2,3. Recent studies have demonstrated PBA in other neurological conditions4 such as Parkinson’s disease (PD), and atypical parkinsonism (aP) such as corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), multiple system atrophy (MSA)5,6.

We have observed that PBA is more common in parkinsonian patients with associated cognitive impairment. However PBA has been observed in ALS patients with or without cognitive impairment

Our objective is to determine whether cognitive and psychiatric co-morbidities correlate with PBA in patients with PD, atypical parkinsonism (aP) and ALS. METHODS

We aimed to enroll 50 PD patients, 30 ALS patients and 30 aP (10 PSP, 10 MSA and 10 CBD). In this IRB approved study patients were recruited from the Parkinson’s disease or ALS centers.

Any person with a definite diagnosis of PD, aP or ALS identified through clinical practice was eligible to participate.

Exclusion criteria:

>30% of all questionnaire was incomplete Patients with advanced disease who are unable to communicate answers Non-English speaking patients

Participating subjects completed a series of self-report questionnaires:

Center for Neurological Study-Lability Scale for PBA (CNS-LS) Beck Depression Inventory-II (BDI) State-Trait Anxiety Inventory- Trait (STAI) Self and Other Apathy Evaluation Scales (AES) The Short Form-36 quality of life measure (SF36-QOL)

SF36 PCS = SF36- QOL physical component score; SF 36- QOL mental component score **statistically significant; * trend towards statistical significance

1. Moore, S.R., Gresham, L.S., Bromberg, M.B., Kasarkis, E.J., Smith, R.A., 1997. A self report measure of affective lability. J Neurol Neurosurg Psychiatry. 63, 89-93.

2. Pioro EP, Brooks BR, Cummings J, et al. Dextromethorphan Plus Ultra Low-Dose Quinidine Reduces Pseudobulbar Affect. Annals of neurology 2010;68:693-70

3. Garnock-Jones KP. Dextromethorphan/quinidine: in pseudobulbar affect. CNS drugs 2011;25:435-445. 4. Work SS, Colamonico JA, Bradley WG, Kaye RE. Pseudobulbar affect: an under-recognized and under-

treated neurological disorder. Advances in therapy 2011;28:586-601. 5. Strowd R, Cartwright M, Okun M, Haq I, Siddiqui M. Pseudobulbar affect: prevalence and quality of life

impact in movement disorders. Journal of Neurology 2010;257:1382-1387. 6. Alvarez-Gonzalez E, Maragoto-Rizo C, Arteche-Prior M, Perez-Parra S, Carballo M, Alvarez-Gonzalez L.

[A clinical and epidemiological description of a series of patients diagnosed as suffering from progressive supranuclear palsy]. Revista de neurologia 2004;39:1006-1010.

7. Colamonico J, Formella A, Bradley W. Pseudobulbar affect: burden of illness in the USA. Advances in therapy 2012;29:775-798.

8. Parvizi J, Coburn KL, Shillcutt SD, Coffey CE, Lauterbach EC, Mendez MF. Neuroanatomy of Pathological Laughing and Crying: A Report of the American Neuropsychiatric Association Committee on Research. J Neuropsychiatry Clin Neurosci 2009;21:75-87

9. Garnock-Jones KP. Dextromethorphan/quinidine: in pseudobulbar affect. CNS drugs 2011;25:435-445.

RESULTS There were no statistically significant differences in degree of PBA as measured on the CNS-

LS scores between groups

There is increased cognitive impairment in the ALS and aP groups compared to the PD cohort.

Figure 1: Distribution of Diagnoses in the Recruited Cohorts

Table 2: Cognitive and Psychiatric correlates of PBA between groups PSP 38%

MSA 34%

CBD 28%

aP 27%

ALS 23%

PD 50% n=53

n=25

n=29 n=10

n=11 n=8

Figure 2 and Table 2: Prevalence of PBA and Mean Questionnaire Scores By Cohorts

Table 1: Patient Demographics

RESULTS (continued…) There was a positive correlation with PBA and anxiety scores in PD and aP

groups, this association was not found in the ALS group.

Depression scores and Mental Health QOL impairments positively correlate with PBA scores only in the PD group.

MoCA scores did not correlate with PBA for any of groups; however there are observed differences between the groups.

This study demonstrates that, despite its definition, PBA correlates with affective disturbance in PD and aP patients but not in ALS patients.

The results suggest that individuals with parkinsonian disorders and PBA symptoms should be evaluated and/or treated for co-morbid mood problems.

Previous studies have reported increased burden of illness7 associated with PBA and an association between depression and PBA in a movement disorders population5. In addition to these observations our study also demonstrates an association between PBA and anxiety in parkinsonian patients.

Limitations of this study include:

Small sample size Exclusion of patients with advanced disease due to impaired language

and communication in all groups MoCA scores may be artificially reduced to disease specific symptoms

affecting writing

There are no statistically significant differences in demographics between the aP subgroups measured through Chi-square/ t-tests and ANOVA.

PD ALS aP

PBA p-value PBA p-value PBA p-value

MoCA -0.193 0.166 -0.288 0.163 0.062 0.751

BDI 0.349 0.011** 0.090 0.670 0.337 0.074*

STAI 0.456 0.001** 0.253 0.222 0.456 0.013**

Self AES 0.033 0.816 0.050 0.812 0.002 0.993

Other AES -0.79 0.630 0.386 0.084 0.052 0.798

SF36 PCS -0.157 0.267 0.110 0.602 0.231 0.228

SF36 MCS -0.286 0.038** -0.129 0.540 -0.314 0.097*

There are no intragroup differences between the 3 subgroups recruited on demographic and individual questionnaires.

The proposed mechanism of PBA is disruption of inhibitory signals descending from the cerebral cortex to motor regions of the brainstem implicated in the regulation of emotional output8.

Our findings suggest that an alternate pathophysiological mechanism for PBA may be present in ALS compared to parkinsonian patients.

Future studies should be directed toward evaluation of the pathophysiologic mechanism of PBA in each neurological conditions.

Additional testing of mood effects of dextromethorphan-quinidine (an FDA- approved treatment for PBA9), or effect of antidepressants on PBA should be considered in in patients with parkinsonian conditions.

CONCLUSION

PD ALS aP p-value

MoCA 25.1±3.94 23.3± 3.30 21.4±5.07 0.001**

PBA 10.1±3.83 11.2±7.00 11.7±5.23 0.378

BDI 10.7±9.36 11.3±6.64 14.1±7.74 0.192

STAI 36.4±10.54 35.9±8.03 37.9±10.1 0.733

Self AE

54.6±6.67 53.9±7.66 50.2±10.2 0.058*

Other AE

53.9±8.32 49.8±9.92 47.6±12.4 0.38

**statistically significant * trend towards statistical significance

OBJECTIVE

PD ALS aP p-value

Age (years) 63.4 ± 10.5 61.6 ± 8.7 68.8 ± 7.9 0.36

Duration of Illness 5.0±4.8 2.4±1.6 3.9±2.3 0.54

Gen

der Male 30 13 17

0.795 Female 23 13 12

Educ

atio

n 16 years 13 2 7

Ethn

icity

Caucasian 48 21 25

0.694 Hispanic 2 3 2

African American 2 1 1

Other 1 0 1

Poster available for download.

Slide Number 1

A Study to Identify the Correlates of Pseudobulbar Affect in Patients with Parkinsonian Disorders and ALS

Neepa Patel, M.D., Michele K. York, Ph.D., Cecile Phan, M.D. and Joohi Jimenez-Shahed, M.D.

Parkinson’s Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, Texas

Amyotrophic Lateral Sclerosis Association Center, Department of Neurology, Baylor College of Medicine, Houston, Texas

RESULTS (continued…)

DISCUSSION

REFERENCES

BACKGROUND

Pseudobulbar affect (PBA) is a frontal disinhibition syndrome associated with inappropriate laughter and crying to minor stimulus, independent of affective disturbance1.

PBA has been primarily studied in amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS)2,3. Recent studies have demonstrated PBA in other neurological conditions4 such as Parkinson’s disease (PD), and atypical parkinsonism (aP) such as corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), multiple system atrophy (MSA)5,6.

We have observed that PBA is more common in parkinsonian patients with associated cognitive impairment. However PBA has been observed in ALS patients with or without cognitive impairment

Our objective is to determine whether cognitive and psychiatric co-morbidities correlate with PBA in patients with PD, atypical parkinsonism (aP) and ALS.

METHODS

We aimed to enroll 50 PD patients, 30 ALS patients and 30 aP (10 PSP, 10 MSA and 10 CBD). In this IRB approved study patients were recruited from the Parkinson’s disease or ALS centers.

Any person with a definite diagnosis of PD, aP or ALS identified through clinical practice was eligible to participate.

Exclusion criteria:

>30% of all questionnaire was incomplete

Patients with advanced disease who are unable to communicate answers

Non-English speaking patients

Participating subjects completed a series of self-report questionnaires:

Center for Neurological Study-Lability Scale for PBA (CNS-LS)

Beck Depression Inventory-II (BDI)

State-Trait Anxiety Inventory- Trait (STAI)

Self and Other Apathy Evaluation Scales (AES)

The Short Form-36 quality of life measure (SF36-QOL)

SF36 PCS = SF36- QOL physical component score; SF 36- QOL mental component score

**statistically significant; * trend towards statistical significance

Moore, S.R., Gresham, L.S., Bromberg, M.B., Kasarkis, E.J., Smith, R.A., 1997. A self report measure of affective lability. J Neurol Neurosurg Psychiatry. 63, 89-93.

Pioro EP, Brooks BR, Cummings J, et al. Dextromethorphan Plus Ultra Low-Dose Quinidine Reduces Pseudobulbar Affect. Annals of neurology 2010;68:693-70

Garnock-Jones KP. Dextromethorphan/quinidine: in pseudobulbar affect. CNS drugs 2011;25:435-445.

Work SS, Colamonico JA, Bradley WG, Kaye RE. Pseudobulbar affect: an under-recognized and under-treated neurological disorder. Advances in therapy 2011;28:586-601.

Strowd R, Cartwright M, Okun M, Haq I, Siddiqui M. Pseudobulbar affect: prevalence and quality of life impact in movement disorders. Journal of Neurology 2010;257:1382-1387.

Alvarez-Gonzalez E, Maragoto-Rizo C, Arteche-Prior M, Perez-Parra S, Carballo M, Alvarez-Gonzalez L. [A clinical and epidemiological description of a series of patients diagnosed as suffering from progressive supranuclear palsy]. Revista de neurologia 2004;39:1006-1010.

Colamonico J, Formella A, Bradley W. Pseudobulbar affect: burden of illness in the USA. Advances in therapy 2012;29:775-798.

Parvizi J, Coburn KL, Shillcutt SD, Coffey CE, Lauterbach EC, Mendez MF. Neuroanatomy of Pathological Laughing and Crying: A Report of the American Neuropsychiatric Association Committee on Research. J Neuropsychiatry Clin Neurosci 2009;21:75-87

Garnock-Jones KP. Dextromethorphan/quinidine: in pseudobulbar affect. CNS drugs 2011;25:435-445.

RESULTS

There were no statistically significant differences in degree of PBA as measured on the CNS-LS scores between groups

There is increased cognitive impairment in the ALS and aP groups compared to the PD cohort.

Figure 1: Distribution of Diagnoses in the Recruited Cohorts

Table 2: Cognitive and Psychiatric correlates of PBA between groups

n=53

n=25

n=29

n=10

n=11

n=8

Figure 2 and Table 2: Prevalence of PBA and Mean Questionnaire Scores By Cohorts

Table 1: Patient Demographics

RESULTS (continued…)

There was a positive correlation with PBA and anxiety scores in PD and aP groups, this association was not found in the ALS group.

Depression scores and Mental Health QOL impairments positively correlate with PBA scores only in the PD group.

MoCA scores did not correlate with PBA for any of groups; however there are observed differences between the groups.

This study demonstrates that, despite its definition, PBA correlates with affective disturbance in PD and aP patients but not in ALS patients.

The results suggest that individuals with parkinsonian disorders and PBA symptoms should be evaluated and/or treated for co-morbid mood problems.

Previous studies have reported increased burden of illness7 associated with PBA and an association between depression and PBA in a movement disorders population5. In addition to these observations our study also demonstrates an association between PBA and anxiety in parkinsonian patients.

Limitations of this study include:

Small sample size

Exclusion of patients with advanced disease due to impaired language and communication in all groups

MoCA scores may be artificially reduced to disease specific symptoms affecting writing

There are no statistically significant differences in demographics between the aP subgroups measured through Chi-square/ t-tests and ANOVA.

There are no intragroup differences between the 3 subgroups recruited on demographic and individual questionnaires.

The proposed mechanism of PBA is disruption of inhibitory signals descending from the cerebral cortex to motor regions of the brainstem implicated in the regulation of emotional output8.

Our findings suggest that an alternate pathophysiological mechanism for PBA may be present in ALS compared to parkinsonian patients.

Future studies should be directed toward evaluation of the pathophysiologic mechanism of PBA in each neurological conditions.

Additional testing of mood effects of dextromethorphan-quinidine (an FDA- approved treatment for PBA9), or effect of antidepressants on PBA should be considered in in patients with parkinsonian conditions.

CONCLUSION

**statistically significant

* trend towards statistical significance

OBJECTIVE

Poster available for download.

PDALSaP

PBAp-valuePBAp-valuePBAp-value

MoCA-0.1930.166-0.2880.1630.0620.751

BDI0.3490.011**0.0900.6700.3370.074*

STAI0.4560.001**0.2530.2220.4560.013**

Self AES0.0330.8160.0500.8120.0020.993

Other AES-0.790.6300.3860.0840.0520.798

SF36 PCS-0.1570.2670.1100.6020.2310.228

SF36 MCS-0.2860.038**-0.1290.540-0.3140.097*

PDALSaPp-value

MoCA25.1±3.9423.3± 3.3021.4±5.070.001**

PBA10.1±3.8311.2±7.0011.7±5.230.378

BDI10.7±9.3611.3±6.6414.1±7.740.192

STAI36.4±10.5435.9±8.0337.9±10.10.733

Self AE54.6±6.6753.9±7.6650.2±10.20.058*

Other AE53.9±8.3249.8±9.9247.6±12.40.38

*

Chart1

PD

ALS

aP

%

% Diagnosed with PBA

20.8

29.2

34.5

Data

Subject IDDate evalAge onsetDOBeducationGEthnicityDiagnosisPsych hxPMHDA modulators5HT modulatorsmood stablizersDementiaAEDsAnxiolyticsSleep aidesStimulantsOtherMoCA TotMoCA ScoreVis/spatialNamingAttenLanguageAbstractionDelay recallorientPBAQ1PBAQ2PBAQ3PBAQ4PBAQ5PBAQ6PBAQ7PBA TotBDI Q1BDI Q2BDIQ3BDIQ4BDIQ5BDIQ6BDIQ7BDIQ8BDIQ9BDIQ10BDIQ11BDIQ12BDIQ13BDIQ14BDIQ15BDIQ16BDIQ17BDIQ18BDIQ19BDIQ20BDIQ21BDI TotAnxQ21AnxQ22AnxQ23AnxQ24AnxQ25AnxQ26AnxQ27AnxQ28AnxQ29AnxQ30AnxQ31AnxQ32AnxQ33AnxQ34AnxQ35AnxQ36AnxQ37AnxQ38AnxQ39AnxQ40AnxTotAnx Sd ScoreSF-36 PFSF-36 RPSF-36 BPSF-36 GHSF-36 VTSF-36 SFSF-36 RESF-36 MHSF-36 PSF-36 MSApQ1SApQ2SApQ3SApQ4SApQ5SApQ6SApQ7SApQ8SApQ9SApQ10SApQ11SApQ12SApQ13SApQ14SApQ15SApQ16SApQ17SApQ18SAptotOap relationOApQ1OApQ2OApQ3OApQ4OApQ5OApQ6OApQ7OApQ8OApQ9OApQ10OApQ11OApQ12OApQ13OApQ14OAp15OApQ16OApQ17OApQ18OApTotMoCA-PBA pDMoCA-noPBAPDBDI-PBA pDBDI-no PBA PDAnx-PBA PDAnx-no PBA PDSFPH-PBA PDSFPH-noPBA PDSFMC-PBA PDSFMC-no pBA PDSA-PBA PDSA-noPBA PDOap-PBA PDOap-noPBA PDMoCA-PBA ALSMoCA-noPBA ALSAnx-PBA ALSAnx-noPBA ALSSFPC-PBA ALSSFPC-noPBASFMC-PBAALSSFMC-noPBA ALSSA-PBA ALSSA-noPBA ALSOA-PBA ALSOA-no PBA ALSMoCA-PBA aPMoCA-noPBA aPBDI-PBA aPBDI-no PBA aPAnx-PBA aPAnx-no PBA aPSFPH-PBA aPSFPH-noPBA aPSFMC-PBA aPSFMC-no pBA aPSA-PBA aPSA-noPBA aPOap-PBA aPOap-noPBA aPBDI-PBA ALSBDI-noPBA-ALS

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MA0263/5/12591/29/53HSFC1depressionAzilect3026 +15351246211111180111001100010011001131322222422311212222322416242.347.0641.4136.2545.8556.8544.2252.8239.8652.9133322124413444343353--4443313441343434446019193116.5552.884261

LL0273/6/12579/7/51UMC1anxiety, depressionET, hypertensionneurontin302753622363332313181101000000--1111101100922132212212322223322415850.2732.3632.9641.0242.7235.0332.5635.9342.8233.6743332324423434332254wife2232222332243332224426155145.1351.026342

BA0283/7/12527/31/52BAFC1anxiety, depressionmigraineMirapexCymbalta302653632162333334211111201211112112122102523342333422333333333588429.6737.2637.1835.339.635.0332.5641.5634.239.5844444143311334343356sister444441444114444444632942447.0822.095648

BK0293/15/12657/30/46BAMC2nonelipidtrazodonemelatonin3024335224512332321602100121110001010110013323223--3232233233232486648.6139.7162.1245.7848.9745.9444.2247.1950.3345.273333--1--3313123333341wife222122222111133222331930264552628.9745.4521.8750.0245633557

JB0303/21/12559/30/56UMC1nonelipid302743632361111111700000000000000001000012321132131121232221254057.0356.8562.1250.5548.9756.8555.8847.1958.7849.1433443133313434343456not completed--------------------------------------2853050.155.283763

VW0313/22/124911/13/59UFAA1nonelipid302543332462221311120111100003130132211332744--11434132233231213436414.9417.6719.8630.5345.8513.2255.8841.5610.2452.8833444144314324344459daughter4244414421422423445522133431.9326.294262

RL0323/22/12543/26/33collegeMC1dementia, depressionAzilect, Stalevoariceptseroquel301223122013222211131102001100113033123332932221432231234132131456314.9417.6737.1823.3845.857.769.2347.1921.7232.3221121313143423211136daughter112113122322221211302322753.0452.196257

RN0333/26/12693/17/4018yrsMC3htn, lipidSinemettrazodone30242363226111111170300101000000111011111232331421122222221322425931.7827.4741.8328.1542.7235.0320.8941.5633.6735.6444--33134413434433354daughter44433133311444334456222887312735.2453.1434.7460.9957595144

VW0343/30/12775/1/30MAFC1mcisinemetlyrica301923422062121112101101102101100022010231921211322121113112112314919.1517.6719.8661.5120.8713.2255.8852.8216.5551.0242112124211433432242daughter2322112221142131223427165063.0157.195863

SB0354/2/12498/2/60collegeFU1depression/anxietyMirapexZoloft,xanax302643522463221211120001001101112111011111533322422232243232232517531.7827.4746.0645.7842.7235.03-2.4335.9345.1322.0944444444311444443363spouse434441443114444444612512551.7657.285451

JW0364/2/12682/8/43MAMC1nonelipid, htn3029536324611111117000000000001001000110411111311111113111111243950.7251.9651.1345.7839.656.8551.9961.2747.0855.2844334124--11423443356daughter4444444441143444446528165067.5935.985357

KT0374/5/12564/5/55collegeMC1ADHDlipid, hypotestosteroneVyvance, Intuniv, Dextrostatlunesta30213261126214213114010100000001001010000532211331222232122121385554.9354.451.1343.448.9729.5855.8850.0151.3445.1434343114311443244453wife344442344113323443562783455.5842.336153

WF0384/5/12849/19/2318yrsMC1noneTIA, cardiac valve replacementRequip, sinemetativan3028535324611111117000000000000001101110511111221113111214122304640.242.1641.8348.1745.8535.03-2.4350.0150.126.2944233124411334--------37not completed--------------------------------------2693255.82256.965758

CS0394/10/12753/21/33collegeMC1mci, EtOH abuseSinemetclonazepam302243522163131111110000000000033011002211313111123112114332111345027.5739.7141.4142.4533.3645.9455.8844.3831.9352.1932224324321223212242wife3342113242111343224228164739.4451.8347

FG0404/11/126012/5/50collegeMC1DM, lipid, hypothyroid30234352216112121210000000000000000100100212231321111111111111274257.0347.0662.1250.5555.2156.8555.8858.4653.0457.2844444134411444444462not completed--------------------------------------2552949.3541.552

EB0414/16/12408/15/69BAMC1anxietyxanax302753532361112213110110101201111111101101622232223323333232323506757.0356.8562.1250.5545.8545.9440.3341.5663.0135.9843344134312444443358??444441434114444433601642735.6843.5859

EM0424/17/12638/1/45collegemC2PBAlipidambiennuedexta302443522262424324210110110110111111111111723232332222223222222456340.239.7151.1343.448.9735.0332.5635.9347.4834.8433333232223332233348??343223223231122222412326147443237.8123.0941.6638.3755474961

RW0434/19/12683/2/38collegeMC2lipidSinemet3013034111322111119110110000301312--021232231331441141333333331516927.5717.6762.1238.6330.2429.5820.8938.7437.8129.911111311123431111128daughter121112111334322111311622189454627.6139.2325.6448.3137605434

GB0445/8/12747/18/33collegeFC1htn, polymyalgia rheumaticazilect30255362216212132112000000000000001000000122211112111111111112254146.5149.5155.3648.1742.7245.9444.2244.3851.7642.3344343133311334443354------------------------------------2502348.1547.3463

PC0455/9/12492/14/62collegeMC1anxietybasal cellativan30285363236111111171101101100111012021101633342332231233231232506857.0356.8562.1255.3245.8540.4932.5633.1167.5926.9633444134311333343353------------------------------------222046.2357.4554

DM0465/9/12499/27/60collegeMC1htnazilect30275353236112121210010000010010101201000823111323211121112222345054.9356.8562.1243.452.0956.8555.8850.0155.5851.8344444134411444344461wife4444313441144444446127482428.6563.5159

BB0475/9/12749/4/36HSMC13025+1534223622111119000100000010101100112914131121111412111113324844.4149.5162.1248.1752.0956.8540.3335.9355.8241.533442344413443233357spouse334222123213323222422104258.2755.0656

LG0485/14/12487/28/63collegeFC1anxiety, migranes, depressionhtnlexaproimitrex3028536224632212121301001000001100101011191211132231111211112284257.0351.9651.1352.9345.8545.9455.8850.0153.5448.4744433244411444333358spouse4443313421131444435326122043.9159.5152

GS0495/21/12534/6/48HSMC1hyperlipid, sleep apnea, COPDrequip, Sinemet, Comtan, Amantidine3027+14352256111111170111101000011111111211632332432221234222221476529.6737.2655.3635.345.8545.9432.5644.3839.4443.5843433223213223332247wife444221243113133433482523351.8655.0161

DT0505/23/12505/2/61BSMC1Azilect3025536122611111117000000000001001001110512131321111113111121294552.8247.0646.0655.3242.7240.4944.2258.4649.3547.3423333224311433344452----------------------------------------2462838.5933.6850

LF0515/24/12785/23/32HSMC1MCIlipid, htnsinemetxanax3015+1323110511111117000000000000001000111422111331111111111112274240.249.5132.9640.0639.656.8555.8852.8235.6857.4544434114411444444459--444441444114444444632854361.516157

SE0525/24/12661/24/44BSFC3hypotension, lipid30305363256212111210010000000000011000010411111111211211212212264229.6737.2662.1257.748.9756.8528.6755.6445.4550.0243444443411444344463husband4443414441144444446227121415462741.9340.4938.7725.8649375060

MS0536/5/12621/10/42CollegeFC1thyroid,htnAzilect, Stalevo3025335323611111117000000000000000000000011141111111111111111233940.256.8555.3652.9367.756.8555.8858.4648.1563.5144444144411444444463none--------------------------------------2992824.0934.7948

MN0546/11/12587/6/5111yrs HSmC1Sinemet, Comtan3021+14352225111111170000000000011111111111111111111203442.342.1662.1260.0848.9729.5855.8864.0946.2355.064314434421434432454wife4344414441144444446226451.9939.1459

TB0556/11/12448/29/50JDMC1thyroidSinemet CR, comtan, azilect30275352246111111170000000000100012101104811111221111121111112243838.0932.3637.1836.2558.3329.5855.8858.4628.6559.5143444143312444443359--4344414241143344345748.4

ST0566/12/126411/25/41MDMC1htn, DM, CADSinemet, Amantidine3021325022611111117000000000000000000000057.0356.8562.1260.0870.8229.5855.8864.0958.2755.0144444331312333334456daughter4444413441443444346351.12

MW0576/13/12537/9/55FC2RLSRequip, amantidine30285353156222112111000100001001101010001712111221211112112211274448.6154.455.3662.4764.5856.8555.8858.4653.1460.9934444134312443344459husband43443134411443443357272784222224.4136.4650.958.2362626355

RM0586/14/128110/16/27MDMC2thrombosis, lipidSinemet3026535223611211118000000001001001101011711221322122112122121324821.2632.3637.1813.8536.4818.6728.6747.1923.0938.3732344323311332422247daughter4333312221133223334414243013472840.2715.5320.4768.7152575344

TT0596/14/12618/12/45collegemC1BPHRequip XL, Sinemet30264363226211121191001001000111011111101233221342232112222122425950.7247.0629.1537.6845.8518.6744.2235.9343.9133.684343313341144443352wife3443313331133444451

MS0606/21/127812/16/32collegeFC1lipid, PN3025536320611111117000000000000001000010211111111111111111111203548.6156.8551.1362.4758.3356.8555.8861.2751.866144444134411444344461none--------------------------------------

JR0616/19/12528/13/56collegeFC3depression, insomiaSinemet, amantidinetrazadoneneurontinoxybutynin3022333223631211211110103000000011001010923233432222222222222466814.9447.0662.1245.7836.4851.432.5652.8239.2348.3144433134411444444460--4443314441144444446116254844.08344850

GM0626/28/12651/1/42collegeMC1CADAzilect, mirapexlyrica3024426322611111117000000000000001201011612141312121212121131334927.5734.8137.1845.7839.645.94-2.4355.6438.5934.7933233233322433323350spouse33332232411444333351

RR0637/2/124910/13/54JDMC1alzect, mirapex, amantidinelexaproklonapin3028536323611111117000000000000000301100522411411111111111111284557.0351.9662.1263.945.8529.5844.2252.8261.5139.1443344144311423444457wife43444134411333344457

JD0645/15/125711/19/40HSMC1htnSinemet, requipklonapinFlexeril, quinine302143322254241414200010000000333123012312322441213111332123123426338.0937.2646.0640.0648.9729.5840.3352.8231.146.2924312333412344414250wife43322222422433322247

MM0657/5/125411/18/508thMH1lipid, stroke, DMStalevo, mirapex, azilectneurontin3016+103211363421132161311002003330011112332933342343432233132341568117.0520.1229.1525.7645.8529.5820.8941.5620.3540.4733213333411444443353wife33322334412443443355

MF0667/9/12564/4/5212thFC1htnsinemetartane3028+15353236313112112010100010000002110110923221432321133222131438017.0529.9132.9636.2542.7240.4928.6750.0124.0948.433333123312433332348--43233133411433344453

SW0677/11/12515/12/59college 2yrMC1htn, DMAzilect,celexaSeroquel3026535223621211119010000000000001101000413211221211211112111284354.9349.5155.3648.1748.9751.455.8850.0151.9951.1244444134413413344459spouse44433134411434444358

DK0687/11/12472/17/63UMC1OSA30265343236113222314000100000001001000100412111311111122111111253954.9356.8555.3655.3255.2129.5855.8858.4654.8349.8144444144413423434461

EC0697/10/12468/25/58UMC3depressionRBDSinemet, nuedextaZoloft,midodrine, florinef30192342035344443325130200000023202221123263434133443113324342557414.9417.6737.1836.2536.4813.229.2327.4828.9721.873222224421433431345--2231212411432412351444422.9459.14921

MG0707/12/12719/15/39HSMC2htn3021+14362106313122315000000000100001101112812111311114141121112314723.3629.9151.1332.9152.0918.6728.6735.9335.2434.7422422344413443444357wife2241122232344444435122152427.3974.815662

CC0717/18/125310/5/55UFC3migraines, RLSSinemetmidrinmidodrine, florinef302313632463223133170101000003111012010201422321442312313112223446648.6144.6137.1825.76336.3629.5855.8841.5637.8141.6644434114311434443355husband3342313441142323334921112831.2643.185943

MH0727/18/12636/25/46UFC425163201464133113160100001111112122011111832321332231213332132456317.0517.6729.1545.7833.3613.2213.1233.1127.6125.6411211111122432443337husband3343323431243343335418124544.2430.945224

EM0732/17/12608/30/50HSFC5amitriptyline, trazadonetopiramateRiluzole3016+1314110612113111001101110030--002--020101313223343111122331141425925.4732.3637.1836.2542.7240.4928.6750.0129.8645.7632323343433444443359husband321213121334323211382217374251.6829.8640.345.7662595938513

AJ0742/17/126/25/52MastersFAA5zolipedemRiluzole3022234322611111117000000000000002201110721111311122111113212294614.9517.6732.9632.9127.1113.229.2338.7424.0425.5443333133413444444459daughter443321224114234333492522352934.0224.0446.4425.546059604967

LL0752/17/124/13/6412th gradeFC5neurontinprovigilneudexta, tizanidine3021+113332362155135220101100001011020101111212111113111121111211253921.2627.4729.1535.348.977.7624.7858.4622.8843.2244444134413444444464daughter444341244134444444622322435125.4423.3627.6437.9615533491524

GS0762/17/1211/23/55UFH5lexapro302233420461112011000131122111132412422442311334332124518114.9420.1232.9636.2542.7224.1317.0144.3823.3637.922444124412443443355son433221432214322344491822414034.5953.4848.1350.8349645768

RL0776/8/129/16/50college 1yrMC5riluzole, baclofen301913431161122115130001002001100021110201222211331111122431121355114.9417.6737.1845.7839.618.679.2341.5628.2930.73332124311334333345--333221233132243333462217294941.5238.2440.9426.38496261519

RB0784/13/126/7/60college 1yrMC5Celexaxanaxriluzole3022336220611111117000101000011010110001823232222321222221212405754.9349.5162.1240.0667.740.4951.9950.0153.4850.8344443444323433344464--34433134323333344457302732.5361.459594

BG0794/13/12439/21/6712FH5headache, PBAcelexaneurontinriluzole, guanfacine3024+133631263434444261111111113111112121222723242313323322323323516714.9417.6762.1225.7639.613.229.2341.5631.2527.123131333313422322241?cousin44444444411444443364273427.3262.459516

JV0803/16/126/5/57college3.5yrMH5PBAneudexta, riluzole30224341235345355530000000000001000111010523121332323111112212375552.8251.9637.18505552.09404944.2238.7451.6840.334444144412444443462263923.8147.68503514

LG0813/16/125/28/3211thMC5htncymbaltaneuontin3016+12342104112111181001001000111122021231923322422322223232242496752.8222.5732.9629.136.4818.6720.8941.5638.2426.384344414441144444446243444144411444344461283235.4351.27514912

LP0826/8/121/1/42FC5lipid, htnneudexta, riluzole, provigil3030536325611112118000110000001001000000412111211112213112111274419.1549.5155.3638.6345.8545.9455.8858.4632.5361.44433414241144444445944444144213332444459222725.4629.71535810

JD0838/30/12659/12/44mastersMC4stroke, hyperlipidSinemettrazodonepropranolol2512312204111111170000000000003033003121521111311121123111111274250.7217.6751.1332.9136.487.769.2358.4640.9425.86313341332333211137spouse3122141212222322113415284421.9845.5527

WH0848/29/12664/29/42collegeMC3sinemetmelatoninFlexeril, vesicare3027436324511211118000000000000001200010412111111112111111111223746.5139.7141.4136.2548.9751.451.9958.4636.4658.2343444134422444434462wife33434133433444434360

DK0858/24/12553/15/4912thFC2htnmetoprolol3023+11362236111111170120110000011112001011312121111212111112141284319.1517.6729.1537.6864.5851.444.2258.4615.5368.7141344334313444423357wife43444223412444422255

CP0868/29/12669/25/42masterMInd3htn, cholesterol, RASinemetmidodrine, coQ, methotrexate301622400352131121111212101211001121111232532332333331123222232486657.0325.0255.3628.1527.1140.4944.2235.9344.083432333223222432333348wife22322223222432333244

CF0874/13/12551/26/55collegeFC5nudexta, flexeril, sudafed30273363246111211180001000000100110101061211121111141144142345319.1532.3650.2948.1748.8540.4955.8858.4627.3262.443434134412444443359spouse43223242412444422251243153.0549.066149

SS0888/24/12462/28/6412thMC5DMamitriptylineneurontinTizanidine3024+1534212632431316011000000100001100010612221222121122222222355127.5729.9155.3629.152.0940.4932.5647.1934.0246.4433444134411444444460none263550.9648.424130

CW0897/13/12618/5/46collegeFC5DMtazodoneriluzole, baclofen30263363236212111190101000000010122011131422221332121232221222395917.0517.6746.0645.7830.2429.5840.3350.0123.8147.6831433233313334432250husband21311321131242421135223632.0936.315341

LD0909/21/12606/5/47F5htnlexapronuedexta302333610463232121140011012310100110000121512412332122144212132436410.7315.2245.6428.1533.3624.1313.1230.325.4427.6432444144412444444461spouse43434144411424444459232825.5947.6345

JK0915/13/123/28/50collegeMC5cognitiveamitriptylineLithiumnorco, nudexta, riluzole2418534015352333322000000000100101011010642311321111144122241415814.9456.5841.8341.0542.7235.0355.8835.9334.5948.1333333322212334333349son44423244421434443460242429.3357.4362

DS0927/13/12569/13/52collegeFC5neurontinTizanidine30285353246111111171010001000100210101121212111221211231221114325017.0537.2651.1343.461.4651.424.7850.0135.4351.274423343431144323351son33233222332344422249

DC0936/8/12607/9/52collegeMC5mucinex, riluzole30225340236413113114000000000001001101010531311331111121111111294544.4127.4762.1237.6830.2435.0332.5658.4641.5240.944442213331342433349wife232111321242232233

AS0945/12/12715/12/379th/GEDMC5htn, DMpaxilriluzole, atenolol, mucinex302233411451111111701010000000000220103010111131222211132111274214.9417.6750.292133.3618.679.2344.3825.4629.7141144234411443433353wife44424124412443434458

LF09510/12/12741/8/37college 2yrFAA4dementia, depression, anxietyhtn,Sinemetpaxil, busparexalon, nameda3014032122411111117011000000000000000101421221332222233232232446614.9434.8129.1541.0258.3345.9444.2247.1922.9459.132332134313434333149daughter42133233332224433350

RB09610/12/12665/6/46MAMC2depress, hallucinationStalevo, Sinemet CR, ParcopanamedaKeppra302743632363241242180211001101010112000111421332322231231333232466440.234.1841.4145.7842.7240.4928.6744.3841.9338.7732234234413223323349wife32434243413223422250

NR09711/8/12726/29/40MC2htnSinemet30221342246111111170302000030000023000021511141111112111111111243914.9437.2662.1236.2570.8256.8555.8864.0927.3974.813344433331144444456daughter111111111212411121

LA09810/17/12524/14/561 yr collegeFC3depressionmirapexeffexor30274353246313112213010000000110001011110812111111111111111112223717.0520.1246.0641.0239.6404936.4450.0124.4150.943444144411444444462spouse43444144412444444463

RB09911/8/12736/4/35high schoolMC3htnmidodrine30213342026111111170001000000011110001231121121221111113212111284321.2617.6762.1233.8736.4845.949.2361.2731.2643.1842443134421444434459wife43333344421444444462

BF10011/8/12677/27/434yr collegeMC4lipidazilect30180352115111111171101002000010110100121232332332131133231132456329.6734.8162.1235.339.635.0336.4424.6644.2430.9432444324311334143352wife23333323311232232243

GR1011/24/135511/4/4710 yearsMH2dementia, depressionhypertensionsinemet CR, azilectcelexanamenda, aricept30143311005345223322132222130130211110130304341324122134142132476525.4725.0262.1225.7633.3624.1317.0124.6640.2720.473112241224444444335221112114444444444453

RM1021/10/13715/28/363rd gradeMH2depressionhtnmirapexcelexanamenda30151321006111111170003000000133032133332841141421141144131141446114.9417.6751.1335.327.1124.1355.8835.9321.9845.5511111411143111211127daughter11111111144111111124

NC10311/10/125510/25/5513 yrFC5Cymbaltariluzole30244363116111111170000000000000010020104111111111111211111111314950.7256.8551.1357.758.3324.1355.8855.6453.0549.0643444134411444444461

KC10411/9/12586/16/5412yrsMC5cholesterolriluzole3026336223611111117010000000000000000010222322232221111122211355154.9347.0662.1237.6852.0940.4951.9952.8250.9648.4234211133313312332241spouse44433134311113433349

BF10510/12/12676/22/45FC5ativan3022334312611211118010100000000011301121112111321221224112142365517.0527.4750.2942.4539.618.6713.1255.6432.0936.3133333143312444333353

RL1068/24/127411/13/37MC5htnlexaprogabapentinriluzole, ultram30234352126111111170101000030000020011331511221321121111111221284331.7827.4746.0625.7627.1124.1351.9952.8225.5947.6331233322312444421145wife21121111322321411130

RA1071/30/13672/15/45MBAMC4aphasiacholesterol3022325312611111117000000000000000000101211114114411111111114324840.247.0662.1217.1827.1129.5851.99-0.6850.7717.3244444134134434344462

HM1082/8/13581/27/53MC5ambien3024536211611111117010000100000011000011621121211111111121111243925.4725.0262.1235.348.9735.0355.8852.8229.3357.4343444144411444444462son4232312111434422241

25 ALS

8 CBD

11 PSP

10 MSA

Cecilia Santa-Maria8/9/12FH425/293352out of 2156mail back questionaire

Cecilia Santa-Maria8/9/12FH425/293352out of 2156mail back questionaire

Sward, Shirley9/12/12>12yrsF3will mail in survey18 out 25--352125mail back questions

Phothivongsa-Jordan, Manilay11/30/12FA2will mail in survey21/305151036mail back questions

Beale, Thomas10/15/12collegeMC4

PD 1

PSP 2

MSA 3

CBD 4

ALS 5

Failed

NG004172223106

Dilworth, Paula3/12/12417/28/68collegeFC1nonenone274362246NOT COMPLETED

Eagan, Ronald3/22/12695/19/42collegeMC1depressionlipid, htn, cog impSinemet15/290/4311023NOT COMPLETED

Ciavarella, susan7/5/12BSF254353226

William Knight MSA

ID

Subject IDfirst namelast name

HB001HowardBurch

SM 002MarciaSaade

JW 003JohnWest

SL 004SandraLankford

DT 005DianaTaylor

TL 006TracyLewis

OM 007OthaMayton

BM 008BeverlyMaffett

DH009DonaldHolloway

PF010PatriciaFurru

LW011LindaWygoda

AS012AnneSullivan

DW013DavidWilhem

CM014CarlMcGinnis

TS015ThomasSparkman

WC016WilliamCrutcher

KC017KathleenCarney

CH018ChristineHemingway

DV019VerlinDouglas

PR020PaulineRab

AC021CortezAnn

JC022JanetCarpenter

KK023KathrynKohlhaas

JP024JamesPate

PP025PatriciaPennington

MA026MargaretAltman

LL027LarryLevien

BA028BarbaraAlford

BK029BillKeene

JB030JohnBowman

VW031VanessaWatley

RL032RobertLee

RN033RichardNewell

VW034VertieWard

SB035ShannonBayard

JW036JohnWorden

KT037KurtThomas

WF038WilliamFagan

CS039CharlesSterling

FG040FrankGargallo

EB041EricBurger

EM042EricMartindell

RW043RobertWoodbridge

GB044GoldaBaker

PC045PhillipCallahan

DM046DouglasMaclay

BB047BobbyBrewer

LG048LisaGary-Jones

GS049GeraldStutsman

DT050DanielThixton

LF051LeeFazzino

SE052SharonEddins

MS053Mary HelenSherrod

MN054MichealNall

TB055TomBeasley

ST056SenenTorres-Dbrasis

MW057MarshaWeets

RM058RobertManning

TT059TommyTrantham

MS060MarilynSweger

JR061JaneRodgers

GM062GeorgeMixson

RR063RichardRikard

JD064JulesDock

MM065martinMorales

MF066MayFreeman

SW067SamWright

DK068DarrellKurtz

EC069EddieChancy

MG070MurphyGuillory

CC071ConnieChambers

MH072MaryHight

EM073ElizabethMetcalf

AJ074AngelaJohnson

LL075LauraLee

GS076GracieSanchez

RL077RoyceLucas

RB078RickBodish

BG079BrendaGonzalez

JV080Joseph CruzValdez

LG081LillianGautreaux

LP082LouisePettigrove

JD083JamesDepoe

WH084WilliamHiltpold

DK085DonaldKonrad

CP086ChanduPatel

CF087ColleenFried

SS088SteveSourders

CW089CherylWarren

LD090LindaDoucette

JK091JamesKrystaponis

DS092DeborahSimmons

DC093DavidComstock

AS094AuburnScheffer

LF095LeocadiaFusilier

RB096RobertBaker

NR097NorbertRobson

LA098LindaAdams

RB099RaymondBrown

BF100BillFugit

GR101GeorgeRivas

RM102RambaldoMartinez

NC103NancyCarmack

KC104KennyCassell

BF105BenneFisher

RL106RobertLimbaugh

RA107RussellAdams

pts-wk

Total patientsParkinsonismEnrolledScreen fail/incomplete

1/24/12-1/27/1211631- incomplete

1/30/12-2/3/1218721-incomplete

2/6/12-2/10/122274FB-not enrolling

2/13/12-2/17/121475FB-not enrolling

2/20/12-2/24/121665FB- missed 1

2/27/12-3/2/121511

3/5/12-3/9/121653FB-missed 1 declined

3/12/12-3/16/1211412 cant read, 1 MK didn’t complete

3/19/12-3/23/1219431-NP not complete

3/26/12-3/30/121533MK, RM- missed

4/2/12-4/6/1217541-no english

4/9/12-4/13/121122

4/16/12-4/20/122322

4/23/12-4/28/12000AAN

04/30/12-5/4/1218511- no eng, 1- decline, FB-2

5/7/12-5/11/121654

5/14/12-5/18/121662

5/21/12-5/25/121874

5/28/12-6/1/12610

6/4/12-6/8/121221

6/11/12-6/15/121665

6/18/12-6/22/12730

6/25/12-6/30-121441

7/2/12-7/6/121252

analysis

DiagnosisnMoCA-PBA PDMoCA-noPBA PDBDI-PBA PDBDI-no PBA PDAnx-PBA PDAnx-no PBA PDSFPH-PBA PDSFPH-noPBA PDSFMC-PBA PDSFMC-no pBA PDSA-PBA PDSA-noPBA PDOap-PBA PDOap-noPBA PDMoCA-PBA ALSMoCA-noPBA ALSBDI-PBA ALSBDI-noPBA-ALSAnx-PBA ALSAnx-noPBA ALSSFPC-PBA ALSSFPC-noPBASFMC-PBAALSSFMC-noPBA ALSSA-PBA ALSSA-noPBA ALSOA-PBA ALSOA-no PBA ALSMoCA-PBA aPMoCA-noPBA aPBDI-PBA aPBDI-no PBA aPAnx-PBA aPAnx-no PBA aPSFPH-PBA aPSFPH-noPBA aPSFMC-PBA aPSFMC-no pBA aPSA-PBA aPSA-noPBA aPOap-PBA aPOap-noPBA aP

PSP11aPD292428137354920.2431.3640.348.45563554422241223254722.8833.1343.2228.326440624229181124433029.618.7441.7945.454355832

MSA10ALS262829215513751.0851.6944.0250.695957616319281217354028.2922.3430.738.984546465321221324284826.9730.6367.9229.6759436156

CBD8PD532428159553260.1243.6931.3551.49605455462526278512731.2526.3927.1261.74152645024241312484250.3333.6745.2735.6441543331

PD532217513374251.6829.8640.345.766259593824131722455147.4837.8134.8429.948284162

ALS2627251810414542.8224.3933.6741.454534458252267352934.0224.0446.4425.54605960491930264552628.9745.4521.8750.0245633557

aP292614217582934.242.6239.5844.195653635323221524435125.4423.3627.6437.96155334927121415462741.9340.4938.7725.8649375060

182268414034.5953.4848.1350.83496457222887312735.2453.1434.7460.9957595144

%PBAntotal%2217519294941.5238.2440.9426.384962612326147443237.8123.0941.6638.3755474961

PD115320.83042732.5361.459591622189454627.6139.2325.6448.3137605434

ALS72629.21229131452421.7236.6832.3250.79365830582763427.3262.45951272784222224.4136.4650.958.2362626355

aP102934.52129149384051.3456.745.1448.325361564226143923.8147.68503514243013472840.2715.5320.4768.7152575344

28123235.4351.27514916254844.08344850

%PBAPDALSaP22102725.4629.7153581444422.9459.14921

%20.829.234.528281312284053.5454.5748.4748.815841536022152427.3974.815662

2122202424231.145.1246.2962.355060475121112831.2643.185943

1725165562520.3539.2540.4751.745355555918124544.2430.945224

15284421.9845.5527

26291423256154.8322.5949.8138.23614161243153.0549.066149

23103634.8344.025260263550.9648.424130

3073250.8230.365555223632.0936.315341

2873144.4254.796334232825.5947.6345

2853340.443.76361242429.3357.4362

27134139.8636.625365

2712558.7852.915642

25274310.2449.145960

19193116.5552.884261

26155145.1351.026342

2942447.0822.095648

2853050.155.283763

22133431.9326.294262

2322753.0452.196257

27165063.0157.195863

2512551.7657.285451

28165067.5935.985357

2783455.5842.336153

2693255.82256.965758

28164739.4451.8347

2552949.3541.552

1642735.6843.5859

2502348.1547.3463

222046.2357.4554

27482428.6563.5159

2104258.2755.0656

26122043.9159.5152

2523351.8655.0161

2462838.5933.6850

2854361.516157

2992824.0934.7948

26451.9939.1459

mean23.090909090925.61904761916.18181818189.24390243943.090909090934.560975609840.121818181843.888571428641.038181818248.4

sd5.00908265963.49181887723.25017482058.762934690511.17546012889.721236496715.135437105112.73709075256.423598396851.12

analysis

%

% Diagnosed with PBA

Prevalence of PBA